Note: Descriptions are shown in the official language in which they were submitted.
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SYSTEMS DEVICES, AND METHODS FOR BODILY FLUID SAMPLE
COLLECTION, TRANSPORT, AND HANDLING
BACKGROUND
[0001] A blood sample for use in laboratory testing is often obtained by
way of
venipuncture, which typically involves inserting a hypodermic needle into a
vein on the
subject. Blood extracted by the hypodermic needle may be drawn directly into a
syringe or
into one or more sealed vials for subsequent processing. When a venipuncture
may be
difficult or impractical such as on a newborn infant, a non-venous puncture
such as a heel
stick or other alternate site puncture may be used to extract a blood sample
for testing. After
the blood sample is collected, the extracted sample is typically packaged and
transferred to a
processing center for analysis.
[0002] Unfortunately, conventional sample collection and testing techniques
of bodily
fluid samples have drawbacks. For instance, except for the most basic tests,
blood tests that
are currently available typically require a substantially high volume of blood
to be extracted
from the subject. Because of the high volume of blood, extraction of blood
from alternate
sample sites on a subject, which may be less painful and/or less invasive, are
often disfavored
as they do not yield the blood volumes needed for conventional testing
methodologies. In
some cases, patient apprehension associated with venipuncture may reduce
patient
compliance with testing protocol. Furthermore, the transportation of small
volumes of
sample fluid, while still maintaining sample integrity, can be problematic.
SUMMARY
[0003] At least some of disadvantages associated with the prior art are
overcome by
at least some or all of the embodiments described in this disclosure. Although
the
embodiments herein are typically described in the context of obtaining a fluid
sample such as
but not limited to a blood sample, it should be understood that the
embodiments herein are
not limited to blood samples and can also be adapted to acquire other fluid(s)
or bodily
sample(s) for analysis.
[0004] In one embodiment described herein, a device is provided for
collecting a
bodily fluid sample. In embodiments, the bodily fluid may be blood. In
embodiments where
blood is collected, this embodiment may be useful for accurately collecting
small volumes of
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bodily fluid sample that are often associated with non-venous blood draws. In
one non-
limiting example, the sample volume is about 1 mL or less. Optionally, the
sample volume is
about 900 uL or less. Optionally, the sample volume is about 800 uL or less.
Optionally, the
sample volume is about 700 uL or less. Optionally, the sample volume is about
600 uL or
less. Optionally, the sample volume is about 500 uL or less. Optionally, the
sample volume
is about 400 uL or less. Optionally, the sample volume is about 300 uL or
less. Optionally,
the sample volume is about 200 uL or less. Optionally, the sample volume is
about 100 uL or
less. Optionally, the sample volume is about 90 uL or less. Optionally, the
sample volume is
about 80 uL or less. Optionally, the sample volume is about 70 uL or less.
Optionally, the
sample volume is about 60 uL or less. Optionally, the sample volume is about
50 uL or less.
100051 In one non-limiting example, this device can be used to split the
bodily fluid
sample directly into two or more different portions that are then deposited
into their
respective sample vessels. In one non-limiting example, the device comprises a
first portion
having at least two sample collection channels configured to draw the fluid
sample into the
sample collection channels via a first type of motive force, wherein one of
the sample
collection channels has an interior coating designed to mix with the fluid
sample and another
of the sample collection channels has another interior coating chemically
different from said
interior coating. The sample collection device includes a second portion
comprising a
plurality of sample vessels for receiving the bodily fluid sample collected in
the sample
collection channels, the sample vessels operably engagable to be in fluid
communication with
the collection channels, whereupon when fluid communication is established,
the vessels
provide a second motive force different from the first motive force to move a
majority of the
bodily fluid sample from the channels into the sample vessels. The sample
vessels may be
arranged such that mixing of the fluid sample between the vessels does not
occur. This
device may be used to collect blood or other bodily fluid. Blood collection
from veins may be
relatively rapid; however, non-venous blood draws may take a longer period of
time to obtain
a desired volume of sample and the early introduction of a material such as an
anti-coagulant
which may coat the channels, can prevent premature clogging of the channels
during
collection.
100061 In another embodiment described herein, a device is provided for
collecting a
bodily fluid sample. The device comprises a first portion comprising a
plurality of sample
collection channels, wherein at least two of the channels are configured to
simultaneously
draw the fluid sample into each of the at least two sample collection channels
via a first type
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of motive force. The device may also include a second portion comprising a
plurality of
sample vessels for receiving the bodily fluid sample collected in the sample
collection
channels, wherein the sample vessels have a first condition where the sample
vessels are not
in fluid communication with the sample collection channels, and a second
condition where
the sample vessels are operably engagable to be in fluid communication with
the collection
channels, whereupon when fluid communication is established, the sample
vessels provide a
second motive force different from the first motive force to move bodily fluid
sample from
the channels into the sample vessels. In embodiments, motive force to move a
bodily fluid
may include motive force derived from capillary action, from reduced pressure
(e.g., vacuum
or partial vacuum drawing fluid into a location having reduced pressure), from
increased
pressure (e.g., to force a fluid away from a location having increased
pressure), from wicking
material, or from other means.
100071 In a still further embodiment described herein, a method is
provided
comprising metering a minimum amount of sample into at least two channels by
using a
sample collection device with at least two of the sample collection channels
configured to
simultaneously draw the fluid sample into each of the at least two sample
collection channels
via a first type of motive force. After a desired amount of sample fluid has
been confirmed to
be in the collection channels, fluid communication is established between the
sample
collection channels and the sample vessels, whereupon the vessels provide a
second motive
force different from the first motive force use to collect the samples to move
bodily fluid
sample from the channels into the vessels. In some alternative embodiments,
devices that use
only a single channel to collect the body fluid or devices that have a
plurality of channels but
do not collect them simultaneously are not excluded. Optionally, the
collection of sample
fluid is performed without the use of a wicking material.
[0008] In one embodiment, there is a discrete amount of time between
sample
collection and introduction of the sample into a sample pre-processing device.
In one non-
limiting example, the process is a non-continuous process. The sample
collection occurs in
one processing station and then the sample is taken to a second station. This
second station
may be in the sample building. Optionally, the second station may be located
at another
location where the sample needs to be walked, driven, flown, conveyor-ed,
placed in a
transport device, or placed in a transport container to reach the second
location. In this
manner, there is a discrete break in the processing to allow for time
associated with sample
transport.
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100091 In another embodiment herein, separator gel(s) can also be
included in the
sample vessels such that the gels will separate cell-free fractions of whole
blood from the
cellular or other solid or semi-solid portions of the sample. Such a gel or
other similar
separator material may be included in the sample vessel prior to, during, or
after sample has
been introduced into the sample vessel. The separator material may have a
density between
that of the cells and solution components, so that the material separates the
sample
components by flowing to a position between the solution and non-solution
sample layers
during separation such as by centrifugation. Following centrifugation, the
separator material
stops flowing and remain as a soft barrier between the layers. In some
embodiments, the
separator material can be further processed to harden into a more rigid
barrier. In on non-
limiting example, the separator material may be a UV-curable material such as
but not
limited to thixotropic gel of sorbitol-based gelator in a diacrylate oligomer.
The sample
vessel may have the entire vessel or optionally, on that portion with the UV-
curable material
exposed to UV light for a period of time such as but not limited to 10 to 30
seconds to harden
the material. Such hardening may involve cross-linking of material in the UV-
curable
material. Optionally, the UV curable material may be used in conjunction with
traditional
separator gel material such that only one side (the solution side or the solid
side) is in contact
with the UV cured material. Optionally, the UV cured material may be used with
a third
material such that the UV cured material is between two separator materials
and is not in
direct contact with the solution and non-solution portions of the sample.
100101 Samples of bodily fluid may be collected by the devices disclosed
and
described herein. Methods of collecting bodily fluid using these devices are
disclosed and
described herein. Samples of bodily fluid, e.g., samples that have been
collected by the
devices and/or methods disclosed and described herein, may be transported from
a sample
collection site to one or more other sites.
100111 In at least one embodiment described herein, methods are provided
for the
physical transport of small volumes of bodily fluid in liquid form from one
location to
another location. By way of nonlimiting example, the samples are collected in
liquid form at
a collection site, transported in liquid form, and arrive at an analysis site
in liquid form. In
many embodiments, the liquid form during transport is not held in a porous
matrix, wicking
material, webbing, or similar material that would prevent sample from being
extracted in
liquid form at the destination site. In one embodiment, small volume of sample
in each
sample vessel is in the range of about 1 ml to about 500 microliters.
Optionally, small
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volumes are in the range of about 500 microliters to about 250 microliters.
Optionally, small
volumes are in the range of about 250 microliters to about 100 microliters.
Optionally, small
volumes are in the range of about 100 microliters to about 50 microliters.
Optionally, small
volumes are in the range of about 80 microliters to about 40 microliters.
Optionally, small
volumes are in the range of about 40 microliters to about 1 microliter.
Optionally, small
volumes are in the range of about 1 microliter to about 0.3 microliters.
Optionally, small
volumes are in the range of about 0.3 microliters or less.
100121 As disclosed and described herein, a transport container may
include a
component configured to receive and retain a sample vessel. In embodiments, a
component
configured to receive and retain a sample vessel may be configured to receive
and retain a
plurality of sample vessels. In embodiments, such a component may comprise a
flat sheet,
such as, e.g., a tray. In embodiments, such a component (e.g., a flat sheet)
may comprise an
opening (e.g., a slot, aperture or receptacle) having an internal surface
configured to accept a
sample vessel. In embodiments, a transport container may include a component
comprising a
plurality of openings (e.g., slots, apertures or receptacles) each having an
internal surface
configured to accept a sample vessel. In embodiments, such an internal surface
may be, at
least in part, substantially complementary to the outer surface, or a portion
thereof, of a
sample vessel.
100131 In another embodiment described herein, the transport container
may provide
a high density of sample vessels per unit area held in a fixed manner during
transport, but
removable at the destination location. In one non-limiting example, the sample
vessels are
positioned in an array where there are at least six sample vessels per square
inch, when
viewing the array from top down. Optionally, there are at least eight sample
vessels per
square inch, when viewing the array from top down. Optionally, there are at
least ten sample
vessels per square inch, when viewing the array from top down. Any traditional
techniques
that ship multiple samples typically use large bags where the sample vessels
therein are in a
loose, unconstrained manner. In some embodiments, the transport container can
hold certain
sample vessels such as those from the same subject, closer together relative
to horizontal or
other spacing to adjacent sample vessels so that they can be visually
identified as being from
a common subject. Optionally, the transport container has openings to receive
carriers that
hold one or more sample vessels together, wherein those vessels have a common
denominator
such as but not limited to being from the same subject.
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10014] In embodiments, the sample vessels are adapted to aid in
maintaining the
samples in liquid form. In embodiments, the sample is treated prior to its
arrival in a sample
vessel in a manner adapted to maintain the sample in liquid form. For example,
a sample
vessel may include an anti-coagulating agent, or a sample may be treated with
an anti-
coagulating agent prior to, or during, transport to or into a sample vessel.
In embodiments, an
anti-coagulating agent may be selected from the group consisting of heparin
(e.g. lithium
heparin or sodium heparin), ethylenediaminetetraacetic acid, 4-hydroxycoumar.
ins, vitamin K
antagonist (VKA) anticoagulant, an anti-coagulant, or other additive. In
addition to the high
density per unit area, some embodiments of the transport container also
contain a high
diversity of samples, including those that contain samples from a plurality of
different
subjects. By way of non-limiting example, the transport container may have
four samples
from one subject, two samples from another subject, and so-on until the
majority or all of the
available openings in the transport container are filled.
100151 It should be understood that each of the samples can be destined
for
individually selected analysis and at least in one embodiment, are not grouped
in the transport
container based on tests to be performed. By way of non-limiting example, not
all of the
samples in the transport container are collected for the same test. A
traditional test system
may only group together for transport those samples destined for the exact
same test. In at
least one of the embodiments herein, there is a diversity of samples, each
designated to
receive its own set of tests. In such an embodiment, grouping in the transport
container is not
restricted to only those samples targeted for the same test. This can further
simplify sample
processing because sample transport does not need to be further segregated
based on tests to
be performed. Some embodiments of the transport container contain samples from
at least
three or more different patients. Some embodiments of the transport container
contain
samples from at least five or more different patients. Some embodiments of the
transport
container contain samples from at least ten or more different patients. Some
embodiments of
the transport container contain samples from at least twenty or more different
patients.
100161 By way of non-limiting example, one embodiment described herein
may
optionally use tray(s) that have slots for holding the sample vessels and/or
sample vessel
holders. In one embodiment, the tray may also double as a holding device
during storage in a
cooling chamber while awaiting more samples or transport. In one embodiment,
the tray can
itself also be cleaned and sterilized, because in some embodiments, the tray
is removable
from the transport container. In some embodiments, the tray in the transport
container may
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be held in manner parallel to a cover of the transport container. Optionally,
the tray may be
held inside the transport container at an angle to the cover of the transport
container.
Optionally, the tray is irremovably fixed to the transport container.
Optionally, the tray is
integrally formed with the transport container itself Optionally, multiple
trays of same or
different size or configuration may be placed inside the transport container.
100171 In yet another embodiment described herein, methods are provided
for
shipping small volume sample vessels using a transport container with
integrated thermal
control unit and/or material that provides active and/or passive cooling. In
one embodiment,
the thermal control material may be but is not limited to embedded phase
change material
(PCM) material that maintains the temperature at a prior, or desired
temperature. By way of
non-limiting example, the phase change material can oppose changes in
temperature around
the critical temperature where the material would undergo a phase change. If
the PCM is
embedded, the vessel and the passive cooling element may be one and the same.
Optionally,
the transport container may use an active cooling system. Optionally, the
transport container
may use an active cooling system to keep and/or extend cooling time associated
with a
passive cooling component. In embodiments, a transport container may include
material
having a high heat capacity (i.e., high as compared to material such as a
plastic or polymeric
material), and may include a mass of such a high heat capacity material
effective to maintain
at least a portion of the transport container at or near to a desired
temperature for an extended
period of time.
100181 Optionally, the method comprises a single step for transferring
multiple
sample vessels from different subjects from a controlled temperature storage
area into a
transport container. By way of non-limiting example, this single step can
transfer twenty-
four or more sample vessels at one time from a storage location into a fixed
position in the
transport container. Optionally, this single step can transfer thirty-six or
more sample
vessels at one time from a storage location into a fixed position in the
transport container.
Optionally, this single step can transfer forty-eight or more sample vessels
at one time from a
storage location into a fixed position in the transport container. In such
embodiments, the
tray may be initially in a controlled thermal environment such as but not
limited= to a
refrigerator wherein samples from various subjects are collected over time
until a desired
number is reached. In one such embodiment, the tray holding the sample
vessel(s) in the
transport container is the same tray holding the sample vessels in the storage
area.
Optionally, the tray may be the same as the storage holder that is used to
hold samples prior
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to loading into the transport container. Because the same tray which holds the
sample vessels
will be used in the transport container, there is reduced risk that samples
will be lost during
this transfer, left out in a non-regulated thermal environment, or the like.
Because
substantially all sample vessels in the tray are accumulated in the controlled
thermal storage
area and then transferred in a single step, the samples all experience
substantially the same
thermal exposure while being transferred from the control thermal storage area
into the
transport container. Because sample vessels experience substantially the same
exposure,
there is less variability sample-to-sample due to different exposure times.
100191 Optionally, the method comprises using an individually addressable
sample
vessel configuration. Optionally, groups of sample vessels such as those in a
common carrier
may be addressed in the pre-defined groups. Optionally, even sample vessels in
a common
carrier may be individually addressed. Although not a requirement for all
embodiments
herein, this can be of particular use when loading and/or unloading samples,
sample vessels,
and/or sample holders from the tray.
100201 Some embodiments may use yet another container (an "outerbox")
outside the
transport container to provide further physical protection and/or thermal
control capability.
One or more of the transport container can be placed inside the outerbox and
the combination
may be shipped from one location to a destination location. By way of non-
limiting example,
this can be in the form of a corrugated plastic outerbox, where the outerbox
is configured to
at least partially encase or enclose a transport container. In embodiments, an
outerbox
provides thermal insulation for a transport container enclosed therein. Some
embodiments
may use closed-cell extruded polystyrene foam outerbox. Some embodiments of
the
outerbox may be formed from thermoformed panels. In some embodiments, an
outerbox may
have grips, handles, pads, wheels, latches, stays, and/or other features
useful in holding,
manipulating, securing, protecting, transporting, or otherwise controlling the
position,
orientation, and/or access to the contents of the outerbox. Some embodiments
of the
outerbox may have its own active and/or passive thermal control unit. In
embodiments, an
outerbox provides cooling and thermal insulation for one or more transport
containers
enclosed therein. One or more embodiments of the outerbox may be configured to
house one
or more transport containers. Optionally, this container can also provide
additional thermal
control to the transport container by providing a thermally regulated
environment between a
desired temperature range to the transport container(s) therein. Optionally,
this temperature
range is between about 1 to 10 C, optionally 2 to 8 C, or between 2 to 6 C.
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[0021] In yet another embodiment described herein, a method is provided
for
thermally characterizing the transport container after a number of cooling
cycles. By way of
non-limiting example, after certain number of cycles, the transport container
may be
thermally characterized to ensure that the container is continuing to perform
within a desired
range.
100221 Some embodiments of the container and/or tray may include a
thermal change
indicator. In one non-limiting example, the indicator is integrated on a
visible surface of the
transport container, tray, and/or on the outerbox. In one non-limiting
example,
thermochromic ink may be used as an indicator of thermal change, particularly
if the thermal
change resulted in temperatures outside a desired range. In one embodiment,
this indicator
may be configured to have the entire box and/or tray change color. The change
can be
reversible or irreversible. Optionally, the indicator is positioned to be on
only select portions
of the transport container and/or tray, not the entire container or tray.
[0023] In one embodiment described herein, a method is provided
comprising
collecting a bodily fluid sample on a surface of a subject, wherein collected
sample is stored
in one or more sample vessels; providing a transport container to house at
least two or more
sample vessels in a first orientation; and arranging to have the sample
vessels shipped in the
transport container from a first location to a second location, wherein each
of the sample
vessels arrives at the second location holding a majority of its bodily fluid
sample in a non-
wicked, non-matrixed form that is removable from the sample vessels in liquid
form and
wherein the amount of sample in each of the sample vessels does not exceed
about 2m1. In
embodiments, the amount of sample in each of the sample vessels does not
exceed about 1
ml, or does not exceed about 500 L, or does not exceed about 250 tiL, or does
not exceed
about 100 vtL, or does not exceed about 501.1t, or less.
[0024] In another embodiment described herein, a method is provided for
shipping a
plurality of sample vessels, the method comprising: providing a container
configured to
house at least five or more sample vessels each containing capillary blood;
and arranging to
have the sample vessels shipped in the transport container from a first
location to a second
location, wherein each of the sample vessels arrives holding a majority of its
capillary blood
in a liquid, non-wicked form that is removable from the sample vessels for
further processing,
and wherein the amount of capillary blood in each of the sample vessels does
not exceed
about 2m1. In embodiments, the amount of capillary blood in each of the sample
vessels does
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not exceed about 1 ml, or does not exceed about 500 L, or does not exceed
about 250 L, or
does not exceed about 100 L, or does not exceed about 50 L, or less.
[0025] In another embodiment described herein, a method is provided for
shipping a
plurality of sample vessels for containing biological sample, the method
comprising:
providing a container configured to house at least five or more of the sample
vessels, wherein
the amount of sample in each of the sample vessels does not exceed about 2m1;
and shipping
the container and sample vessels from a first location to a second location,
wherein each of
the sample vessels arrives at the second location holding a majority of its
biological in a
liquid, non-wicked form that is removable from the sample vessels for further
processing. In
embodiments, the amount of sample in each of the sample vessels does not
exceed about 1
ml, or does not exceed about 500 [IL, or does not exceed about 250 pt, or does
not exceed
about 100 tiL, or does not exceed about 50 4, or less.
[0026] In another embodiment described herein, a method is provided for
shipping a
plurality of sample vessels containing capillary blood, the method comprising:
providing a
container having a thermally-regulated interior region that is configured to
house at least five
or more sample vessels in a controlled configuration such that at least one
cooling surface of
the container is directed towards the sample vessels and transmits a
controlled release of
thermal cooling in accordance with a temperature profile that maintains the
interior region
between about 1 to 10 C during transport and without freezing the blood
samples; and
shipping the container from a first location to a second location, wherein
each of the sample
vessels arrives holding a majority of its capillary blood in a liquid, non-
wicked form that is
removable from the sample vessels for further processing.
[0027] In another embodiment described herein, a method is provided for
shipping a
plurality of blood sample vessels, the method comprising shipping a container
having a
thermally-controlled interior that is configured to house 10 or more sample
vessels in an array
configuration, wherein each of the vessels holds a majority of its blood
sample in a free-
flowing, non-wicked form and wherein there is about 1 ml or less of blood in
each of the
vessels and each of the vessels has an interior with at least a partial vacuum
atmosphere;
wherein sample vessels are held in the array configuration to position said
sample vessels at
controlled distance and orientation from a cooling surface, wherein there is
at least one
preferential thermal pathway from the surface to the sample vessel.
[0028] In another embodiment described herein, a method is provided for
shipping a
plurality of sub-1 ml sample vessels, the method comprising mixing sample with
anti-
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coagulant prior to transferring sample into each of the sample vessels;
associating each of the
sample vessels with a subject and a panel of requested sample tests; and
shipping a thermally-
controlled container that houses the plurality of sub-1 ml sample vessels in
an array
configuration, wherein each of the vessels holds a majority of its sample in a
free-flowing,
non-wicked form, wherein vessels are arranged such that there are at least two
vessels in each
container is associated with each subject, wherein at least a first sample
includes a first
anticoagulant and a second sample includes a second anticoagulant in the
matrix.
[0029] In another embodiment described herein, a method is provided
comprising a)
placing said plurality of sample vessels in a temperature controlled transport
container
comprising a controlled uniform thermal profile, high heat of fusion material
configured to be
in thermal communication with the sample vessels, wherein the material does
not cause
freezing of sample fluid in the sample vessels; b) placing said thermal
profile transport
container in a product cavity defined by at least top and bottom walls of a
transport
container; c) placing an active cooling device in thermal communication with
said cavity
whereby said cooling device is adapted to cool said cavity upon activation,
said sorption
cooling device comprising an absorber positioned so as to dissipate heat
generated in said
absorber outside of said product cavity; d) activating said cooling device to
initiate cooling of
said cavity; e) transporting said transport container from a first location to
a second location;
and f) removing said product from said cavity.
[0030] In another embodiment described herein, a method of shipping a
plurality of
sub-lml sample vessels is provided comprising: shipping a thermally-controlled
container
that houses the plurality of sub-lml sample vessels in an array configuration,
wherein each of
the vessels holds a majority of its sample in a free-flowing, non-wicked form
and wherein
vessels are arranged such that there are at least two vessels in each
container is associated
with each subject, wherein at least a first sample includes a first
anticoagulant and a second
sample includes a second anticoagulant in the matrix.
[0031] It should be understood that any of the embodiments herein can be
adapted to
have one or more of the following features. In one non-limiting example, the
bodily fluid
sample is blood. Optionally, the bodily fluid sample is capillary blood.
Optionally,
collecting the bodily fluid sample comprises making at least one puncture on
the subject to
release the bodily fluid, wherein the puncture is not a venipuncture.
Optionally, collecting
comprises using at least one microneedle to make at least one puncture on the
subject.
Optionally, collecting comprises using at least one lancet to make at least
one puncture on the
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subject. Optionally, the puncture is formed by finger prick. Optionally, the
puncture is
formed by pricking skin on a forearm of the subject. Optionally, the puncture
is formed by
pricking skin on a limb of the subject. Optionally, the surface is the skin of
the subject.
Optionally, the transport container has an interior that is initially at sub-
atmospheric
pressure. Optionally, the sub-atmospheric pressure is at least a partial
vacuum. Optionally,
the interior of the transport container is at a sub-atmospheric pressure that
is at least at a
pressure below ambient pressure. Optionally, the sub-atmospheric pressure is
selected to
provide sufficient force to draw a desired volume of sample into the sample
vessel.
Optionally, the transport container contains at least five or more sample
vessels. Optionally,
the transport container ships bodily fluid samples from a plurality of
different subjects.
Optionally, information associated with each of the sample vessels determine
what tests will
be run on the bodily fluid sample therein. Optionally, the transport container
is placed inside
another container during shipping. Optionally, the method further comprises
pre-processing
sample in the sample vessels prior to shipping to the second location.
100321 Optionally, the transport container has a sample vessel array
density of at least
about 4 vessels per square inch. Optionally, a cooling surface in the
transport container
provides a temperature profile within a desired range for sample vessels in
the vessel.
Optionally, the sample vessels are individually addressable. Optionally, the
method further
comprises using a cooled tray to hold the samples vessels in a cooling chamber
prior to
loading the vessels into the container and the same tray is used to hold the
sample vessels in
the vessel, wherein the samples are placed into container with the cooled
tray. Optionally,
sample vessels are arranged such that there are at least two vessels in each
container with
bodily sample fluid from the same subject, wherein at least a first sample
includes a first
anticoagulant and a second sample includes a second anticoagulant in the
matrix. Optionally,
the fluid sample comprises capillary blood for use in testing by FDA-cleared
or FDA-
certified assay devices and procedures, or testing by a CLIA-certified
laboratory.
Optionally, the fluid sample comprises blood for use in testing by FDA-cleared
or FDA-
certified assay devices and procedures, or testing by a CLIA-certified
laboratory.
Optionally, a housing providing a controlled thermal profile and high heat of
fusion material
providing at least one cooling surface facing the vessels. Optionally, a high
heat of fusion
material is embedded in material used to form the vessel. Optionally, a
controlled thermal
profile, high heat of fusion material comprises about 30% to 50%. Optionally,
a controlled
thermal profile, high heat of fusion material comprises about 10% to 30%.
Optionally, the
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method further comprises a housing of metallic material having a resting
temperature less
than ambient temperature.
100331 Optionally, the method further comprises scanning an information
storage unit
on each sample at the receiving site and automatically placing the vessel into
a cartridge.
Optionally, the method further comprises scanning an information storage unit
on each
sample at the receiving site and automatically placing the vessel into a
cartridge. Optionally,
the method further comprises using the same tray to hold sample vessels in the
array
configuration when in a refrigeration device prior to transport and in the
transport container
during transport. Optionally, the method further comprises using a tray for
holding the
sample vessels that comprises a highly thermally conductive material.
Optionally, the tray
comprises a plurality of slots having a shape to hold sample vessels holders
in a preferential
orientation. Optionally, the tray is configured to directly engage sample
vessel holders.
Optionally, a tray locking mechanism is used to hold the tray within the
vessel, wherein the
tray locking mechanism releases the tray only upon application of magnetic
force.
Optionally, the method comprises maintaining a temperature range in the 2 C
to 8 C during
transport. Optionally, the method further comprises a temperature control
material that
maintains above freezing but about 10 C or less during transport. Optionally,
the method
comprises using a temperature threshold detector to indicate if the sample
vessel reaches a
temperature outside a threshold level. Optionally, the method further
comprises scanning a
vessel in the tray prior to shipping to determine if a processing step on the
sample had not
been performed; using a processor to perform or re-perform a step. Optionally,
the method
further comprises a single-step loading of the sample vessel(s) into the tray
and then a single-
step loading of the tray into the transport container.
100341 Optionally, the transport container has a first surface configured
to define a
thermally conductive pathway to the controlled thermal profile, high heat of
fusion material
in the transport container. Optionally, the first surface is configured to be
in direct contact
with another surface cooled by a sorption cooling device. Optionally, the
method comprises
simultaneous bar code scanning of sample vessels in the tray. Optionally, the
method
comprises simultaneous bar code scanning undersides of sample vessels in the
tray.
Optionally, the method comprises bar code scanning rows of sample vessels.
Optionally, the
method comprises bar code scanning undersides of rows of sample vessels.
Optionally, the
method comprises shipping a plurality of the sample vessels in an inverted
orientation.
Optionally, the method comprises shipping a plurality of the sample vessels
wherein blood
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cells and plasma are separated by a barrier material in the sample vessels.
Optionally, the
method comprises opening the transport container by unlocking it and opening
it, wherein at
least one hinge holds two pieces together. Optionally, the tray has at least
one magnetic
contact point for removing the tray from the vessel. Optionally, a computer
controlled end
effector is used to load and/or unload sample vessels from the transport
container, wherein
before, during, or after unloading, a reader obtains information from at least
one information
storage unit attached to one or more sample vessels. It should be understood
that although
the transport container is often used for transport, it can also be used as a
storage container
for the tray and/or sample vessels when the transport container is not used
for transport.
Accordingly, the uses for the container are not limited to transport and other
suitable uses for
any of the embodiments are not excluded.
100351 In yet another embodiment herein, a thermal-controlled transport
container is
provided for use in shipping a plurality of sample vessels, the transport
container comprising:
a container having at least a top, bottom, and side walls together defining a
cavity, wherein at
least one of said top, bottom and side walls comprises a phase change
material; a frame sized
to fit within the cavity and defining openings configured for holding a
plurality of sample
vessels and having sidewalls configured to be in contact with sidewalls of the
sample vessels,
wherein vessels are arranged such that each patient has at least a first
sample with a first
anticoagulant and a second sample with a second anticoagulant in the matrix.
100361 In another embodiment described herein, a thermal-controlled
transport
container is provided for use in shipping a plurality of sample vessels, the
transport container
comprising: a) a bottom container portion comprising a bottom wall and at
least a first
sidewall defining a cavity adapted to contain a product therein; b) a top
container portion
comprising a top surface and a bottom surface and adapted to combine with said
bottom
container portion to define a product cavity, said top container portion
forming a top wall for
said vessel; wherein at least one of said top, bottom and side walls comprises
a phase change
material.
100371 In another embodiment described herein, a thermal-controlled
transport
container is provided for use in shipping a plurality of sample vessels, the
transport container
comprising: a) a bottom container portion comprising a bottom wall and at
least a first
sidewall defining a cavity adapted to contain a product therein; b) a top
container portion
comprising a top surface and a bottom surface and adapted to combine with said
bottom
container portion to define a product cavity, said top container portion
forming a top wall for
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said vessel; c) a holder for defining a plurality of sample vessel holding
spaces to position the
sample vessels in a pre-determined orientation; wherein at least one of said
top, bottom and
side walls comprises a phase change material.
[0038] In another embodiment described herein, a transport container is
provided for
shipping sample vessels, the container comprising: a generally rectangular
floor; generally
parallel sides projecting from longitudinal edges of the floor; generally
parallel ends
projecting from end edges of the floor and bridging the sides; a cover
liftable over the sides
and ends and forming therewith and with the floor a generally closed space; a
sample vessel
holder removably coupled to the floor in an interior of the container and
configured to define
vessel-holding spaces. Optionally, the vessel holding spaces are configured to
hold air-
evacuated blood collection tubes having an interior volume of about 2m1 or
less. In at least
one embodiment, the vessel holding spaces are configured to hold vessels such
as but not
limited to air-evacuated collection tubes having an interior volume of about 1
ml, or less than
about 500 [IL, or less than about 250 tfL, or less than about 100 IAL, or less
than about 50 L,
or less.
100391 In another embodiment described herein, a thermal-controlled
transport
container is provided for use in shipping a plurality of sample vessels, the
transport container
comprising: means for holding a plurality of sample vessels in at least one
fixed orientation;
means for thermally controlling temperature of the sample vessels to be within
a desired
range of about 0 C to 10 C; wherein the means from holding the plurality of
sample vessels
is removable from the transport container. Optionally, the vessel holding
spaces are
configured to hold air-evacuated blood collection tubes having an interior
volume of about
2m1 or less. In embodiments, the vessel holding spaces are configured to hold
air-evacuated
collection tubes having an interior volume of about 1 ml, or less than about
500 p.L, or less
than about 250 tit, or less than about 100 tiL, or less than about 50 tfL, or
less.
[0040] It should be understood that some embodiments may comprise a kit
that
includes a transport container as recited in any of the above. Optionally, the
kit includes a
transport container and instructions for their use.
[0041] In one embodiment described herein, a method is described for
providing a
whole blood sample and/or partition thereof from a sender to a recipient. The
method
comprises transporting a package comprising a sample vessel comprising one or
more
channels that contains (a) a whole blood sample and/or partition thereof in
fluid state having
a volume less than or equal to about 200 microliters (u1) and (b) one or more
reagents used
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for preserving one or more analytes in the whole blood sample and/or partition
thereof for
analysis until at least when whole blood sample and/or partition thereof
reaches the recipient,
and wherein the depositing results in delivery of the sample vessel to the
recipient. By way
of non-limiting example, transporting the sample vessel may occur by using a
parcel delivery
service, a courier, or other shipping service.
[0042] In one embodiment described herein, a method is described for
preparing a
whole blood sample for delivery to a sample processing station. The method
comprises
depositing a sample vessel having a whole blood sample in fluid state and a
volume less than
or equal to about 200 ul with a delivery service for delivering the sample
vessel to the sample
processing location for processing the whole blood sample. The sample vessel
may be
prepared by (a) drawing the whole blood sample from a subject with the aid of
a capillary
channel and (b) placing the whole blood sample into the sample vessel, wherein
the whole
blood sample is preserved in fluid state with one or more reagents contained
in the capillary
channel and/or the sample vessel.
[0043] It should be understood that any of the embodiments herein may be
adapted to
have one or more of the following features. By way of non-limiting example,
the sample in
some embodiments may be a semi-solid or gel state. This may occur after the
sample is in
the sample vessel. Optionally, the delivery service is a mail delivery
service. Optionally, the
blood sample is collected from the subject at a point of care location.
Optionally, the point of
care location is a home of the subject. Optionally, the point of a care
location is the location
of a healthcare provider.
[0044] In another embodiment described herein, a method for processing a
whole
blood sample comprises receiving at a processing station from a parcel
delivery service, a
sample vessel having a whole blood sample less than or equal to about 200 ul,
wherein the
sample vessel is received at the processing station with the whole blood
sample in a fluid
state; and performing, at the processing station, at least one pre-analytical
and/or analytical
assay on the whole blood sample in a fluid state.
[0045] It should be understood that any of the embodiments herein may be
adapted to
have one or more of the following features. By way of non-limiting example,
the assay has
one or more steps. Optionally, the sample vessel is included in a housing
having one or more
environmental control zones. Optionally, the housing is adapted to control a
humidity of
each of the environmental control zones. Optionally, the housing is adapted to
control a
pressure of each of the environmental control zones.
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[0046] In yet another embodiment described herein, a computer-implemented
method
is provided for queuing a blood sample for processing at a processing
location. The method
comprises (a) identifying, with the aid of a geolocation system having a
computer processor,
the geolocation of a transport container having the blood or other bodily
fluid sample; (b)
estimating, with the aid of a computer processer, delivery time of the
transport container to
the processing location; and (c) based on the estimated time of delivery,
providing a
notification for preparative work for processing the sample at the processing
location.
[0047] In yet another embodiment described herein, a method is described
for
preparing a whole blood sample for delivery to a sample processing station.
The method
comprises depositing a sample vessel having a whole blood sample in fluid
state with a
delivery service for delivering the sample vessel to the sample processing
location for
processing the whole blood sample, wherein the sample vessel is prepared by
(a) drawing the
whole blood sample from a subject using a device and (b) placing the whole
blood sample
into the sample vessel.
[0048] Optionally, depositing may encompass pick-up and/or drop-off of a
sample
vessel. Optionally, processing may include pre-analytic, analytic and post-
analytic
processing of a sample. Optionally, delivery service may include a subject's
delivery service
or a third party delivery service. Optionally, the whole blood sample is
preserved in fluid
state with one or more reagents contained in the capillary channel or the
sample vessel.
[0049] In yet anotheiembodiment described herein, a method is provided
for
processing a whole blood sample at a processing station. The method comprises
receiving, at
the processing station from a delivery service, a sample vessel having a whole
blood sample,
wherein the sample vessel is prepared by (a) drawing the whole blood sample
from a subject
using a collection device and (b) placing the whole blood sample into the
sample vessel. The
method also includes performing, at the processing station, at least one pre-
analytical or
analytic assay on the whole blood sample.
[0050] It should be understood that any of the embodiments herein may be
adapted to
have one or more of the following features. By way of non-limiting example,
with the aid of
a computer processor, providing a time for completion of the processing from
the estimated
time of delivery. Optionally, the method includes queuing the sample vessel
for processing
upon estimating the time of delivery of the sample vessel at the processing
location.
Optionally, the geolocation of the sample vessel is identified with the aid of
a
communications network.
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[0051] In one embodiment described herein, a computer-implemented method
is
described for providing an estimated time of completion for the processing of
a blood sample.
The method comprises receiving information about a transport container
transported through
a delivery service to a processing station that is for sample processing, the
transport container
having a blood sample removed from a subject. The method also includes
calculating, with
the aid of a computer processor, a position of the blood sample in a
processing queue at the
processing station, wherein the predicting is based on (i) information about
the position of
blood or other bodily fluid samples from other subjects in the processing
queue and (ii)
information about the geographic location of other sample vessels having blood
samples from
other subjects in relation to the sample vessel having the blood sample
removed from the
subject. The method includes predicting a time for processing the blood sample
at the
processing station upon delivery of the sample vessel by the delivery service
to the
processing station; and based on the predicting and an estimated time of
delivery of the
sample vessel to the processing station, providing the subject or a healthcare
provider
associated with the subject an estimated time for processing the blood sample
from the
subject, the estimated time measured from the point the sample vessel is
deposited with the
delivery service. Optionally, the sample is transported to a plurality of
processing stations. It
should be understood that processing as used herein is to be broadly
interpreted and may
include pre-analytical, analytical, and/or post-analytical step(s).
[0052] In yet another embodiment described herein, a computer-implemented
method
is described for providing an estimated time of completion for the processing
of a blood
sample from a subject. The method comprises receiving information about a
transport
container transported through a delivery service to a processing station that
is for sample
processing, the transport container having at least one blood or bodily fluid
sample removed
from the subject. The method also includes calculating, with the aid of a
computer processor,
a position of the blood sample in a processing queue at the processing
station, wherein the
predicting is based on (i) information about the position of blood samples
from other subjects
in the processing queue and (ii) information about the geographic location of
other sample
vessels having blood samples from other subjects in relation to the transport
container having
the blood sample removed from the subject. The method includes predicting a
time for
processing the blood sample at the processing station upon delivery of the
transport container
by the delivery service to the processing station; and based on the predicting
and an estimated
time of delivery of the transport container to the processing station,
allocating one or more
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resources at the processing station for processing the blood sample upon
delivery to the
processing station.
100531 It should be understood that any of the embodiments herein may be
adapted to
have one or more of the following features. By way of non-limiting example,
the transport
container has an information storage unit that allows identification of the
transport container
by the delivery service and/or the processing location. Optionally, the
information storage
unit is a radiofrequency identification (RFID) tag. Optionally, the
information storage unit is
a barcode. Optionally, the information storage unit is a microchip.
Optionally, the transport
containe comprises one or more sensors for collecting one or more of the
temperature of the
bodily fluid sample (e.g., a blood sample), the pressure of the sample vessel,
the pH of the
sample, the turbidity of the sample, the viscosity of the sample, or other
characteristic of the
sample. Optionally, the processing location processes collected bodily fluid
samples on an
on-demand basis. Optionally, the transport container includes a geo-location
device for
providing the location of the sample vessel. Optionally, the anti-coagulating
agent is selected
from the group consisting of heparin, ethylenediaminetetraacetic acid, an anti-
coagulant, or
other additive. Optionally, the transport container, wherein the container
holding spaces are
configured to hold air-evacuated blood collection tubes, are configured to
hold air-evacuated
sample collection tubes having a partial vacuum of at most about 30% vacuum,
or at most
about 40% vacuum, or at most about 50% vacuum , or at most about 60% vacuum,
or at
most about 70% vacuum, or at most about 80% vacuum, or at most about 90%
vacuum.
100541 In embodiments described herein involving a first vessel and a
second vessel,
in certain embodiments, the interior volume of the first vessel and second
vessel is each 1000,
750, 500, 400, 300, 250, 200, 150, 100, 90, 80, 70, 60, 50, 40, 30, 25, 20,
15, 10, 9, 8, 7, 6, 5,
4, 3, 2 microliters, or less. In embodiments described herein involving a
first vessel and a
second vessel, in certain embodiments, the interior volume of neither the
first vessel nor the
second vessel exceeds 1000, 750, 500, 400, 300, 250, 200, 150, 100, 90, 80,
70, 60, 50, 40,
30, 25, 20, 15, 10, 9, 8, 7, 6, 5, 4, 3, or 2 microliters. In embodiments
described herein
involving one or more vessels, in certain embodiments, the interior volume of
each of the one
or more vessels is 1000, 750, 500, 400, 300, 250, 200, 150, 100, 90, 80, 70,
60, 50, 40, 30,
25, 20, 15, 10, 9, 8, 7, 6, 5, 4, 3, 2 microliters, or less. In embodiments
described herein
involving one or more vessels, in certain embodiments, the interior volume of
none of the one
or more vessels exceeds 1000, 750, 500, 400, 300, 250, 200, 150, 100, 90, 80,
70, 60, 50, 40,
30, 25, 20, 15, 10, 9, 8, 7, 6, 5, 4, 3, or 2 microliters.
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[0055] In embodiments described herein involving a first vessel and a
second vessel,
each containing a portion of a small volume bodily fluid sample, in certain
embodiments,
neither the first vessel nor the second vessel contains a portion of the small
volume bodily
fluid sample having a volume of greater than 500, 400, 300, 250, 200, 150,
100, 90, 80, 70,
60, 50, 40, 30, 25, 20, 15, 10, 9, 8, 7, 6, 5, 4, 3, or 2 microliters.
[0056] In embodiments described herein involving a vessel containing a
small volume
bodily fluid sample, in certain embodiments, the volume of the small volume
bodily fluid
sample in the vessel is no greater than 500, 400, 300, 250, 200, 150, 100, 90,
80, 70, 60, 50,
40, 30, 25, 20, 15, 10, 9, 8, 7, 6, 5, 4, 3, or 2 microliters.
[0057] In embodiments described herein involving one or more vessels
containing
bodily fluid sample, in certain embodiments, at least one of the one or more
vessels contains
bodily fluid sample which fills at least 99, 98, 97, 96, 95, 90, 85, 80, 75,
70, 60, 50, 40, 30,
20, 10, or 5 % of the interior volume of the vessel. In embodiments described
herein
involving one or more vessels containing bodily fluid sample, in certain
embodiments, all of
the one or more vessels contains bodily fluid sample which fills at least 99,
98, 97, 96, 95, 90,
85, 80, 75, 70, 60, 50, 40, 30, 20, 10, or 5 % of the interior volume of the
vessel.
[0058] In embodiments described herein involving a sample collection site
and a
sample receiving site, in embodiments, the sample collection site and sample
receiving site
may be in the same room, building, campus, or collection of buildings. In
embodiments
described herein involving a sample collection site and a sample receiving
site, in
embodiments, the sample collection site and sample receiving site may be in
different rooms,
buildings, campuses, or collection of buildings. In embodiments, a sample
collection site and
a sample receiving site may be separated by at least 1 meter, 5 meters, 10
meters, 50 meters,
100 meters, 500 meters, 1 kilometer, 5 kilometers, 10 kilometers, 15
kilometers, 20
kilometers, 30 kilometers, 50 kilometers, 100 kilometers, or 500 kilometers.
In
embodiments, a sample collection site and sample receiving site may be
separated by no
more than 5 meters, 10 meters, 50 meters, 100 meters, 500 meters, 1 kilometer,
5 kilometers,
kilometers, 15 kilometers, 20 kilometers, 30 kilometers, 50 kilometers, 100
kilometers,
500 kilometers, or 1000 kilometers. In embodiments, a sample collection site
and a sample
receiving site may be separated by at least 1 meter, 5 meters, 10 meters, 50
meters, 100
meters, 500 meters, 1 kilometer, 5 kilometers, 10 kilometers, 15 kilometers,
20 kilometers,
30 kilometers, 50 kilometers, 100 kilometers, or 500 kilometers and no more
than 5 meters,
10 meters, 50 meters, 100 meters, 500 meters, 1 kilometer, 5 kilometers, 10
kilometers, 15
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kilometers, 20 kilometers, 30 kilometers, 50 kilometers, 100 kilometers, 500
kilometers, or
1000 kilometers. In embodiments, a first location described herein may be a
sample
collection site and a second location described herein may be a sample
receiving site.
[0059] In embodiments described herein involving a vessel containing at
least a
portion of a small volume bodily fluid sample being transported from a sample
collection site
to a sample receiving site, in embodiments, the bodily fluid sample may be
maintained in
liquid form during the transport of the vessel. In embodiments described
herein involving
two or more vessels, each containing at least a portion of a small volume
bodily fluid sample,
being transported from a sample collection site to a sample receiving site, in
embodiments,
the bodily fluid sample in each of the vessels may be maintained in liquid
form during the
transport of the vessels.
[0060] In embodiments described herein involving one or more vessels
being
transported from a sample collection site to a sample receiving site, in
embodiments, the one
or more vessels may be transported in a transport container. In embodiments
described
herein involving one or more vessels being transported in a transport
container, in
embodiments, the one or more vessels may be positioned in an array in the
transport
container, and the array may contain at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10,
15, 20, 25, 30, 35, 40,
50, or 100 vessels per square inch, when viewed from the top down.
[0061] In embodiments described herein involving transporting one or more
vessels
in a transport container, in embodiments, the transport container may contain
bodily fluid
samples from at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25, 30, 35, 40,
50, or 100 different
subjects.
[0062] In embodiments described herein involving a vessel containing at
least a
portion of a bodily fluid sample, in embodiments, the vessel may contain an
anticoagulant. In
embodiments involving two or more vessels which each contain a portion of a
bodily fluid
sample from a subject, in embodiments, at least one or all of the vessels may
contain an
anticoagulant. In embodiments, when two or more vessels which each contain a
portion of a
bodily fluid sample from a subject also each contain an anticoagulant, the
vessels may
contain the same anticoagulants or different anticoagulants. An anticoagulant
in a vessel may
be, for example, heparin or EDTA.
[0063] In methods described herein involving the transport of a bodily
fluid sample in
one or more vessels from a sample collection site to a sample receiving site,
in embodiments,
the bodily fluid sample may arrive at the sample receiving site no more than
48 hours, 36
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hours, 24 hours, 16 hours, 12 hours, 8 hours, 7 hours, 6 hours, 5 hours, 4
hours, 3 hours, 2
hours, 60 minutes, 45 minutes, 30 minutes, 20 minutes, 15 minutes, 10 minutes,
or 5 minutes
after the bodily fluid sample was obtained from the subject.
[0064] In methods described herein involving transporting at least a
vessel from a
sample collection site to a sample receiving site, in embodiments, the method
may further
comprise centrifuging the vessel before it is transported. In methods
described herein
involving transporting a plurality of vessels from a sample collection site to
a sample
receiving site, in embodiments, the method may further comprise centrifuging
the plurality of
vessels before they are transported.
100651 In methods described herein involving transporting at least a
first vessel from
a sample collection site to a sample receiving site, in embodiments, at the
sample receiving
site and prior to the removal of sample from the first vessel, the first
vessel is inserted into a
sample processing device comprising an automated fluid handling apparatus. In
methods
described herein involving transporting at least a first vessel and a second
vessel from a
sample collection site to a sample receiving site, in embodiments, at the
sample receiving site
and prior to the removal of sample from the first vessel, the first vessel and
second vessel are
inserted into a sample processing device comprising an automated fluid
handling apparatus.
In embodiments, when a vessel comprising a sample is inserted into a sample
processing
device comprising an automated fluid handling apparatus, sample may be removed
from the
vessel by the automated fluid handling apparatus. In embodiments, prior to the
insertion of a
vessel comprising a sample into a sample processing device comprising an
automated fluid
handling apparatus, the vessel is inserted into a cartridge, and the cartridge
is then inserted
into the sample processing device. A cartridge may accommodate any number of
vessels
containing sample, such as at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25,
50, or 100 vessels.
A cartridge may further comprise one or more reagents for performing one or
more
laboratory tests with the sample. In embodiments, a cartridge may comprise all
of the
reagents necessary to perform all of the tests that are to be performed with
the sample(s) in
the cartridge.
100661 In embodiments, a portion of a portion of a bodily fluid sample of
a vessel
may be of any amount. For example, in embodiments, a portion of a portion of a
bodily fluid
sample of a first vessel may be a portion of a first vessel original sample or
a portion of a first
vessel dilution sample. In another example, in embodiments, a portion of a
portion of a
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bodily fluid sample of a second vessel may be a portion of a second vessel
original sample or
a portion of a second vessel dilution sample.
[0067] In embodiments provided herein involving transporting one or more
vessels,
each containing at least a portion of a bodily fluid sample from a sample
collection site to a
sample receiving site, in embodiments, one or more steps of any number of
laboratory tests
may be performed with a portion of the at least a portion of the bodily fluid
sample in the
vessel. For example, in embodiments, one or more steps of 1, 2, 3, 4, 5, 6, 7,
8, 9, 10, 15, 20,
25, 30, 40, 50, 60, 70, 80, 90, 100, 200, 300, 400, 500, or 1000 or more
different laboratory
tests may be performed with a portion of the at least a portion of bodily
fluid sample. Each
different laboratory test may use a separate portion of the bodily fluid
sample, or in
embodiments, more than one different laboratory test may be performed with a
particular
portion of the bodily fluid sample. The different laboratory tests may be of
the same type,
different types, or a mixture of same and different types. The one or more
vessels may be,
for example, a first vessel or a first vessel and second vessel.
[0068] In embodiments, when a bodily fluid sample from a subject
transported
according to systems or methods provide herein is used for more than one
laboratory test,
each of the laboratory tests may use the equivalent of no more than 50, 40,
30, 25, 20, 15, 10,
9, 8, 7, 6, 5, 4, 3, 2, 1, 0.5, 0.1, 0.05, or 0.01 of neat bodily fluid sample
(e.g. undiluted whole
blood, saliva, or urine) per test.
[0069] In embodiments provided herein involving obtaining at a sample
collection
site a plurality of vessels collectively containing a small volume bodily
fluid sample from a
subject, in embodiments, the total volume of the small volume bodily fluid
sample obtained
from the subject between all of the vessels of the plurality of vessels may be
no greater than
500, 400, 300, 250, 200, 150, 100, 90, 80, 70, 60, 50, 40, 30, 25, 20, 15, 10,
9, 8, 7, 6, 5, 4, 3,
or 2 microliters.
[0070] In embodiments provided herein involving transporting a vessel
containing at
least a portion of a bodily fluid sample from a sample collection site to a
sample receiving
site, removing at the sample receiving site from the vessel an original
sample, and then
generating a dilution sample from the original sample, in embodiments, the
dilution may be
generated step-wise or serially. In embodiments, the dilution sample may have
a total
volume of no more than 1000, 900, 800, 700, 600, 500, 400, 300, 250, 200, 150,
100, 90, 80,
70, 60, 50, 40, 30, 25, 20, 15, 10, 9, 8, 7, 6, 5, 4, 3, or 2 microliters. In
embodiments, the
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dilution sample may be diluted at least 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20,
50, 100, 200, 300, 400,
500, 1000, 5,000, 10,000, 50,000, or 100,000-fold relative to the original
sample.
[0071] In embodiments provided herein involving transporting at least a
first vessel
and a second vessel, each containing a portion of the small volume bodily
fluid sample
obtained from the subject, from a sample collection site to a sample receiving
site, in
embodiments, at the sample receiving site, a first vessel original sample may
be removed
from the first vessel and a second vessel original sample may be removed from
the second
vessel. From the first vessel original sample a first vessel dilution sample
may be generated.
From the second vessel original sample a second vessel dilution sample may be
generated.
The first vessel dilution sample and second vessel dilution samples may have
the same or -
different volumes and degrees of dilution. In embodiments, multiple different
dilution
samples may be generated from one or both of the first vessel original sample
or second
vessel original sample. The different dilution samples may be used for one or
more different
laboratory tests, which may be of different types. In embodiments, a first
vessel dilution
sample may be diluted at least 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 50, 100,
200, 300, 400, 500,
1000, 5,000, 10,000, 50,000, or 100,000-fold relative to the first vessel
original sample and
= have a total volume of no more than 1000, 900, 800, 700, 600, 500, 400,
300, 250, 200, 150,
100, 90, 80, 70, 60, 50, 40, 30, 25, 20, 15, 10, 9, 8, 7, 6, 5, 4, 3, or 2
microliters, and a second
vessel dilution sample may be diluted at least 2, 3, 4, 5, 6, 7, 8, 9, 10, 15,
20, 50, 100, 200,
300, 400, 500, 1000, 5,000, 10,000, 50,000, or 100,000-fold relative to the
second vessel
original sample and have a total volume of no more than 1000, 900, 800, 700,
600, 500, 400,
300, 250, 200, 150, 100, 90, 80, 70, 60, 50, 40, 30, 25, 20, 15, 10, 9, 8, 7,
6, 5, 4, 3, or 2
microliters.
[0072] In embodiments provided herein involving obtaining at a sample
collection
site a vessel, the vessel containing a small volume bodily fluid sample
obtained from a
subject, in embodiments, volume of the small volume bodily fluid sample in the
vessel may
be no greater than 500, 400, 300, 250, 200, 150, 100, 90, 80, 70, 60, 50, 40,
30, 25, 20, 15,
10, 9, 8, 7, 6, 5, 4, 3, or 2 microliters.
100731 In embodiments provided herein involving obtaining at a sample
collection
site a vessel, the vessel containing a small volume bodily fluid sample
obtained from a
subject and transporting the vessel from the sample collection site to a
sample receiving site,
in embodiments, the small volume bodily fluid sample may be dividied into any
number of
portions, such as, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25, 30, 40, 50, 60, 70,
80, 90, 100, 200, 300,
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400, 500, or 1000 different portions. The portions may be diluted in the same
or in varying
amounts, and may be used for, for example, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15,
20, 25, 30, 40, 50,
60, 70, 80, 90, 100, 200, 300, 400, 500, or 1000 or more different laboratory
tests.
[0074] In embodiments provided herein involving obtaining at a sample
collection
site at least a vessel containing at least a portion of a small volume bodily
fluid sample from a
subject, in embodiments, the obtaining step may include collecting the small
volume bodily
fluid sample from the subject (e.g. from a fingerstick or venous draw).
[0075] In embodiments provided herein involving performing at least a
portion of a
laboratory test in an assay unit, in embodiments, the assay unit maybe
movable, such as by a
fluid handling apparatus. In embodiments including two or more assay units, in
embodiments, the assay units may be independently movable.
[0076] In embodiments provided herein involving transport of one or more
vessels
containing a bodily fluid sample, in some embodiments, the vessels may have
any of the
characteristics of vessels described herein, or of other vessels suitable for
the storage of
bodily fluids. In some embodiments, the vessels may be loaded with bodily
fluid sample by
any of the devices or methods provided herein, or by other suitable techniques
for loading a
vessel have a small interior volume. For example, in certain embodiments, a
vessel to be
transported according to a system or method provided herein may be loaded with
a sample by
a syringe or a pipette tip.
[0077] Optionally, at least one embodiment of a sample collection device
herein can
separate a single blood sample into different vessels for different pre-
analytical processing.
This can be achieved through fluid pathways in the device and/or through
different inlet ports
on the device.
[0078] This Summary is provided to introduce a selection of concepts in a
simplified
form that are further described below in the Detailed Description. This
Summary is not
intended to identify key features or essential features of the claimed subject
matter, nor is it
intended to be used to limit the scope of the claimed subject matter.
INCORPORATION BY REFERENCE
[0079] All publications, patents, and patent applications mentioned in
this
specification are herein incorporated by reference to the same extent as if
each individual
publication, patent, or patent application was specifically and individually
indicated to be
incorporated by reference.
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BRIEF DESCRIPTION OF THE DRAWINGS
[0080] Figures 1A-1B show perspective views of a sample collection device
according to one embodiment as described herein.
[0081] Figures 2A-2C show perspective views of a sample collection device
without
a cap according to one embodiment as described herein.
[0082] Figures 3A-3B show side and cross-sectional views of a sample
collection
device according to one embodiment as described herein.
[0083] Figures 4A-4B show side and cross-sectional views of a sample
collection
device according to one embodiment as described herein.
[0084] Figures 5A-5B show perspective views of a sample collection device
according to another embodiment as described herein.
[0085] Figures 6A-6B show side views of a sample collection device
according to one
embodiment as described herein.
[0086] Figures 7A-8B show side and cross-sectional views of a sample
collection
device according to one embodiment as described herein.
[0087] Figures 9A-9C show side cross-sectional views of a sample collection
device
at various stages of use according to one embodiment as described herein.
[0088] Figures 10A-10B show perspective views of a sample collection device
according to one embodiment as described herein.
[0089] Figures 11A-11Z show views of various examples of sample collection
devices according embodiment as described herein.
[0090] Figure 12 shows a schematic of a tip portion of a sleeve and
associated
balance of forces associated with one embodiment as described herein.
[0091] Figures 13A-13D show views of various collection devices with an
upward
facing collection location according to embodiments as described herein
[0092] Figures 14-15 show various views of a collection device with a
single
collection location according to one embodiment as described herein.
[0093] Figures 16-17 show perspective and end views of a sample collection
device
using vessels having identifiers according to one embodiment as described
herein.
[0094] Figures 18A-18G show various views of sample vessels according to
embodiments as described herein.
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[0095] Figures 19A-19C show view of various embodiments of a front
end of a
sample collection device.
[0096] Figures 20-21 show various embodiments of sample collection
device with an
integrated tissue penetrating member.
[0097] Figure 22 shows a perspective view of a collection device for
use with a blood
vessel or other tissue penetrator and sample collector according to an
embodiment described
herein.
[0098] Figure 23 -28 show various view of collection devices for use
with various
sample collectors according to embodiments described herein.
[0099] Figures 29A-29C show schematics of various embodiments as
described
herein.
[00100] Figures 30-31 show schematic of methods according to
embodiments
described herein.
[00101] Figure 32 shows a schematic view of one embodiment of system
described
, herein.
[00102] Figures 33 to 37 show yet another embodiment of a collection
device
described herein
[00103] Figures 38A-39 show various views of a thermally controlled
transport
container transport device according to at least one embodiment described
herein.
[00104] Figures 40A-40C show schematics of various embodiments
described herein.
[00105] Figure 41 shows a perspective view of one portion of a
transport container
having a plurality of sample vessels therein according to at least one
embodiment described
herein.
[00106] Figure 42 is an exploded perspective view of one portion of a
transport
container having a plurality of sample vessels therein according to at least
one embodiment
described herein.
[00107] Figure 43 shows a perspective view of a transport container
according to yet
another embodiment described herein.
[00108] Figure 44 shows a schematic of a sample collection and
transport process
according to one embodiment described herein.
[00109] Figure 45 shows a schematic of a sample collection and
transport process
according to yet another embodiment described herein.
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[00110] Figure 46 shows a sample collection device according to one
embodiment
described herein.
[00111] Figure 47 shows a schematic view of one system for unloading
sample vessels
from a transport container according to one embodiment described herein.
[00112] Figure 48 is a graph showing the stability of an analyte in a
sample in a vessel
provided herein.
[00113] Figures 49 to 51 show one non-limiting example of tests according
to at least
one embodiment described herein.
[00114] Figures 52 to 55 show various views of devices and systems
according to
embodiments herein.
1001151 Figures 56 to 59 show various views of sample transport devices
according to
at least some embodiments herein.
DESCRIPTION OF THE SPECIFIC EMBODIMENTS
[00116] It is to be understood that both the foregoing general description
and the
following detailed description are exemplary and explanatory only and are not
restrictive of
the invention, as claimed. It may be noted that, as used in the specification
and the appended
claims, the singular forms "a", "an" and "the" include plural referents unless
the context
clearly dictates otherwise. Thus, for example, reference to "a material" may
include mixtures
of materials, reference to "a compound" may include multiple compounds, and
the like.
References cited herein are hereby incorporated by reference in their
entirety, except to the
extent that they conflict with teachings explicitly set forth in this
specification.
[00117] In this specification and in the claims which follow, reference
will be made to
a number of terms which shall be defined to have the following meanings:
[00118] "Optional" or "optionally" means that the subsequently described
circumstance may or may not occur, so that the description includes instances
where the
circumstance occurs and instances where it does not. For example, if a device
optionally
contains a feature for a sample collection well, this means that the sample
collection well may
or may not be present, and, thus, the description includes both structures
wherein a device
possesses the sample collection well and structures wherein sample collection
well is not
present.
[00119] As used herein, the terms "substantial" means more than a minimal
or
insignificant amount; and "substantially" means more than a minimally or
insignificantly.
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Thus, for example, the phrase "substantially different", as used herein,
denotes a sufficiently
high degree of difference between two numeric values such that one of skill in
the art would
consider the difference between the two values to be of statistical
significance within the
context of the characteristic measured by said values. Thus, the difference
between two
values that are substantially different from each other is typically greater
than about 10%, and
may be greater than about 20%, preferably greater than about 30%, preferably
greater than
about 40%, preferably greater than about 50% as a function of the reference
value or
comparator value.
1001201 As used herein, a "sample" may be but is not limited to a blood
sample, or a
portion of a blood sample, may be of any suitable size or volume, and is
preferably of small
size or volume. In some embodiments of the assays and methods disclosed
herein,
measurements may be made using a small volume blood sample, or no more than a
small
volume portion of a blood sample, where a small volume comprises no more than
about 5
mL; or comprises no more than about 3 mL; or comprises no more than about 2
mL; or
comprises no more than about 1 mL; or comprises no more than about 500 L; or
comprises
no more than about 250 L; or comprises no more than about 100 L; or
comprises no more
than about 75 L; or comprises no more than about 50 L; or comprises no more
than about
35 !AL; or comprises no more than about 25 L; or comprises no more than about
20 L; or
comprises no more than about 15 L; or comprises no more than about 10 L; or
comprises
no more than about 8 L; or comprises no more than about 6 L; or comprises no
more than
about 5 L; or comprises no more than about 4 L; or comprises no more than
about 3 [iL; or
comprises no more than about 2 L; or comprises no more than about 1 pt; or
comprises no
more than about 0.8 L; or comprises no more than about 0.5 L; or comprises
no more than
about 0.3 L; or comprises no more than about 0.2 L; or comprises no more
than about 0.1
L; or comprises no more than about 0.05 [IL; or comprises no more than about
0.01 L.
1001211 As used herein, the term "point of service location" may include
locations
where a subject may receive a service (e.g. testing, monitoring, treatment,
diagnosis,
guidance, sample collection, ID verification, medical services, non-medical
services, etc.),
and may include, without limitation, a subject's home, a subject's business,
the location of a
healthcare provider (e.g., doctor), hospitals, emergency rooms, operating
rooms, clinics,
health care professionals' offices, laboratories, retailers [e.g. pharmacies
(e.g., retail
pharmacy, clinical pharmacy, hospital pharmacy), drugstores, supermarkets,
grocers, etc.],
transportation vehicles (e.g. car, boat, truck, bus, airplane, motorcycle,
ambulance, mobile
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unit, fire engine/truck, emergency vehicle, law enforcement vehicle, police
car, or other
vehicle configured to transport a subject from one point to another, etc.),
traveling medical
care units, mobile units, schools, day-care centers, security screening
locations, combat
locations, health assisted living residences, government offices, office
buildings, tents, bodily
fluid sample acquisition sites (e.g. blood collection centers), sites at or
near an entrance to a
location that a subject may wish to access, sites on or near a device that a
subject may wish to
access (e.g., the location of a computer if the subject wishes to access the
computer), a
location where a sample processing device receives a sample, or any other
point of service
location described elsewhere herein.
[00122] As used herein, a "bodily fluid" may be any fluid obtained or
obtainable from
a subject. A bodily fluid may be, for example, blood, urine, saliva, tears,
sweat, a bodil
secretion, a bodily excretion, or any other fluid originating in or obtained
from a subject. In
particular, bodily fluids include, without limitation, blood, serum, plasma,
bone marrow,
saliva, urine, gastric fluid, spinal fluid, tears, stool, mucus, sweat,
earwax, oil, glandular
secretions, cerebral spinal fluid, semen, vaginal fluid, interstitial fluids
derived from
tumorous tissue, ocular fluids, placental fluid, amniotic fluid, cord blood,
lymphatic fluids,
cavity fluids, sputum, pus, meconium, breast milk and/or other secretions or
excretions.
[00123] As used herein, "a bodily fluid sample collector" or any other
collection
mechanism can be disposable. For example, a bodily fluid collector can be used
once and
disposed. A bodily fluid collector can have one or more disposable components.
Alternatively, a bodily fluid collector can be reusable. The bodily fluid
collector can be
reused any number of times. In some instances, the bodily fluid collector can
include both
reusable and disposable components.
[00124] As used herein, "a sample collection unit" and/or any other
portion of the
device may be capable of receiving a single type of sample, or multiple types
of samples. For
example, the sample collection unit may be capable of receiving two different
types of bodily
fluids (e.g., blood, tears). In another example, the sample collection unit
may be capable of
receiving two different types of biological samples (e.g., urine sample, stool
sample).
Multiple types of samples may or may not be fluids, solids, and/or semi-
solids. For example,
the sample collection unit may be capable of accepting one or more of, two or
more of, or
three or more of a bodily fluid, secretion and/or tissue sample.
[00125] As used herein, "non-wicked, non-matrixed form" means that a
liquid or
suspension is not absorbed by or pulled into a webbing, mesh, fiber pad,
absorbent material,
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absorbent structure, percolating network of fibers, or the like which alters
the form of the
liquid or suspension or traps components of the sample therein to an extent
that the integrity
of sample in liquid form is changed and the sample cannot be extracted in
liquid form while
still maintaining sample integrity for sample analysis.
[00126] The term "sample handling system," as used herein, refers to a
device or
system configured to aid in sample imaging, detecting, positioning,
repositioning, retention,
uptake and deposition. In an example, a robot with pipetting capability is a
sample handling
system. In another example, a pipette which may or may not have (other)
robotic capabilities
is a sample handing system. A sample handled by a sample handling system may
or may not
include fluid. A sampling handling system may be capable of transporting a
bodily fluid,
secretion, or tissue. A sampling handling system may be able to transport one
or more
substance within the device that need not be a sample. For example, the sample
handling
system may be able to transport a powder that may react with one or more
sample. In some
situations, a sample handling system is a fluid handling system. The fluid
handling system
may comprise pumps and valves of various types or pipettes, which, may
comprise but not be
limited to a positive displacement pipette, air displacement pipette and
suction-type pipette.
The sample handling system may transport a sample or other substance with aid
of a robot as
described elsewhere herein.
[00127] The term "health care provider," as used herein, refers to a
doctor or other
health care professional providing medical treatment and/or medical advice to
a subject. A
health care professional may include a person or entity that is associated
with the health care
system. Examples of health care professionals may include physicians
(including general
practitioners and specialists), surgeons, dentists, audiologists, speech
pathologists, physician
assistants, nurses, midwives, pharmaconomists/pharmacists, dietitians,
therapists,
psychologists, chiropractors, clinical officers, physical therapists,
phlebotomists, occupational
therapists, optometrists, emergency medical technicians, paramedics, medical
laboratory
technicians, medical prosthetic technicians, radiographers, social workers,
and a wide variety
of other human resources trained to provide some type of health care service.
A health care
professional may or may not be certified to write prescriptions. A health care
professional
may work in or be affiliated with hospitals, health care locations and other
service delivery
points, or also in academic training, research and administration. Some health
care
professionals may provide care and treatment services for patients in private
or public
domiciles, community centers or places of gathering or mobile units. Community
health
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workers may work outside of formal health care institutions. Managers of
health care
services, medical records and health information technicians and other support
workers may
also be medical care professionals or affiliated with a health care provider.
A health care
professional may be an individual or an institution that provides preventive,
curative,
promotional or rehabilitative health care services to individuals, families,
or communities.
[00128] In some embodiments, the health care professional may already be
familiar
with a subject or have communicated with the subject. The subject may be a
patient of the
health care professional. In some instances, the health care professional may
have prescribed
the subject to undergo a clinical test. The health care professional may have
instructed or
suggested to the subject to undergo a clinical test conducted at the point of
service location or
by a laboratory. In one example, the health care professional may be the
subject's primary
care physician. The health care professional may be any type of physician for
the subject
(including general practitioners, referred practitioners or the patient's own
physician
optionally selected or connected through telemedicine services, and/or
specialists). The
health care professional may be a medical care professional.
[00129] The term "rack," as used herein, refers to a frame or enclosure
for mounting
multiple modules. The rack is configured to permit a module to be fastened to
or engaged
with the rack. In some situations, various dimensions of the rack are
standardized. In an
example, a spacing between modules is standardized as multiples of at least
about 0.5 inches,
or 1 inch, or 2 inches, or 3 inches, or 4 inches, or 5 inches, or 6 inches, or
7 inches, or 8
inches, or 9 inches, or 10 inches, or 11 inches, or 12 inches.
[00130] The term "cells," as used in the context of biological samples,
encompasses
samples that are generally of similar sizes to individual cells, including but
not limited to
vesicles (such as liposomes), cells, virions, and substances bound to small
particles such as
beads, nanoparticles, or microspheres. Characteristics include, but are not
limited to, size;
shape; temporal and dynamic changes such as cell movement or multiplication;
granularity;
whether the cell membrane is intact; internal cell contents, including but not
limited to,
protein content, protein modifications, nucleic acid content, nucleic acid
modifications,
organelle content, nucleus structure, nucleus content, internal cell
structure, contents of
internal vesicles , ion concentrations, and presence of other small molecules
such as steroids
or drugs; and cell surface (both cellular membrane and cell wall) markers
including proteins,
lipids, carbohydrates, and modifications thereof.
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[00131] As used herein, "sample" refers to an entire original sample or
any portion
thereof, unless the context clearly dictates otherwise.
[00132] The invention provides systems and methods for multi-purpose
analysis of a
sample or health parameter. The sample may be collected and one or more sample
preparation step, assay step, and/or detection step may occur on a device.
Various aspects of
the invention described herein may be applied to any of the particular
applications, systems,
and devices set forth below. The invention may be applied as a stand alone
system or
method, or as part of an integrated system, such as in a system involving
point of service
health care. In some embodiments, the system may include externally oriented
imaging
technologies, such as ultrasound or MRI or be integrated with external
peripherals for
integrated imaging and other health tests or services. It shall be understood
that different
aspects of the invention can be appreciated and practice individually,
collectively, or in
combination with each other.
[00133] Referring now to Figures 1A-1B, one embodiment of a sample
collection
device 100 will now be described. In this non-limiting example, the sample
collection device
100 may include a collection device body 120, support 130, and base 140. In
some instances,
a cap 110 may be optionally provided. In one embodiment, the cap may be used
to protect
the opening, keeping it clean, and for covering up the bloody tip after
collection. Optionally
or alternatively, the cap may also be used to limit flow rate during transfer
of sample fluid
into the sample vessels by controlling the amount of venting provided to the
capillaries.
Some embodiments may include vents pathways (permanently open or operably
closable) in
the cap while others do not. Optionally, the collection device body 120 can
include a first
portion of the device 100 having one or more collection pathways such as but
not limited to
collection channels 122a, 122b therein, which may be capable of receiving
sample B. Figure
1A shows that sample B only partially filling the channels 122a, 122b, but it
should be
understood that, although partial fills are not excluded in some alternative
embodiments, in
most embodiments, the channels will be fully filled with sample B when the
fill process is
completed. In this embodiment, the base 140 may have one or more fill
indicators 142a,
142b, such as but not limited to optical indicators, that may provide an
indication of whether
sample has reached one or more vessel housed in the base. It should be
understood that
although this indication may be by way of a visual indication, other
indication methods such
as audio, vibratory, or other indication methods may be used in place of or in
combination
with the indication method. The indicators may be on at least one of the
vessels. There may
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be variations and alternatives to the embodiments described herein and that no
single
embodiment should be construed to encompass the entire invention.
(00134] Although not shown for ease of illustration, the support 130 may
also include
one or more fill indicators showing whether a desired fill level has been
reached in the
channels 122a and 122b. This may be in place of or in addition to fill
indicators 142a, 142b.
Of course, the one or more pathway fill indicators can be positioned on a
different part and is
not limited to being on support 130. It should be understood that although
this indication of
fill level in one or more of the channels 122a and 122b may be by way of a
visual indication,
other indication methods such as audio, vibratory, or other indication methods
may be used in
place of or in combination with the indication method. The indicator may be on
at least one
of the collection pathways. Optionally, indicators are on all of the
collection pathways.
1001351 In the present embodiment, the support 130 can be used to join the
body 120
and the base 140 to form an integrated device. It should be understood that
although the
device body 120, support 130, and base 140 are recited as separate parts, one
or more of those
parts may be integrally formed to simplify manufacturing and such integration
is not
excluded herein.
100136] In some embodiments herein, a cap 110 may be optionally provided.
In one
non-limiting example, the cap May be fitted over a portion of the collection
device body 120.
The cap 110 may be detachable from the collection device body 120. In some
instances, the
cap 110 may be completely separable from the collection device body 120, or
may retain a
portion that is connected to the collection device body, such as but not
limited to being
hinged or otherwise linked to the collection device. The cap 110 may cover a
portion of the
collection device body 120 containing exposed ends of one or more channels
therein. The
cap 110 may prevent material, such as air, fluid, or particulates, from
entering the channels
within the device body, when the cap is in place. Optionally, the cap 110 may
attach to the
collection body 120 using any technique known or later developed in the art.
For instance,
the cap may be snap fit, twist on, friction-fit, clamp on, have magnetic
portions, tie in, utilize
elastic portions, and/or may removably connect to the collection device body.
The cap may
form a fluid-tight seal with the collection device body. The cap may be formed
from an
opaque, transparent, or translucent material.
100137] In one embodiment, a collection device body 120 of a sample
collection
device may contain at least a portion of one or more collection pathways such
as but not
limited to channels 122a, 122b therein. It should be understood that
collection pathways that
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are not channels are not excluded. The collection device body may be connected
to a support
130 that may contain a portion of one or more channels therein. The collection
device body
may be permanently affixed to the support or may be removable with respect to
the support.
In some instances, the collection device body and the support may be formed of
a single
integral piece. Alternatively, the collection device body and support may be
formed from
separate pieces. During the operation of the device the collection device and
support do not
move relative to one another.
1001381 Optionally, the collection device body 120 may be formed in whole
or in part
from an optically transmissive material. For example, the collection device
body may be
formed from a transparent or translucent material. Optionally, only select
potions of the body
are transparent or translucent to visualize the fluid collection channel(s).
Optionally, the
body comprises an opaque material but an opening and/or a window can be formed
in the
body to show fill levels therein. The collection device body may enable a user
to view the
channels 122a, 122b within and/or passing through the device body. The
channels may be
formed of a transparent or translucent material that may permit a user to see
whether sample
B has traveled through the channels. The channels may have substantially the
same length.
In some instances a support 130 may be formed of an opaque material, a
transparent material,
or a translucent material. The support may or may not have the same optical
characteristics
of the collection device body. The support may be formed from a different
material as the
collection device body, or from the same material as the collection device
body.
1001391 The collection device body 120 may have any shape or size. In some
examples, the collection device body may have a circular, elliptical,
triangular, quadrilateral
(e.g., square, rectangular, trapezoidal), pentagonal, hexagonal, octagonal, or
any other cross-
sectional shape. The cross-sectional shape may remain the same or may vary
along the
length of the collection device body. In some instances, the collection device
body may have
a cross-sectional area of less than or equal to about 10 cm2, 7 cm2, 5 cm2, 4
cm2, 3 cm2, 2.5
cm2, 2 cm2, 1.5 cm2, 1 cm2, 0.8 cm2, 0.5 cm2, 0.3 cm2, or 0.1 cm2. The cross-
sectional area
may vary or may remain the same along the length of the collection device body
120. The
collection device body may have a length of less than or equal to about 20 cm,
15 cm, 12 cm,
cm, 9 cm, 8 cm, 7 cm, 6 cm, 5 cm, 4 cm, 3 cm, 2 cm, 1 cm, 0.5 cm, or 0.1 cm.
The
collection device body 120 may have a greater or lesser length than the cap,
support or base,
or an equal length to the cap, support, or base. There may be variations and
alternatives to
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the embodiments described herein and that no single embodiment should be
construed to
encompass the entire invention.
[00140] In one embodiment, the collection pathways such as but not limited
to
channels 122a, 122b may also have a selected cross-sectional shape. Some
embodiments of
the channels may have the same cross-sectional shape along the entire length
of the channel.
Optionally, the cross-sectional shape may remain the same or may vary along
the length.
For example, some embodiments may have one shape at one location and a
different shape at
one or more different locations along the length of the channel. Some
embodiments may
have one channel with one cross-sectional shape and at least one other channel
of a different
cross-sectional shape. By way of non-limiting example, some may have a
circular, elliptical,
triangular, quadrilateral (e.g., square, rectangular, trapezoidal),
pentagonal, hexagonal,
octagonal, or any other cross-sectional shape. The cross-sectional shape may
be the same for
the body, support, and base, or may vary. Some embodiments may select a shape
to
maximize volume of liquid that can be held in the channels for a specific
channel width
and/or height. Some may have one of the channels 122a, 122b with one cross-
sectional shape
while another channel has a different cross-sectional shape. In one
embodiment, the cross-
sectional shape of the channel can help maximize volume therein, but
optionally, it can also
optimize the capillary pulling forces on the blood. This will allow for
maximized rate of
filling. It should be understood that in some embodiments, the cross-sectional
shape of the
channel can directly affect the capillary forces. By way of non-limiting
example, a volume of
sample can be contained in a shallow but wide channel, or a rounded channel,
both
containing the same volume, but one might be desirable over the other for
filling speed, less
possibility of air entrapment, or factors related the performance of the
channel.
[00141] Although the channels may have any shape or size, some embodiments
are
configured such that the channel exhibits a capillary action when in contact
with sample
fluid. In some instances, the channel may have a cross-sectional area of less
than or equal to
about 10 mm2, 7 mm2, 5 mm2, 4 mm2, 3 mm2, 2.5 mm2, 2 mm2, 1.5 mm2, 1 mm2, 0.8
mm2,
0.5 mm2, 0.3 mm2, or 0.1 1111112. The cross-sectional size may remain the same
or may vary
along the length. Some embodiments may tailor for greater force along a
certain length and
then less in a different length. The cross-sectional shape may remain the same
or may vary
along the length. Some channels are straight in configuration. Some
embodiments may have
curved or other shaped path shapes alone or in combination with straight
portions. Some may
have different orientations within the device body 120. For example, when the
device is held
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substantially horizontally, one or more channels may slope downward, slope
upward, or not
slope at all as it carries fluid away from the initial collection point on the
device.
[00142] The channels 122a, 122b may be supported by the device body 120
and/or the
support 130. In some instances, the entire length of the channels may be
encompassed within
the combination of the device body and the support. In some instances, a
portion of the
channels may be within the device body and a portion of the channels may be
within the
support. The position of the channels may be affixed by the device body and/or
the support.
In some embodiments, the channels may be defined as lumens inside a hollow
needle. In
some embodiments, the channels are only defined on three sides, with at least
one side that is
open. Optionally, a cover layer separate from the body may define the side
that would
otherwise be open. Some embodiments may define different sides of the channel
with
different materials. These materials can all be provided by the body or they
may be provided
by different pieces of the collection device. Some embodiments may have the
channels all in
the same plane. Optionally, some may have a shape that takes at least a
portion of the
channel to a different plane and/or orientation. Optionally, some channels may
be entirely in
a different plane and/or orientation.
[00143] In some instances, a plurality of channels may be provided. In
some
embodiments, one channel splits into two or more channels. Optionally, some
channels split
into an even larger number of channels. Some channels may include a control
mechanism
such as but not limited to a valve for directing flow in the channel(s). At
least a portion of
the channels may be substantially parallel to one another. Alternatively, no
portion of the
channels need be parallel to one another. In some instances, at least a
portion of the channels
are not parallel to one another. Optionally, the channels may be slightly
bent. Optionally,
channels may have one cross-sectional area at one location and a smaller cross-
sectional area
at a different location along the channel. Optionally, channels may have one
cross-sectional
area at one location and a larger cross-sectional area at a different location
along the channel.
For some embodiments of the Y design, it may be desirable that the channels
would have
vents placed appropriately to define the sample for each vial such that there
would not be
sample pulled or cross contamination from other channels. By way of non-
limiting example,
one embodiment with vents is shown in Figure 11I.
[00144] A base 140 may be provided within the sample collection device.
The base
may be connected to the support 130. In some instances, a portion of the base
may insertable
within the support and/or a portion of the support may be insertable within
the base. The
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base may be capable of moving relative to the support. In some instances, a
sample
collection device may have a longitudinal axis extending along the length of
the sample
collection device. The base and/or support may move relative to one another in
the direction
of the longitudinal axis. The base and/or support may be capable of moving a
limited
distance relative to one another. Alternatively, the base may be fixed
relative to the support.
The base may be provided at an end of the sample collection device opposite an
end of the
sample collection device comprising a cap 110. Optionally, some embodiments
may
include an integrated base/vessel part so that there are no longer separate
vessels that are
assembled into the base pieces. There may be variations and alternatives to
the embodiments
described herein and that no single embodiment should be construed to
encompass the entire
invention.
1001451 A base 140 may house one or more vessel therein. The vessels may
be in
fluidic communication with the channels and/or may be brought into fluidic
communication
with the channels. An end of a channel may be within the vessel or may be
brought within
the vessel. A base may have one or more optical indicator 142a, 142b that may
provide a
visual indication of whether sample has reached one or more vessel housed in
the base. In
some embodiments, the optical indicators may be optical windows that may
enable a user to
see into the base. The optical window may be formed from a transparent and/or
translucent
material. Alternatively, the optical window may be an opening without any
material therein.
The optical window may enable a user to directly view a vessel within the
base. The vessel
within the base may be formed from a transparent and/or translucent material
that may enable
a user to see if a sample has reached the vessel of the base. For example, if
blood is
transported along the channel to the vessels, the vessels may visually
indicate the presence of
blood therein. In other embodiments, the optical indicators may include other
features that
may indicate the vessel has been filled. For example, one or more sensors may
be provided
within the base or vessel that may determine whether a sufficient amount of
sample has been
provided within the vessel. The one or more sensors may provide a signal to an
optical
indicator on the base that may indicator whether the sample has been provided
to the vessel
and/or the amount of sample that has been provided to the vessel. For example,
the optical
indicator may include a display, such as but not limited to an LCD display,
light display (e.g.,
LED display), plasma screen display that may provide an indication that the
vessels have
been sufficiently filled. In alternative embodiments, an optical indicator
need not be
provided, but alternative indicators may be provided, such as but not limited
to an audio
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indicator or temperature controlled indicator can be used to indicate when the
vessels have
been filed.
[00146] Figures 2A-2C provide views of a sample collection device 200
without a cap
110. The sample collection device 200 may include a body 220, support 230, and
base 240.
The body may be connected to the support. In the present embodiment, the base
240 may be
connected to the support at an end opposing the end connected to the body. The
body may
support and/or contain at least a portion of one, two, or more channels 222a,
222b. The
channels may be capable of receiving a sample 224a, 224b from a sample
receiving end 226
of the device.
[00147] The body 220 may have a hollow portion 225 therein. Alternatively,
the body
may be formed from a solid piece. The channels 222a, 222b may be integrally
formed into
the body. For example, they may be passageways that pass through a solid
portion of the
body. The passageways may have been drilled through, or formed using
lithographic
techniques. Alternatively, the channels may be separate structures that may be
supported by
the body. For example, the channels may be formed of one or more tube that may
be
supported by the body. In some instances, the channels may be held in place at
certain solid
portions of the body and may pass through one or more hollow portion of the
body.
Optionally, the body 220 may be formed from two pieces joined together to
define the
channels 222a and 222b therein.
[00148] The channels 222a, 222b may include one or more features or
characteristics
mentioned elsewhere herein. At least a portion of the channels may be
substantially parallel
to one another. Alternatively, the channels may be at angles relative to one
another. In some
embodiments, the channels may have a first end that may be at a sample
receiving end 226 of
the sample collection device. The first end of a channel may be an open end
capable of
receiving a sample. In some embodiments, the ends of each of the channels may
be provided
at the sample receiving end of the sample collection device. One, two, or more
channels may
have a first end at the sample receiving end of the sample collection device.
Separate
channels can be used to minimize the risk of cross contamination of blood
between one
channel and another channel. Optionally, the channels may have an inverted Y
configuration
with the channels starting with a common channel and the splitting into two or
more separate
channels. This Y configuration may be useful in situation where contamination
is not an
issue. Optionally, an alternative method to a Y configuration would be a
straight channel and
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have the sample collection vessels move to sequentially to engage the same
needle from a
straight channel.
[00149] In some instances, a plurality of channels may be provided. The
ends of the
channels at the sample receiving end may be in close proximity to one another.
The ends of
the channels at the sample receiving end may be adjacent to one another. The
ends of the
channels at the sample receiving end may be contacting one another, or may be
within about
0.5 mm, 1 mm, 2 mm, 3 mm, 4 mm, 5 mm, 6 mm, 7 mm, 8 mm, 9 mm, 10 mm, 12 mm, 15
mm, or 20 mm of one another edge to edge, or center to center. The channels
may diverge
from one another from the sample receiving end. For example, the other ends of
the channels
opposing the ends of the channels at the sample receiving ends may be further
apart from one
another. They may be greater than or equal to about 3 mm, 4 mm, 5 mm, 6 mm, 7
mm, 8
mm, 9 mm, 10 mm, 12 mm, 15 mm, 20 mm, 25 mm, or 30 mm apart from one another
edge
to edge or center to center.
[00150] In some embodiments, the body 220 may have an elongated shape. The
body
may have one or more tapered portion 228 at or near the sample receiving end
226. The sides
of the body may converge at the sample receiving end. The tapered portion
and/or sample
receiving end may be curved. Alternatively, edges may be provided. A surface
of the
tapered portion may be provided at any angle relative to the longitudinal axis
of the device.
For example, the tapered portion may be about 5 degrees, 10 degrees, 15
degrees, 30 degrees,
45 degrees, 60 degrees, or 75 degrees relative to the longitudinal axis.
[00151] The sample receiving end 226 of the device may be contacted to a
sample.
The sample may be provided directly from the subject. The sample receiving end
may
contact the subject or a sample that is contacting or being exuded from the
subject. For
example, the sample receiving end may contact a drop of blood on a subject's
finger. The
blood may enter the channels. The blood may be transported through the
channels via
capillary action, pressure differential, gravity, or any other motive force.
The blood may
travel through the channels from a sample receiving end to a sample delivery
end. The
sample delivery end may be in fluid communication or may be brought into fluid
communication with one or more vessels housed within a base of the device. The
sample
may pass from the channels to the vessels. The sample may be driven into the
vessels via
pressure differential, capillary action, gravity, friction, and/or any other
motive force.
Optionally, the sample might also be blood introduced with a pipette, syringe,
etc... It should
be understood that although Figure 2B shows that sample B only partially
filling the channels
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222a, 222b, but in most embodiments, the channels will be fully filled with
sample B when
the fill process is completed.
[00152] Figures 3A-3B show an example of a sample collection device 300
prior to
bringing the channels 322a, 322b into fluid communication with one or more
vessels 346a,
346b housed within a base 340 of the device. The sample collection device may
include a
cap 310, body 320, support 330, and base 340. The body and/or support may
support and/or
encompass at least a portion of one, two, or more channels. The base may
support and/or
encompass one, two, or more vessels.
[00153] In one embodiment, a body 320 and/or support 330 may support one or
more
channels 322a, 322b in the sample collection device. In one example, two
channels are
provided, although descriptions relating to a two-channel embodiment may apply
to any
number of channels including but not limited to 1, 3, 4, 5, 6, or more
channels. Each of the
channels may have a first end 323a, 323b that may be provided at a sample
receiving end 326
of the device. The first ends of the respective channels may be open. The
channels may be
open to ambient air. When the first ends of the channels contact a fluid, such
as blood, the
fluid may be drawn into the channels. Blood may be drawn in via capillary
action, or any
other of the techniques described elsewhere herein. The blood may travel along
the length of
the channels to the respective second ends 325a, 325b of the channels. The
channels may be
fluidically segregated from one another. For example, a fluid may enter a
first channel 322a
via a first end 323a, pass through the length of the channel, and exit the
first channel at the
second end 325a. Similarly, fluid may enter a second channel 322b via a first
end 323b, pass
through the length of the channel, and exit the second channel at the second
end 325b. The
first and second channels may be fluidically segregated so that fluid from the
first channel
does not pass into the second channel and vice versa. In some embodiments, the
fluid may
pass to the second ends of the channels without exiting initially.
[00154] The channels 322a, 322b may have a diverging configuration. For
example,
the first ends 323a, 323b of the channels may be closer together than the
second ends 325a,
325b of the channels. More space may be provided between the second ends of
the channels
than between the first ends of the channels. The first ends of the channels
may or may not be
in contact with one another. The first ends of the channels may be adjacent to
one another.
[00155] A base 340 may be connected to a support 330 of the sample
collection
device. The base 340 may or may not directly contact the support. The base may
be movable
relative to the support during use of the device. In some embodiments, the
base may slide in
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a longitudinal direction relative to the support. In some instances, the base
may slide in a
longitudinal direction relative to the support without rotating. In some
instances, the base
may slide co-axially with the support without rotating. In some instances, a
base may rotate
while moving relative to the support. A portion of the base may fit within a
portion of the
support, or vice versa. For example, a portion of the base may be insertable
into a portion of
the support and/or a portion of the support may be insertable into the base.
One or more stop
feature may be provided in the base and/or the frame to provide a controlled
degree of
movement between the base and the support. The stop feature may include a
shelf,
protrusion or groove.
[00156] The base 340 may be capable of supporting one or more vessels
346a, 346b.
The base may have a housing that may at least partially surround the one or
more vessels. In
some instances, the vessels may be completely surrounded when the base is
engaged with a
support 330. The base may have one or more indentation, protrusion, groove, or
shaped
feature to accept the vessels. The base may be formed with a shape that is
complementary to
the shape of the vessels. The vessels may be maintained in an upright position
relative to the
base.
[00157] The same number of vessels may be provided as the number of
channels. For
example, if N channels are provided, then N vessels may be provided, wherein N
is a positive
whole number (e.g., 1, 2, 3, 4, 5, 6, 7, 8, or more). Each channel may
correspond to a
respective vessel. In one example, a sample collection device may have a first
channel and a
second channel, as well as a respective first vessel and second vessel. A
first channel 322a
may be in or may be configured to be brought into fluid communication with a
first vessel
346a, and a second channel 322b may be in or may be configured to be brought
into fluid
communication with a second vessel 346b.
[00158] In some embodiments, each vessel may have a body 349a, 349b and a
cap
348a, 348b. In some instances, the vessel body may be formed from a
transparent or
translucent material. The vessel body may permit a sample provided within the
vessel body
to be visible when viewed from outside the vessel. The vessel body may have a
tubular
shape. In some instances, the vessel body may have a cylindrical portion. The
bottom of the
vessel may be flat, tapered, rounded, or any combination thereof. The vessels
may comprise
an open end and a closed end. The open end may be a top end of the vessel,
which may be at
the end of the vessel closer to one or more channel. The closed end may be a
bottom end of
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the vessel, which may be at the end of the vessel further from one or more
channel. Various
embodiments of vessels may be described in greater detail elsewhere herein.
[00159] A base 340 may have one or more optical indicators, such as
optical windows
342a, 342b. The optical windows may be positioned over the vessels 346a, 346b.
In some
instances, the optical windows may be positioned over the vessel bodies. A
single window
may provide a view to a single vessel or to multiple vessels. In one example,
the same
number of optical windows may be provided as vessels. Each optical window may
correspond to a respective vessel. Both the optical window and vessels may be
formed of an
optically transmissive material that may permit a user to view whether a
sample has reached
the vessel from outside the sample collection device.
[00160] In some embodiments, there may be optical windows of the channels
322a and
322b so that a user may observe when a desired fill level has been reached in
the channels.
Some embodiments where the body 320 is entirely transparent or translucent,
there may be a
marker or indicator mark along the channels to note when a desired fill level
has been
reached.
[00161] The vessels may be sized to contain a small fluid sample. In some
embodiments, the vessels may be configured to contain no more than about 5 ml,
4 ml, 3 ml,
2 ml, 1.5 mL, 1 mL, 900 uL, 800 uL, 700 uL, 600 uL, 500 uL, 400 uL, 300 uL,
250 uL, 200
uL, 150 uL, 100 uL, 80 uL, 50 uL, 30 uL, 25 uL, 20 uL, 10 uL, 7 uL, 5 uL, 3
uL, 2 uL, 1 uL,
750 nL, 500 nL, 250 nL, 200 nL, 150 nL, 100 nL, 50 nL, 10 nL, 5 nL, or 1 nL.
The vessels
may be configured to contain no more than several drops of blood, a drop of
blood, or no
more than a portion of a drop of blood.
[00162] The vessels may contain a cap 348a, 348b. The plug may be
configured to fit
over an open end of the vessel. The cap may block the open end of the vessel.
The cap may
fluidically seal the vessel. The cap may form a fluid-tight seal with the
vessel body. For
example, the cap may be gas and/or liquid impermeable. Alternatively, the cap
may permit
certain gases and/or liquids to pass through. In some instances, the cap may
be gas
permeable while being liquid impermeable. The cap may be impermeable to the
sample. For
example, the cap may be impermeable to whole blood, serum or plasma. In some
instances, a
portion of the cap may fit into a portion of the vessel body. The cap may form
a stopper with
the vessel body. The cap may include a lip or shelf that may hang over a
portion of the vessel
body. The lip or shelf may prevent the cap from sliding into the vessel body.
In some
instances, a portion of a cap may overlie a top and/or side of the vessel
body. Any
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description herein of vessels may be applied in combination with the sample
collection
device. Optionally, some embodiments may include an additional part in the
vessel
assembly such as cap holder. In one embodiment, the purpose of the cap holder
is to
maintain a tight seal between the cap and vessel. In one embodiment, the cap
holder engages
an attachment, lip, indentation, or other attachment location on the outside
of the vessel to
hold the cap in position. Optionally, some embodiments can combine the
function of both the
cap and the cap holder into one component.
[00163] One or more engagement assemblies may be provided. The
engagement
assembly may include a channel holder 350 and/or a force-exerting component,
such as a
spring 352 or elastic. In one embodiment, the holder 350 may keep the adapter
channel 354
affixed to the support. As will be described elsewhere herein, the adaptor
channel 354 may
be formed integrally with the collection channel or may be a discrete element
that may be a
stand-alone piece, part of the collection channel, or part of the vessel. In
one embodiment,
the holder 350 may prevent the adapter channel 354 from sliding relative to
the support. The
holder 350 may optionally provide a support upon which a force-exerting
component, such as
a spring, may rest.
[00164] In one example, the engagement assemblies may each include a
spring 352
which may exert a force so that the base 340 is at an extended state, when the
spring is at its
natural state. When the base is at its extended state, space may be provided
between the
vessels 346a, 346b and the engagement assemblies. In some instances, when the
base 340 is
in its extended state, the second ends of the channels may or may not contact
the caps of the
vessels. The second ends of the channels 325a, 325b may be in a position where
they are not
in fluid communication with the interiors of the vessels.
[00165] A sample collection device may have any number of engagement
assemblies.
For example, the same number of engagement assemblies may be provided as
number of
channels. Each channel may have an engagement assembly. For example, if a
first channel
and a second channel are provided, a first engagement assembly may be provided
for the first
channel, and a second engagement assembly may be provided for the second
channel. The
same number of engagement assemblies and vessels may be provided.
[00166] In one embodiment, the engagement assembly may house an
adapter channel
354 such as but not limited to an elongate member with angled, tapered or
pointed end 327a
= and 327b. It should be understood that in some embodiments, the ends 327a
and 327b are
part of a needle that is formed separate from the channels 322a and 322b and
then coupled to
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the channels 322a and 322b. The needles may be formed of the same or different
material
from the body defining the channels 322a and 322b. For example, some may use a
metal to
form the needles and a polymer or plastic material for the body defining
channels 322a and
322b. Optionally, some embodiments may form the ends 327a and 327b on a member
that is
integrally formed with the channels 322a and 322b. In some instances, the
second end of the
channel may be configured to penetrate a material, such as a cap 348a, 348b of
the vessel. In
some embodiments, a portion of the adaptor channel 354 may be insertable
within the
collection channel or a portion of the collection channel may be insertable
within the adaptor
channel, or the two may be configured to align flush. Optionally, some
embodiments may
integrally form the adapter channel 354 with the collection channel 322a. It
should be
understood that Figure 3B (and 4B) shows that sample B only partially filling
the channels
122a, 122b, but, in most embodiments, the channels will be fully filled with
sample B when
the fill process is completed. There may be variations and alternatives to the
embodiments
described herein and that no single embodiment should be construed to
encompass the entire
invention.
[00167] Figures 4A-4B show an example of a sample collection device 400
having
channels 422a, 422b that are in fluid communication with the interior of
vessels 446a, 446b
within the device. The sample collection device may include a cap 410, body
420, support
430, and base 440. The body and/or support may support and/or encompass at
least a portion
of one, two, or more channels. The base may support and/or encompass one, two,
or more
vessels.
[00168] In one embodiment, a body 420 and/or support 430 may support one
or more
channels 422a, 422b in a sample collection device. For example, a first
channel and second
channel may be provided. Each of the channels may have a first end 423a, 423b
that may be
provided at a sample receiving end 426 of the device. The first ends of the
respective
channels may be open. The channels may be open to ambient air. When the first
ends of the
channels contact a fluid, such as blood, the fluid may be drawn into the
channels. The fluid
may be drawn in via capillary action, or any other of the techniques described
elsewhere
herein. The fluid may travel along the length of the channels to the
respective second ends
425a, 425b of the channels. In some embodiments, the fluid may reach the
second ends of
the channels via capillary action or other techniques described herein. In
other embodiments,
the fluid need not reach the second ends of the channels. The channels may be
fluidically
segregated from one another.
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1001691 In some embodiments, the fluid may pass to the second ends of the
channels
without exiting when the channels are not in fluid communication with the
interiors of the
vessels 446a, 446b. For example, the fluid may be drawn into the channel via
capillary
action, which may cause the fluid to flow to or near the end of the channel
without causing
the fluid to exit the channel.
1001701 A base 440 may be connected to a support 430 of the sample
collection
device. The base may be movable relative to the support during use of the
device. In some
embodiments, the base may slide in a longitudinal direction relative to the
support. In one
example, the base may have (i) an extended position where the channels are not
in fluid
communication with the interior of the vessels, and (ii) a compressed position
where the
channels are in fluid communication with the interior of the vessels. A sample
collection
device may be initially provided in an extended state, as shown in Figure 3.
After the sample
has been collected and flown through the length of the channel, a user may
push the base in
to provide the sample collection device in its compressed state, as shown in
Figure 4. Once
the base has been pushed in, the base may naturally remain pushed in, or may
spring back out
to an extended state, once the pushing force is removed. In some instances, a
base may be
pulled out to an extended state, or may be pulled out completely to provide
access to vessels
therein.
[00171] The base 440 may be capable of supporting one or more vessels
446a, 446b.
The base may have a housing that may at least partially surround the one or
more vessels. In
some instances, the vessels may be completely surrounded when the base is
engaged with a
support 430. The base may have one or more indentation, protrusion, groove, or
shaped
feature to accept the vessels. The base may be formed with a shape that is
complementary to
the shape of the vessels. The vessels may be maintained in an upright position
relative to the
base.
[00172] The same number of vessels may be provided as the number of
channels.
Each channel may correspond to a respective vessel. In one example, a sample
collection
device may have a first channel and a second channel, as well as a respective
first vessel and
second vessel. A first channel 422a may be in or may be configured to be
brought into fluid
communication with a first vessel 446a, and a second channel 422b may be in or
may be
= configured to be brought into fluid communication with a second vessel
446b. The first
channel may initially not be in fluid communication with a first vessel and
the second
channel may initially not be in fluid communication with the second vessel.
The first and
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second channels may be brought into fluid communication with the interiors of
the first and
second vessels respectively when the base is pushed in relative to the
support. The first and
second channels may be brought into fluid communication with the first and
second vessels
simultaneously. Alternatively, they need not be brought into fluid
communication
simultaneously. The timing of the fluid communication may depend on the height
of the
vessel and/or the length of the channel. The timing of the fluid communication
may depend
on the relative distances between the second end of the channel and the
vessel.
[00173] In some embodiments, each vessel may have a body 449a, 449b and a
cap
448a, 448b. The vessel body may have a tubular shape. In some instances, the
vessel body
may have a cylindrical portion. The bottom of the vessel may be flat, tapered,
rounded, or
any combination thereof. The vessels may comprise an open end and a closed
end. The open
end may be a top end of the vessel, which may be at the end of the vessel
closer to one or
more channel. The closed end may be a bottom end of the vessel, which may be
at the end of
the vessel further from one or more channel.
[00174] A base 440 may have one or more optical indicators, such as optical
windows
442a, 442b. The optical windows may be positioned over the vessels 446a, 446b.
In some
instances, the optical windows may be positioned over the vessel bodies. Both
the optical
window and vessels may be formed of an optically transmissive material that
may permit a
user to view whether a sample has reached the vessel from outside the sample
collection
device. In some embodiments, the vessels may incorporate markings on the
vessels
themselves to indicate fill level requirements.
[00175] The vessels may contain a cap 448a, 448b. The cap may be configured
to fit
over an open end of the vessel. The cap may block the open end of the vessel.
The cap may
fluidically seal the vessel. The cap may form a fluid-tight seal with the
vessel body. For
example, the cap may be impermeable to whole blood, serum or plasma. In some
instances, a
portion of the cap may fit into a portion of the vessel body. The cap may
include a lip or
shelf that may hang over a portion of the vessel body. In some embodiments,
the cap may
have a hollow or depression. The hollow or depression may assist with guiding
a second end
of the channel to a center of the cap. In some instances, when the sample
collection device is
in an extended state, a second end of a channel 425a, 425b may lie above the
cap of the
vessel. The second end of the channel may or may not contact the vessel cap.
In some
instances, the second end of the channel may rest within a hollow or
depression of the cap. In
some instances, the second end of the channel may partially penetrate the cap
without
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reaching the interior of the vessel. Optionally, some embodiments of the cap
might include a
crimping piece to hold vacuum.
[00176] A second end of a channel may have an angled, tapered or pointed
end 427a
and 427b. It should be understood that in some embodiments, the ends 427a and
427b are
part of a needle that is formed separate from the channels 422a and 422b and
then coupled to
the channels 422a and 422b. The needles may be formed of the same or different
material
from the body defining the channels 422a and 422b. For example, some may use a
metal to
form the needles and a polymer or plastic material for the body defining
channels 422a and
422b. Optionally, some embodiments may form the ends 427a and 427b on a member
that is
integrally formed with the channels 422a and 422b. In some instances, the
second end of the
channel may be configured to penetrate a material, such as a cap 448a, 448b of
the vessel.
The cap may be formed of a material that may prevent sample from passing
through in the
absence of a penetrating member. The cap may be formed from a single solid
piece.
Alternatively, the cap may include a slit, opening, hole, thin portion, or any
other feature that
may accept a penetrating member. A slit or other opening may be capable of
retaining
sample therein, when the penetrating member is not in the slit or opening, or
when the
penetrating member is removed from the slit or opening. In some instances, the
cap may be
formed from a self-healing material, so that when a penetrating member is
removed, the
opening formed by the penetrating member closes up. The second end of the
channel may be
a penetrating member that may pass through the cap and into the interior of
the vessel. In
some embodiment, it should be clear that the penetrating member may be hollow
needles that
allow sample to pass through, and not just needles for piercing. In some
embodiments, the
piercing tip can be a non-coring design such as but not limited to a tapered
cannula that
pierces without coring the cap material.
[00177] One or more engagement assemblies may be provided. The engagement
assembly may include a channel holder 450 and/or a force-exerting component,
such as a
spring 452 or elastic. In one embodiment, the holder 450 may keep the adaptor
channel 454
affixed to the support. As will be described elsewhere herein, the adaptor
channel 454 may
be formed integrally with the collection channel or may be a discrete element
that may be a
stand-alone piece, part of the collection channel, or part of the vessel. In
one embodiment,
the holder 450 may prevent the adaptor channel 454 from sliding relative to
the support. The
holder 450 may optionally provide a support upon which a force-exerting
component, such as
a spring, may rest.
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[00178] In one example, the engagement assemblies may include a spring 452
which
may exert a force so that the base is at its extended state, when the spring
is at its natural
state. When the base is at its extended state, space may be provided between
the vessels
446a, 446b and the engagement assemblies. The second ends of the channels
425a, 425b
may be in a position where they are not in fluid communication with the
interiors of the
vessels.
[00179] A sample collection device may have any number of engagement
assemblies.
For example, the same number of engagement assemblies may be provided as
number of
channels. Each channel may have an engagement assembly. For example, if a
first channel
and a second channel are provided, a first engagement assembly may be provided
for the first
channel, and a second engagement assembly may be provided for the second
channel. In one
embodiment, the same number of engagement assemblies and vessels may be
provided.
[00180] When the base is pressed in, the spring 452 may be compressed. The
second
ends 425a, 425b of the channels may penetrate the caps of the vessels. The
second ends of
the channels may enter the interior of the vessel. In some instances, a force
may be provided
to drive the fluid from the channels into the vessels. For example, a pressure
differential may
be generated between the first and second ends of the channels. A positive
pressure may be
provided at the first end 423a, 423b of the channels and/or a negative
pressure may be
provided at the second end of the channels. The positive pressure may be
positive relative to
the pressure at the second end of the channel, and/or ambient air. The
negative pressure may
be negative relative to the pressure at the first end of the channel and/or
ambient air. In one
example, the vessels may have a vacuum therein. When the second end of a
channel
penetrates a vessel, the negative pressure within the vessel may pull the
sample into the
vessel. In alternative embodiments, the sample may enter the vessel driven by
capillary
forces, gravity, or any other motive force. In embodiments, the vessel does
not have a
vacuum therein. There may be variations and alternatives to the embodiments
described
herein and that no single embodiment should be construed to encompass the
entire invention.
[00181] In some instances, different types of motive forces may be used at
different
stages of sample collection. Thus, one type of motive force may be used to
draw the sample
into the channel, and then a different type of motive force may be used to
move sample from
the channel into the vessel. For example, a capillary force may draw the
sample into a
channel, and a pressure differential may drive the sample from the channel
into the vessel.
Any combinations of motive forces may be used to draw sample into the channel
and into the
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vessel. In some embodiments, the motive force(s) used to draw sample into the
channel is
different from motive force(s) used to draw sample into the vessel. In some
alternative
embodiments, the motive force(s) may be the same for each stage. In some
embodiments, the
motive force(s) are applied sequentially or at defined time periods. By way of
non-limiting
example, motive force(s) to draw sample into the vessel is not applied until
the at least one
channel has reach a minimum fill level. Optionally, motive force(s) to draw
sample into the
vessel is not applied until the at least two channels have each reach a
minimum fill level for
that channel. Optionally, motive force(s) to draw sample into the vessel is
not applied until
all channels have each reach a minimum fill level for that channel. In some
embodiments,
the motive force(s) are applied simultaneously.
1001821 Some embodiments may use a pressurized gas source coupled to the
sample
collection device and configured to push collected bodily fluid from the one
or more channels
into their respective vessels. Optionally, some may use a vacuum source not
associated with
the vessels to pull sample fluid towards the vessels.
[00183] Additional, some embodiments of the channel may be configured such
that
there is sufficient capillary force within the channel such that once filled,
the force is greater
than that of gravity so that sample does not escape from the channel based
only on gravitation
force. An additional motive force is used to break the hold of the capillary
action of the
channel(s). Optionally, as described elsewhere herein, a device such as but
not limited to a
sleeve may contain the bodily fluid from exiting the channel at the end
closest to the vessel,
thus minimizing any loss until transfer to the vessel is initiated.
[00184] Optionally, other materials such as but not limited to a lyosphere,
sponge, or
other motive force provider may be used to provide motive force that draws
sample into the
vessel. When multiple forces are being used, this may be a primary, secondary,
or tertiary
motive force to draw sample into the vessel. Optionally, some embodiments may
include a
push-type motive force provider such as but not limited to a plunger to move
the sample in a
desired manner.
[00185] Some time may elapse after a sample has been introduced to a
channel for
traveling along the length of the channel. A user may introduce a sample to
the sample
collection device and may wait for the sample to travel the length of the
channel. One or
more optical indicator may be provided, which may indicate whether the sample
has reached
a desired fill level, such as not limited to the end of the channel. In other
embodiments, the
user may wait a predetermined amount of time before pushing in the base. The
base may be
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pushed in after the user has determined the sample has traveled a sufficient
length of the
channel and/or a sufficient amount of time has passed since the sample was
introduced. After
the base is pushed in, the channels may be brought into fluid communication
with the vessels,
and sample may flow from the channel into the vessels. An optical indicator
may be
provided so that a user may know when the vessels have been filled.
[00186] Once the vessels have been filled, they may be transferred to a
desired
location, using systems and methods described elsewhere herein. In some
instances, the
entire sample collection device may be transferred. The cap may be placed on
the sample
collection device for transfer. In other embodiments, the base portion and/or
support portion
may be removable from the rest of the device. In one example, the base may be
removed
from the sample collection device, and the vessels may be transferred along
with the base.
Alternatively, the base may be removed from the sample collection device to
provide access
to the vessels, and the vessels may be removed from the device and
transmitted. The removal
of the base may involve some disassembly of the sample collection device to
detach the base.
This may involve using sufficient force to overcome detents or stops built
into the device to
prevent accidental disengagement. Optionally, some other positive act such as
but not
limited to disengaging a latch or other locking mechanism may be performed by
a user before
detaching the base. Optionally, some embodiments may allow for removal of the
vessels
without removal of the base, but allow for access to the vessels by way of
openings, access
ports, or open-able covers on the base.
[00187] In some embodiments, one or more of the channels and/or vessels
may
comprise features described elsewhere herein, such as separation members,
coatings, anti-
coagulants, beads, or any other features. In one example, the sample
introduced to the
sample collection device may be whole blood. Two channels and respective
vessels may be
provided. In this non-limiting example, each of the channels has a coating
such as but not
limited to an anti-coagulant coating in the channel. Such an anti-coagulant
coating can serve
one or more of the following functions. First, the anti-coagulant can prevent
whole blood
from clotting inside the channel during the sample collection process.
Depending on the
amount of whole blood to be collected, clotting could prematurely clog the
channel before
sufficient amount of blood has been brought into the channel. Another function
is to
introduce anti-coagulant into the whole blood sample. By have the anti-
coagulant in the
channel, this process can begin earlier in the collection process versus some
embodiments
which may only have it the vessels 446a or 446b. This early introduction of
anti-coagulant
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may also be advantageous in case the whole blood sample will be led along a
pathway that
may have portions that are not coated with anti-coagulant, such as but not
limited to, the inner
surfaces of a needle connected to the channels 422a or 422b. Optionally, some
embodiments
may include surfactants that can be used to modify the contact angle
(wettability) of a
surface.
[00188] In some embodiments the inner surface of the channel and/or
other surfaces
along the fluid pathway such as but not limited to the sample inlet to the
interior of a sample
collection vessel may be coated with a surfactant and/or an anti-coagulant
solution. The
surfactant provides a wettable surface to the hydrophobic layers of the
fluidic device and
facilitate filling of the metering channel with the liquid sample, e.g.,
blood. The anti-
coagulant solution helps prevent the sample, e.g., blood, from clotting when
provided to the
fluidic device. Exemplary surfactants that can be used include without
limitation, Tween,
TWEENC20, Thesit , sodium deoxycholate, Triton, Triton X-100, Pluronic and/or
other
non-hemolytic detergents that provide the proper wetting characteristics of a
surfactant.
EDTA and heparin are non-limiting anti-coagulants that can be used. In one non-
limiting
example, the embodiment the solution comprises 2% Tween, 25 mg/mL EDTA in 50%
Methanol/50% H20, which is then air dried. A methanol/water mixture provides a
means of
dissolving the EDTA and Tween, and also dries quickly from the surface of the
plastic. The
, solution can be applied to the channel or other surfaces along the fluid
flow pathway by any
technique that will ensure an even film over the surfaces to be coated, such
as, e.g., pipetting,
spraying, printing, or wicking.
[00189] It should also be understood for any of the embodiments
herein that a coating
in the channel may extend along the entire path of the channel. Optionally,
the coating may
cover a majority but not all of the channel. Optionally, some embodiments may
not cover the
channel in the areas nearest the entry opening to minimize the risk of cross-
contamination,
wherein coating material from one channel migrates into nearby channels by way
of the
channels all being in contact with the target sample fluid at the same time
and thus having a
connecting fluid pathway.
[00190] Although embodiments herein are shown with two separate
channels in the
sample collection device, it should be understood that some embodiments may
use more than
two separate channels. Optionally, some embodiments may use less than two
fully separate
channels. Some embodiments may only use one separate channel. Optionally, some
embodiments may use an inverted Y-channel that starts initially as one channel
and then
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splits into two or more channels. Any of these concepts may be adapted for use
with other
embodiments described herein.
Collection Device with Self-Supporting Collection Channels
[00191] Figures 5A-5B provide another example of a sample collection device
500
provided in accordance with an embodiment described herein. The sample
collection device
may include a collection device body 520, support 530, and base 540. In some
instances, a
cap may be optionally provided. The collection device body may contain one or
more
collection channels 522a, 522b defined by collection tubes, which may be
capable of
receiving sample. A base may have one or more optical indicator 542a, 542b
that may
provide a visual indication of whether sample has reached one or more vessel
housed in the
base. A support may have one or more optical indicator 532a, 532b that may
provide a visual
indication of whether sample has reached or passed through a portion of the
channels.
[00192] A collection device body 520 of a sample collection device may
contain at
least a portion of one or more tubes with channels 522a, 522b therein.
Optionally, the device
collection body 520 may also define channels that couple to channels 522a,
522b defined by
the tubes. In some embodiments, a portion of the channels may extend beyond
the collection
device body. The channels may extend beyond one end or two ends of the
collection device
body.
[00193] The collection device body 520 may be connected to a support 530.
The
support may contain a portion of one or more channels therein. The collection
device body
may be permanently affixed to the support or may be removable with respect to
the support.
In some instances, the collection device body and the support may be formed of
a single
integral piece. Alternatively, the collection device body and support may be
formed from
separate pieces.
[00194] During the operation of the device the collection device body 520
and support
530 may move relative to one another. In some instances, a portion of the body
520 may be
insertable within the support 530 and/or a portion of the support may be
insertable within the
body. The body may be capable of moving relative to the support. In some
instances, a
sample collection device may have a longitudinal axis extending along the
length of the
sample collection device. The body and/or support may move relative to one
another in the
direction of the longitudinal axis. The body and/or support may be capable of
moving a
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limited distance relative to one another. The body and/or support may move co-
axially
without rotational motion. Alternatively, rotational motion may be provided.
1001951 The collection device body 520 may be formed from an optically
transmissive
material. For example, the collection device body may be formed from a
transparent or
translucent material. Alternatively, the body may be formed from an opaque
material. The
support 530 may be formed from an optically opaque, translucent, or
transparent material.
The support may or may not have the same optical characteristics of the
collection device
body. The support may be formed from a different material as the collection
device body, or
from the same material as the collection device body. There may be variations
and
alternatives to the embodiments described herein and that no single embodiment
should be
construed to encompass the entire invention.
[00196] The collection device body, support, and/or base may have any
shape or size.
In some examples, the collection device body, support, and/or base may have a
circular,
elliptical, triangular, quadrilateral (e.g., square, rectangular,
trapezoidal), pentagonal,
hexagonal, octagonal, or any other cross-sectional shape. The cross-sectional
shape may
remain the same or may vary along the length. The cross-sectional shape may be
the same
for the body, support, and base, or may vary. In some instances, the
collection device body,
support, and/or base may have a cross-sectional area of less than or equal to
about 10 cm2, 7
cm2, 5 cm2, 4 cm2, 3 cm2, 2.5 cm2, 2 cm2, 1.5 cm2, 1 cm2, 0.8 cm2, 0.5 cm2,
0.3 cm2, or
0.1 cm2. The cross-sectional area may vary or may remain the same along the
length. The
cross-sectional size may be the same for the collection body, support, and/or
base, or may
vary. The collection device body, support, and/or base may have a length of
less than or
equal to about 20 cm, 15 cm, 12 cm, 10 cm, 9 cm, 8 cm, 7 cm, 6 cm, 5 cm, 4 cm,
3 cm, 2 cm,
1 cm, 0.5 cm, or 0.1 cm. The collection device body may have a greater or
lesser length than
support or base, or an equal length to the support, or base.
[00197] The channels 522a, 522b may be supported by the device body 520
and/or the
support 530. In some instances, the entire length of the tubes or the channels
therein may be
encompassed within the combination of the device body and the support.
Alternatively, the
channels may extend beyond the device body and/or support as seen in Figure 5.
In some
instances, the channels may extend beyond one end of the device body/support
combination,
or beyond both ends. In some instances, a portion of the channels may be
within the device
body and a portion of the channels may be within the support. The position of
the channels
may be affixed by the device body and/or the support. In some instances, the
channels may
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be affixed to device body and/or not move relative to the device body. The
channels may be
movable relative to the support. In some instances, a plurality of channels
may be provided.
At least a portion of the channels may be substantially parallel to one
another. The channels
may be parallel to one another and/or a longitudinal axis extending along a
length of the
sample collection device. Alternatively, no portion of the channels need be
parallel to one
another. In some instances, at least a portion of the channels are not
parallel to one another.
The channels may be slightly bent. Optionally, they may be straight, but
aligned to be closer
to one another as they near the sample collection point. It should be
understood that the tubes
defining the channels 522a and 522b may be made of optically transparent,
transmissive, or
other material sufficient to provide a detectable change that sample has
reached a desired fill
level in at least one channel. Optionally, the detectable change can be used
to detect when
both channels reach at least the desired fill level.
1001981 A base 540 may be provided within the sample collection device.
The base
may be connected to the support 530. In some instances, a portion of the base
540 may
insertable within the support 530 and/or a portion of the support may be
insertable within the
base. The base may be fixed relative to the support or may be movable relative
to the
support. The base may be provided at an end of the support opposite an end of
the support
connected to the body. The base may be formed as a separate piece from the
support. The
base may be separable from the support. Alternatively, the base may be affixed
to the
support and/or formed as an integral piece with the support.
[00199] A base 540 may house one or more vessel therein. The vessels may
be in
fluidic communication with the channels and/or may be brought into fluidic
communication
with the channels. An end of a channel may be within the vessel or may be
brought within
the vessel. A base may have one or more optical indicator 542a, 542b that may
provide a
visual indication of whether sample has reached one or more vessel housed in
the base. In
some embodiments, the optical indicators may be optical windows that may
enable a user to
see into the base. The optical window may be formed from a transparent and/or
translucent
material. Alternatively, the optical window may be an opening without any
material therein.
The optical window may enable a user to directly view a vessel within the
base. The vessel
within the base may be formed from a transparent and/or translucent material
that may enable
a user to see if a sample has reached the vessel of the base. For example, if
blood is
transported along the channel to the vessels, the vessels may show the blood
therein. In other
embodiments, the optical indicators may include other features that may
indicate the vessel
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has been filled. For example, one or more sensor may be provided within the
base or vessel
that may determine whether a sufficient amount of sample has been provided
within the
vessel. The sensor may provide a signal to an optical indicator on the base
that may indicator
whether the sample has been provided to the vessel and/or the amount of sample
that has
been provided to the vessel. For example, the optical indicator may include a
display, such as
an LCD display, light display (e.g., LED display), plasma screen display that
may provide an
indication that the vessels have been sufficiently filled. In alternative
embodiments, an
optical indicator need not be provided, but alternative indicators may be
provided, such as but
not limited to, an audio indicator, temperature controlled indicator, or other
device that may
indicate by a detectable signal, such as one detectable by a user, when the
vessels have been
filed.
[00200] A support 530 may have one or more optical indicator 532a, 532b
that may
provide a visual indication of whether sample has reached or pass through a
portion of a
channel housed by the support. In some embodiments, the optical indicators may
be optical
windows that may enable a user to see into the support. The optical window may
be formed
from a transparent and/or translucent material. Alternatively, the optical
window may be an
opening without any material therein. The optical window may enable a user to
directly view
a portion of a channel within the support. The channels may be formed from a
transparent
and/or translucent material that may enable a user to see if a sample has
reached the portion
of the channel underlying the optical window. In other embodiments, the
optical indicators
may include other features that may indicate the sample has passed through a
portion of the
channel, such as sensors described elsewhere herein.
[00201] Referring now to Figures 6A-6B, additional views of a sample
collection
device 500 are provided in accordance with one embodiment described herein.
[00202] In some embodiments, a portion of the tubes containing channels
522a, 522b
may extend beyond the collection device body 520. The portion of the channels
that extend
beyond may include portions of the channels that are configured to receive a
sample from the
subject. In one example, the channels may have a first end 523a, 523b that may
be a sample
receiving end of the channels.
[00203] The channels may optionally be defined by a rigid material.
Alternatively, the
channels may be defined by a flexible material or may have flexible
components. The
channels may or may not be designed to bend or curve. The channels may or may
not be
substantially parallel to one another. In some instances, the first ends of
the channels may be
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some distance apart when in a relaxed state. The first ends of the channels
may remain that
distance apart during operation of the device. Alternatively, the first ends
of the channels
may be brought closer together. For example, the first ends of the channels
may be squeezed
together. Each open end of the channels may separately receive a sample. The
sample may
be received sequentially. The sample may be from the same subject.
Alternatively, the
channels may be capable of receiving the same sample simultaneously.
[00204] The channels 522a, 522b may include one or more features or
characteristics
mentioned elsewhere herein. At least a portion of the channels may be
substantially parallel
to one another. Alternatively, the channels may be at angles relative to one
another. In some
embodiments, the channels may have a first end that may be at a sample
receiving end 526 of
the sample collection device. The first end of a channel may be an open end
capable of
receiving a sample. In some embodiments, the ends of each of the channels may
be provided
at the sample receiving end of the sample collection device. One, two, or more
channels may
have a first end at the sample receiving end of the sample collection device.
[00205] In some embodiments, the device body 520 may be movable relative
to the
support 530. A portion of the device body may be insertable within the support
or vice versa.
In one example, the device body may have a lip 527 and an interior portion
529. The lip may
have a greater cross-sectional area than the interior portion. The interior
portion may be
capable of being inserted into the support. The lip may act as a stop to
prevent the entire
body from being inserted into the support. The lip may rest on a shoulder of
the support.
[00206] Figures 7A-7B shows partial cutaway views of an example of a
sample
collection device 700 provided in accordance with an embodiment described
herein. The
sample collection device in an extended state, prior to bringing the channels
722a, 722b into
fluid communication with one or more vessels 746a, 746b housed within a base
740 of the
device. The sample collection device may include a body 720, support 730, and
base 740.
The body and/or support may support and/or encompass at least a portion of
one, two or more
channels. The base may support and/or encompass one, two or more vessels.
There may be
variations and alternatives to the embodiments described herein and that no
single
embodiment should be construed to encompass the entire invention.
[00207] In one embodiment, a body 720 and/or support 730 may support one
or more
channels 722a, 722b in a sample collection device. In one example, two
channels are
provided, though descriptions relating to a two-channel embodiment may apply
to any
number of channels including but not limited to I, 3, 4, 5, 6 or more
channels. Each of the
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channels may have a first end 723a, 723b that may be a sample receiving end of
the device.
The first ends of the respective channels may be open. The channels may be
open to ambient
air. When the first ends of the channels contact a fluid, such as blood, the
fluid may be drawn
into the channels. Fluid may be drawn in via capillary action, or any other of
the techniques
described elsewhere herein. The fluid may travel along the length of the
channels to the
respective second ends of the channels. The channels may be fluidically
segregated from one
another. For example, a fluid may enter a first channel 722a via a first end
723a, pass
through the length of the channel, and exit the first channel at the second
end. Similarly,
fluid may enter a second channel 722b via a first end 723b, pass through the
length of the
channel, and exit the second channel at the second end. The first and second
channels may
be fluidically segregated so that fluid from the first channel does not pass
into the second
channel and vice versa. In some embodiments, the fluid may pass to the second
ends of the
channels without exiting initially.
[00208] The channels 722a, 722b may have a parallel configuration. For
example, the
first ends 723a, 723b of the channels may be about the same distance apart as
the second ends
of the channels. The first ends of the channels may or may not be in contact
with one
another.
[00209] A support 730 may have one or more optical indicators, such as
optical
windows 732a, 732b. The optical windows may be positioned over the channels
722a, 722b.
In some instances, the optical windows may be positioned over portions of the
channels. A
single window may provide a view to a single channel portion or to multiple
channel
portions. In one example, the same number of optical windows may be provided
as channels.
Each optical window may correspond to a respective channel. Both the optical
window and
channels may be formed of an optically transmissive material that may permit a
user to view
whether a sample has reached and/or passed through the underlying portion of
the channel
from outside the sample collection device. Such determination may be useful in
determining
when to compress the sample collection device.
[00210] A base 740 may be connected to a support 730 of the sample
collection
device. The base may or may not directly contact the support. The base may be
fixed
relative to the support during use of the device. In some instances, the base
may be
removable from the support. A portion of the base may be insertable into the
support and/or
vice versa. In some embodiments, the base may slide out from the support in a
longitudinal
direction relative to the support. In some instances, the base may slide co-
axially with the
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support without rotating. In some instances, a base may rotate while moving
relative to the
support.
[00211] The base 740 may be capable of supporting one or more vessels
746a, 746b.
The base may have a housing that may at least partially surround the one or
more vessels. In
some instances, the vessels may be completely surrounded when the base is
engaged with a
support 730. The height of the base may extend beyond the height of the
vessels.
Alternatively, the height of the base may extend to the same degree or less
than the height of
the vessels. The base may have one or more indentation, protrusion, groove, or
shaped
feature to accept the vessels. The base may be formed with a shape that is
complementary to
the shape of the vessels. For example, the base may have one or more tube
shaped
indentation into which tube shaped vessels may snugly fit. The vessels may
friction-fit into
the base. The vessels may be maintained in an upright position relative to the
base. There
may be variations and alternatives to the embodiments described herein and
that no single
embodiment should be construed to encompass the entire invention.
[00212] The same number of vessels may be provided as the number of
channels. For
example, if N channels are provided, then N vessels may be provided, wherein N
is a positive
whole number (e.g., I, 2, 3, 4, 5, 6, 7, 8, or more). Each channel may
correspond to a
respective vessel. In one example, a sample collection device may have a first
channel and a
second channel, as well as a respective first vessel and second vessel. A
first channel 722a
may be in or may be configured to be brought into fluid communication with a
first vessel
746a, and a second channel 722b may be in or may be configured to be brought
into fluid
communication with a second vessel 746b.
[00213] In some embodiments, each vessel may have a body 749a, 749b and a
cap
748a, 748b. The vessels may have any features or characteristics as described
elsewhere
herein.
[00214] A base 740 may have one or more optical indicators, such as
optical windows
742a, 742b. The optical windows may be positioned over the vessels 746a, 746b.
In some
instances, the optical windows may be positioned over the vessel bodies. A
single window
may provide a view to a single vessel or to multiple vessels. In one example,
the same
number of optical windows may be provided as vessels. Each optical window may
correspond to a respective vessel. Both the optical window and vessels may be
formed of an
optically transmissive material that may permit a user to view whether a
sample has reached
the vessel from outside the sample collection device. Such visual assessment
may be useful
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in determining when the sample has reached the vessels, and when the base can
be removed
from the sample collection device.
[00215] One or more engagement assemblies may be provided. The engagement
assembly may include a channel holder 750 and/or a force-exerting component,
such as a
spring 752 or elastic. In one embodiment, the holder 750 may keep the adaptor
channel 754
affixed to the support. As will be described elsewhere herein, the adaptor
channel 754 may
be formed integrally with the collection channel or may be a discrete element
that may be a
stand-alone piece, part of the collection channel, or part of the vessel. In
one embodiment,
the holder 750 may prevent the adaptor channel 754 from sliding relative to
the support. The
holder 750 may optionally provide a support upon which a force-exerting
component, such as
a spring, may rest.
[00216] In one example, the engagement assemblies may include a spring 752
which
may exert a force so that the body 720 is at an extended state, when the
spring is at its natural
state. When the body is at its extended state, space may be provided between
the vessels
746a, 746b and the engagement assemblies. When a body is in its extended
state, the interior
portion 729 of the body may be exposed and/or uncovered by the support 730. In
some
instances, when the body is in its extended state, the second ends of the
channels 722a, 722b
may or may not contact the caps of the vessels. The second ends of the
channels may be in a
position where they are not in fluid communication with the interiors of the
vessels. There
may be variations and alternatives to the embodiments described herein and
that no single
embodiment should be construed to encompass the entire invention.
[00217] A sample collection device may have any number of engagement
assemblies.
For example, the same number of engagement assemblies may be provided as
number of
channels. Each channel may have an engagement assembly. For example, if a
first channel
and a second channel are provided, a first engagement assembly may be provided
for the first
channel, and a second engagement assembly may be provided for the second
channel. The
same number of engagement assemblies and vessels may be provided.
[00218] Figures 8A-8B provide an example of a sample collection device 800
having
channels 822a, 822b that are in fluid communication with the interior of
vessels 846a, 846b
within the device. The sample collection device may include a body 820,
support 830, and
base 840. The body and/or support may support and/or encompass at least a
portion of one,
two or more channels. The channels may extend beyond an end of the body. The
base may
support and/or encompass one, two or more vessels.
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[00219] In one embodiment, a body 820 and/or support 830 may support one
or more
channels 822a, 822b in a sample collection device. For example, a first
channel and second
channel may be provided. Each of the channels may have a first end 823a, 823b
that may be
provided at a sample receiving end of the device that may extend beyond the
body. The first
ends of the respective channels may be open. The channels may be open to
ambient air. The
channels may be rigid or may be flexible. In some embodiments, the channels
may have a
length that may permit them to be bent into contact with one another. When the
first ends of
the channels contact a fluid, such as blood, the fluid may be drawn into the
channels. Each
channel end may be separately contacted to a fluid, which is drawn into the
respective
channel. This may involve angling the sample collection device so that only
one opening into
the channel is in contact with the sample fluid at any one time.
Alternatively, all channels
may be simultaneously contacted to the same sample which is simultaneously
drawn into the
respective channels. Alternatively, multiple but not all channels may be
simultaneously
contacted to the same sample which is then simultaneously drawn into the
respective
channels. The fluid may be drawn in via capillary action, or any other of the
techniques
described elsewhere herein. The fluid may travel along the length of the
channels to the
respective second ends of the channels. In some embodiments, the fluid may
reach the
second ends of the channels via capillary action or other techniques described
herein. In
other embodiments, the fluid need not reach the second ends of the channels.
The channels
may be fluidically segregated from one another.
[00220] In some embodiments, the fluid may pass to the second ends of the
channels
without exiting when the channels are not in fluid communication with the
interiors of the
vessels 846a, 846b. For example, the fluid may be drawn into the channel via
capillary
action, which may cause the fluid to flow to. or near the end of the channel
without causing
the fluid to exit the channel.
[00221] The body 820 may be movable relative to the support 830 during use
of the
device. In some embodiments, the body may slide in a longitudinal direction
relative to the
support. In one example, the body may have (i) an extended position where the
channels are
not in fluid communication with the interior of the vessels, and (ii) a
compressed position
where the channels are in fluid communication with the interior of the
vessels. A sample
collection device may be initially provided in an extended state, as shown in
Figure 7. After
the sample has been collected and flown through the length of the channel, a
user may push
the body in to provide the sample collection device in its compressed state,
as shown in
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Figure 8. In some instances, when the body is in an extended state, an
interior portion of the
body is exposed. When the body is in a compressed state, the interior portion
of the body
may be covered by the support. A lip of the body may contact the support. Once
the body
has been pushed in, the body may naturally remain pushed in, or may spring
back out to an
extended state, once the pushing force is removed. In some instances, a body
may be pulled
out to an extended state, or may be pulled out completely to provide access to
vessels therein.
Optionally, in some assemblies, removal of the body will not provide access to
the vessels.
[00222] A base 840 may be connected to a support 830 of the sample
collection
device. The base 840 may be capable of supporting one or more vessels 846a,
846b. The
base may have a housing that may at least partially surround the one or more
vessels. In
some instances, the vessels may be completely surrounded when the base is
engaged with a
support 830. The base may have one or more indentation, protrusion, groove, or
shaped
feature to accept the vessels. The base may be formed with a shape that is
complementary to
the shape of the vessels. The vessels may be maintained in an upright position
relative to the
base.
[00223] The same number of vessels may be provided as the number of
channels.
Each channel may correspond to a respective vessel. In one example, a sample
collection
device may have a first channel and a second channel, as well as a respective
first vessel and
second vessel. A first channel 822a may be in or may be configured to be
brought into fluid
communication with a first vessel 846a, and a second channel 822b may be in or
may be
configured to be brought into fluid communication with a second vessel 846b.
The first
channel may initially not be in fluid communication with a first vessel and
the second
channel may initially not be in fluid communication with the second vessel.
The first and
second channels may be brought into fluid communication with the interiors of
the first and
second vessels respectively when the body is pushed in relative to the
support. The first and
second channels may be brought into fluid communication with the first and
second vessels
simultaneously. Alternatively, they need not be brought into fluid
communication
simultaneously. The timing of the fluid communication may depend on the height
of the
vessel and/or the length of the channel. The timing of the fluid communication
may depend
on the relative distances between the second end of the channel and the
vessel.
[00224] In some embodiments, each vessel may have a body 849a, 849b and a
cap
848a, 848b. The vessel body may have a tubular shape. In some instances, the
vessel body
may have a cylindrical portion. The bottom of the vessel may be flat, tapered,
rounded, or
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any combination thereof. The vessels may comprise an open end and a closed
end. The open
end may be a top end of the vessel, which may be at the end of the vessel
closer to one or
more channel. The closed end may be a bottom end of the vessel, which may be
at the end of
the vessel further from one or more channel. There may be variations and
alternatives to the
embodiments described herein and that no single embodiment should be construed
to
encompass the entire invention.
[00225] A support 830 may have one or more optical indicators, such as
optical
windows 832a, 832b. The optical windows may be positioned over portions of the
channels
822a, 822b. The optical windows may provide an indicator of whether a sample
has reached
and/or passed through the portion of the channels shown by the optical
windows. This may
be useful to assess whether the sample has flowed sufficiently for the user to
push the body
into the sample collection device. In some instances, it may be desirable for
the sample to
reach the second end of the channels, or to near the second end of the
channels, before
causing the channels to enter into fluid communication with the vessels. In
some instances,
the sample may need to reach a certain portion of the channel before pushing
the body in to
bring the channels into fluid communication with the vessels. The certain
portion of the
channel may underlie the optical windows.
[00226] A base 840 may have one or more optical indicators, such as
optical windows
842a, 842b. The optical windows may be positioned over the vessels 846a, 846b.
In some
instances, the optical windows may be positioned over the vessel bodies. The
optical
windows may provide an indicator of whether a sample has entered the vessels.
The optical
windows may show how much sample has filled the vessels. This may be useful to
assess
whether a sufficient amount of sample has entered the vessels. In some
instances, it may be
desirable for a particular amount of sample to enter the vessels before
removing the vessels
from fluid communication with the channels. A predetermined volume of sample
in the
vessels may be desired before removing a base of the device, thereby bringing
the vessels out
of fluid communication with the channels.
[00227] The vessels and/or interfaces with the channels may have any
characteristic or
feature, such as those described elsewhere herein. In some instances, a second
end of the
channel may penetrate a cap of the vessel, thereby bringing the channel into
fluid
communication with the vessel. In some instances, the channel may be withdrawn
from the
vessel, and the cap of the vessel may form a fluid-tight seal, thereby
permitting a fluid-tight
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environment within the vessel when the channel is brought out of fluid
communication with
the vessel.
[00228] One or more engagement assembly may be provided. The engagement
assembly may include a channel holder and/or a force-exerting component, such
as a spring
or elastic. The holder may keep the channel affixed to the body. The holder
may prevent the
channel from sliding relative to the body. The holder may optionally provide a
support upon
which a force-exerting component, such as a spring, may rest.
[00229] In one example, the engagement assemblies may include a spring
which may
exert a force so that the body is at its extended state, when the spring is at
its natural state.
When the body is at its extended state, space may be provided between the
vessels 846a,
846b and the bottom portion of the sample body 820. The second ends of the
channels may
be in a position where they are not in fluid communication with the interiors
of the vessels.
[00230] When the body is pressed in, the spring 852 may be compressed (see
also
Figures 9A-9C). The second ends of the channels may penetrate the caps of the
vessels. The
second ends of the channels may enter the interior of the vessel. In some
instances, a force
may be provided to drive the fluid from the channels into the vessels. For
example, a
pressure differential may be generated between the first and second ends of
the channels. A
positive pressure may be provided at the first end 823a, 823b of the channels
and/or a
negative pressure may be provided at the second end of the channels. The
positive pressure
may be positive relative to the pressure at the second end of the channel,
and/or ambient air.
The negative pressure may be negative relative to the pressure at the first
end of the channel
and/or ambient air. In one example, the vessels 846a and 846b may each have a
vacuum
therein. When the second end of a channel penetrates a vessel, the negative
pressure within
the vessel may suck the sample into the vessel. In alternative embodiments,
the sample may
enter the vessel driven by capillary forces, gravity, or any other motive
force. Optionally,
there may be single or multiple combinations of forces to fill the vessel with
fluid.
[00231] In some instances, different types of motive forces may be used to
draw the
sample into the channel, and from the channel into the vessel. For example, a
capillary force
may draw the sample into a channel, and a pressure differential may drive the
sample from
the channel into the vessel. Any combinations of motive forces may be used to
draw sample
into the channel and into the vessel.
[00232] Some time may elapse after a sample has been introduced to a
channel for
traveling along the length of the channel. A user may introduce a sample to
the sample
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collection device and may wait for the sample to travel the length of the
channel. One or
more optical indicator along the length of the channel may be provided, which
may indicate
whether the sample has reached the end of the channel. In other embodiments,
the user may
wait a predetermined amount of time before pushing in the body. The body may
be pushed in
after the user has determined the sample has traveled a sufficient length of
the channel and/or
a sufficient amount of time has passed since the sample was introduced. The
body may have
a flat surface which may be easy for the user to push. In some instances, the
flat surface may
have a cross-sectional area that may be sufficient for a user's fingers to
press down on the
body. After the body is pushed in, the channels may be brought into fluid
communication
with the vessels, and sample may flow from the channel into the vessels. An
optical indicator
may be provided so that a user may know when the vessels have been filled.
1002331 Once the vessels have been filled, they may be transferred to a
desired
location, using systems and methods described elsewhere herein. As previously
described,
the entire sample collection device may be transferred. In other embodiments,
the base
portion may be removable from the rest of the device. In one example, the base
may be
removed from the sample collection device, and the vessels may be transferred
along with the
base. Alternatively, the base may be removed from the sample collection device
to provide
access to the vessels, and the vessels may be removed from the device and
transmitted
[00234] Referring now to Figures 9A-9C, examples of a sample collection
device 900
and method of use will now be described. In one nonlimiting example, the
device may have
a body 920, support 930, and base 940. The body 920, support 930, and base 940
may be
movable relative to one another. In some instances, the various components of
the devices
may be movable during different stages of use. Examples of stages of use may
include when
the device is in an extended state, compressed state, and separated state.
[00235] Figure 9A shows an example of the device 900 in an extended state.
The body
920 may be extended relative to the support. Channels 922a, 922b configured to
transport a
sample may be affixed to the body. A first end of a channel may extend out
from the body
and/or the rest of the sample collection device. A second end of the channel
may be within
and/or encompassed by a portion of the sample collection device. The channel
may be
fluidically isolated from a respective vessel housed by the base 940. The
support 930 may be
positioned between the body and base. The support may at least partially
encompass a
portion of the channel. In some instances, the support may encompass the
second end of the
channel.
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[00236] When in an extended state, the device may have an extended length.
The
length of the device may be from the bottom of the base to the first end of
the channels.
Alternatively, the length of the device may be measured from the bottom of the
base to the
top of the body.
1002371 As seen in Figure 9A, the device 900 may be in an extended state
when the
sample is introduced to the device. For example, a sample may be contacted by
at least a first
end of a channel. The sample may be drawn into the channel via capillary
action or any other
technique or motive force described herein. The forces may act alone or in
combination to
draw sample into the device. The device 900 may remain in an extended state
while the
sample is traversing the channel. The sample may fill the entire length of the
channel, a
portion of the length of the channel, or at least a minimum portion to meet a
desired sample
acquisition volume.
1002381 Figure 9B shows an example of the device 900 in a compressed
state. The
body 920 may be compressed relative to the support. The channels 922a, 922b
may be
affixed to the body. The channels may be fluidic communication with their
respective
vessels. When the device is brought into a compressed state, a first channel
may be brought
into fluid communication with an interior of a first vessel, and a second
channel may be
brought into fluid communication with an interior of a second vessel.
[00239] By way of nonlimiting example, a user may push the body 920 toward
the
support 930 (or vice versa) to bring the device into a compressed state. The
relative motion
between parts may involve movement of both pieces. Optionally, movement may
involve
moving only one of them. In the present example, the body 920 may be pushed
all the way to
the support 930 so that no interior portion of the body is exposed and/or a
lip of the body
contacts the support. Any stop mechanism may be used that may be engaged when
the
device is completely compressed. Alternatively, the body may only be partially
pushed. For
example, a portion of the interior portion of the body may be exposed. The
support may be
positioned between the body and base. The support may at least partially
encompass a
portion of the channel. In some instances, the second end of the channel may
extend beyond
the support of the device.
[00240] When in a compressed state, it should be understood that the
device 900 may
have a compressed length. The length of the device 900 may be from the bottom
of the base
to the first end of the channels. Alternatively, the length of the device may
be measured from
the bottom of the base to the top of the body. The compressed length of the
device may be
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less than the extended length of the device. In some embodiments, the
compressed length of
the device may be at least about 0.1 cm, 0.5 cm, 1.0 cm, 1.5 cm, 2.0 cm, 2.5
cm, 3.0 cm, 3.5
cm, 4.0 cm, or 5.0 less than the extended length of the device. The compressed
length of the
device may be less than or equal to about 50%, 60%, 70%, 75%, 80%, 85%, 90%,
95%, 97%
or 99% of the extended length of the device.
[00241] One or more engagement assemblies may be provided with the device
900.
The engagement assembly may include a channel holder 950 and/or a force-
exerting
component, such as a spring 952 or elastic. The holder 950 may keep the
adaptor channel
954 affixed to the support. As will be described elsewhere herein, the adaptor
channel 954
may be formed integrally with the collection channel or may be a discrete
element that may
be a stand-alone piece, part of the collection channel, or part of the vessel.
In one
embodiment, the holder 950 may prevent the adaptor channel 954 from sliding
relative to the
support. The holder 950 may optionally provide a support upon which a force-
exerting
component, such as a spring, may rest. The force-exerting component, such as a
spring may
be in a compressed state when the device is in a compressed state. The spring
may exert a
force on the body of the device when the device is in a compressed state.
[00242] The device may be in a compressed state when the sample is
transferred from
the channels to the respective vessels. In some examples, the transfer may
occur via pressure
differential between the channels and the interiors of the vessels, when they
are brought into
fluidic communication. For example, a second end of the channel may be brought
into
fluidic communication with the interior of the vessel. The vessel may have a
vacuum and/or
negative pressure therein. The sample may be sucked into the vessel when the
channel is
brought into fluidic communication with the vacu-vessel. The device may remain
in a
compressed state while the sample is being transferred to the vessel. The
sample may fill the
entire vessel or a portion of the vessel. The entirety of the sample (and/or
greater than 90%,
95%, 97%, 98%, 99%, 99.5% or 99.9% of the sample) from the channels may be
transferred
to the vessels. Alternatively, only a portion of the sample from the channels
may be
transferred to the vessels.
[00243] Referring now to Figure 9C, an example of a device 900 in a
separated state
will now be described. The base 940 may be separated from the rest of the
device 900. The
body 920 may be extended or compressed relative to the support 930. In one
example, the
extended state may be the natural state, so that when the force is no longer
exerted on the
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body by the user, the body may extend back to the extended state. The channels
922a, 922b
may be affixed to the body.
[00244] When the device 900 is in a separated state, the base 940 may be
separated
from the support 930 of the device. The channels 922a, 922b may be removed
from fluidic
communication with their respective vessels 946a, 946b. When the device 900 is
brought
into the separated state, a first channel may be brought out of fluid
communication with an
interior of a first vessel, and a second channel may be brought out of fluid
communication
with an interior of a second vessel. This may occur sequentially or
simultaneously. When
the channels are removed from the vessels, the vessels may assume a sealed
state to prevent
undesired material from entering the vessels. In some embodiments, the vessels
may be
fluid-tight after removal of the channels. Optionally, the vessels may be gas-
tight after
removal of the channels.
[00245] A user may separate the base 940 from the support 930 to bring the
device into
a separated state to remove the vessels therein. In some embodiments, the base
may be
separated from the support or vice versa. Separating the base from the support
may expose
the vessels 946a, 946h that are supported by the base. The vessels may be
press-fit or
otherwise held within the base. The vessels 946a, 946b may be removable from
the base. By
way of non-limiting example, removing the vessels 946a, 946b allows them to be
placed with
other vessels in a climate controlled transport container for transport to a
receiving site such
as but not limited to an analysis site. Optionally, the vessels 946a, 946b may
be removed to
allow for pre-treatment such as but not limited to centrifugation prior to
being sent on for
processing at a receiving site such as but not limited to an analysis site.
Alternatively, the
vessels 946a, 946b may remain with the base.
[00246] Figures 10A-10B provide additional views of a sample collection
device 1000
in a separated state. When in a separated state, the base 1040 may be
separated (partially or
completely) from the support 1030 and/or body 1020 of the device. This allows
for the
removal of the vessels 1046a and 1046b through the end of base 1040 previously
not
externally exposed when the device 1000 was not in a separate state.
[00247] When the device is in a separated state, one or more channels
1022a, 1022b
may be fluidically isolated from one or more vessels 1046a, 1046b housed by
the base 1040.
The vessels may be fluidically sealed from their environment. The vessels may
contain
sample therein, that had been transported through the collection channels,
reached a
minimum fill level, and then substantially fully deposited into the respective
vessels. The
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base 1040 may include one or more optical indicator 1046a, 1046b. The optical
indicator
may show a portion of the vessels therein such that the device 1000 is not
moved into the
separate state until a minimum fill level has been reached in the vessels. By
way of non-
limiting example, the vessels may have an optically transmissive material that
may permit a
user to view the sample within the vessels from outside the base.
[00248] In some embodiments, the base 1040 may encompass at least a
portion of the
vessels. The base may have a hollow interior and walls surrounding the hollow
interior. The
base may have one or more shaped feature that may support the vessels. The
vessels may be
provided within the hollow interior. The walls may surround the vessel. The
base may have
an open top though which the vessels may be exposed. The vessels may or may
not be
removed through the open top.
Collection Device with Multiple Collection Channels
[00249] Referring now to Figures 11A-11F, a still further embodiment as
described
herein will now be described. This embodiment provides a bodily fluid sample
collection
device 1100 for use in collecting a fluid sample that may be pooled or
otherwise formed on a
surface, such as but not limited to the skin or other target area of a
subject. Although this
embodiment shows a device body which defines at least two collection channels
of different
volumes therein, it should be understood that devices with fewer or greater
numbers of
collection channels are not excluded. Embodiments where the same collection
volume is
used for one or more the channels are also not excluded. There may be
variations and
alternatives to the embodiments described herein and that no single embodiment
should be
construed to encompass the entire invention.
[00250] Figure 11A shows a perspective view of one embodiment of a bodily
fluid
sample collection device 1100 with a distal end 1102 configured to engage a
fluid sample on
a surface. In this embodiment, the distal end 1102 may have a configuration
designed to
better engage a droplet or pool of bodily fluid or sample formed on a surface.
Some
embodiments, in addition to a desired shape, may also have surface treatments
at the distal
end 1102, such as but not limited to, chemical treatments, texturing, surface
features, or
coatings to encourage fluid flow towards the one or more openings 1104 and
1106 on the
distal end 1102 leading to the channels in the device 1100.
[00251] As seen in Figure 11A, this embodiment of the sample collection
device 1100
has two openings 1104 and 1106 for receiving the sample fluid. It should be
understood that
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some embodiments may have more than two openings at the distal end. Some
embodiments
may only have one opening at the distal end. Optionally, some embodiments may
have
additional openings along a side or other surfaces leading away from the
distal end 1102 of
the device 1100. The openings 1104 and 1106 may have any cross-sectional
shape. In some
non-limiting examples, the openings may have a circular, elliptical,
triangular, quadrilateral
(e.g., square, rectangular, trapezoidal), pentagonal, hexagonal, octagonal, or
any other cross-
sectional shape. The cross-sectional shape may remain the same or may vary
along the
length of the collection device body. In some instances, the openings may have
a cross-
sectional area of less than or equal to about 2 mm2, 1.5 mm2, 1 mm2, 0.8 mm2,
0.5 mm2, 0.3
mm2, or 0.1 mm2. Some embodiments have the opening be the same shape. Others
may use
different shapes for the one or more openings.
1002521 The sample fill portion 1120 which may be the body of the sample
collection
device 1100 may be formed from a transparent and/or translucent material that
may enable a
user to see if a sample has entered sample collection channel(s) (see Figure
11B) in the
sample fill portion 1120. In some embodiments, the entire sample fill portion
1120 is
transparent or translucent. Alternatively, some embodiments may only have all
areas over
the channel or only select portions of the channel or sample fill portion 1120
be transparent or
translucent to allow a user to visualize the filling of sample into the sample
collection device
1100. Optionally, the sample fill portion is made of an opaque material but
has an opening or
a window to allow for visualization of fill level therein. The device 1100 may
further include
one or more visualization windows 1112 and 1114 to allow a user to see when a
desired fill
level has been reached. The visualization window may be formed from a
transparent and/or
translucent material. Alternatively, the visualization window may be an
opening without any
material therein. Additional visualization windows can also be used to
determine of all of the
fluid in the collection channels have been emptied into the vessels 1146a and
1146b (see
Figure 11B).
1002531 Figure 11A also shows that some embodiments of support 1130 may
have
optical windows 1132 and 1134 which are positioned to show fill levels in the
vessels 1146a
and 1146b to show if the vessels in base 1140 have been moved into position to
receive
sample fluid. Optionally, the windows 1132 and 1134 may be cutouts that act as
guides for
the snap feature of based in order to define the start and end positions
during activation. It
should be understood that the base can be configured to hold one or more
sample vessels. By
way of example and not limitation, the entire base 1140 can be removed from
the sample
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collection device before or after sample fill. The base 1140 can be used as
holder to retain
the sample vessels therein during transport, and in such an embodiment, the
base 1140 along
with the sample vessels would be loaded into a shipping tray or other holder
for transport.
Alternatively, some embodiments may remove the sample vesssels from the base
1140 and
then transport the vessels without the base 1140 holding them.
[00254] Figure 11B shows a cross-sectional view along section lines B-B of
the
embodiment shown in Figure 11C. Figure 11B shows the channels 1126 and 1128 in
the
portion 1120. The sample fill portion 1120 may be formed from two or more
pieces which
join together to define the portion 1120. Some may define the channels in one
piece and then
have another piece which mates to the first piece to define an opposing or top
wall surface of
the channel. In terms of manufacturing, this allows one piece to have channels
molded or
otherwise formed into the body and the opposing piece will mate to act as a
cover for the
channels or may also include portions of the channel too. The channels 1126
and 1128 may
be formed only in portion 1120 or may also extend into support 1130 that has
features to
connect with the vessels held in base or carrier 1140. Some embodiments may
integrally
form portions 1120 and 1130 together. Support 1130 may also be configured to
hold adapter
channel 1150 which will fluidically connect the channels 1126 and 1128 with
their respective
vessels 1146a and 1146b.
[00255] Although these embodiments herein are described using two channels
and two
vessels, it should be understood that other numbers of channels and vessels
are not excluded.
Some embodiments may have more channels than vessels, wherein some channels
will
couple to the same vessel. Some embodiments may have more vessels than
channels, in
which case multiple vessels may operably couple to the same channel.
[00256] As seen in Figure 11B, the channels 1126 and 1128 may be of
different sizes.
This allows for different fluid volumes to be collected in each channel before
they are
simultaneously transferred into the vessels 1146a and 1146b. Optionally, some
embodiments
may have the channels 1126 and 1128 sized to contain the same volume of fluid.
In some
embodiments, the fluid pathway of the channels 1126 and 1128 are shaped and/or
angled so
that openings near the distal end 1102 are closer together than proximal ends,
which may be
further apart to align them for entry into the vessels 1146a and 1146b. There
may be
variations and alternatives to the embodiments described herein and that no
single
embodiment should be construed to encompass the entire invention.
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[00257] Figure 11B also shows that some embodiments may use needles for the
adapter channels 1150 and 1152 in the body 1130 which are in communication
with the
channels 1126 and 1128. The needles each has a channel to allow for fluid to
pass
therethrough from the collection channels 1126 and 1128 to the ends of the
needles. As seen
in Figure 11B, the vessels 1146a and 1146b in the base 1140 are slidable
relative to the
support 1130 as indicated by arrow 1156. Relative motion between support 1130
and base
1140 can close the gap 1154. Closing the gap 1154 brings the adapter channels
1150 into the
cap 1148a of the vessel 1146a until there is fluid communication between the
interior of
vessel 1146a and the collection channel 1126. At that time, motive force in
the form will
then move fluid in the channel 1126 into the vessel 1146a.
[00258] By way of example and not limitation, any combinations of motive
forces may
be used to draw sample into the vessel. Some embodiment may use pull from
vacuum in the
vessels 1146a to draw sample into the vessel. Some may use pushing force from
external
pressure to move fluid into the vessel. Some embodiments may use both. Some
may rely on
capillary and/or gravity. In some embodiments, the motive force(s) used to
draw sample into
the channel is different from motive force(s) used to draw sample into the
vessel. In some
alternative embodiments, the motive force(s) may be the same for each stage.
In some
embodiments, the motive force(s) are applied sequentially or at defined time
periods. By way
of non-limiting example, motive force(s) to draw sample into the vessel is not
applied until
the at least one channel has reach a minimum fill level. Optionally, motive
force(s) to draw
sample into the vessel is not applied until the at least two channels have
each reach a
minimum fill level for that channel. Optionally, motive force(s) to draw
sample into the
vessel is not applied until all channels have each reach a minimum fill level
for that channel.
In some embodiments, the motive force(s) are applied simultaneously. This
features recited
may be applicable to any of the embodiments herein.
[00259] Referring now to Figure 11E, an enlarged cross-sectional view of
the device
1100 is shown. This embodiment shows that the support 1130 has a lip portion
1136 sized to
extend over the adapter channels 1150 and 1152 in an amount sufficient to
prevent a user
from inserting a finger into the gap 1154 and piercing the finger on one of
the needle.
[00260] Additionally, as shown in Figures 11B and 11E, the present
embodiment has
at least two channels in the sample collection device 1100. This allows for
each of the
channels 1128 and 1126 to each introduce a different material into the sample.
By way of
non-limiting example, if the sample is whole blood, one channel can introduce
heparin into
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the blood while another channel introduces ethylenediaminetetraacetic acid
(EDTA). Not
only do these anti-coagulants prevent premature clogging of the channels
during fill, but also
introduce anti-coagulant into the whole blood in preparation for transport in
the vessels 1146a
and 1146b. Optionally, the channel(s) may also be plasma coated in addition to
or in place of
the anti-coagulants. The plasma coating can reduce the flow resistance of the
body fluid
sample in the channels. Such a coating can be applied in patterns such as but
not limited to
strips, rings, or other patterns along with any other coating(s) to be used in
the channels.
[00261] Optionally, there is sufficient quantity of anti-coagulant in the
respective
channel such that the sample fluid will contain a desired level of anti-
coagulant in the sample
fluid after only a single pass of the fluid through the channel. In
traditional blood vials, the
blood sample does not contain anti-coagulant until it enters the vial and once
in the vial, the
technician typically repeatedly tilts, shakes, and/or agitates the vial to
enable mixing of anti-
coagulant in the vials. In the present embodiment, the sample fluid will
contain anti-
coagulant prior to entering the sample vessel and it will do so without having
to repeatedly
tilt or agitate the sample collection device. In the embodiment herein, a
single pass provides
enough time and sufficient concentration of additive such as anti-coagulant
into the sample
fluid. In one embodiment, an EDTA channel has a volume of 54uL coated by 200
mg/mL
EDTA; a channel for Heparin has a volume of about 22uL coated by 250 units/mL
Heparin.
In another embodiment, the EDTA channel has a volume of 70uL coated by 300
mg/mL
EDTA; the channel for Heparin has a volume of about 30uL and is coated by 250
units/mL
Heparin. By way of non-limiting example, a channel of volume from 50 to 70 uL
can be
coated by EDTA in the range from about 200 to 300 mg/mL EDTA. Optionally, a
channel of
volume from 70 to 100 uL can be coated by EDTA in the range from about 300 to
450
mg/mL EDTA. Optionally, a channel of volume from 20 to 30 uL can be coated by
Heparin
in the range from 250 units/mL Heparin. By way of example, the material may be
solution
coated onto the target surface for less than 1 hour and then dried overnight.
There may be
variations and alternatives to the embodiments described herein and that no
single
embodiment should be construed to encompass the entire invention.
1002621 Referring now to Figure 11G, a still further embodiment will now
be
described. The embodiment of Figure 11G shows that at a distal end 1202 of the
sample
collection device 1200, instead of having one opening 1204 for each of the
channels, the
sample collection device 1200 merges two or more of the channels into a single
channel. The
embodiment of FigurellG shows that there is common channel portion prior to
the split of
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the common channel into to a plurality of separate channels. As will be
described below in
Figure 11I, optionally, there may be back flow preventer such as but not
limited to a vent
positioned along the separate channel to reduce the possibility of drawing
sample from one
channel into another channel during filling and/or extraction of sample from
the channels into
the sample vessel(s).
[00263] As seen in Figure 11H, this use of common flow paths can result in
a reduced
number of openings on the exterior of the sample collection device 1200, which
may make it
align the opening 1204 to engage the bodily fluid sample. It may also increase
the capillary
force for drawing bodily fluid sample into the sample collection device 1200
by having more
capillaries pulling on the same channel where the bodily fluid sample enters
the collection
device.
[00264] Referring now to Figure 11I, a cross-sectional view of select
components of a
sample collection device will now be described. Figure 11I shows that the
sample collection
device can have two channels 1182 and 1184 that have a common portion 1186
leading
towards an inlet opening on the device. In some embodiments, the common
portion 1186 is a
continuation of one of the channels 1182 or 1184 in terms of size, shape,
and/or orientation.
Optionally, the common portion 1186 is not of the same size, shape, and/or
orientation of any
of the channels 1182, 1184, or any other channel that may be in fluid
communication with the
common portion 1186. Figure 11I shows that in one non-limiting example, there
may be a
step at the interface 1188 between the channel 1182 and 1184. This interface
1188 may be
configured to ensure flow into both of the channels so that they will both
reach a full fill. In
one embodiment, the interface 1188 has a size greater than the channel 1182
leading away
from the interface 1188. Although other sizes are not excluded, this interface
1188 of greater
size may ensure that sufficient flow will enter the channel 1182, which in the
present
embodiment, has a smaller diameter and reduced volume relative to the channel
1184. There
may be variations and alternatives to the embodiments described herein and
that no single
embodiment should be construed to encompass the entire invention.
[00265] Figure 11I also shows that there may be vents 1190 and 1192 that
can be used
to prevent cross-flow between channels, particularly when sample is being
transferred into
the sample vessels. In one embodiment, the vents 1190 and 1192 are open at all
times. In
another embodiment, the vents 1190 and 1192 may be open only at select times,
such as but
not limited to after the channels 1182 and 1184 are filled or substantially
filled. Some
embodiments may use a dissolvable material the plugs the vents 1190 and 1192
until they are
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in contact with sample fluid. Optionally, some embodiments may use a slidable
covers one
or more of the vents 1190 and 1192 such that they are only opened at times
selected by the
user. In one embodiment, the covers are linked to the sample vessels such that
movement of
the sample vessels to move into fluid communication with the channels will
also open one or
more vents 1190 and 1192 to reduce the risk of cross-flow between channels.
Optionally,
other anti-crossflow mechanisms such as but not limited to valves, gates, or
plugs can also be
used to prevent fluid transfer between channels 1190 and 1192.
1002661 Figure 11I also shows that there may be anti-leakage devices 1194
positioned
over the adapters 1150 and 1152. In this embodiment, the anti-leakage devices
1194 are frits
which may be slidably moved from a first position where they prevent sample
from leaking
out from the adapters 1150 and 1152 to a second position wherein they allow
the adapters to
deliver fluid into the sample vessels. In one non-limiting example, the anti-
leakage devices
1194 will slide when they are engaged by the sample vessels or the housing
that holds the
sample vessels. The movement of the sample vessels or the housing in this non-
limiting
example shows that the movement of those elements will also cause movement of
the anti-
leakage devices 1194.
1002671 Referring now Figure 11J, yet another embodiment of a sample
collection
device 1160 will now be described. This embodiment of the sample collection
device 1160
shows that the device 1160 has a sample entry location 1204 that leads to a
plurality of
channels 1162 and 1164 in the device 1160. Although Figure 11J show that the
channels
1162 and 1164 may have different shapes and/or sizes, some embodiments may be
configured to have the same volumes and/or shapes. It should also be
understood that the
sample entry location 1204 can be on the surface of the device 1160, or
optionally, it can be
part of a tip, nozzle, stub, or other protrusion that extends from the body of
the device 1160.
This protrusion may be in the same plane and aligned parallel with the body of
the device or
optionally, it may be angled so that the axis of the protrusion intersects the
plane of the
device 1160.
1002681 Figure 11J further shows that for some embodiments, there may be
sample
flow features 1166 and 1168 to draw or otherwise preferentially direct sample
in a desired
direction. In some embodiments, the features 1166 and 1168 are guides that
operate to
decrease channel dimension in at least one axis, such as but not limited to
width or height,
and thus increase capillary action through those areas of reduced dimension.
In one non-
limiting example, these flow features 1166 and 1168 can assist fluid flow
through the channel
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areas positioned near the anti-crossflow features 1170 during sample entry
into the channels.
In one embodiment, the flow features 1166 and 1168 are sized so as to
preferentially improve
flow in the inbound direction when flow is drawn primarily by capillary
action. Outbound
flow, in one scenario, is not based on capillary force but on vacuum pulling
force (such as
from an adjacent channel), and these flow features 1166 and 1168 of the
present embodiment
are not configured to provide assistance under those vacuum, non-capillary
flow conditions.
Thus, some but not all embodiments of flow features 1166 and 1168 are
configured to assist
under at least one type of flow condition but not certain other flow
condition(s). Optionally,
some embodiments may use other techniques alone or in combination with the
guides, such
as but not limited to, shaped features, hydrophobic material(s), hydrophilic
material(s), or
other techniques to push/pull samples towards a desired location.
[00269] Figure 11J also shows that in the one or more embodiments herein,
there may
be angled side wall features 1167 that conically or otherwise narrow the cross-
sectional area
of the channel in a manner that funnels sample to minimize the amount of
sample that may be
retained in the channel and not collected. Figure 11J also shows that there
may be locating
feature(s) 1169 to facilitate joining of parts together in a define location
and orientation
during manufacturing.
[00270] Figure 11K shows a side view of this embodiment of the sample
collection
device 1160. The side view of the device 1160 shows that there are embodiments
where
there are one or more anti-crossflow features 1170 such as but not limited to
vents to
minimize undesired crossflow of sample between the channels 1162 and 1164,
particularly
once a desired fill level has been reached in the respective channels. The
anti-crossflow
features 1170 and 1172 can prevent crossflow due to the break in fluid pathway
created by
the vents. The crossflow issue presents itself most commonly when the vessels
in the holder
1140 are engaged and provide an additional motive force to pull the sample
from the
channels into the vessels. This "pulling" effect may inadvertently draw sample
from one
channel to an adjacent channel. To minimize crossflow, forces associated with
pulling sample
from the channel into the vessel will pull from the vent and not fluid in an
adjacent channel,
thus minimizing undesired comingling of sample.
[00271] Figure 11K also shows that in some embodiments herein, there may
be
common portions 1130 and 1140 which can be adapted for use with different
sample fill
portions 1120. Some may use different capillary fill portions 1120. Some
embodiments may
use fill portions that use different types of capture techniques, such as but
not limited to,
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samples acquired from venous draws, arterial draws, or other sample drawn from
an interior
location or target site of the subject.
[00272] Referring now to Figure 11L, one embodiment of the sample flow
features
1166 and 1168 are shown. This cross-sectional view of sample collection
portion with the
channels 1162 and 1164 and the sample flow features 1166 and 1168 near the
common inlet
pathway 1165 shows that the features are desired in one embodiment near where
the sample
is entering the channels. Figure 11L also shows, for channels of different
volumes, it can be
desirable to position the inlet 1165 closer to the channel 1164 that has the
larger volume, as
seen by the asymmetric location of inlet 1165. It can also be seen that in
some embodiments,
location(s) of the sample flow features 1166 and 1168 can also be selected to
control filling
rate, filling volume, or the like in the sample collection device 1160. It
should be understood
that one or more of features described can be adapted for use with other
embodiments herein.
[00273] Referring now to Figure 11M, channels 1162 and 1164 with sample
anti-
crossflow features are shown. In one embodiment, the sample anti-crossflow
features are
vents 1170 and 1172 located on at least one surface of the channels 1162 and
1164. In one
nonlimiting example, these sample anti-crossflow features are located near any
sample flow
features 1166 and 1168 in the device. In one embodiment, these anti-crossflow
features are
configured to prevent flow between channels. These anti-crossflow features can
be located
near the maximum fill locations of each of the channels such that as the
channel is at or near
its maximum sample capacity, the anti-crossflow features 1170 and 1172 are
positioned to
prevent overfilled sample from causing sample that has been treated in one
channel from
entering another channel and undesirably mixing samples from two channels
together.
[00274] Figure 11N shows a perspective view of the sample collection
device 1160
with sample fill indicators 1112 and 1114. In one embodiment, these indicators
1112 and
1114 are openings or transparent portions of the device 1160 that allows for
observation of at
least one portion of the channel(s) 1162 or 1164. When sample is visible in at
least one of the
indicators 1112 and 1114, it provides a cue to the user to then take another
action such as but
not limited to engaging the sample vessels in the holder 1140. In some
embodiments, there is
only one sample fill indicator which is a proxy for sufficient fill of sample
in two or more of
the channels. In some embodiments, the action to engage the sample vessels is
only taken
when indicated by indicators 1112 and 1114. In some embodiments, the action to
engage the
sample vessels is only taken when indicated by only one of the indicators.
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[00275] Referring now to Figures 110, 11P, and 11Q, cross-section at
various
locations along one embodiment of the device 1160 in Figure 11J are shown.
Figure 110
shows a cross-section showing the sample flow features 1166 and 1168. The anti-
crossflow
features 1170 and 1172 are also shown. Engagement features 1174 can also be
provided to
enable mating of pieces together to form the device 1160.
[00276] Figure 11P shows that the adapter channels 1150 and 1152 are
positioned to
extend into or at least be in fluid communication with the sample channels
1162 and 1164.
Optionally, some embodiments may have multi-lumen adapter channels 1150 or
1152.
Optionally, some embodiments may have multiple adapter channels per sample
channel,
wherein such additional channels may be parallel to, angled, wrapped, or
otherwise oriented
relatively to each other.
[00277] Figure 11Q shows that in some embodiments, the vessel holder 1140
can be
shaped asymmetrically (in the cross-sectional plane) or otherwise shaped to
enable only one
orientation that the holder 1140 can be received in the device 1160. This can
be particularly
desirable when it is desired to direct sample from a certain channel into a
selected vessel. If
the holder 1140 can be inserted in various orientations, the sample from one
channel may end
up in the wrong vessel. Optionally, other features such as alignment features,
slots, visual
cues, texture cues, and/or the like may be used to encourage a preferred
orientation of sample
vessels in the device.
Integrated Tissue Penetrating Member
[00278] Referring now to Figure 11R, yet another embodiment of a sample
collection
device will now be described. This sample collection device 1210 comprises
features similar
to that shown in Figure 11G, except that it further includes a tissue
penetrating member 1212
that is mounted to the sample collection device 1210. An actuation mechanism
1214 such as
but not limited to a spring actuator can be used to launch the tissue
penetrating member.
Figure 11R shows the actuation mechanism 1214 in a resting state and that it
can be a spring
that can be compressed to launch a tissue penetrating member 1212 towards
target tissue.
The tissue penetrating member 1212 can be housed inside a housing 1216 (shown
in
phantom). In one embodiment, the housing 1216 comprises a portion that can be
peeled
back, pierced, released or otherwise opened to allow the tissue penetrating
member 1212 to
exit the housing but also maintain sterility of the tissue penetrating member
1212 prior to its
use. In some embodiments, the portion may be a foil, a cap, a polymer layer,
or the like.
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There may be variations and alternatives to the embodiments described herein
and that no
single embodiment should be construed to encompass the entire invention.
1002791 In one embodiment, the tissue penetrating member 1212 path can be
controlled along both the "normal" (i.e., forward direction of the tissue
penetrating member)
and "orthogonal" (i.e., perpendicular to main motion vector) of the
trajectory. Some
embodiments may have not have a hard stop or bang stop at the deepest point of
penetration
(i.e., return point), which is the main cause for spontaneous pain. Some
embodiments may
use a cushion, a cam pathway, or other non-hardstop mechanism to prevent pain
associated
with the shockwave of a sudden stop. Such a shockwave is detrimental even if
the tissue
penetrating member successfully avoids hitting nerves near the wound location
as the
shockwave can activate such nerves even if direct contact was avoided.
Optionally, some
embodiments may have the tissue penetrating member follow a non-jitter path,
to prevent a
rough wound channel (residual pain). This may be achieved in some embodiments
through
tighter tolerance in any guide pathway used with tissue penetrating member or
a pin
associated with the tissue penetrating member. This may be a non-jitter path
when
penetrating the tissue. Optionally, this may be a non-jitter path for the
tissue penetrating
member both outside the tissue and when it is inside the tissue. This can
reduce overall
motion "wobble" of the tissue penetrating member that may cause residual pain,
long-lasting
trauma, and scarring.
[00280] Some embodiments may have a controlled outbound speed to prevent
slow
and delayed wound closure and after bleeding. By way of nonlimiting example,
the
controlled outbound speed of the tissue penetrating member can be controlled
by mechanical
mechanisms such as but not limited cams or higher friction materials.
[00281] Some embodiments may also include anti-bouncing mechanisms to
prevent
unintended re-lancings that can be associated with an uncontrolled tissue
penetrating member
that rebounds into the tissue after initial wound creation. Some embodiments
herein may
have "parking" mechanisms or lock-out mechanisms that will engage the tissue
penetrating
member or its attachments to prevent re-entry of the tissue penetrating member
once it has
retracted out of the tissue or some other desired distance.
[00282[ The abruptness with which the lancet comes to a stop in the skin
at maximum
depth, before it starts its outbound motion and returning to its starting
position, is an inherent
issue of this design. With the lancet at its deepest point of penetration, the
greatest amount of
force is applied to the skin. The drive mechanism simply bounces off the end
of the device
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like a ball bounces back from the floor. The lancet, coming to an abrupt stop
at the end point
of its inbound motion, sends a shockwave into the skin, causing many pain
receptors in the
vicinity of the lancet to fire, even though they are not directly struck. This
amplifies
spontaneous pain substantially.
[00283] As mentioned, instead of simple spring actuated tissue penetrating
members,
some embodiments may use mechanical cam actuation. Devices with cam-actuation
design
can minimize "hard stopping" of the tissue penetrating member. A cam mechanism
is usually
spring driven and generally offers a better guided actuation. The trajectory
of the tissue
penetrating member is tightly controlled through a guided path of the tissue
penetrating
member holder via a pin riding in a cam. The cam mechanism allows for a
predetermined
speed profile with a softer return and distinct speed control for the tissue
penetrating member
outbound trajectory. This mechanism also effectively avoids a bounce back of
the lancet into
the skin when the mechanism reaches its motion end point. In addition, the
mechanical
oscillation (or jitter/ wobble) of the lance path in both directions is
reduced when fired in air.
Some embodiments herein may also minimize any mechanical wobble of the drive
mechanism (e.g., due to uneven or rough cam slots) to prevent transfer of such
drive
mechanism wobble directly into the tissue because of its "forced motion
profile."
[00284] Optionally, some embodiments may use electronic actuation through
an
electronically controlled drive mechanism. This technology uses a miniaturized
electronic
motor (e.g., voice coil, solenoid) coupled with a very accurate position
sensor, moving the
tissue penetrating member into and out of the skin with precisely controlled
motion and
velocity. Following rapid entry, the device decelerates the tissue penetrating
member to an
exact, preset depth to return smoothly, without jitter, and relatively slowly.
This allows quick
wound closure and avoids long-term trauma. With this device, the force
required to penetrate
the lancet into the skin is controlled while the tissue penetrating member is
progressing. The
benefit of tightly controlling the tissue penetrating member actuation
"profile" is a
reproducible painless lancing that yields a sufficient and consistent blood
sample for testing.
1002851 In terms of puncture site creation for blood sample extraction, it
may be
desirable to elect the appropriate puncture site on one of the patient's
fingers (ring or middle)
on their non-dominant hand. The puncture sites may be on the sides of the tips
of the fingers.
In one nonlimiting example, it may be desirable to hold the hand warmer strip
against the
patient's selected finger for 15 seconds. Optionally, some may warm the
patient's finger(s)
from 10 to 60 seconds. Others may warm for longer. The warming will increase
blood flow
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to the target site. To prepare the target site, it may be desirable to wipe
the side tip of the
selected finger or surface of the subject with an alcohol wipe or similar
cleaning agent, being
sure to wipe the selected puncture site. In some embodiments, it is desirable
to wait until the
skin is completely dry. Typically, one does not dry with gauze or blow air on
the fingertip to
accelerate drying.
[00286] After a puncture has been formed, hold the finger downward, below
the
patient's waist, in order to allow blood to flow. Massage the finger lightly
from base to tip
until a blood drop has formed. Carefully fill the blood collection device by
touching the tip
of the device to the bead of blood on the finger. Make sure the device is
completely filled.
Once the blood collection device is filled, press the bleeding area of the
finger against the
gauze pad on the table. Transfer the blood sample into the collection vessels.
Place a
bandage over the finger. Place the vessels with the sample into the shipping
box inside the
refrigerator. Discard all supplies in the biohazard sharps vessel. All
supplies are single-use
only.
[00287] If enough blood is not obtained from the first puncture, carefully
place the
blood collection device on the table surface, ensuring that the device remains
horizontal.
Place a bandage over the finger that was punctured. Select the appropriate
puncture site on a
different finger on the patient's same hand. If the ring finger was punctured
first, choose a
new puncture site on the middle finger, and vice versa. Hold the hand warmer
strip against
the patient's selected finger for 60 seconds. Optionally, some may warm the
patient's
finger(s) from 30 to 90 seconds. This will increase blood flow to the finger.
These
techniques for blood collection using a sample collection device such as any
of those herein
can enable sufficient sample collection of capillary blood for use in
laboratory testing at
Clinical Laboratory Improvement Amendments (CLIA) certified facility and/or
standards.
[00288] Referring now to Figure 11S, yet another embodiment of a sample
collection
device 1220 will now be described. In this embodiment, the tissue penetrating
member 1222
may be mounted at an angled relative to the sample collection device 1220.
This angled
configuration allows for tissue penetrating member to create a wound at a
location that aligns
with sample acquisition opening(s) 1103 and 1105. Although a standard spring-
launched
actuator is shown as the drive mechanism 1224 for the tissue penetrating
member 1222, it
should be understood that cam and/or electrical drive systems may also be used
in place of or
in combination with the spring launcher. When the drive mechanism 1224 is a
spring, the
spring can be compressed to move the tissue penetrating member 1222 to a
launch position
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and the released to penetrate into the target tissue. Figure 11S shows the
tissue penetrating
member 1222 in a resting position. Although the figures show a spring for the
drive
mechanism 1224, it should be understood that other drive mechanism suitable
for use in
launching a tissue penetrating member to create a healable wound on a subject
are not
excluded. There may be variations and alternatives to the embodiments
described herein and
that no single embodiment should be construed to encompass the entire
invention.
[00289] A housing 1226, similar to that described for housing 1216, may be
formed
around the tissue penetrating member 1222. Although Figure 11S shows two
tissue
penetrating members 1222 mounted on the sample collection device, it should be
understood
that devices with more or fewer tissue penetrating members are not excluded.
For example,
some embodiments may have only one tissue penetrating member 1222 mounted to
the
sample collection device 1220. There may be variations and alternatives to the
embodiments
described herein and that no single embodiment should be construed to
encompass the entire
invention.
[00290] Referring now to Figure 11T, another embodiment of a sample
collection
device 1230 will now be described. This embodiment shows that the tissue
penetrating
member 1232 is contained within the sample collection device 1230 and as seen
in Figure
11T, it is actually co-axially aligned with the central axis of the sample
collection device.
This positions the tissue penetrating member 1232 to extend outward from the
sample
collection device 1230 at a location close to where openings 1103 and 1105 are
positioned on
the sample collection device 1230. Of course, devices having more or fewer
openings are not
excluded and the embodiment of Figure 11T is exemplary and non-limiting.
Figure 11T
shows that in one embodiment of the sample collection device, a firing button
1234 may be
mounted on the sample collection device 1230. Optionally, some embodiments may
have the
shaped front end 1236 function as the actuation button, wherein upon pressing
the tissue
against the front end 1236 to a certain depth and/or certain pressure, the
tissue penetrating
member will be actuated.
[00291] Once fired, the tissue penetrating member 1232 moves as indicated
by arrow
1233. In some embodiments, the tissue penetrating member 1232 is fully
contained inside
the sample collection device 1230 prior to actuation. Some embodiments may
have a visual
indicator 1235 on the device 1230 to help guide the user on where the tissue
penetrating
member 1232 will exit the device and where approximately the wound will be
formed.
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[00292] In this non-limiting example, the entire device 1230 may be in a
sterile pouch
or package that is only opened before the device 1230 is used. In this manner,
sterile
conditions are maintained for the tissue penetrating member and the collection
device prior to
use. This external sterile pouch or package is also applicable to any of the
other
embodiments herein. Figure 11L also shows that a shaped front end 1236 (shown
in
phantom) that can be integrally formed or separately attached to the sample
collection device
1230. This shaped front end 1236 can provide suction to draw sample fluid into
the sample
collection device 1230. Optionally, the shaped front end 1236 can be used to
stretch the
target tissue and/or force it into the shaped front end to apply pressure to
increase sample
fluid yield from wound formed by the tissue penetrating member 1232. 'It
should be
understood that any of the embodiments herein can be adapted to have a shaped
front end
1236. Optionally, the shaped front end may have select hydrophobic area(s) to
direct sample
fluid to towards one or more collection areas on the front end. Optionally,
the shaped front
end may have select hydrophilic area(s) to direct sample fluid to towards one
or more
collection areas on the front end.
[00293] Referring now to Figure 11U, yet another embodiment of a sample
collection
device will now be described. This embodiment is similar to that of Figure 11T
except that,
instead of single tissue penetrating member such as a lancet, the embodiment
of Figure 11T
uses a plurality of tissue penetrating members 1242. In one embodiment, these
tissue
penetrating members are microneedles 1242 that are of reduced diameter as
compared to
traditional lancets. A plurality of microneedles 1242 can be simultaneously
actuated for
device 1240 and create multiple wound sites on the tissue. The spacing of the
microneedles
1242 can result in more capillary loops being pierced and more channels being
available for
blood to reach the tissue surface. This also allows for a more "square"
penetration profile as
compared to a lancet which has a pointed tip and a tapered profile. This may
enable the
microneedles 1242 to engage more capillary loops over a larger area without
penetrating too
deep into deeper tissue layers that are more densely populated with nerve
endings.
[00294] Referring now to Figures 11V and 11W, a still further embodiment
of a
sample collection device will now be described. In the embodiment shown in
these figures,
the sample collection device 1100 may be mounted angled to a dedicated wound
creation
device 1250 that has a tissue penetrating member 1252 configured to extend
outward from
the device 1250. The sample collection device 1100, which may optionally be
configured to
have a shaped front end 1236 (with or without an opening to accommodate the
tissue
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penetrating member 1252), can be removably mounted to the wound creation
device 1250.
Optionally, the sample collection device 1100 may be flat mounted to the
device 1250.
Optionally, there may be a shaped cut-out on device 1250 for press-fit holding
the sample
collection device 1100. It should be understood that other techniques for
removably
mounting the sample collection device 1100 are not excluded. This de-coupling
of the
collection device and the wound creation device allows for the use of a more
sophisticated,
possible non-disposable wound creation device 1250 that can create a more
controlled,
reduced-pain wound creation experience.
[00295] Figure 11W shows that the sample collection device 1100 can be
aligned to be
more or less horizontal to be neutral with regards to gravity effects on the
sample collection.
Other mounting configurations of device 1100 to would creation device 1250 are
not
excluded.
[00296] Referring now to Figures 11X to 11Z, still further embodiments of
various
sample collection devices will now be described. Figure 11X shows a sample
collection
device 1240 where a shaped front end 1236 may be used with the device 1240.
This shaped
front end 1236 is similar to that previously described. A vacuum source 1270
can be used to
assist in drawing bodily fluid sample into the device 1240. The vacuum source
1270 may be
linked to the body of device 1240 and/or to the shaped front end 1236. It
should be
understood that any of the embodiments described in this disclosure can be
adapted for use
with a sample acquisition assist device such as but not limited to a vacuum
source 1270.
[00297] Figure 11Y shows yet another embodiment of a sample collection
device.
This embodiment uses a pipette system having a tip 1280 for collecting sample
fluid. The tip
may include a coaxially mounted tissue penetrating member 1282. Optionally, a
side mount
or angled tissue penetrating member 1284 is shown to create the wound at the
target site. The
pipette system with tip 1280 can apply vacuum to pull sample fluid from the
subject.
Optionally, a shaped front end 1236 may be used with the tip 1280 to assist in
skin stretching
or tissue reshaping at the target site.
[00298] Figure 11Z shows that some embodiments may use a diaphragm 1291
linked
actuation mechanism to create a vacuum for drawing blood sample. This linkage
allows for
the diaphragm to create a vacuum on the return stroke of the tissue
penetrating member 1292
from the target site. In one embodiment, the tissue penetrating members 1292
are
microneedles. The actuation of the tissue penetrating members as indicated by
arrows 1294
launches the tissue penetrating members 1292 and on the return path, creates
the vacuum due
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to the motion of the diaphragm linked to the motion of the tissue penetrating
member 1292.
One or more vessels 1296 can be coupled to hold fluid collected by the device
1290. Some
embodiments may have only one vessel 1296. Some embodiments may have one set
of
vessels 1296. Some embodiments may have multiple sets of vessels 1296. Some
embodiments may be mounted externally on device 1290. Some embodiments may be
mounted internally in device 1290. There may be variations and alternatives to
the
embodiments described herein and that no single embodiment should be construed
to
encompass the entire invention.
Vertical Outflow Restrictors
[00299] Figure 11E also more clearly shows that there are sleeves 1156
around the
adapter 1150 and 1152. Although only shown in Figures 11A-11F, it should be
understood
that sleeves with or without vents may be configured for use with any of the
embodiments
contemplated herein. As seen in the embodiment of Figure 11E, the channels may
be defined
by needles. These sleeves 1156 prevent premature flow of fluid sample out from
the adapter
channels 1150 and 1152 before the vessels 1146a and 1146b engage the needles.
Because of
the low volumes of sample fluid being acquired, preventing premature flow
reduces the
amount of fluid loss associated with transfer of fluid from the channels to
the vessels. In one
embodiment, the sleeves 1156 can minimize that fluid loss by providing a
sleeve that is liquid
tight, but not air tight. If the sleeve were airtight, it may prevent the
capillary action of the
channels from working properly. Optionally, some embodiments may locate vents
near the
base of the needle, away from the tip, such that the sleeve can contain the
sample at locations
away from the vents.
[00300] Figure 11F shows that in an exemplary embodiment, the sleeve 1156
is
configured to have an opening 1158 through the sleeve. This provides an
improved
embodiment over traditional sleeves which are typically loosely fitted over a
needle. Because
of the loose fit, in traditional sleeves, there is sleeve space in the tip and
in side wall space
between the needle and the sleeve within which fluid sample can accumulate.
Although a
sleeve of this design can help prevent greater loss of fluid by restricting
the loss to a defined
amount as compared to a needle without a sleeve which can lose fluid
continuously, the fluid
accumulating in the sleeve area along the tip and side wall is still lost and
not collected by the
vessels 1146a or 1146b. The sleeve 1156 may also include a narrowed area 1176
to facilitate
engagement of the sleeve against the device providing fluid communication with
the channels
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1126 and 1128, such as but not limited to the needle, probe, tube, channel, or
other adapter
channel 1150.
1003011 In the embodiment of Figure 11F, the opening 1158 is sized based
on
calculations which are sufficient to withstand fluid pressure associated with
the flow from the
capillary action of the channels in sample fill portion 1120. This forces
allows the opening
1158 to be there to vent air from the channel but also prevent fluid from
exiting the sleeve
until the vessels 1146a and 1146b are pushed to engage the adapter channels
1150 and 1152.
Because of the vent effect created by the opening 1158, the side wall and
other areas of the
sleeve can be made to much more tightly engage the needle than in traditional
sleeves. This
reduces the gap space between the needle and the sleeve and thus minimizes the
amount of
fluid that can be lost as compared to sleeves without a vent hole which have a
much greater
gap space due to the looseness of the fit. Additionally, the opening 1158 can
also be sized
such once fluid reaches the opening, that it provides enough resistance so
that flow out from
the channel or needle is also stopped so that here is minimal fluid loss in
any gap between the
sleeve and the needle tip.
[00302] The calculations for sizing the opening are as shown in Figure 12.
The desire
is to balance the forces such that there is sufficient leak-prevention force
associated with the
hydrophobic material defining the vent to contain outflow of sample fluid
outside of the
sleeve. In Figure 12, the side walls of the sleeve 1156 may be in direct
contact with the
needle or in some embodiments, there may be a gap along the sidewall with the
sleeve. In
one embodiment, the sleeve 1156 comprises a hydrophobic material such as but
not limited to
thermoplastic elastomer (TPE), butyl rubber, silicone, or other hydrophobic
material. In one
embodiment, the thickness of the sleeve will also determine the length of the
side walls of the
opening or vent 1158 in the sleeve 1156.
[00303] The opening 1158 may be located at one or more positions along the
sleeve
1156. Some may have it as shown in Figure 12. Alternatively, some embodiments
may have
the opening 1158 on a side wall of the sleeve. Other locations are not
excluded. Optionally,
the sleeve 1156 may have multiple openings through the sleeve, but configured
such that
fluid does not exit from the sleeve and resistance from the openings is
sufficient to prevent
additional outflow from the channel until the vessels 1146a or 1146b are
engaged and in fluid
communication with the channels.
1003041 With regards to how the device 1100 is used to collect a sample,
in one
technique, the sample collection device 1100 is held to engage the target
bodily fluid and is
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held in place until a desired fill level is reached. During this time, the
device 1100 may be
held horizontally to minimize gravitational force that would need to be
overcome if the
device 1100 were held more vertically. After a fill level is reached, the
device 1100 may
either be disengaged from the target fluid and then vessels 1146a and 1146b
engaged to draw
collected fluid into the vessels. Optionally, the device 1100 may be left in
contact with the
target fluid and the vessels engaged into fluid contact with the channels so
that the fill will
draw fluid in the channel and perhaps also any additional sample fluid that
remains at the
target site. This may ensure that enough bodily fluid is drawn into the
vessels.
[00305] After filling the vessels 1146a and 1146b, they may be prepared
for shipment.
Optionally, they may be sent for pre-treatment before being shipped. Some
embodiments of
the vessels 1146a and 1146b include a material in the vessel of a density such
that after a pre-
treatment such as centrifugation, the material due to its selected density
will separate one
portion of the centrifuged sample from another portion of the centrifuged
sample in the same
vessel.
[00306] The vessel 1146a or 1146b may have a vacuum and/or negative
pressure
therein. The sample may be drawn into the vessel when the channel is brought
into fluidic
communication with the vacu-vessel. Optionally, the vessel may take the form
of a test tube-
like device in the nature of those marketed under the trademark "Vacutainer"
by Becton-
Dickinson Company of East Rutherford, NJ. The device may remain in a
compressed state
with the base 1140 closing gap 1154 while the sample is being transferred to
the vessel. The
sample may fill the entire vessel or a portion of the vessel. The entirety of
the sample (and/or
greater than 90%, 95%, 97%, 98%, 99%, 99.5% or 99.9% of the sample) from the
channels
may be transferred to the vessels. Alternatively, only a portion of the sample
from the
channels may be transferred to the vessels.
[00307] In one embodiment as described herein, a two-stage filling of the
sample fluid
into the sample collection device 1100 allows for i) metered collection of the
sample fluid to
ensure that a sufficient amount is obtained in a collection channel that is
treated to prevent
premature clotting and then ii) an efficient manner of transferring a high
percentage of the
sample fluid into the vessel. This low loss filling of vessel from pre-fill
channels to meter a
minimum amount of sample fluid into the vessel 1146 provides for multiple
advantages,
particularly when dealing with collecting small volumes of sample fluid. Pre-
filling the
channels to a desired level ensures sufficient volume is present in the vessel
to perform the
desired testing on the sample fluid.
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[00308] As described herein, the entire device including the sample fill
portion 1120,
support 1130, and base 1140 are entirely transparent or translucent to allow
for visualization
of the components therein. Optionally, only one of the sample fill portion
1120, support
1130, and base 1140 are fully transparent or translucent. Optionally, only
select portions of
sample fill portion 1120, support 1130, or base 1140 are transparent or
translucent. The user
may then more accurately determine when to perform various procedures based on
progression of sample fluid filling and engagement of the sample vessels to
the channels in
sample fill portion 1120. Air bubbles in the collection channel may be visible
during filling
and if they are seen, a user may adjust the position of the sample collection
device 1100 to
better engage the target sample fluid to minimize air being drawn into the
channels. It will
also allow the user to know when to breakaway or disengage pieces such as the
base or vessel
holder 1140 when filling is completed.
[00309] It should be understood that other methods can be used to prevent
outward
sample flow from the adapter channels 1150 and 1152 if the device is held at a
non-horizontal
angle such as but not limited to downwardly in a vertical manner. In one
embodiment, a frit
1194 can be used with needles with a central bore that are used as the adapter
channels 1150
and 1152. The frits can be in the body of sample collection device or on
the collection
vessels. In some embodiments, the frits comprise of a material such as but not
limited to
PTFE. Optionally, some embodiments may use tape / adhesive over the needles
that are
functioning as the adapter channels 1150 and 1152. In one embodiment, the tape
and/or
adhesive may be used to cover the needle openings to prevent premature
discharge of sample.
Optionally, some embodiments may have adapter channels 1150 and 1152 having
hydrophobic surface to prevent controlled outflow from the adapter channel
openings leading
toward the sample vessels. In some embodiments, the adapter channels 1150 and
1152 are
needles with hydrophobic material only on the interior surfaces near an exit.
Optionally, the
hydrophobic material is only on the exterior needle surfaces near an exit.
Optionally, the
hydrophobic material is on interior and exterior needle surfaces. Optionally,
another method
of preventing downward flow is increasing the surface area of the capillaries
by varying the
cross-section. By way of non-limiting example, some embodiments may introduce
teeth- or
finger-like structures within the capillary in order increase surface are in
the cross-section of
the capillary. Optionally, some embodiments may include fins oriented toward
ancVor against
the fluid flow within the capillary in order increase surface are in the cross-
section of the
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capillary. There may be variations and alternatives to the embodiments
described herein and
that no single embodiment should be construed to encompass the entire
invention.
One sample collector location to multiple channels
[00310] Referring now to Figures 13A-13B, yet another embodiment as
described
herein will now be described. Figure 13A shows a top down view of a sample
fill portion
1320 with a single collection location 1322 such as but not limited to a
collection well where
two channels 1324 and 1326 meet to draw fluid away from the single collection
location
1322. Optionally, some embodiments may use an Y-split channel configuration
wherein only
a single channel lead away from the collection location 1322 and then splits
into channels
1324 and 1326 after having been a single common channel leading away from the
collection
location 1322. Members providing fluid communication to the channels 1324 and
1326, such
as but not limited to a needle, probe, tube, channel, hollow elongate member,
or other
structure, may be coupled to one end of the sample fill portion 1320.
[00311] Figure 13B shows a side-cross-sectional view, wherein the
collection location
1322 is shown and in fluidic communication with channel 1326 which is in turn
in fluid
communication with an adapter channel 1352 such as but not limited to a fluid
communication member. Some embodiments, the fluid communication member may
have
sufficient stiffness and a sufficiently penetrating tip to pierce a septum,
cap, or other structure
of the vessel. Some may have the adapter channel 1352, 1150, or the like to be
a non-coring
structure so as not to leave behind a hole that will not seal in the septum,
cap, or other
structure of the vessel.
[00312] As seen in Figure 13B, sample fluid may be applied or dropped into
the
collection location 1322 as indicated by droplet D. Optionally, some may
directly apply or
directly contact the collection location 1322 to apply the sample fluid.
Although the
embodiments herein are shown to use only a single collection location 1322, it
should be
understood that other embodiments where multiple channels couple to a common
sample
collection point are envisioned. By way of nonlimiting example, one embodiment
of a
collection device may have two collection locations 1322, each with its own
set of channels
leading away from its respective collection location. Some embodiments may
combine
common collection point channels shown in Figures 13A-B with channels that are
separate
such as shown in Figures 11A-11F. Other combinations of common collection
location
structure with other structures with separate channels are not excluded.
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1003131 Figure 13B also shows that this embodiment may include one or more
tissue
penetrating members 1327 configured to extend outward from the collection
location 1322.
In one embodiment, this enables the user to place target tissue simultaneously
over the
collection location 1322 and the wound creation location for fluid sample
acquisition.
Optionally, a trigger 1323 can be positioned to launch the tissue penetrating
member.
Optionally, the trigger is built into a tissue interface of the device to
enable launch of the
device when the target tissue is contacted and/or when sufficient pressure or
contact is in
place. This overlap of these two locations allows for simplified protocol for
users to follow
for successful sample acquisition. The tissue penetration member(s) 1327 may
be actuated
by one or more actuation techniques such as but not limited to spring
actuated, spring/cam
actuated, electronically actuated, or single or multiple combinations of the
foregoing. It
should be understood that other assist methods such as but not limited to
vacuum sources,
tissue stretching devices, tissue engagement nose pieces, or the like may be
used alone or in
combination with any of the foregoing for improved sample acquisition.
1003141 Referring now to Figure 13C, a still further embodiment of a
sample collection
device will now be described. This embodiment shows a cartridge 1400 with a
sample
collection device 1402 integrated therein. There is a collection location 1322
and one or
more sample openings 1325and 1329 where sample collection at location 1322 can
then be
accessed such as but not limited to handling by a pipette tip (not shown). The
sample from
droplet D will travel along pathway 1326 as indicated by arrow towards the
openings 1325
and 1329, where the sample in the opening and any in the pathways 1324 and/or
1326 leading
towards their respective openings 1325 and 1329 are drawn into the pipette P.
As indicated
by arrows near the pipette P, the pipette P is movable in at least one axis to
enable transport
of sample fluid to the desired location(s). In this embodiment, the cartridge
1400 can have a
plurality of holding vessels 1410 for reagents, wash fluids, mixing area,
incubation areas, or
the like. Optionally, some embodiments of the cartridge 1400 may not include
any holding
vessels or optionally, only one or two types of holding vessels. Optionally,
in some
embodiments, the holding vessels may be pipette tips. Optionally, in some
embodiments, the
holding vessels are pipette tips that are treated to contain reagent(s) on the
tip surface
(typically the interior tip surface although other surfaces are not excluded).
Optionally, some
embodiments of the cartridge 1400 may include only the sample collection
device 1402
without the tissue penetrating member or vice versa.
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[00315] Referring now to Figure 13D, a side cross-sectional view of the
embodiment
of Figure 13C is shown. Optionally, a tissue penetrating member 1327 may be
included for
use with creating the wound for the sample fluid to be collected at location
1322.
[00316] Figure 14 shows that the sample fill portion 1320 may be joined
with support
1330 and 1340 to form the sample collection device 1300. There may be a
visualization
window 1312 to see if sample fluid has reached a desired fill level. A force-
exerting
component, such as a spring 1356 or elastic may be included. The channel
holder may keep
the channel affixed to the support. In one embodiment, the holder may prevent
the channel
from sliding relative to the support. It may use a press fit, mechanical
fastening, adhesive, or
other attachment technique to couple to the channel. The holder may optionally
provide a
support upon which a force-exerting component, such as a spring, may rest.
[00317] In one example, the engagement assemblies may include a spring
1356 which
may exert a force so that the base 1340 is at an extended state, when the
spring is at its=
natural state. When the base is at its extended state, space may be provided
between the
vessels 1346a, 1346b and the engagement assemblies. In some instances, when
the base
1340 is in its extended state, the second ends of the channels may or may not
contact the caps
of the vessels. The second ends of the fluid communication members 1352 may be
in a
position where they are not in fluid communication with the interiors of the
vessels.
[00318] Bringing the support 1330 and the base 1340 together will bring
the channels
1324 and 1326 into fluid communication with the vessels 1346a and 1346b when
the
members 1352 penetrate through the cap on the vessels and thus draw sample
fluid into the
vessels 1346a and 1346b.
[00319] The vessel 1346a or 1346b may have a vacuum and/or negative
pressure
therein. The sample may be drawn into the vessel when the channel is brought
into fluidic
communication with the vacu-vessel. The device may remain in a compressed
state with the
base 1340 positioned so that vessels are in fluid communication with the
channels 1326 and
1328 when the sample fluid is being transferred to the vessels. The sample may
fill the entire
vessel or a portion of the vessel. The entirety of the sample (and/or greater
than 90%, 95%,
97%, 98%, 99%, 99.5% or 99.9% of the sample) from the channels may be
transferred to the
vessels. Alternatively, only a portion of the sample from the channels may be
transferred to
the vessels.
[00320] As seen in Figure 15, in one embodiment as described herein, a two-
stage
filling of the sample fluid into the sample collection device 1300 allows for
i) metered
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collection of the sample fluid to ensure that a sufficient amount is obtained
in a collection
channel that is treated to prevent premature clotting and then ii) an
efficient manner of
transferring a high percentage of the sample fluid into the vessel. This low
loss filling of
vessel from pre-fill channels to meter a minimum amount of sample fluid into
the vessel 1346
provides for multiple advantages, particularly when dealing with collecting
small volumes of
sample fluid. Pre-filling the channels to a desired level ensures sufficient
volume is present
in the vessel to perform the desired testing on the sample fluid.
1003211 Referring now to Figures 16 and 17, still further embodiments will
now be
described. Figure 16 shows a blood collection device 1300 with a secondary
collection area
1324 around the collection location 1322. The secondary collection area 1324
can be used to
direct any overflow, spilled, or mis-directed fluid sample towards the
collection location
1322.
1003221 Figure 17 further shows that the vessels 1346a and 1346b may each
have an
identifier associated with the vessels 1346a and 1346b. Figure 17 shows that
in one
nonlimiting example, the identifier 1600 and 1602 may be at least one of: a
barcode (e.g., 1-
D, 2-D, or 3-D), quick response (QR) code, image, shape, word, number,
alphanumeric
string, color, or any combination thereof, or any type of visual identifier.
Others may use
identifiers that are not in the visible spectrum. Others may use RFID tags, RF
identifiers, IR
emitting tags, or other markers that do not rely on identification through
signals sent through
the visual spectrum.
1003231 Identifiers 1600 and 1602 may be used to identify sample and/or
types of
sample in a sample collection device. There may be one or more identifiers per
vessel.
Some may also use identifiers on the vessel holders. Identifiers may identity
the sample
collection device, one or more individual vessels within the device, or
components of the
device. In some instances, the sample collection device, a portion of the
sample collection
device, and/or the vessels may be transported. In one example, the sample
collection device,
portion of the sample collection device may be transported via a delivery
service, or any other
service described elsewhere herein. The sample may be delivered to perform one
or more
test on the sample.
1003241 The sample identity and/or the identity of the individual who
provided the
sample could be tracked. Information associated with the individual or
individuals (e.g.,
name, contact information, social security number, birth date, insurance
information, billing
information, medical history) and other information of who provided the sample
may be
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included. In some instances, the type of sample (e.g., whole blood, plasma,
urine, etc.) may
be tracked. The types of reagents that the sample will have encountered (e.g.,
anticoagulants,
labels, etc.) could also be tracked. Additional information about the sample
collection, such
as date and/or time of collection, circumstances under which sample was
collected, types of
tests to be run on the sample, insurance information, medical records
information, or any
other type of information may be considered.
[00325] Identifiers may assist with tracking such information. The
identifiers may be
associated with such information. Such information may be stored off-board the
sample
collection device, on-board the sample collection device, or any combination
thereof In
some instances, the information may be stored on one or more external devices,
such as
servers, computers, databases, or any other device having a memory. In some
instances, the
information may be stored on a cloud computing infrastructure. One or more
resources that
store the information may be distributed over the cloud. In some instances, a
peer-to-peer
infrastructure may be provided. The information may be stored in the
identifier itself, or may
be associated with the identifier elsewhere, or any combination thereof.
1003261 An identifier may provide unique identification, or may provide a
high
likelihood of providing unique identification. In some instances, the
identifier may have a
visible component. The identifier may be optically detectable. In some
instances, the
identifier may be discernible using visible light. In some examples, the
identifier may be a
barcode (e.g., 1-D, 2-D, or 3-D), quick response (QR) code, image, shape,
word, number,
alphanumeric string, color, or any combination thereof, or any type of visual
identifier.
[00327] In other embodiments, the identifier may be optically detectable
via any other
sort of radiation. For example, the identifier may be detectable via infrared,
ultraviolet, or
any other type of wavelength of the electromagnetic spectrum. The identifier
may utilize
luminescence, such as fluorescence, chemiluminescence, bioluminescence, or any
other type
of optical emission. In some instances, the identifier may be a radio
transmitter and/or
receiver. The identifier may be a radiofrequency identification (RFID) tag.
The identifier
may be any type of wireless transmitter and/or receiver. The identifier may
send one or more
electrical signal. In some instances, GPS or other location-related signals
may be utilized
with the identifier.
1003281 An identifier may include an audio component, or acoustic
component. The
identifier may emit a sound that may be discernible to uniquely identify the
identified
component.
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[00329] The identifier may be detectable via an optical detection device.
For example,
a bar code scanner may be capable of reading the identifier. In another
example, a camera
(e.g., for still or video images) or other image capture device may be capable
of capturing an
image of the identifier and analyzing the image to determine the
identification.
[00330] Figures 16 and 17 show examples of identifiers provided for use
with a sample
collection device 1300 in accordance with an embodiment described herein. In
one example,
a sample collection device may include a base 1340 which may support and/or
contain one or
more vessels 1346a, 1346b. Sample may be provided to the sample collection
device. The
sample may be provided to the sample collection device via an inlet 1322. The
sample may
travel to one or more vessels 1346a, 1346b within the device.
[00331] One or more identifier 1600, 1602 may be provided on the sample
collection
device. In some embodiments, identifiers may be positioned on a base 1340 of
the sample
collection device. The identifiers may be positioned on a bottom surface of
the base, side
surface of the base, or any other portion of the base. In one example, the
base may have a flat
bottom surface. The identifiers may be on the flat bottom surface of the base.
One or more
indentation may be provided in the base. The identifier may be located within
the
indentation. The indentations may be on the bottom or side surface of the
base. In some
embodiments, the base may include one or more protrusion. The identifier may
be located on
the protrusion. In some instances, the identifiers may be provided on an
exterior surface of
the base. The identifiers may alternatively be positioned on an interior
surface of the base.
The identifiers may be detected from outside the sample collection device.
[00332] In some embodiments, the identifiers may be provided on the
vessels 1346a,
1346b. The identifiers may be on an exterior surface of the vessels or an
interior surface of
the vessels. The identifiers may be detectable from outside the vessels. In
some
embodiments, the identifiers may be provided on a bottom surface of the
vessels.
1003331 In one example, the base may include an optically transmissive
portion. The
optically transmissive portion may be on a bottom of the base or a side of the
base. For
example, a transparent or translucent window may be provided. In another
example, the
optically transmissive portion may be a hole without requiring a window. The
optically
transmissive portion may permit a portion inside the base to be visible. The
identifiers may
be provided on an exterior surface of the base on the optically transmissive
portion, an
interior surface of the base but may be visible through the optically
transmissive portion, or
on an exterior or interior surface of the vessel but may be visible through
the optically
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transmissive portion. In some instances, the identifier may be provided on an
interior surface
of the vessel, but the vessel may be optically transmissive so that the
identifier is viewable
through the vessel and/or optically transmissive portion.
1003341 The identifier may be a QR code or other optical identifier that
may be
optically visible from outside the sample collection device. A QR code may be
visible
through an optical window or hole at the bottom of the base of the sample
collection device.
The QR code may be provided on the sample collection device base or on a
portion of the
vessel visible through the base. An image capturing device, such as a camera
or scanner may
be provided externally to the sample collection device, and may be capable of
reading the QR
code.
[00335] A single or a plurality of QR codes or other identifiers may be
provided on a
sample collection device. In some instances, each vessel may have at least one
identifier,
such as a QR code associated with it. In one example, at least one window may
be provided
in a base per vessel, and each window may permit a user to view a QR code or
other
identifier. For example, two vessels 1346a, 1346b may be housed within a base
1340, each
of which has an associated identifier 1600, 1602 discernible from outside the
sample
collection device.
1003361 The base 1340 may be separable from the support 1330 or other
portions of
the sample collection device. The identifier(s) may be separated from the rest
of the sample
collection device along with the base.
[00337] In some embodiments, the identifiers may be provided with vessels
housed by
the base. Separating the base from the rest of the sample collection device
may cause the
vessels to be separated from the rest of the sample collection device. The
vessels may remain
within the base or may be removed from the base. The identifiers may remain
with the
vessels even if they are removed from the base. Alternatively, the identifiers
may remain
with the base even if vessels are removed. In some instances, both the base
and vessels may
have identifiers so that the vessels and bases may be individually tracked
and/or matched
even when separated.
[00338] In some instances, any number of vessels may be provided within
the sample
collection device. The sample vessels may be capable of receiving sample
received from a
subject. Each sample vessel may have a unique identifier. The unique
identifier may be
associated with any information relating to the sample, subject, device, or
component of the
device.
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1003391 In some instances, each identifier for each vessel may be unique.
In other
embodiments, the identifier on the vessel need not be unique, but may be
unique for the
device, for the subject, or for the type of sample.
1003401 A sample collection device may receive a sample from a subject.
The subject
may directly contact the sample collection device or provide the sample to the
device. The
sample may travel through the device to one or more vessels within the device.
In some
instances, the sample may be treated prior to reaching the vessels. One or
more coating or
substance may be provided within a sample collection unit and/or channel that
may convey
the sample to the vessels. Alternatively, no treatment is provided to the
sample prior to
reaching the vessel. In some embodiments, the sample may or may not be treated
within the
vessel. In some instances, a plurality of different types of treatments may be
provided to a
sample before or when the sample reaches the vessel. The treatments may be
provided in a
preselected order. For example, a first treatment desired first, and may be
provided upstream
of a second treatment. In some instances, the sample is not treated at any
point.
[00341] In some embodiments, the sample may be a blood sample. A first
vessel may
receive whole blood and a second vessel may receive blood plasma.
Anticoagulants may be
provided along the fluid path and/or in the vessels.
[00342] Once the sample has been provided to the vessels and the vessels
have been
sealed, the vessels may be sent to a separate location for sample analysis.
The separate
location may be a laboratory. The separate location may be a remote facility
relative to the
sample collection site. The entire sample collection device may be sent to the
separate
location. One or more identifiers may be provided on the sample collection
device and may
be useful for identifying the sample collection device and/or vessels therein.
Alternatively,
the base 1340 may be removed from the sample collection device and may be sent
to the
separate location with the vessels therein. One or more identifiers may be
provided on the
base and may be useful for identifying the base and/or vessels therein. In
some instances,
vessels may be removed from the base and may be sent to the separate location.
One or more
identifier may be provided on each vessel, and may be useful for identifying
the vessels.
[00343] The identifiers may be read by any suitable technique. By way of
example
and not limitation, in some instances, the identifiers are read using an
optical detector, such as
an image capture device or barcode scanner. In one example, an image capture
device may
capture an image of a QR code. Information relating to the vessel may be
tracked. For
example, when a vessel arrives at a location, the identifier may be scanned,
and record of the
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arrival of the vessel may be kept. The progress and/or location of the vessel
may be updated
actively and/or passively. In some instances, the identifier may need to be
scanned
intentionally in order to determine.the location of the vessel. In other
examples, the identifier
may actively emit a signal that may be picked up by signal readers. For
example, as an
identifier travels through a building, signal readers may track the location
of the identifier.
[00344] In some instances, reading the identifier may permit a user to
access additional
information associated with the identifier. For example, the user may capture
an image of the
identifier using a device. The device or another device may display
information about the
sample, subject, device, component of the device, or any other information
described
elsewhere herein. Information about tests to be conducted and/or test results
may be
included. The user may perform subsequent tests or actions with the sample
based on
information associated with the identifier. For example, the user may direct
the vessel to the
appropriate location for a test. In some instances, the vessel may be directed
to an
appropriate location and/or have appropriate sample processing (e.g., sample
prep, assay,
detection, analysis) performed on the contents of the vessel in an automated
fashion without
requiring human intervention.
[00345] Information relating to sample processing may be collected and
associated
with the identifier. For example, if a vessel has an identifier and sample
processing has been
performed on the contents of the vessel, one or more signals produced in
response to the
sample processing may be stored and/or associated with the identifier. Such
updates may be
made in an automated fashion without requiring human intervention.
Alternatively, a user
may initiate the storing of information or may manually enter information.
Thus, medical
records relating to a subject may be aggregated in an automated fashion. The
identifiers may
be useful for indexing and/or accessing information related to the subject.
Sample vessels
1003461 Figures 18A-18B show one nonlimiting example of a sample vessel
1800 that
may be utilized with a sample collection device in accordance with an
embodiment described
herein. In some instances, the sample vessels may be supported by the sample
collection
device. Optionally, the sample vessels may be encompassed or surrounded by a
portion of
the sample collection device. In one example, the sample collection device may
have a first
configuration where the sample vessels are completely enclosed. A second
configuration
may be provided where the sample collection device may be opened and at least
a portion of
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the sample vessels may be exposed. In some examples, the sample vessels may be
supported
and/or at least partially enclosed by a holder of the sample collection
device. The holder may
be separable from the rest of the sample collection device, thereby providing
access to the
sample vessels therein.
[00347] In the case of bodily fluid collection, the sample fluid may be
extracted from
the patient using a sample collection device such as but not limited to that
described in U.S.
Patent Application Ser. No. 61/697,797 filed September 6, 2012 and U.S. Patent
Application
Ser. No. 61/798,873 filed March 15, 2013, both of which are fully incorporated
herein by
reference for all purposes. In the non-limiting example of blood samples, some
embodiments
may collect the blood sample through collection of capillary blood from the
subject. This
may occur by way of a wound, a penetration site, or other access site to
capillary blood from
the subject. Optionally, blood could also be collected by venipuncture or
other puncture of a
blood vessel to obtain blood sample for loading into the sample vessel(s). For
example, the
blood could be collected by a device configured for collection of a small
volume of blood by
venipuncture. Such a device, for example, may include a hollow needle
fluidically connected
with or capable of being fluidically connected with a vessel having a small
interior volume.
The vessel having a small interior volume may have an interior volume, for
example, of equal
to or no more than 5 ml 4 ml, 3 ml, 2 ml, 1 ml, 750 1, 500 1, 400 I, 300
200 1, 100 I,
90 1, 80 1, 70 I, 60 1, 50 jtl, 40 1, 30 1, 20 1, 10 1, or 5 1. Other
types of devices
and techniques used to collect bodily fluid are not excluded.
[00348] A bodily fluid may be drawn from a subject and provided to a
device in a
variety of ways, including but not limited to, fingerstick, lancing,
injection, pumping,
swabbing, pipetting, venous draw, venipuncture, and/or any other technique
described
elsewhere herein. In some embodiments, the sample may be collected from the
subject's
breath. The bodily fluid may be provided using a bodily fluid collector. A
bodily fluid
collector may include a lancet, capillary, tube, pipette, syringe, needle,
microneedle, pump, or
any other collector described elsewhere herein. In some embodiments, the
sample may be a
tissue sample which may be provided from the subject. The sample may be
removed from
the subject or may have been cast off by the subject.
1003491 In one embodiment, a lancet punctures the skin of a subject and
withdraws a
sample using, for example, gravity, capillary action, aspiration, pressure
differential or
vacuum force. The lancet, or any other bodily fluid collector, may be part of
the device, part
of a cartridge of the device, part of a system, or a standalone component.
Where needed, the
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lancet or any other bodily fluid collector may be activated by a variety of
mechanical,
electrical, electromechanical, or any other known activation mechanism or any
combination
of such methods.
[00350] In one example, a subject's finger (or other portion of the
subject's body) may
be punctured to yield a bodily fluid. The bodily fluid may be collected using
a capillary tube,
pipette, swab, drop, or any other mechanism known in the art. The capillary
tube or pipette
may be separate from the device and/or a cartridge of the device that may be
inserted within
or attached to a device, or may be a part of a device and/or cartridge. In
another embodiment
where no active mechanism is required, a subject can simply provide a bodily
fluid to the
device and/or cartridge, as for example, with a saliva sample.
[00351] A bodily fluid may be drawn from a subject and provided to a
device in a
variety of ways, including but not limited to, fingerstick, lancing,
injection, and/or pipetting.
The bodily fluid may be collected using venous or non-venous methods. The
bodily fluid
may be provided using a bodily fluid collector. A bodily fluid collector may
include a lancet,
capillary, tube, pipette, syringe, venous draw, or any other collector
described elsewhere
herein. In one embodiment, a lancet punctures the skin and withdraws a sample
using, for
example, gravity, capillary action, aspiration, or vacuum force. The lancet
may be part of the
device, part of the cartridge of the device, part of a system, or a standalone
component.
Where needed, the lancet may be activated by a variety of mechanical,
electrical,
electromechanical, or any other known activation mechanism or any combination
of such
methods. In one example, a subject's finger (or other portion of the subject's
body) may be
punctured to yield a bodily fluid. Examples of other portions of the subject's
body may
include, but are not limited to, the subject's hand, wrist, arm, torso, leg,
foot, or neck. The
bodily fluid may be collected using a capillary tube, pipette, or any other
mechanism known
in the art. The capillary tube or pipette may be separate from the device
and/or cartridge, or
may be a part of a device and/or cartridge. In another embodiment where no
active
mechanism is required, a subject can simply provide a bodily fluid to the
device and/or
cartridge, as for example, could occur with a saliva sample. The collected
fluid can be placed
within the device. A bodily fluid collector may be attached to the device,
removably
attachable to the device, or may be provided separately from the device.
[00352] Sample obtained from a subject may be stored in a sample vessel
1800. In one
embodiment described herein, the sample vessel 1800 comprises a body 1810 and
a cap 1820.
In some instances, at least portions of the sample vessel body may be formed
from a
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transparent or translucent material. The sample vessel body may permit a
sample provided
within the sample vessel body to be visible when viewed from outside the
sample vessel.
The sample vessel body may be optically transmissive. The sample vessel body
may be
formed of a material that may permit electromagnetic radiation to pass
through. In some
instances, the sample vessel body may be formed of a material that may permit
selected
wavelengths of electromagnetic radiation to pass through while not permitting
other non-
selected wavelengths of electromagnetic radiation to pass through. In some
instances a
portion or all of the body may be formed of a material that is opaque along
selected
wavelengths of electromagnetic radiation, such as wavelengths for visible
light. Optionally,
some portions of the sample vessel body may be shaped to provide a certain
optical path
length. Optionally, some portions of the sample vessel body may be shaped to
provide a flat
surface (exterior and/or interior) or other structure to allow for analysis of
sample while it is
in the sample vessel.
[00353] In one embodiment, an open end and a closed end may be
provided on a
sample vessel body 1810. The open end may be a top end 1812 of the sample
vessel 1800,
which may be at the end which may be configured to engage with a cap. The
closed end may
be a bottom end 1814 of the sample vessel, which may be at the end of the
sample vessel
opposite the cap. In alternative embodiments, a bottom end may also be an open
end that
may be closable with a floor. In some embodiments, the cross-sectional area
and/or shape of
the top end and the bottom end may be substantially the same. Alternatively,
the cross-
sectional area of the top end may be larger than the cross-sectional area of
the bottom end, or
vice versa. There may be variations and alternatives to the embodiments
described herein
and that no single embodiment should be construed to encompass the entire
invention.
[00354] In one embodiment, a sample vessel body may have an interior
surface and an
exterior surface. The surfaces of the sample vessel body may be smooth, rough,
textured,
faceted, shiny, dull, contain grooves, contain ridges, or have any other
feature. The surface
of the sample vessel body may be treated to provide a desired optical
property. The interior
surfaces and exterior surfaces may have the same properties or may be
different. For
example, an exterior surface may be smooth while the interior surface is
rough.
[00355] Optionally, the sample vessel body may have a tubular shape.
In some
instances, the sample vessel body may have a cylindrical portion. In some
instances, the
= sample vessel may have a circular cross-sectional shape. Alternatively,
the sample vessel
may have any other cross-sectional shape which may include elliptical,
triangular,
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quadrilateral (e.g., square, rectangular, trapezoidal, parallelogram),
pentagonal, hexagonal,
heptagonal, octagonal, or any other shape. The cross-sectional shape of the
sample vessel
may or may not have a convex and/or concave shape. The cross-sectional shape
of the
sample vessel may remain the same along the length of the sample vessel, or
may vary. The
sample vessel may have a prismatic shape along the length of the body. The
prism may have
a cross-sectional shape as those described herein.
100356] Optionally, the bottom 1814 of the sample vessel may be flat,
tapered,
rounded, or any combination thereof. In some instances, the sample vessel may
have a
hemispherical bottom. In other embodiments, the sample vessel may have a
rounded bottom
with a flat portion. The sample vessel may or may not be capable of standing
on a flat
surface on its own.
100357] In one embodiment, the sample vessels 1800 may be sized to contain
a small
fluid sample. In some embodiments, the sample vessels may be configured to
contain no
more than about 5 ml, 4 ml, 3 ml, 2 ml, 1.5 mL, 1 mL, 900 uL, 800 uL, 700 uL,
600 uL, 500
uL, 400 uL, 300 uL, 250 uL, 200 uL, 150 uL, 100 uL, 80 uL, 50 uL, 30 uL, 25
uL, 20 uL, 10
uL, 7 uL, 5 uL, 3 uL, 2 uL, 1 uL, 750 nL, 500 nL, 250 nL, 200 nL, 150 nL, 100
nL, 50 nL, 10
nL, 5 nL, 1 nL, 500 pL, 300 pL, 100 pL, 50 pL, 10 pL, 5 pL, or 1 pL. By way of
non-limiting
example, the sample vessels may have the information storage units thereon
such as
discussed for Figures 1F and 1G. In one non-limiting example, the sample
vessels 100 may
hold the small volume of sample fluid in liquid form without the use of a
wicking material,
mesh, solid matrix, or the like to hold the sample fluid during transport.
This allows the
sample fluid to be substantially removed in liquid form from the sample vessel
without loss
of sample or sample integrity due to liquid being absorbed by the wicking or
other material.
1003581 Optionally, the sample vessels 1800 may be configured to contain
no more
than several drops of blood, a drop of blood, or no more than a portion of a
drop of blood.
For example, the sample vessel may have an interior volume of no greater than
the amount of
fluid sample it is configured to contain. Having a small volume sample vessel
may
advantageously permit storage and/or transport of a large number of sample
vessels within a
small volume. This may reduce resources used to store and/or transport the
sample vessels.
For example, less storage space may be required. Additionally, less cost
and/or fuel may be
used to transport the sample vessels. For the same amount of exertion, a
larger number of
sample vessels may be transported.
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[00359] In some embodiments, the sample vessel 1800 may have a small
length. For
example, the sample vessel length may be no greater than 8 cm, 7 cm, 6 cm, 5
cm, 4 cm, 3.5
cm, 3 cm, 2.5 cm, 2 cm, 1.7 cm, 1.5 cm, 1.3 cm, 1.1 cm, 1 cm, 0.9 cm, 0.8 cm,
0.7 cm, 0.6
cm, 0.5 cm, 0.4 cm, 0.3 cm, 0.2 cm, 0.1 cm, 700 um, 500 m, 300 um, 100 um, 70
um, 50 um,
30 um, 10 um, 7 um, 5 um, 30 um, or 1 um. In some instances, the greatest
dimension of the
sample vessel (e.g., length, width, or diameter) may be no greater than 8 cm,
7 cm, 6 cm, 5
cm, 4 cm, 3.5 cm, 3 cm, 2.5 cm, 2 cm, 1.7 cm, 1.5 cm, 1.3 cm, 1.1 cm, 1 cm,
0.9 cm, 0.8 cm,
0.7 cm, 0.6 cm, 0.5 cm, 0.4 cm, 0.3 cm, 0.2 cm, 0.1 cm, 700 um, 500 m, 300 um,
100 um, 70
um, 50 um, 30 um, 10 um, 7 um, 5 um, 30 um, or 1 um.
[00360] The sample vessel 1800 may have any cross-sectional area. The
cross-
sectional area may be no greater than about 16 cm2, 8 cm2, 7 cm2, 6 cm2, 5
cm2, 4 cm2, 3.5
cm2, 3 cm2, 2.5 cm2, 2 cm2, 1.5 cm2, 1 cm2, 0.9 cm2, 0.8 cm2, 0.7 cm2, 0.6
cm2, 0.5 cm2, 0.4
cm2, 0.3 cm2, 0.2 cm2, 0.1 cm2, 0.07 cm2, 0.05 cm2, 0.03 cm2, 0.02 cm2, 0.01
cm2, 0.5 cm2,
0.3 cm2, or 0.1 cm2. The cross-sectional area may remain the same or may vary
along the
length of the sample vessel.
[00361] The sample vessel 1800 may have any thickness. The thickness may
remain
the same along the length of the sample vessel or may vary. In some instances,
the thickness
may be selected and/or may vary in order to provide a desired optical
property. In some
instances, the thickness may be no greater than 5 mm, 3 mm, 2 mm, 1 mm, 700
um, 500 um,
300 um, 200 um, 150 um, 100 um, 70 um, 50 um, 30 um, 10 um, 7 um, 5 um, 3 um,
1 um,
700 nm, 500 nm, 300 nm or 100 nm.
[00362] In one embodiment, the sample vessel 1800 may have a shape
conducive to
enabling centrifugation of small volume blood samples. This allows the
collected sample in
the sample vessels to be taken directly to a centrifuge without having to
further transfer the
sample fluid to yet another sample vessel that is used in the centrifuge
device.
[00363] Optionally, the sample vessels may contain a cap 1820. The cap
1820 may be
configured to fit over an open end of the sample vessel. The cap may block the
open end of
the sample vessel. The cap may fluidically seal the sample vessel. The cap may
form a fluid-
tight seal with the sample vessel body. For example, the cap may be gas and/or
liquid
impermeable. Alternatively, the cap may permit certain gases and/or liquids to
pass through.
In some instances, the cap may be gas permeable while being liquid
impermeable. The cap
may be impermeable to the sample. For example, the cap may be impermeable to
whole
blood, serum or plasma.
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1003641 Optionally, the cap may be configured to engage with the sample
vessel body
in any manner. For example, the cap may be press-fit with the sample vessel
body. A
friction fit and/or interference fit may permit the cap to stay on the body.
In other examples,
a locking mechanism may be provided, such as a sliding mechanism, clamp,
fastener, or other
technique. In some instances, the cap and/or the sample vessel body may be
threaded to
permit a screw-type engagement. In other examples, adhesives, welding,
soldering, or
brazing may be utilized to connect the cap to the sample vessel body. The cap
may be
removably attached to the sample vessel body. Alternatively, the cap may be
permanently
affixed to the sample vessel body.
1003651 In some instances, a portion of the cap may fit into a portion of
the sample
vessel body. The cap may form a stopper with the sample vessel body. In some
instances, a
portion of the sample vessel body may fit into a portion of the cap. The plug
may include a
lip or shelf that may hang over a portion of the sample vessel body. The lip
or shelf may
prevent the cap from sliding into the sample vessel body. In some instances, a
portion of a
cap may overlie a top and/or side of the sample vessel body. Optionally, some
embodiments may include an additional part in the vessel assembly such as cap
holder. In
one embodiment, the purpose of the cap holder is to maintain a tight seal
between the cap and
sample vessel. In one embodiment, the cap holder engages an attachment, lip,
indentation, or
other attachment location on the outside of the sample vessel to hold the cap
in position.
Optionally, some embodiments can combine the function of both the cap and the
cap holder
into one component.
1003661 In some embodiments, the sample vessel body may be formed of a
rigid
material. For example, the sample vessel body may be formed of a polymer, such
as
polypropylene, polystyrene, or acrylic. In alternate embodiments, the sample
vessel body
may be semi-rigid or flexible. The sample vessel body may be formed from a
single integral
piece. Alternatively, multiple pieces may be used. The multiple pieces may be
formed from
the same material or from different materials.
[00367] Optionally, the sample vessel cap may be formed of an elastomeric
material,
or any other material described elsewhere herein. In some instances, the cap
may be formed
from a rubber, polymer, or any other material that may be flexible and/or
compressible.
Alternatively, the cap may be semi-rigid or rigid. The sample vessel cap may
be formed from
a high friction material. The sample vessel cap may be capable of being
friction-fit to engage
with the sample vessel body. When the sample vessel cap is engaged with the
sample vessel
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body, a fluid-tight seal may be formed. The interior of the sample vessel body
may be
fluidically isolated from the ambient air. In some instances, at least one of
the cap and/or
portion of the sample vessel body contacting the cap may be formed from a high
friction
and/or compressible material.
[00368] In one embodiment, the cap 1820 may be a needle and/or a cannula-
penetrable
self-sealing gas-proof closure in sealing engagement in the open end of the
sample vessel so
as to maintain a vacuum and/or a close atmosphere inside the sample vessel. In
some
embodiments, the interior of the sample vessel is only at a partial vacuum and
not at a full
vacuum. Excessive vacuum can damage formed blood components in the sample
fluid. By
way of non-limiting example, the partial vacuum is in the range of about 50 to
60% of a full
vacuum. Optionally, the partial vacuum does not exceed about 60% of a full
vacuum.
Optionally, the partial vacuum does not exceed about 50% of a full vacuum.
Optionally, the
partial vacuum does not exceed about 40% of a full vacuum. By way of non-
limiting
example, the partial vacuum is in the range of about 10% to about 90% of a
full vacuum, or
between about 20% to about 70%, or between about 30% to about 60% of a full
vacuum. By
way of non-limiting example, the partial vacuum is in the range Of about 10%
to about 60%
of a full vacuum, or between about 20% to about 50%, or between about 30% to
about 50%
of a full vacuum. In this manner, a reduced amount of force is exerted on the
bodily fluid
sample to minimize issues with regards to sample integrity. Optionally, after
sample transfer,
the atmosphere is at ambient pressure. Optionally, after sample transfer, the
atmosphere is at
some partial vacuum. Optionally, only one of the plurality of sample vessels
is at partial
vacuum, while others are at higher vacuum levels or at full vacuum.
[00369] In some embodiments, the cap 1820 may be a closure device having
one end
interior of the sample vessel and another end exterior of the sample vessel,
wherein the end
interior having a surface in continuous sealing contact with the sample
vessel, the end interior
having an annular sleeve extending from the surface toward the closed end, the
annular
sleeve having a first notch extending through a wall of the annular sleeve and
juxtaposed
against the sample vessel. In one embodiment, the closure has an indented ring
formed about
the first notch of the end interior and the indented ring engaging a hump of
the tubular sample
vessel.
[00370] Optionally, the sample vessel cap may be formed from a single
integral piece.
Alternatively, multiple pieces may be used. The multiple pieces may be formed
from the
same material or from different materials. The cap material may be the same as
or different
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from the sample vessel body material. In one example, the sample vessel body
may be
formed from an optically transmissive material while the cap is formed from an
opaque
material.
[00371] Optionally, the cap 1820 may be removably engaged with the body. A
portion
of the cap may be insertable into the body. The cap may include a lip which
may rest on top
of the body. The lip is not inserted into the body. In this non-limiting
example, the lip may
prevent the cap from being entirely inserted into the body. The lip may form a
continuous
flange around the cap. In some instances, a portion of the lip may overlap or
overlie a portion
of the body. A portion of the body may be insertable into a portion of the
cap.
[00372] Optionally, the portion of the cap that may be insertable into the
body may
have a rounded bottom. Alternatively, the portion may be flat, tapered,
curved, contoured, or
have any other shape. The cap may be shaped to be easily insertable into the
body.
[00373] In some instances, a depression may be provided at the top of the
cap. The
depression may follow the portion of the cap that is inserted into the body.
In some
instances, a hollow or depression may be provided in the cap. The depression
may be
capable of accepting a portion of a channel that may be used to deliver a
sample to the sample
vessel. The depression may assist with guiding the channel to a desired
portion of the cap. In
one example, the channel may be positioned within the depression prior to
bringing the
channel and interior of the sample vessel into fluid communication.
[00374] Optionally, the channel and cap may be pressed together so that
the channel
penetrates the cap and enters the interior of the sample vessel, thereby
bringing the channel
and interior of the sample vessel into fluid communication. In some instances,
the cap may
have a slit through which the channel passes. Alternatively, the channel may
poke through
uninterrupted cap material. The channel may be withdrawn from the sample
vessel, thereby
bringing the channel and sample vessel out of fluid communication. The cap may
be capable
of resealing when the channel is removed. For the example, the cap may be
formed of a self-
healing material. In some instances, the cap may have a slit that may close up
when the
channel is removed, thereby forming a fluid tight seal.
[00375] In some embodiments, the body may include one or more flange or
other
surface feature. Examples of surface features may include flanges, bumps,
protrusions,
grooves, ridges, threads, holes, facets, or any other surface feature. The
flange and/or other
surface feature may circumscribe the body. The flange and/or surface feature
may be located
at or near the top of the body. The flange and/or other surface feature may be
located at the
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top half, top third, top quarter, top fifth, top sixth, top eighth, or top
tenth of the body. The
surface features may be useful for support of the sample vessel within a
sample collection
device. The surface features may be useful for removing the sample vessel from
the sample
collection device and/or positioning the sample vessel within the sample
collection device.
The flange and/or other surface feature may or may not engage with the cap.
[00376] Optionally, the cap may have any dimension relative to the sample
vessel
body. In some instances, the cap and/or body may have similar cross-sectional
areas. The cap
may have the same or a substantially similar cross-sectional area and/or shape
as the top of
the body. In some instances, the cap may have a lesser length than the body.
For example,
the cap may have a length that may be less than 60%, 50%, 40%, 30%, 25%, 20%,
15%,
10%, 7%, 5%, 3% or 1% of the length of the body.
[00377] Referring now to Figures 18C to 18E, a still further embodiment of
sample
vessel 1800 may include a cap holder 1830 that fits over the cap to hold the
cap in place. By
way of non-limiting example, the cap holder 1830 may also include an opening
in the cap
holder 1830 that allows for a member such as an adapter to slide through and
penetrate the
cap 1820. Figure 18C shows the parts in an exploded view.
[00378] Figure 18D shows a cross-section view showing one embodiment
wherein the
sample vessel body 1810 having a cap 1820 covered by a cap holder 1830. As
seen in Figure
18D, the cap holder 1830 has a locking feature 1832 for securing the cap
holder 1830 to the
sample vessel body 1810 and/or the cap 1820. In one embodiment, the locking
feature 1832
comprises an interior ridge which will engage one or more of the ridges 1812
and 1814 on the
sample vessel body 1810. Figure 18E shows a side view of the cap holder 1830
coupled to
the sample vessel body 1810.
[00379] In some instances, a surface (interior and/or exterior) of the
sample vessel may
be coated and/or treated with a material. For example, an interior surface of
the sample
vessel may be coated with fixatives, antibodies, optical coatings,
anticoagulant, sample
additives and/or preservatives. These may be the same or different from any
material
coatings in the channels. In one non-limiting example, the coating may be but
are not limited
to polytetrafluoroethylene, poly-xylene, polysorbate surfactant (e.g.
polysorbate 20) or other
material as a treatment for surfaces to reduce the surface tension.
[00380] In embodiments, sample vessels may contain a blood clotting
activator (e.g.
thrombin, silica particles, glass particles), an antiglycolytic agent (e.g.
sodium floride), or a
gel to facilitate the separation of blood cells from plasma. In examples,
sample vessels may
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contain sodium polyanethol sulfonate (SPS), acid citrate dextrose additives,
perchloric acid,
or sodium citrate. Some embodiments may include at least one material from
each of the
above groupings. Optionally, it should also be understood that other additives
or materials
are not excluded, particularly if the additives do not interfere with each
other in terms of
functionality.
[00381] Optionally, the coating is applied on all interior surfaces of the
sample vessel.
Optionally, some embodiments may apply the coating in a pattern covering only
select areas
in the sample vessel. Some embodiments may only cover upper interior regions
of the
sample vessel. Optionally, some may cover only lower interior regions of the
sample vessel.
Optionally, some may cover strips, lanes, or other geometric patterns of the
interior regions
of the sample vessel. Optionally, some embodiments may also coat the surfaces
of the cap,
plug, or cover that is used with the sample vessel. Some embodiments may have
the surfaces
where sample enters the sample vessel to be coated to provide for a smooth
transfer of sample
away from the entry area and towards a destination site such as but not
limited to a bottom
portion of the vessel.
[00382] Optionally, the coating may be a wet or dry coating. Some
embodiments may
have at least one dry coating and at least one wet coating. In some instances
one or more
reagents may be coated and dried on the interior surface of the sample vessel.
The coating
may alternatively be provided in a moist environment or may be a gel. Some
embodiments
may include a separator gel in the sample vessel to keep select portions of
the sample away
from other portions of the sample. Some embodiments may include serum
separator gel or
plasma separator gel such as but not limited to polyester-based separator gels
available from
Becton Dickinson.
[00383] Optionally, one or more solid substrates may be provided within
the sample
vessel. For example, one or more beads or particles may be provided within the
sample
vessel. The beads and/or particles may be coated with reagents or any other
substance
described herein. The beads and/or particles may be capable of dissolving in
the presence of
the sample. The beads and/or particles may be formed from one or more reagents
or may be
useful for treating the sample. A reagent may be provided in a gaseous form
within the
sample vessel. The sample vessel may be sealed. The sample vessel may remain
sealed
before the sample is introduced into the sample vessel, after the sample has
been introduced
to the sample vessel, and/or while the sample is being introduced into the
sample vessel. In
one embodiment, the sample vessels may have smooth surfaces and/or round
bottoms. This
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is helpful to minimize the stress on the blood sample, especially during
centrifugation. Of
course, in alternative embodiments, other shapes of the bottom of the sample
vessel are not
excluded.
[00384] In
embodiments, a bodily fluid sample in a sealed sample vessel may retain
dissolved gases in the bodily fluid sample, such that sample stored in the
sealed sample vessel
retains a dissolved gas composition similar to or the same as that of bodily
fluid sample
freshly extracted from a subject's body or of a freshly prepared from a
different sample (e.g.
plasma freshly prepared from whole blood). In embodiments, a bodily fluid
sample in a
sealed sample vessel may retain at least 99%, 98%, 95%, 90%, 80%, 70%, 60%,
50%, 40%,
30%, or 20% of a dissolved gas over 10 minute, 20 minute, 30 minute, 45
minute, 1 hour, 2
hour, 4 hour, 6 hour, 8 hour, 12 hour, 16 hour, 24 hour, 48 hour, or 72 hour
time period. In
such embodiments, typically, the time period starts at the time of depositing
a sample into a
sample vessel or the time of sealing the sample vessel. To facilitate the
preservation of
dissolved gases in a bodily fluid sample, the sample may be stored in a sealed
sample vessel
at a selected temperature, such as, for example, 20 C, 15 C, 10 C, 4 C, or at
a freezing
temperature below 0 C. Other temperatures for sample storage are not excluded.
[00385]
Similarly, in embodiments, a bodily fluid sample in a sealed sample vessel
may retain analytes in the bodily fluid sample, such that sample stored in the
sealed sample
vessel retains an analyte composition similar to or the same as that of bodily
fluid sample
freshly extracted from a subject's body or of a freshly prepared bodily fluid
sample (e.g.
plasma freshly prepared from whole blood). In embodiments, a bodily fluid
sample in a
sealed sample vessel may retain at least 99%, 98%, 95%, 90%, 80%, 70%, 60%,
50%, 40%,
30%, or 20% of an analyte over 10 minute, 20 minute, 30 minute, 45 minute, 1
hour, 2 hour,
4 hour, 6 hour, 8 hour, 12 hour, 16 hour, 24 hour, or 48 hour time period. In
such
embodiments, typically, the time period starts at the time of depositing a
sample into a
sample vessel or the time of sealing the sample vessel. To facilitate the
preservation of one
or more analytes in a bodily fluid sample, the sample may be stored in a
sealed sample vessel
at a selected temperature, such as, for example, 20 C, 15 C, 10 C, 4 C, or at
a freezing
temperature below 0 C. Other temperatures for sample storage are not excluded.
Optionally,
a sample vessel may be centrifuged after a sample is introduced into the
vessel. For example,
a sample vessel may be centrifuged within 30 seconds, 1 minute, 2 minutes, 3
minutes, 4
minutes, 5 minutes, 10 minutes, 15 minutes, 20 minutes, 30 minutes, 45
minutes, 1 hour, 2
hours, 4 hours, 8 hours, 24 hours, 2 days, 3 days, 4 days, 5 days, 7 days, or
10 days of
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introduction of the sample into the vessel. Centrifuging a sample vessel
containing a sample
may, for example, in the case of a whole blood sample, facilitate the
separation of blood cells
from plasma, to yield plasma and pelleted cells. In some circumstances,
centrifuging a
sample increases the stability of one or more analytes in blood or plasma.
[00386] Figure 18F further shows that the sample vessels may each have at
least one
information storage unit associated with the sample vessels. Optionally, some
embodiments
may have one information storage unit convey information about a plurality of
sample
vessels, particularly (but not exclusively) in cases where the sample vessels
all contain
sample from the same subject. Such an information storage unit could be on the
carrier that
holds the multiple sample vessels, instead of being on the sample vessels
themselves.
1003871 Figure 18F shows a bottom-up view of an underside of one of the
sample
vessels that in one nonlimiting example, the information storage unit 1860 may
be at least
one of: a barcode (e.g., 1-D, 2-D, or 3-D), quick response (QR) code, image,
shape, word,
number, alphanumeric string, color, or any combination thereof, or any type of
visual
information storage unit. Others may use information storage units that are
not in the visible
spectrum. Others may use RFID tags, RF information storage units, IR emitting
tags, or
other markers that do not rely on identification through signals sent through
the visual
spectrum. Of course, the information storage unit 1860 may also be positioned
to be on a top
end surface of the sample vessel. Figure 18G shows that, optionally, an
information storage
unit 1860 may also be included on a side surface of the sample vessel. This
may be in
addition to or in place of the top or bottom positioned information storage
unit(s) 1860.
[00388] In one non-limiting example, information storage unit 1860 may be
used to
identify sample and/or types of sample in a sample collection device.
Optionally, there may
be one or more information storage units per sample vessel. Some may also use
information
storage units on the sample vessel holders. Information storage units may
identify the sample
collection device, one or more individual sample vessels within the device, or
components of
the device. In some instances, the sample collection device, a portion of the
sample
collection device, and/or the sample vessels may be transported. In one
example, the sample
collection device or a portion of the sample collection device, may be
transported via a
delivery service, or any other service described elsewhere herein. The sample
vessel may be
delivered so that one or more tests may be performed on the sample.
[00389] Optionally, the sample identity and/or the identity of the
individual who
provided the sample could be tracked. By way of non-limiting example,
information
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associated with the individual or individuals (e.g., name, contact
information, social security
number, birth date, insurance information, billing information, medical
history) and other
information of who provided the sample may be included. In some instances, the
type of
sample (e.g., whole blood, plasma, urine, etc.) may be tracked. Optionally,
the types of
reagents that the sample will have encountered (e.g., anticoagulants, labels,
etc.) could also
be tracked. Additional information about the sample collection, such as date
and/or time of
collection, circumstances under which sample was collected, types of tests to
be run on the
sample, setting(s) for the tests, test protocols, insurance information,
medical records
information, or any other type of information may be considered.
[00390] In at least one or more embodiments described herein, information
storage
units may assist with tracking such information. The information storage units
may be
associated with such information. Such information may be stored off-board the
sample
collection device, on-board the sample collection device, or any combination
thereof In
some instances, the information may be stored on one or more external devices,
such as
servers, computers, databases, or any other device having a memory. In some
instances, the
information may be stored on a cloud computing infrastructure. One or more
resources that
store the information may be distributed over the cloud, through the interne
from a remote
server, wireless to a remote computer processor, or the like. In some
instances, a peer-to-peer
infrastructure may be provided. The information may be stored in the
information storage
unit itself, or may be associated with the information storage unit elsewhere,
or any
combination thereof
[00391] Optionally, an information storage unit may provide unique
identification, or
may provide a high likelihood of providing unique identification. In some
instances, the
information storage unit may have a visible component. The information storage
unit may be
optically detectable. In some instances, the information storage unit may be
discernible using
visible light. In some examples, the information storage unit may be a barcode
(e.g., 1-D, 2-
D, or 3-D), quick response (QR) code, image, shape, word, number, alphanumeric
string,
color, or any combination thereof, or any type of visual information storage
unit.
[00392] In other embodiments, the information storage unit may be
optically
detectable via any other sort of radiation. For example, the information
storage unit may be
detectable via infrared, ultraviolet, or any other type of wavelength of the
electromagnetic
spectrum. The information storage unit may utilize luminescence, such as
fluorescence,
chemiluminescence, bioluminescence, or any other type of optical emission. In
some
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instances, the information storage unit may be a radio transmitter and/or
receiver. The
information storage unit may be a radiofrequency identification (RFID) tag.
The information
storage unit may be any type of wireless transmitter and/or receiver. The
information storage
unit may send one or more electrical signal. In some instances, GPS or other
location-related
signals may be utilized with the information storage unit.
1003931 Optionally, an information storage unit may be and/or include an
audio
component or acoustic component. The information storage unit may emit a sound
that may
be discernible to uniquely identify the identified component.
[00394] Optionally, the information storage unit may be detectable via an
optical
detection device. For example, a bar code scanner may be capable of reading
the information
storage unit. In another example, a camera (e.g., for still or video images)
or other image
capture device may be capable of capturing an image of the information storage
unit and
analyzing the image to determine the identification.
[00395] Optionally, the information storage units may be on the holder of
the sample
vessel(s). One or more indentation may be provided in the holder. The
information storage
unit may be located within the indentation. The indentations may be on the
bottom or side
surface of the holder. In some embodiments, the holder may include one or more
protrusion.
The information storage unit may be located on the protrusion. In some
instances, the
information storage units may be provided on an exterior surface of the
holder. The
information storage units may alternatively be positioned on an interior
surface of the holder.
The information storage units may be detected from outside the sample
collection device.
[00396] In some embodiments, the information storage units may be on an
exterior
surface of the sample vessels or an interior surface of the sample vessels.
The information
storage units may be detectable from outside the sample vessels. In some
embodiments, the
information storage units may be provided on a bottom surface of the sample
vessels.
[00397] In one non-limiting example, the holder may include an optically
transmissive
portion. The optically transmissive portion may be on a bottom of the holder
or a side of the
holder. For example, a transparent or translucent window may be provided. In
another
example, the optically transmissive portion may be a hole without requiring a
window. The
optically transmissive portion may permit a portion inside the holder to be
visible. The
information storage units may be provided on an exterior surface of the holder
on the
optically transmissive portion, an interior surface of the holder but may be
visible through the
optically transmissive portion, or on an exterior or interior surface of the
sample vessel but
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may be visible through the optically transmissive portion. In some instances,
the information
storage unit may be provided on an interior surface of the sample vessel, but
the sample
vessel may be optically transmissive so that the information storage unit is
viewable through
the sample vessel and/or optically transmissive portion.
[00398] Optionally, the information storage unit may be a QR code, bar
code, or other
optical information storage unit that may be optically visible, such as but
not limited to being
visible from outside the sample collection device. A QR code may be visible
through an
optical window, hole, or the like at the bottom of the holder of the sample
collection device.
The QR code may be provided on the sample collection device holder or on a
portion of the
sample vessel visible through the holder. An image capturing device, such as a
camera or
scanner may be provided external to the sample vessels or the transport
container, and may be
capable of reading the QR code.
[00399] In some embodiments, a single or a plurality of QR codes or other
information
storage units may be provided on a sample collection device. In some
instances, each sample
vessel may have at least one information storage unit, such as a QR code
associated with it.
In one example, at least one window may be provided in a holder per sample
vessel, and each
window may permit a user to view a QR code or other information storage unit.
For
example, two sample vessels may be housed within a holder, each of the sample
vessels
having an associated information storage unit discernible from outside the
holder.
[00400] In some embodiments, the information storage units may be provided
with
sample vessels housed by the holder. Separating the holder from the rest of
the sample
collection device may cause the sample vessels to be separated from the rest
of the sample
collection device. The sample vessels may remain within the holder or may be
removed from
the holder. The information storage units may remain with the sample vessels
even if they
are removed from the holder. Alternatively, the information storage units may
remain with
the holder even if sample vessels are removed. In some instances, both the
holder and sample
vessels may have information storage units so that the sample vessels and
holders may be
individually tracked and/or matched even when separated.
[00401] In some instances, any number of sample vessels may be provided
within the
sample collection device. Some embodiments may connect all of these sample
vessels to the
sample collection device all at once. Optionally, the sample vessels may be
coupled in a
sequential or other non-simultaneous manner. The sample vessels may be capable
of
receiving sample received from a subject. Each sample vessel may optionally
have a unique
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information storage unit. The unique information storage unit may be
associated with any
information relating to the sample, subject, device, or component of the
device.
[00402] In some instances, each information storage unit for each sample
vessel may
be unique or contain unique information. In other embodiments, the information
storage unit
on the sample vessel need not be unique. Optionally, some embodiments may have
information unique for the device, for the subject, and/or for the type of
sample. In some
embodiments, the information on the information storage unit may be used to
associate
several sample vessels with the same subject or the same information.
[00403] In some embodiments, the information storage unit is attached to
or otherwise
associated (physically or by non-physical association such as database pointer
or linkage)
with the sample vessel or groups of sample vessels at the collection
appointment. If
associated by group, the association can be based on all being from the same
user or other
factor as set forth herein. Optionally, some embodiments may have information
storage
units already on the sample vessels or groups of sample vessels. In one non-
limiting
example, the information storage unit provides identifier information that is
then associated
with the subject at or near the time of sample collection. In this example,
the information on
the information storage unit remains the same but is then linked to the
subject. In another
embodiment, the information on the information storage unit is changed to
include
information about the subject. Optionally, some embodiments may have both,
wherein some
information is changed and some is not (but may be then associated with the
subject or other
information about the collection event such as time date or the like).
[00404] Referring now to Figures 19A to 19C, various embodiments of a
front end of a
sample collection device will now be described. Figure 19A shows on view of a
front end of
the sample collection device with openings 1103 and 1105 for their respective
channels. In
the present embodiment, the openings 1103 and 1105 are placed in close
proximity to each
other with the divider wall 1910 between the openings 1103 and 1105. In one
non-limiting
example, the thickness of divider wall 1910 is set to be the minimum thickness
that can be
reliably formed through a manufacturing process used to form the sample
collection device.
In one embodiment, wall thickness should be about 1-10 mm. In some
embodiments, instead
of being side by side, the openings 1103 and 1105 may be in a top-bottom
configuration,
diagonal configuration, or other configuration where the two openings are in
close proximity
to one another.
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[00405] Referring now to Figure 19B, this embodiment shows the openings
1910 and
1912 configured to be coaxial, relative to one another. This coaxial
configuration of
openings 1910 and 1912 allows for greater overlap between the two openings.
[00406] Referring now to Figure 19C, this embodiment is similar to that of
Figure 19B
except that instead of square shaped openings, these openings 1920 and 1922
are round. It
should be understood that any variety of shapes may be used including but not
limited to
circular, elliptical, triangular, quadrilateral (e.g., square, rectangular,
trapezoidal), pentagonal,
hexagonal, octagonal, or any other cross-sectional shape. Of course, it should
be understood
that different shapes can be used for each opening and that a collection
device need not have
the same cross-sectional shape for all openings. Some embodiments may have a
one cross-
sectional shape for the opening but have a different cross-sectional shape for
channel
downstream from the opening.
Single Channel Sample Collection Device
[00407] Referring now to Figures 20A-20B, although the embodiments herein
are
typically described as sample collection devices with two separate channels,
it should be
understood that some embodiments may use a single entry channel 2010. This
single entry
channel 2010 may or may not be coated. Suitable coatings include but not are
limited to an
anti-coagulant, plasma, or other materials.
[00408] Figure 20A shows that in this embodiment of sample collection
device 2000, a
tissue penetrating member 2112 can be mounted coaxially within the single
entry pathway
2010. This allows the wound at the target tissue to be formed in a manner that
will be aligned
with the single entry pathway 2010. The tissue penetrating member 2012 can be
activated by
one of a variety of techniques such as but not limited to actuation upon
pressing a trigger,
actuation upon contact of the device front end with the target tissue, or by
pressure once the
device is pressed against the target tissue with sufficient pressure. After
actuation, the tissue
penetrating member 2012 can remain in the single entry pathway 2010.
Optionally, the tissue
penetrating member 2012 may retract out of the single entry pathway 2010.
[00409] The sample fluid entering the sample collection device 2000 may
split into
two or more separate pathways 2014 and 2016 from the single entry pathway
2010. This
enables the sample fluid to be split into at least two portions from a sample
collected from a
single point of contact. The two portions may optionally be held in two
separate holding
chambers 2018 and 2020. These chambers may each have one or more adapter
channels
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2022 and 2024 to transfer the sample fluid to the vessels such as but not
limited to vessels
1146a and 1146b. It should be understood that the holding chambers 2018 and
2020 and/or
the vessels 1146a and 1146b may contain anti-coagulant therein to prepare the
sample fluid
for processing.
[00410] Referring now to Figure 20B, this embodiment shows that the single
entry
pathway 2010 with a tissue penetrating member 2012 therein that, after
actuation, is
configured to remain in whole or in part within the single entry pathway 2010.
It should be
understood that this embodiment may use a solid penetrating member or one that
is hollow,
with a lumen therein.
[00411] Referring now to Figure 21, yet another embodiment of a sample
collection
device 2030 will now be described. This embodiment shows a reduced length
single entry
pathway 2032 with a tissue penetrating member 2012 configured to extend
outward from the
pathway 2032. After actuation, the tissue penetrating member 2012 may be in
the pathway
2032 or optionally, retracted to not be in the pathway 2032. The sample fluid
entering the
sample collection device 2030 may split into two or more separate pathways
2034 and 2036
from the single entry pathway 2032. This enables the sample fluid to be split
into at least two
portions from a sample collected from a single point of contact. This
embodiment shows that
the pathways 2034 and 2036 remain in capillary channel configuration and do
not enlarge to
become chambers such as the embodiments of Figures 20A-20B. It should be
understood
that any of the embodiments herein may include one or more fill indicators for
the collection
pathways and/or the vessels on the devices so that users can know when
sufficient fill levels
have been reached.
[00412] It should also be understood that due to the small sample volume
collected
with vessels such as but not limited to vessels 1146a and 1146b, the "pull"
from reduced
pressure, such as but not limited to vacuum pressure, in the vessels is
minimally or not
transferred into the body of subject in a manner that may collapse or
detrimentally reshape
the blood vessel or other lumen from which sample fluid is being collected.
For example,
pediatric and geriatric patients typically have small and/or weak veins that
can collapse when
traditional, large volume vacutainers are used, due the higher vacuum forces
associated with
drawing larger sample volumes into those traditional vessels. In at least one
embodiment of
the device, it will not have this problem because it will not impart a vacuum
(suction) force
on the vein. In one embodiment, the amount of vacuum force draws no more than
120 uL of
sample fluid into the vessel 1146a. Optionally, the amount of vacuum force
draws no more
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than 100 uL into the vessel 1146a. Optionally, the amount of vacuum force
draws no more
than 80 uL into the vessel 1146a. Optionally, the amount of vacuum force draws
no more
than 60 uL into the vessel 1146a. Optionally, the amount of vacuum force draws
no more
than 40 uL into the vessel 1146a. Optionally, the amount of vacuum force draws
no more
than 20 uL into the vessel 1146a. In one embodiment, this type of draw is
performed without
the use of a syringe and based primarily on pulling force from the vessels and
any force from
the fluid exiting the subject. Optionally, the shaped pathway through the
device to draw
sample that has reached an interior of the device can assist in reducing force
transfer from the
vessels 1146a and 1146b to the subject's blood vessel or other body lumen.
Some
embodiments may use about three-quarter vacuum or less in the small volume
vessels listed
above to minimize hemolysis of the sample and to prevent collapsing of blood
vessel in the
subject. Some embodiments may use about half vacuum or less in the small
volume vessels
listed above to minimize hemolysis of the sample and to prevent collapsing of
blood vessel in
the subject. Some embodiments may use about one quarter vacuum or less in the
small
volume vessels listed above to minimize hemolysis of the sample and to prevent
collapsing of
blood vessel in the subject. Vacuum herein is full vacuum, relative to
atmospheric pressure.
[00413] It should also be understood that, in one embodiment, the chamber
cross-
sectional area in the device is greater than the cross-sectional diameter of
the needle and/or
flexible tubing used for drawing the bodily fluid from the subject. This
further assists in
reducing the force transfer to the subject. The vacuum pull from the vessels
are drawing
most immediately on liquid sample in the device, not directly on sample in the
needle which
is more proximate to the subject. The longer pathway, buffered by the larger
volume
chamber in the collection device dampens the pull on the blood vessel in the
subject.
Additionally, the initial peak force pull is substantially less in a small
volume vessel versus a
larger volume vessel that is also under vacuum. The duration of the "pull" is
also longer to
enable the larger amount of sample to enter the vessel. In a smaller volume, a
significant
portion of the sample to be collected is already in the device and there is
less that is drawn
from the subject that is not already in the device prior to beginning the
sample pull.
[00414] Referring now to Figure 22, yet another embodiment of a sample
collection
device will now be described. This embodiment shows a collection device 2100
that has a
connector 2102 such as but not limited to Luer connector that allows for
connection to a
variety of sample acquisition devices such as a tissue penetrating member,
needle, or the like.
Some Luer connectors may use a press-fit to engage other connectors while some
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embodiments of the connector 2102 may include threads to facilitate
engagement. Figure 22
shows that in this current embodiment, a butterfly needle 2104 is coupled to a
fluid
connection pathway 2106 such as but not limited to a flexible tube that leads
to a connector
2108 to connect the sample acquisition features to the sample collection
device 2100. The
flexible tubing 2106 allows the needle portion 2104 to be located away from
but still
operably fluidly coupled to the sample collection device 2100. This allows for
greater
flexibility in terms of positioning of the needle 2104 to acquire sample fluid
without having
to also move the sample collection device 2100. Optionally, some embodiments
may directly
couple the tissue penetrating member to the device 2100 without the use of
flexible tubing.
[00415] At least some or all of the embodiments can have a fill indicator
such as but
not limited to a view window or opening that shows when sample is present
inside the
collection device and thus indicate that it is acceptable to engage the sample
vessel(s).
Optionally, embodiments that do not have a fill indicator are not excluded.
Some
embodiments may optionally include one or more vents, such as but not limited
to a port, to
allow air escape as the channels in the collection device are filled with
sample. In most
embodiments, the filled sample vessel(s) may be disconnected from the sample
collection
device after a desired fill level is reached. Optionally, additional sample
vessel(s) can be
engaged to the sample collection device to collect additional amounts of
bodily fluid sample.
Optionally, the interior conditions of the sample vessels are such that the
vessels has a
reduced pressure configure to draw in only a pre-determined amount of sample
fluid.
[00416] Figure 23 shows an exploded view of one embodiment of the sample
collection device 2100. In this non-limiting example, the portion 1130 may be
configured to
hold the vessel holder 1140 and the portion with sampling device holder 2160.
The device
2100 may include an anti-leakage device 2162 that can engage the open ends of
the adapter
channels 2022 and 2024 to minimize sample loss through the open ends until the
vessels in
holder 1140 are engaged to draw sample in any vessel(s) therein. In the
current embodiment,
the anti-leakage device 2162 covers at least two adapter channels 2022 and
2024 and is
configured to be movable. The present embodiment of anti-leakage device 2162
is sized so
that it can be moved to uncover the openings on adapter channels 2022 and 2024
while still
allowing the adapter channels 2022 and 2024 to engage the vessel(s) in the
holder 1140.
1004171 Referring now to Figures 24 and 25, one embodiment of the sampling
device
holder 2160 is shown in more detail. Figure 24 shows the sampling device
holder 2160 as an
assembled unit. Figure 25 shows an exploded view of the sampling device holder
2160 with
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a first portion 2164 and a second portion 2166. The adapter channels 2022 and
2024 are also
show as being removable from the second portion 2166. Although this embodiment
of the
sampling device holder 2160 is shown as two separate portions, it should be
understood that
some alternative embodiments can configure the sample device holder 2160 as a
single
unitary unit. Optionally, some embodiments may configure to have more than two
portions
that are assembled together to form the holder 2160. Optionally, some
embodiments may
create separate portions along a longitudinal axis 2165 or other axis of the
holder 2160,
instead of along a lateral axis of holder 2160 this is shown by the separation
in Figure 25.
1004181 Referring now to Figures 26 through 28, various cross-sectional
views of
embodiments of the sample device holder 2160 and the device 2100 are shown.
Figure 26
shows a cross-sectional view of the portions 2164 and 2166. Although not being
bound by
any particular theory, the use of the separation portions 2164 and 2166 can be
selected
simplify manufacturing, particularly for forming the various internal channels
and chambers
in the holder 2160. For example, at least one wall 2167 of the chamber can be
formed in the
first portion 2164 while complementary walls 2168 of the chamber can be formed
in the
second portion 2166. Figure 27 shows a top-down end view of the portion 2166
with the wall
2168 visible from the end view.
1004191 Referring now to Figure 28, a cross-sectional view of the
assembled device
2100 will now be described. This Figure 28 shows that sample entering the
device through
the connector 2102 will enter the common chamber 2170 before leading to the
adapter
channels 2022 and 2024. From the adapter channels 2022 and 2024, movement of
the holder
1140 in the direction indicated by arrow 2172 will operably fluidically couple
the vessels
1146a and 1146b to the adapter channels 2022 and 2024, moving sample from the
channels
into the vessels. In the present embodiment, there is sufficient space 2174 to
allow for
movement of the vessels 1146a and 1146b to have the adapter channels 2022 and
2024
penetrate the caps of the vessels 1146a and 1146b so that the adapter channels
2022 and 2024
are in fluid communication with the interior of the vessels 1146a and 1146b.
Although only
two vessel and adapter channel sets are shown in the figures, it should be
understood that
other configuration with more or less sets of vessels and adapter channels can
be configured
for use with a device such as that shown in Figure 28.
Modular Sample Collection Device
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[00420] Referring now to Figures 29A-29C, although the embodiments herein
typically describe sample collection device as having an adapter channel for
connecting the
sample collection channels with the vessels, it should be understood that
embodiments
without such configurations are not excluded.
[00421] By way of non-limiting example in Figure 29A, as previously
suggested
herein, some embodiments may be without a discrete, separate adapter channel.
Herein the
collection channel 2422 may connect directly to the vessel 2446 by way of
relative motion
between one or both of those elements as indicated by the arrow 2449.
[00422] By way of non-limiting example in Figure 29B, one or more adapter
channels
2454 may be discrete elements not initially in direct fluid communication with
either the
collection channel 2422 or the vessels 2446. Herein the collection channel
2422 may connect
to the vessel 2446 by way of relative motion between one or more of the
collection channel,
the adapter channel(s) 2454, or the vessel 2446 (sequentially or
simultaneously) to create a
fluid pathway from the collection channels through the one or more adapter
channels into the
vessels.
[00423] By way of non-limiting example in Figure 29C, one or more adapter
channels
2454 may be elements initially in contact with the vessels 2446. The adapter
channels 2454
may not be directly in communication with the interior or the vessels. Herein
the collection
channel 2400 may connect to the vessel by way of relative motion between one
or more of
those elements (sequentially or simultaneously) to create a fluid pathway from
the collection
channels through the one or more adapter channels into the vessels. Some
embodiments may
have a septum, sleeve, sleeve with vent, or cover 2455 over the end of the
collection channel
which will be engaged by the adapter channel. The engagement of the various
elements may
also move the adapter channel 2454 into the interior of the vessel 2446, as
initially, the
adapter channel 2454 may not be in fluid communication with the interior. Some
embodiments herein may have more than adapter channel and some embodiments may
use
adapter channels with pointed ends on both ends of the channel. There may be
variations and
alternatives to the embodiments described herein and that no single embodiment
should be
construed to encompass the entire invention.
[00424] It should be understood that any of the embodiments herein could
be modified
to include the features recited in the description for Figures 29A-29C.
Sample Processing
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1004251 Referring now to Figure 30, one embodiment of bodily fluid sample
collection
and transport system will now be described. Figure 30 shows a bodily fluid
sample B on a
skin surface S of the subject. In the non-limiting example of Figure 30, the
bodily fluid
sample B can be collected by one of a variety of devices. By way of non-
limiting example,
collection device 1530 may be but is not limited to those described in U.S.
Patent Application
Ser. No. 61/697,797 filed September 6, 2012, which is fully incorporated
herein by reference
for all purposes. In the present embodiment, the bodily fluid sample B is
collected by one or
more capillary channels and then directed into sample vessels 1540. By way of
non-limiting
example, at least one of the sample vessels 1540 may have an interior that is
initially under a
partial vacuum that is used to draw bodily fluid sample into the sample vessel
1540. Some
embodiments may simultaneously draw sample from the sample collection device
into the
sample vessels 1540 from the same or different collection channels in the
sample collection
device. Optionally, some embodiments may simultaneous draw sample into the
sample
vessels
[00426] In the present embodiment after the bodily fluid sample is inside
the sample
vessels 1540, the sample vessels 1540 in their holder 1542 (or optionally,
removed from their
holder 1542) are loaded into the transport container 1500. In this embodiment,
there may be
one or more slots sized for the sample vessel holder 1542 or slots for the
sample vessels in
the transport container 1500. By way of non-limiting example, they may hold
the sample
vessels in an arrayed configuration and oriented to be vertical or some other
pre-determined
orientation. It should be understood that some embodiments of the sample
vessels 1540 are
configured so that they hold different amount of sample in each of the
vessels. By way of
non-limiting example, this can be controlled based on the amount of vacuum
force in each of
the sample vessels, the amount of sample collected in the sample collection
channel(s) of the
collection device, and/or other factors. Optionally, different pre-treatments
such as but not
limited to different anti-coagulants or the like can also be present in the
sample vessels.
[00427] As seen in Figure 30, the sample vessels 1540 are collecting
sample at a first
location such as but not limited to a sample collection site. By way of non-
limiting example,
the bodily fluid samples are then transported in the transport container 1500
to a second
location such as but not limited to a receiving site such as but not limited
to an analysis site.
The method of transport may be by courier, postal delivery, or other shipping
technique. In
many embodiments, the transport may be implemented by having a yet another
vessel that
holds the transport container therein. In one embodiment, the sample
collection site may be a
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point-of-care. Optionally, the sample collection site is a point-of-service.
Optionally, the
sample collection site is remote from the sample analysis site.
[00428] Although the present embodiment of Figure 30 shows the collection
of bodily
fluid sample from a surface of the subject, other alternative embodiments may
use collection
techniques for collecting sample from other areas of the subject, such as by
venipuncture, to
fill the sample vessel(s) 1540. Such other collection techniques are not
excluded for use as
alternative to or in conjunction with surface collection. Surface collection
may be on exterior
surfaces of the subject. Optionally, some embodiments may collect from
accessible surfaces
on the interior of the subject. Presence of bodily fluid sample B on these
surfaces may be
naturally occurring or may occur through wound creation or other techniques to
make the
bodily fluid surface accessible.
[00429] Referring now to Figure 31, yet another embodiment is described
herein
wherein bodily fluid sample can be collected from an interior of the subject
versus collecting
sample that is pooled on a surface of the subject. This embodiment of Figure
31 shows a
collection device 1550 with a hypodermic needle 1552 that is configured to
collect bodily
fluid sample such as but not limited to venous blood. In one embodiment, the
bodily fluid
sample may fill a chamber 1554 in the device 1550 at which time sample
vessel(s) 1540 may
be engaged to draw the sample into the respective vessel(s). Optionally, some
embodiments
may not have a chamber 1554 but instead have very little void space other than
channel(s),
pathway(s), or tube(s) used to direct sample from the needle 1552 to the
sample vessel(s)
1540. For bodily fluid samples such as blood, the pressure from within the
blood vessel is
such that the blood sample can fill the chamber 1554 without much if any
assistance from the
collection device. Such embodiments may optionally include one or more vents,
such as but
not limited to a port, to allow air escape as the channels in the collection
device are filled
with sample. Optionally, some embodiments may have, instead of tubing
connection to a
needle, a direct needle attach to the collection device 1550, similar to that
shown in Figure 44
where the needle is rigidly or substantially rigidly connected to the
collection device. Some
embodiments may have a removable connection, a releasable connection, a Luer
connection,
a threaded connection, or other needle connection technique that may be
developed in the
future.
[00430] At least some or all of the embodiments can have a fill indicator
such as but
not limited to a view window or opening that shows when sample is present
inside the
collection device and thus indicate that it is acceptable to engage the sample
vessel(s) 1540.
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Optionally, embodiments that do not have a fill indicator are not excluded.
The filled sample
vessel(s) 1540 may be disconnected from the sample collection device after a
desired fill
level is reached. Optionally, additional sample vessel(s) 1540 can be engaged
to the sample
collection device 1550 (or 1530) to collect additional amounts of bodily fluid
sample.
Point of Service System
[00431] Referring now to Figure 32, it should be understood that the
processes
described herein may be performed using automated techniques. The automated
processing
may be used in an integrated, automated system. In some embodiments, this may
be in a
single instrument having a plurality of functional components therein and
surrounded by a
common housing. The processing techniques and methods for sedimentation
measure can be
pre-set. Optionally, that may be based on protocols or procedures that may be
dynamically
changed as desired in the manner described in U.S. patent applications Ser.
Nos. 13/355,458
and 13/244,947, both fully incorporated herein by reference for all purposes.
[00432] In one non-limiting example as shown in Figure 32, an integrated
instrument
2500 may be provided with a programmable processor 2502 which can be used to
control a
plurality of components of the instrument. For example, in one embodiment, the
processor
2502 may control a single or multiple pipette system 2504 that is movable X-Y
and Z
directions as indicated by arrows 2506 and 2508. The same or different
processor may also
control other components 2512, 2514, or 2516 in the instrument. In one
embodiment, tone of
the components 2512, 2514, or 2516 comprises a centrifuge.
[00433] As seen in Figure 32, control by the processor 2502 may allow the
pipette
system 2504 to acquire blood sample from cartridge 2510 and move the sample to
one of the
components 2512, 2514, or 2516. Such movement may involve dispensing the
sample into a
removable vessel in the cartridge 2510 and then transporting the removable
vessel to one of
the components 2512, 2514, or 2516. Optionally, blood sample is dispensed
directly into a
vessel already mounted on one of the components 2512, 2514, or 2516. In one
non-limiting
example, one of these components 2512, 2514, or 2516 may be a centrifuge with
an imaging
configuration to allow for both illumination and visualization of sample in
the vessel. Other
components 2512, 2514, or 2516 perform other analysis, assay, or detection
functions.
[00434] All of the foregoing may be integrated within a single housing
2520 and .
configured for bench top or small footprint floor mounting. In one example, a
small footprint
floor mounted system may occupy a floor area of about 4m2 or less. In one
example, a small
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footprint floor mounted system may occupy a floor area of about 3m2 or less.
In one example,
a small footprint floor mounted system may occupy a floor area of about 2m2 or
less. In one
example, a small footprint floor mounted system may occupy a floor area of
about 1m2 or
less. In some embodiments, the instrument footprint may be less than or equal
to about 4 m2,
3 m2, 2.5 m2, 2 m2, 1.5 m2, 1 m2, 0.75 m2, 0.5 m2, 0.3 m2, 0.2 m2, 0.1 m2,
0.08 m2, 0.05 m2,
0.03 m2, 100 cm2, 80 cm2, 70 cm2, 60 cm2, 50 cm2, 40 cm2, 30 cm2, 20 cm2, 15
cm2, or 10
cm2. Some suitable systems in a point-of-service setting are described in U.S.
patent
applications Ser. Nos. 13/355,458 and 13/244,947, both fully incorporated
herein by
reference for all purposes. The present embodiments may be configured for use
with any of
the modules or systems described in those patent applications.
[00435] Referring now to Figures 33 to 37, a still further embodiment of a
sample
collection device will now be described. As seen in Figures 33 and 34, at
least one
embodiment shows a sample collection region 2600 that has a capillary channel
region and
then a lower flow resistance region 2610 that increases the cross-sectional
area of the channel
to provide for lower flow resistance and increased flow rates. In at least one
embodiment,
this lower flow resistance region 2610 is still a capillary channel, but one
with lower flow
resistance. Optionally, other embodiments may increase the size wherein the
sample flows
therein but not under capillary action. The increased size of the channel can
also be used to
store sample therein. By way of non-limiting example, this storage can be
temporary during
collection, longer term such as for transport from collection site to
refrigeration, from
collection site to receiving site, other location to location transport, or
other purpose. One
embodiment can be configured to have caps that go on both ends of the device
so that sample
is contained therein without need for transferring to vessels 1146a and 1146b.
[00436] Because the joint between regions 2600 and 2610 can be located
across the
mid-line 2620, this can also reduce the amount of bonding material used to
join the items
together. It should be understood that embodiments can have channels 2612 and
2614 be of
the same cross-sectional size and/or be configured to contain the same or
substantially same
volume in the channel. Optionally, the channels 2612 and 2614 can be
configured to hold
different volumes. The same may be true for the channels as they continue into
region 2610.
Optionally, some embodiments may have different sizes when in region 2610
while have the
same in region 2600 or vice versa. Other configurations of sizes are not
excluded. Although
the channels here are shown as linear, it should be understood that for any of
embodiments
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disclosed herein, some embodiments may have curved or other non-straight
portion of the
channel(s).
[00437] The other parts are similar to those previously described herein
with regards to
the vessels 1146a and 1146b, adapter channels, frits, holders 130, etc...
Wicking of both
channels at the junction (both fill times < 6-secs) has been improved (step
removed) and
blood got in to the channel easily and passed the junction area without need
for tilting. The
parts may be made of PMMA, PET, PETG, etc... In this embodiment, this can
provide a
7.5x faster fill relative to a capillary channel of one cross-sectional size
because the increase
in size of channel in region 2610 will allow for easier flow into this region.
[00438] The flow resistance decreases to the fourth power in region 2610
based on
changes in channel size as seen in the formula:
n-pg aD3 H D41
=
3 2/1 p L 4 L
[00439] It should be understood that once a desired amount of sample is in
the
channel(s), some embodiments may be configured so that the sample can be
manipulated to
be moved into a storage vessel. By way of non-limiting example, this movement
of sample
can be by way of a pull force, a push force, or both. In one embodiment, pull
force may be
provided by a vessel that has vacuum therein, a vessel with a plunger or other
movable
surface that moves to increase volume and draw sample therein, or an active
vacuum force.
In one embodiment, push force can be pressure from air or other gas provided
from behind a
bolus or other fluid grouping. In embodiment, compressed gas, pressure from a
cap with a
seal around the device being slid over the collection device, a syringe
coupled to one end and
apply gas pressure, or other force can be exerted to urge gas forward. Force
being provided
may be different from the motive force used to collect the sample in the
channel(s).
Optionally, some embodiments may use, different motive force per channel.
Optionally,
some may use a different motive force in region 2600 relative to zone 2610.
[00440] While the teachings has been described and illustrated with
reference to
certain particular embodiments thereof, those skilled in the art will
appreciate that various
adaptations, changes, modifications, substitutions, deletions, or additions of
procedures and
protocols may be made without departing from the spirit and scope of the
invention. For
example, with any of the above embodiments, it should be understood that the
fluid sample
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may be whole blood, diluted blood, interstitial fluid, sample collected
directly from the
patient, sample that is on a surface, sample after some pre-treatment, or the
like. Those of
skill in the art will understand that alternative embodiments may have more
than one vessel
that may be sequentially operably coupled to the needle or opening of the
channel to draw
fluid in the vessel. Optionally, some embodiments may have the vessels
configured to
operably couple to the channels simultaneously. Some embodiments may integrate
a lancing
device or other wound creation device with the sample collection device to
bring targeted
sample fluid to a tissue surface and then collect the sample fluid, all using
a single device.
By way of nonlimiting example, a spring actuated, mechanically actuated,
and/or
electromechanically actuated tissue penetrating member may be mounted to have
a
penetrating tip exiting near an end of the sample collection device near
sample collection
channel openings so that the wound site that is created will also be along the
same end of the
device as the collection openings. Optionally, an integrated device may have
collection
openings on one surface and tissue penetrating elements along another surface
of the device.
In any of the embodiments disclosed herein, the first opening of the
collection channel may
have a blunt shape, which is configured to not readily puncture human skin.
[00441] Additionally, the use of heat patches on the finger or other
target tissue can
increase blood flow to the target area and thus increase the speed with which
sufficient blood
or other bodily fluid can be drawn from the subject. The heating is used to
bring the target
tissue to about 40C to 50C. Optionally, the heat brings target tissue to a
temperature range of
about 44 to 47C.
[00442] Furthermore, those of skill in the art will recognize that any of
the
embodiments as described herein can be applied to collection of sample fluid
from humans,
animals, or other subjects. Some embodiments as described herein may also be
suitable for
collection =of non-biological fluid samples. Some embodiment may use vessels
that are not
removable from the carrier. Some may have the fluid sample, after being
metered in the
sample collection portion, be directed by the second motive force to a
cartridge that is then
placed into an analyte or other analysis device. Optionally, it should be
understood although
many embodiments show the vessels in the carriers, embodiments where the
vessels are bare
or not mounted in carrier are not excluded. Some embodiments may have the
vessels that are
separate from the device and are only brought into fluid communication once
the channels
have reached minimum fill levels. For example, the vessels may be held in a
different
location and are only brought into contact by a technician once sufficient
amount of blood or
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sample fluid is in the sample collection device. At that time, the vessels may
be brought into
fluid communication simultaneously or sequentially to one or more of the
channels of the
sample collection device.
[00443] Additionally, concentrations, amounts, and other numerical data
may be
presented herein in a range format. It is to be understood that such range
format is used
merely for convenience and brevity and should be interpreted flexibly to
include not only the
numerical values explicitly recited as the limits of the range, but also to
include all the
individual numerical values or sub-ranges encompassed within that range as if
each
numerical value and sub-range is explicitly recited. For example, a size range
of about 1 nm
to about 200 nm should be interpreted to include not only the explicitly
recited limits of about
1 nm and about 200 nm, but also to include individual sizes such as 2 nm, 3
nm, 4 nm, and
sub-ranges such as 10 nm to 50 nm, 20 nm to 100 nm, etc....
Transport container
[00444] Referring now to Figures 38A-38B, an exploded perspective view is
shown of
one non-limiting example of a transport container 3200 provided in accordance
with one
embodiment described herein. It should be understood that the transport
container 3200 may
be configured to have one or more features of any other transport container
described
elsewhere herein. By way of non-limiting example, the transport container 3200
may be
useful for transporting one or more sample vessels therein. In some
embodiments, the
transport container 3200 provides a thermally controlled interior area to
minimize undesired
thermal decomposition of the sample during transport to another location, such
as but not
limited to an analysis facility. It should be understood that the transport
container may be
placed inside one or more other vessels during transport.
[00445] In one embodiment, the sample vessels may be provided from a
sample
collection device that collected the bodily fluid sample. By way of non-
limiting example, the
sample vessels may contain sample therein in liquid form. In most embodiments,
liquid form
also includes embodiments that are suspensions.
[00446] By way of non-limiting example, the transport container 3200 may
have any
dimension. In some instances, the transport container 3200 may have a total
volume of less
than or equal to about 1 m3, 0.5 m3, 0.1 m3, 0.05 m3, 0.01 m3, 1000 cm3, 500
cm3, 300 cm3,
200 cm3, 150 cm3, 100 cm3, 70 cm3, 50 cm3, 30 cm3, 20 cm3, 15 cm3, 10 cm3, 7
cm3, 5 cm3, 3
cm3, 2 cm3, 1.5 cm3, 1 cm3, 700 mm3, 500 mm3, 300 mm3, 100 mm3, 50 mm3, 30
mm3, 10
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mm3, 5 mm3, or 1 mm3. The footprint and/or a largest cross-sectional area of
the transport
container may be less than or equal to about 1 m2, 0.5 m2, 0.1 m2, 0.05 m2,
100 cm2, 70 cm2,
50 cm2, 30 cm2, 20 cm2, 15 cm2, 10 cm2, 7 cm2, 5 cm2, 3 cm2, 2 cm2, 1.5 cm2, 1
cm2, 70 mm2,
50 mm2, 30 mm2, 10 mm2, 5 mm2, or 1 mm2. In some instances, the transport
container may
have a dimension (e.g., height, width, length, diagonal, or circumference) of
less than or
equal to about 1 m, 75. cm, 50 cm, 30 cm, 25 cm, 20 cm, 15 cm, 12 cm, 10 cm, 9
cm, 8 cm, 7
cm, 6 cm, 5 cm, 4 cm, 3 cm, 2 cm, 1 cm, 0.7 cm, 0.5 cm, 0.3 cm, or 1 mm. In
some
instances, the largest dimension of the transport container may be no greater
than about 1 m,
75 cm, 50 cm, 30 cm, 25 cm, 20 cm, 15 cm, 12 cm, 10 cm, 9 cm, 8 cm, 7 cm, 6
cm, 5 cm, 4
cm, 3 cm, 2 cm, 1 cm, 0.7 cm, 0.5 cm, 0.3 cm, or 1 mm.
[00447] Optionally, the transport container may be lightweight. In some
embodiments,
the transport container may weigh less than or equal to about 10 kg, 5, kg, 4
kg, 3 kg, 2 kg,
1.5 kg, 1 kg, 0.7 kg, 0.5 kg, 0.3 kg. 100 g, 70 g, 50 g, 30 g, 20 g, 15 g, 10
g, 7 g, 5 g, 3 g, 2 g,
1 g, 500 mg, 300 mg, 200 mg, 100 mg, 70 mg, 50 mg, 30 mg, 10 mg, 5 mg, or 1
mg, with or
without the sample vessels having sample therein.
[00448] As seen in Figures 38A and 38B, one embodiment of the transport
container
may have a top cover 3210, a housing for a thermal regulating device 3220, one
or more
insert trays for the transport containers 3230a, 3230b, and a bottom plate
3240.
[00449] In one embodiment, the top cover 3210 has a substantially flat
shape although
other shapes are not excluded. The top cover 3210 may cover a thermal
regulating device
such as but not limited to heater or cooler contained in the transport
container. The top cover
may or may not have the same footprint as a housing 3220 for the thermal
regulating device.
A cooler, heater, or other thermal regulating device 3220 may be provided
within the
transport container 3200. Optionally, the device 3220 may be active or passive
units. The
thermal regulating device may keep the sample vessels within the transport
container 3200 at
a desired temperature or below a predetermined threshold temperature.
Optionally, the
thermal regulating device may be any temperature control unit known in the
art. Optionally,
the thermal regulating device may be capable of heating and/or cooling.
Optionally, the
thermal regulating device may be a thermoelectric cooler. Optionally, the
thermal regulating
device may be encased between the top cover and the housing for the cooler.
[00450] Optionally, the top cover and the housing may or may not form an
airtight
seal. The top cover and/or housing may be formed from a material with a
desired thermal
conductivity. For example, the housing 3220 may have a selectable thermal
conductivity. In
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one embodiment, the housing may include an embedded phase change material
(PCM) within
the box material, so the temperature is substantially uniform throughout. PCM
holds a very
good temperature profile. It is desirable not to have supercooling of the
sample, such as that
associated with ice, which may create a negative drop to -5 C. PCM can be
configured to
control to temperature ranges above freezing. By way of nonlimiting example,
thermal
conductivity may be in the range between about 100 - 250 W/m/K
(watts/meter/Kelvin).
Optionally, each sample vessel will come into contact with the PCM. Some
embodiments
may have one PCM for each layer. The PCM material may be flow molded into the
transport
container material. Optionally, there may be a chamber for the PCM material.
Optionally,
gaps in the tray may be filled with PCM. The PCM can provide a passive thermal
control
technique.
[00451] Optionally, the PCM may be incorporated into the injection molding
material.
In such an embodiment, the entire vessel may be a cooling medium. This can
also prevent
leakage of PCM from chambers in the transport container. Transport container
size can also
shrink when the PCM is directly integrated into the transport container
material. Energy
density is greater since storage capacity per mass is increased. Mixing
plastics with PCM
material can be configured to have both strength and cooling. By way of non-
limiting
example, 30% of the material may be PCM and the remainder is plastic for
rigidity. By way
of non-limiting example, between 20% to 40% of the material may be PCM while
the
remainder is another material such as but not limited to plastic for
mechanical rigidity. Some
embodiments may use a blow-molded outer that is filled with PCM or other
material. Inner
could be formed with a different technique as it is may not be critical for
the interior to be
cosmetically appealing. Optionally, cast molding or other lower temperature
molding
process could also be used in place of or in combination with injection
molding of the PCM
integrated transport container material. Embedded PCM could also be in the
trays. Some
embodiments could be a tray that is much more thermally conductive to achieve
even,
uniform cooling profile. Optionally, the PCM material is contained in a
chamber inside the
chassis of the transport container, wherein the wall of the chamber may be
thinner than wall
thickness of other areas of the shipping box chassis.
[00452] In one embodiment, the transport container 3200 may also have each
of the
trays 3230a and 3230b configured so that any information storage units on the
sample vessels
are easily readable without having to remove the sample vessels from the trays
3230a and
3230b. In one example, the holders have openings at the bottom that allow
information
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storage units on the bottom to be visualized while the sample vessels are
still in the trays
3230a and 3230b.
[00453] Figure 39 shows a plurality of views of the transport container
3200. Some
show that the sample vessel holders in the trays 3230a or 3230b may have open
bottoms such
that any information= storage unit, such as but limited to a barcode or other
information
storage unit, can be read from underneath or other orientation that does not
require that
sample vessels be removed from the transport container 3200. Optionally, only
certain
portions of the transport container 3200 such as but not limited to a layer, a
tray, or the like is
removed to obtain the desired information. Optionally, bar codes or other
information
storage units can be accessed through one or more openings in the tray. That
allows for bar
code scanning of very small transport container. Optionally, one could scan
rows of sample
vessels individually or can scan entire tray all at once. Optionally, a user
can see all sample
vessel holders. Optionally, a computer vision system can also scan to see if a
step such as
centrifugation was completed. This can be at either end of the shipping
process. The
computer vision system can visualize the sample vessel and determine if the
sample there is
in a form that confirms that a desired step was completed. If it detects an
error, the system
can inform the user or the system of the issue and/or re-perform the missing
and/or
incorrectly performed step. Optionally, the holders may have closed bottoms
and information
may be on the sides or other surfaces of the transport container 3200.
[00454] In some embodiments, the shapes of the holders may also be
designed to
follow the contours of the sample vessels 3134 therein to increase surface
area contact and
improve thermal control of the sample vessels. Optionally, thermal control of
the sample
vessels may occur through thermal transfer with tray and/or the PCM, but not
in direct
contact with the PCM. Optionally, some sample vessels 3134 could also be in
direct contact
with the vessel and/or the PCM. The openings for the sample vessels and/or the
holders may
be in linear rows, in a honeycomb pattern, or be in another pattern.
[00455] Referring now to Figures 40A and 40B, a transport container 3200
is shown
fully assembled. Figure 40B shows a plurality of sample vessels 3134 such as
those
associated with the sample collection device. The sample vessels 3134 can all
be from sample
associated with one subject in which case an information storage unit
associated with tray
3230a can be used to provide information about this group of samples.
Optionally, individual
sample vessels may still each have an information storage unit that is the
same as that of the
tray 3230a or they may each be unique. Some embodiments may insert sample
vessels from
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multiple subjects into the same tray 3230a. Optionally, some may only
partially fill each
tray. Some may fill each opening in the tray, but not every sample vessel will
have sample
therein (i.e. some may be empty sample vessels inserted to provide uniform
thermal profile).
These stackable trays 3230a may have closure devices that use elements such as
but not
limited to magnets, mechanical latches, or other coupling mechanisms to couple
trays
together. In some embodiments, magnets may be used to engage the tray holding
the sample
vessels to enable ease of opening during automation of loading and unloading.
Optionally,
the user cannot remove the tray from the transport container. Optionally, the
user cannot
remove the tray from the transport container without the use of a tool to
release the tray.
Some embodiments have a keying mechanism (magnetic or other technique). In
this manner,
the patient service center can put sample in but cannot take it out.
Optionally, some
embodiments can have shaped openings selected so that one cannot put the
sample vessels
and/or their holders in the wrong way to prevent user error.
[00456] In one embodiment, the loading and/or unloading may occur in a
temperature
regulated room or chamber to maintain samples in a desired temperature range.
In one
embodiment, it is desirable to have a temperature range between about 1 to 10
C.
Optionally, it is desirable to have the temperature range between about 2 to
8 C.
Optionally, it is desirable to have a temperature range between about 4 to 5
C. Optionally,
the materials of the trays 230a and 230b may be used to provide thermally
controlled
atmosphere for the sample vessels. Some use convection to control thermal
profile inside the
transport container 200.
[00457] Figure 40B also shows that in this particular embodiment, there may
be a
groove 3232 for an o-ring or other seal that can provide a tight connection
between layers of
the transport container. The system may also include closure mechanisms 3234
such as but
not limited magnetic closure devices to maintain the stackable insert tray in
the desired
position. It should also be understood that some embodiments may have through-
holes 3236
for wiring sensor(s) to detect conditions experienced the stackable insert
tray during
shipment.
[00458] Figure 40C shows various perspective views of the embodiment of
Figures
40A and 40B when the various components such the stackable trays and the lids
are joined
together to form the transport container 3200. As seen in Figure 40C, the
transport container
may be comprised of multiple layers of sample vessels or trays having sample
vessels.
Optionally, some embodiments may have only a single layer of sample vessels.
Some
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embodiments may use actively cooling or thermal control in one or more layers
of the
transport container 3200. By way of non-limiting example, one embodiment may
have a
thermo-electric cooler in the top layer. Optionally, some embodiments may use
a
combination of active and passive thermal control. By way of non-limiting
example, one
embodiment may have a thermal mass such as but not limited to a phase change
material
(PCM) that is already at a desired temperature. An active thermal control unit
may be
included to keep the PCM in the desired temperature range. Optionally, some
embodiments
may use only a thermal mass such as but not limited to a PCM to maintain
temperature in a
desired range.
Transport container with Removable Tray
[00459] Referring now to Figure 41, yet another embodiment of a transport
container
will now be described. Figure 41 shows a transport container 3300 having a
thermally-
controlled interior 3302 that houses a tray 3304 that can hold a plurality of
sample vessels
3306 in an array configuration, wherein each of the vessels 3306 holds a
majority of its
sample in a free-flowing, non-wicked form and wherein there is about 1 ml or
less of sample
fluid in each of the vessels. Optionally, there is about 2 ml or less of
sample fluid in each of
the vessels. Optionally, there is about 3 ml or less of sample fluid in each
of the vessels. In
one non-limiting example, the vessels are arranged such that there are at
least two vessels in
each transport container with sample fluid from the same subject, wherein at
least a first
sample includes a first anticoagulant and a second sample includes a second
anticoagulant in
the matrix.
[00460] Although Figure 41 shows the sample vessels 3306 are held in an
array
configuration, other predetermined configurations are not excluded. Some may
place the
sample vessels into hinged, swinging, or other retaining mechanism in the tray
that may allow
for motion in one or two degrees of freedom. Some embodiments may place the
sample
vessels into a device that has first configuration during loading and then
assumes a second
configuration to retain the sample vessels during transport. Some embodiments
may place
the sample vessels into a material that has first material property during
loading and then
assumes a second property such as but not limited to hardening to retain the
sample vessels
during transport.
[00461] In some embodiments, the sample vessels are in holders 3310 and
the tray
3304 defines openings and/or cavities sized to fit the holders 3310 and not
the sample vessels.
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By way of non-limiting example, the holders 3310 can be used to keep
associated vessels
3306 physically together while in the tray 3304. Some embodiments have the
holders 3310
directly contacting the tray 3304 so that the vessels are protected from
direct contact with the
tray 3304. In one non-limiting example, the tray can hold at least 100
vessels, or optionally,
at least 50 holders each having two vessels.
[00462] Referring still to Figure 41, this embodiment of transport
container 3300 may
have some retaining mechanism 3320 such as but not limited to clips, magnetic
areas, or the
like to hold the tray 3306. The retaining mechanism 3320 may be configured to
hold the tray
3304 in a manner releasable when desired. Optionally, the retaining mechanism
3320 may be
configured to hold the tray 3304 in an un-releasable manner. In the embodiment
shown in
Figure 41, the retaining mechanism 3320 is shown as magnetic and/or metallic
members in
tray 3304 that are attracted to metal and/or magnetic members in the transport
container
3300. When the transport container 3300 arrives at a processing facility, the
tray 3304 may
be configured to be removed from the transport container 3300. This can occur
by use of one
or more techniques including but not limited to using strong magnets to engage
the magnetic
and/or metallic members in tray 3304. Some embodiments may use grippers,
hooks, or other
mechanical mechanisms to remove the tray 3304 from the transport container
3300. Some
embodiments may use a combination of techniques to remove the tray 3304. It
should also
be understood that some embodiments may opt to remove the vessels 3306 and/or
the holders
3310 while the tray 3304 remains in the transport container 3300. Some
techniques may
perform at two or more of the foregoing techniques.
[00463] It should also be understood that the transport container 3300 may
itself be a
cooling device, comprising a thermal control material such as but not limited
to ice, a PCM,
or the like. Other embodiments may directly integrate the thermal control
material into the
material used to form the transport container 3300. As seen in Figure 41, some
embodiments
of the transport container 3300 may have a substantial void space 3324 in
which one or more
the thermal control material is housed or integrated therein.
[00464] Referring still to Figure 41, the transport container 3300 may
also include
openings 3330 for attachment of hinges or other connection devices for covers
or connections
to other layers of the transport container 3300. For ease of illustration, the
cover and/or
connections to the cover or other layer are not shown in Figure 41. Although
some
embodiments may only use a single layer, it should be understood that multi-
layer
embodiments are not excluded.
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[00465] Referring now to Figure 42, an exploded perspective view of yet
another
embodiment of a transport container 3400 will now be described. The embodiment
of Figure
42 is designed to hold a tray 3402 in the transport container interior 3404.
The exploded
perspective view shows a plurality of vessels 3406 in holders 3410 in a tray
3402. The tray
3402 may be configured to have some or all portions of the retention mechanism
3420 similar
to retention mechanisms 3320 in the tray 3402. It should also be understood
that the tray
3402 may have one or more cutouts, protrusions, or features to allow the tray
3402 to be
inserted into the interior in a limited number of pre-determined orientations.
Some
embodiments may be configured to only enable one orientation of the tray in
the vessel.
Some embodiments may be configured to only enable two possible orientations of
the tray in
the vessel.
[00466] Figure 42 shows that in one embodiment, the transport container
3400 may be
formed from two separate pieces 3430 and 3432. Optionally, some embodiment may
be
formed from three or more pieces. Optionally, some embodiment may be a single
piece. The
pieces 3430 and 3432 can have openings that filled by plugs 3434 and 3436. The
interior
3438 of the transport container 3400 can retain a thermal control material
such as but not
limited to ice, a phase change material, or the like. Other embodiments may
directly integrate
the thermal control material into the material used to form the transport
container 3400.
[00467] In one instance, the interior 3433 of the piece 3432 can be filled
with a thermal
control material such as but not limited to a PCM. Optionally, one embodiment
could use an
active thermal control material such as but not limited to a thermoelectric
cooler to cool the
interior.
[00468] Referring now to Figure 43, yet another embodiment of the
transport container
3500 will now be described. Figure 43 shows that the transport container 3500
may include a
lid 3502 for covering the features and/or sample vessels therein. In some
embodiments, the
lid 3502 may contain thermal insulating material. Optionally, the lid 3502 may
include a
thermal control unit to assist in keeping the interior of the transport
container 3500 within a
desired temperature range. Optionally, some embodiments may configure lid 3502
to be a
thermally conductive material that can be useful in keeping the interior of
the transport
container 3500 within a desired temperature range through thermal transfer
from an external
thermal control source. By way of non-limiting example, the thermal control
source may be
a cooling source, a heating source, a thermoelectric heat exchanger, or other
thermal control
device. It should also be understood that similar thermal control source such
as but not
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limited to a PCM or an active cooling device can also be included in the void
space 3514
below the layer 3516.
[00469] It should be understood that the features 3512 for retaining
holders 3310,
3410, or other shaped holders for the vessels may be in a piece separate from
the transport
container or they can be integrally formed inside of the transport container.
Optionally, the
features 3512 can be part of a tray such as the trays 3302 and 3402 shown in
Figures 41 and
42. Such a tray can be fixed or removable from the transport container 3500.
Retaining
mechanisms 3520 may also be incorporated into the tray to allow it to be held
in place during
transport.
Sample Collection and Transport
[00470] In embodiments, provided herein are systems and methods for
collection or
transport of small volumes of bodily fluid sample.
[00471] In embodiments, a sample vessel containing a small volume of
bodily fluid
sample may be transported. The sample and sample vessel may have any of the
respective
characteristics described elsewhere herein. In embodiments, a sample vessel
may contain
less than or equal to 5 ml, 3 ml, 4 ml, 2 ml, 1.5 ml, 1 ml, 750 1, 500 1,
400 1, 300 1, 200
1, 150 1, 100 1, 75 I, 50 ;Al, 40 1, 30 1, 20 1, 10 1, or 5 .1 bodily
fluid sample. In
embodiments, a sample vessel may have an interior volume of less than or equal
to 5 ml, 3
ml, 4 ml, 2 ml, 1.5 ml, 1 ml, 750 1, 500 1, 400 1, 300 1, 200 1, 150 1,
100 1, 75 1, 50
1, 40 1, 30 1, 20 1, 10 1, or 5 I. In embodiments, a sample vessel may
have an interior
volume of less than or equal to 5 ml, 4 ml, 3 ml, 2 ml, 1.5 ml, 1 ml, 750 1,
500 1, 400 1,
300 1, 200 1, 150 I, 100 1, 75 1, 50 1, 40 ;Al, 30 1, 20 1, 10 ?Al, or
5 1, and may
contain bodily fluid sample which fills at least 10 %, 20 %, 30 %, 40 %, 50 %,
60 %, 70 %,
80 %, 90 %, 95 %, 98 %, 99 %, or 100% of the interior volume of the vessel. In
embodiments, the sample vessel may be sealed, for example, with a cap, lid, or
membrane.
Any of the vessel interior dimensions or sample dimensions described herein
may apply to
the interior dimensions of a sealed sample vessel, or to the dimensions of a
sample therein,
respectively. In embodiments, a sealed sampje vessel may have an interior
volume of less
than or equal to 5 ml, 4 ml, 3 ml, 2 ml, 1.5 ml, 1 ml, 750 IA, 500 1, 400 1,
300 1, 200 I,
150 1, 100 1, 75 j.d, 50 IA, 40 I, 30 1, 20 1, 10 I, or 5 1, and it may
contain bodily fluid
sample which fills at least 10 %, 20 %, 30 %, 40 %, 50 %, 60 %, 70 %, 80 %, 90
%, 95 %, 98
%, 99 %, or 100% the interior volume of the vessel, such that less than or
equal to 2 ml, 1.5
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ml, 1 ml, 750 1, 500 pl, 400 p.1, 300 I, 200 I, 150 1, 100 IA, 75 p.1, 50
I, 40 1, 30 1, 20
1, 10 1, 5 IA, 4 I, 3 ill, 2 1, or 1 1 of air is present in the interior
volume of the sealed
vessel. Thus, for example, a sealed sample vessel may have an interior volume
of less than or
equal to 300 1 and it may contain bodily fluid sample which fills at least
90% of the interior
volume of the vessel, such that less than or equal to 30 ul of air is present
in the interior
volume of the sealed vessel. In another example, a sealed sample vessel may
have an interior
volume of less than or equal to 500 1 and it may contain bodily fluid sample
which fills at
least 80% of the interior volume of the vessel, such that less than or equal
to 100 ul of air is
present in the interior volume of the sealed vessel. In another example, a
sealed sample
vessel may have an interior volume of less than or equal to 150 I and it may
contain bodily
fluid sample which fills at least 98% of the interior volume of the vessel,
such that less than
or equal to 3 pl of air is present in the interior volume of the sealed
vessel.
[00472] In embodiments, sample vessels containing a sample may also
contain an
anticoagulant. The anticoagulant may be dissolved in the sample or otherwise
present in the
vessel (e.g. dried on one or more interior surfaces of the vessel or in solid
form at the bottom
of the vessel). A sample vessel containing a sample may have a "total
anticoagulant
content", wherein the total anticoagulant content is the total amount of
anticoagulant present
in the interior volume of the vessel, and includes anticoagulant dissolved in
the sample (if
any), as well as anticoagulant in the vessel which is not dissolved in the
sample (if any). In
embodiments, a sample vessel containing a sample may contain no more than 1 ml
sample
and have a total anticoagulant content of no more than 3 mg EDTA, may contain
no more
than 750 1 sample and have a total anticoagulant content of no more than 2.3
mg EDTA,
may contain no more than 500 I sample and have a total anticoagulant content
of no more
than 1.5 mg EDTA, may contain no more than 400 IA sample and have a total
anticoagulant
content of no more than 1.2 mg EDTA, may contain no more than 300 p.1 sample
and have a
total anticoagulant content of no more than 0.9 mg EDTA, may contain no more
than 200 I
sample and have a total anticoagulant content of no more than 0.6 mg EDTA, may
contain no
more than 150 I sample and have a total anticoagulant content of no more than
0.45 mg
EDTA, may contain no more than 100 I sample and have a total anticoagulant
content of no
more than 0.3 mg EDTA, may contain no more than 75 1 sample and have a total
anticoagulant content of no more than 0.23 mg EDTA, may contain no more than
50 I
sample and have a total anticoagulant content of no more than 0.15 mg EDTA,
may contain
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no more than 40 ttl sample and have a total anticoagulant content of no more
than 0.12 mg
EDTA, may contain no more than 30 i..t1 sample and have a total anticoagulant
content of no
more than 0.09 mg EDTA, may contain no more than 20 1 sample and have a total
anticoagulant content of no more than 0.06 mg EDTA, may contain no more than
10 til
sample and have a total anticoagulant content of no more than 0.03 mg EDTA, or
may
contain no more than 5 [t1 sample and have a total anticoagulant content of no
more than
0.015 mg EDTA. In embodiments, a sample vessel containing a sample may contain
no more
than 1 ml sample and have a total anticoagulant content of no more than 2 mg
EDTA, may
contain no more than 750 ttl sample and have a total anticoagulant content of
no more than
1.5 mg EDTA, may contain no more than 500 1 sample and have a total
anticoagulant
content of no more than 1 mg EDTA, may contain no more than 4001.11 sample and
have a
total anticoagulant content of no more than 0.8 mg EDTA, may contain no more
than 300 [t1
sample and have a total anticoagulant content of no more than 0.6 mg EDTA, may
contain no
more than 200 1 sample and have a total anticoagulant content of no more than
0.4 mg
EDTA, may contain no more than 150 jtl sample and have a total anticoagulant
content of no
more than 0.3 mg EDTA, may contain no more than 100 ill sample and have a
total
anticoagulant content of no more than 0.2 mg EDTA, may contain no more than 75
jtl sample
and have a total anticoagulant content of no more than 0.15 mg EDTA, may
contain no more
than 50 [t1 sample and have a total anticoagulant content of no more than 0.1
mg EDTA, may
contain no more than 40 Ill sample and have a total anticoagulant content of
no more than
0.08 mg EDTA, may contain no more than 30 jtl sample and have a total
anticoagulant
content of no more than 0.06 mg EDTA, may contain no more than 20 jtl sample
and have a
total anticoagulant content of no more than 0.04 mg EDTA, may contain no more
than 10 1
sample and have a total anticoagulant content of no more than 0.02 mg EDTA, or
may
contain no more than 5 ttl sample and have a total anticoagulant content of no
more than 0.01
mg EDTA. In embodiments, a sample vessel containing a sample may contain no
more than
1 ml sample and have a total anticoagulant content of no more than 30 US
Pharmacopeia
(USP) units heparin, may contain no more than 750 ttl sample and have a total
anticoagulant
content of no more than 23 USP units heparin, may contain no more than 500 jtl
sample and
have a total anticoagulant content of no more than 15 USP units heparin, may
contain no
more than 400 jtl sample and have a total anticoagulant content of no more
than 12 USP units
heparin, may contain no more than 300 pi sample and have a total anticoagulant
content of no
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more than 9 USP units heparin, may contain no more than 200 1 sample and have
a total
anticoagulant content of no more than 6 USP units heparin, may contain no more
than 150 I
sample and have a total anticoagulant content of no more than 4.5 USP units
heparin, may
contain no more than 100 I sample and have a total anticoagulant content of
no more than 3
USP units heparin, may contain no more than 75 I sample and have a total
anticoagulant
content of no more than 2.3 USP units heparin, may contain no more than 50 1
sample and
have a total anticoagulant content of no more than 1.5 USP units heparin, may
contain no
more than 40 1 sample and have a total anticoagulant content of no more than
1.2 USP units
heparin, may contain no more than 30 I sample and have a total anticoagulant
content of no
more than 0.9 USP units heparin, may contain no more than 20 .1 sample and
have a total
anticoagulant content of no more than 0.6 USP units heparin, may contain no
more than 10 1
sample and have a total anticoagulant content of no more than 0.3 USP units
heparin, or may
contain no more than 5 1 sample and have a total anticoagulant content of no
more than 0.15
USP units heparin. In embodiments, a sample vessel containing a sample may
contain no
more than 1 ml sample and have a total anticoagulant content of no more than
15 USP units
heparin, may contain no more than 750 1 sample and have a total anticoagulant
content of no
more than 11 USP units heparin, may contain no more than 500 1 sample and
have a total
anticoagulant content of no more than 7.5 USP units heparin, may contain no
more than 400
I sample and have a total anticoagulant content of no more than 6 USP units
heparin, may
contain no more than 300 1 sample and have a total anticoagulant content of
no more than
4.5 USP units heparin, may contain no more than 200 1 sample and have a total
anticoagulant content of no more than 3 USP units heparin, may contain no more
than 150 1
sample and have a total anticoagulant content of no more than 2.3 USP units
heparin, may
contain no more than 100 I sample and have a total anticoagulant content of
no more than
1.5 USP units heparin, may contain no more than 75 1 sample and have a total
anticoagulant
content of no more than 1.2 USP units heparin, may contain no more than 50 1
sample and
have a total anticoagulant content of no more than 0.75 USP units heparin, may
contain no
more than 40 1 sample and have a total anticoagulant content of no more than
0.6 USP units
heparin, may contain no more than 30 I sample and have a total anticoagulant
content of no
more than 0.45 USP units heparin, may contain no more than 20 1 sample and
have a total
anticoagulant content of no more than 0.3 USP units heparin, may contain no
more than 10 1
sample and have a total anticoagulant content of no more than 0.15 USP units
heparin, or
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may contain no more than 5 [t1 sample and have a total anticoagulant content
of no more than
0.08 USP units heparin.
[00473] In embodiments, two or more sample vessels containing sample from
a single
subject may be obtained or transported. When two or more sample vessels
containing sample
from a single subject are obtained or transported, the two or more sample
vessels may be
stored or transported in a vessel that does or does not contain samples from
other subjects. In
embodiments, at least 2, 3, 4, 5, 6, 7, 8, 9, or 10 sample vessels containing
sample from a
single subject may be obtained or transported. In embodiments, no more than 2,
3, 4, 5, 6, 7,
8, 9, or 10 sample vessels containing sample from a single subject may be
obtained or
transported. In embodiments, at least 2, 3, 4, 5, 6, 7, 8, or 9 sample vessels
and no more than
3, 4, 5, 6, 7, 8, 9, or 10 sample vessels containing sample from a single
subject may be
obtained or transported. In embodiments involving two or more sample vessels
containing
sample from the same subject, the sample in each sample vessel may be obtained
from a
subject at the same or at different times. In some embodiments involving two
or more
sample vessels containing sample from the same subject, the sample in each
sample vessel
may be from the same location or source site on the subject. For example, two
sample
vessels containing whole blood from the same subject may be obtained, in which
both sample
vessels contain whole blood from the same fingerstick site. In other
embodiments involving
two or more sample vessels containing sample from the same subject, the sample
in each
sample vessel be from a different location / source site on the subject. For
example, two
sample vessels containing whole blood from the same subject may be obtained,
in which one
sample vessel contains whole blood from a first fingerstick site (e.g. on a
first digit) and a
second sample vessel contains whole blood from a second fingerstick site (e.g.
on a second
digit). In embodiments involving two or more sample vessels containing sample
from a
single subject, the two or more sample vessels may contain different types of
anticoagulants
or other blood additives. For example, a first sample vessel may contain whole
blood with
EDTA and a second sample vessel may contain whole blood with heparin, wherein
the
samples are from the same subject. In another example, a first and second
sample vessel may
contain whole blood with EDTA and a third sample vessel may contain whole
blood with
heparin, wherein the samples are from the same subject. In another example, a
first sample
vessel may contain whole blood with EDTA, a second sample vessel may contain
whole
blood with heparin, and a third sample vessel may contain whole blood with
sodium citrate,
wherein the samples are from the same subject. In embodiments involving two or
more
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sample vessels containing sample from a single subject, the two or more sample
vessels may
contain different types of sample from the subject. For example, a first
sample vessel may
contain whole blood and a second sample vessel may contain plasma from the
same subject.
In another example, a first sample vessel may contain whole blood and a second
sample
vessel may contain urine from the same subject. In another example, a first
and second
sample vessel may contain whole blood and a third sample vessel may contain
saliva from
the same subject.
[00474] In systems and methods provided herein, a total volume of bodily
fluid sample
may be obtained from a subject. The total volume of bodily fluid sample may be
transferred
into a single sample vessel, or into two or more sample vessels. For example,
a total volume
of 500 microliters of bodily fluid sample may be obtained from a subject, and
it may be
transferred into a single sample vessel, wherein the single sample vessel has
a maximum
interior volume of 600 microliters. In another example, a total volume of 500
microliters of
bodily fluid sample may be obtained from a subject, and it may be transferred
into a two
sample vessels, wherein each sample vessel has a maximum interior volume of
300
microliters. In another example, a total volume of 500 microliters of bodily
fluid sample
may be obtained from a subject, and it may be transferred into a two sample
vessels, wherein
one sample vessel has a maximum interior volume of 400 microliters and one
sample vessel
has a maximum interior volume of 100 microliters. In systems and methods
provided herein,
a total volume of bodily fluid sample of less than or equal to 5 ml, 4 ml, 3
ml, 2 ml, 1.5 ml, 1
ml, 750 1, 500 I, 400 1, 300 I, 200 I, 150 1, 100 1, 75 1, 50 1, 40
1, 30 1, 20 1, 10
I, 5 j.tl or 1 1 may be obtained from a subject. The total volume of bodily
fluid sample from
the subject may be divided between 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or more
sample vessels, as
described elsewhere herein. When a total volume of a bodily fluid sample from
a subject is
divided between two or more sample vessels, portions of the total volume of
bodily fluid
sample in some or all of the different sample vessels may contain different
anticoagulants or
other additives. For example, a total volume of 500 microliters of bodily
fluid sample may be
obtained from a subject, and it may be transferred into a two sample vessels,
wherein one
sample vessel contains 250 microliters of the bodily fluid sample mixed with
EDTA, and one
sample vessel contains 250 microliters of the bodily fluid sample mixed with
heparin.
Typically, as used herein, a total volume of bodily fluid sample refers to a
single type of
bodily fluid sample ¨ e.g. whole blood or urine or saliva, etc.
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[00475] In embodiments, a sample vessel containing whole blood may be
centrifuged
before it is stored or shipped, such that the whole blood is separated into
plasma and pelleted
cells in the sample vessel before it is shipped. In other embodiments, a
sample vessel
containing whole blood is not centrifuged before it is stored or shipped.
[00476] In some embodiments of systems and methods provided herein, a
bodily fluid
sample may be dried after it is collected and before it is transported. In
embodiments, a dried
sample may later be reconstituted into liquid form, such as at a time of
analysis or processing
of the sample.
[00477] In embodiments of systems and methods provided herein, a sample
vessel may
be transported from a first location to a second location. A first location
may be a location
where a sample is collected from a subject, and a second location may be a
location where
one or more steps are performed for processing or analyzing the sample. The
sample and
sample vessel may have any of the respective characteristics described
elsewhere herein. For
example, the sample may be in a liquid, non-matrixed, non-wicked form. The
sample vessel
may be transported in a transport container as described herein or other
structure. For
example in some optional embodiments, a sample vessel may be transported in a
bag, pouch,
envelope, box, capsule, or other structure. In embodiments, the first location
and the second
location may be within the same room, building, campus, or collection of
buildings. In
embodiments, a first location and second location may be separated by at least
1 meter, 5
meters, 10 meters, 50 meters, 100 meters, 500 meters, 1 kilometer, 5
kilometers, 10
kilometers, 15 kilometers, 20 kilometers, 30 kilometers, 50 kilometers, 100
kilometers, or
500 kilometers. In embodiments, a first location and second location may be
separated by no
more than 5 meters, 10 meters, 50 meters, 100 meters, 500 meters, 1 kilometer,
5 kilometers,
kilometers, 15 kilometers, 20 kilometers, 30 kilometers, 50 kilometers, 100
kilometers,
500 kilometers, or 1000 kilometers. In embodiments, a first location and
second location
may be separated by at least 1 meter, 5 meters, 10 meters, 50 meters, 100
meters, 500 meters,
1 kilometer, 5 kilometers, 10 kilometers, 15 kilometers, 20 kilometers, 30
kilometers, 50
kilometers, 100 kilometers, or 500 kilometers and no more than 5 meters, 10
meters, 50
meters, 100 meters, 500 meters, 1 kilometer, 5 kilometers, 10 kilometers, 15
kilometers, 20
kilometers, 30 kilometers, 50 kilometers, 100 kilometers, 500 kilometers, or
1000
kilometers. In embodiments in which a first location is a location where a
sample is obtained
from a subject, a sample vessel may be transported from a first location to a
second location
within 48 hours, 36 hours, 24 hours, 12 hours, 8 hours, 6 hours, 4 hours, 3
hours, 2 hours, 1
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hour, 45 minutes, 30 minutes, 15 minutes, 10 minutes, 5 minutes, 1 minute, or
30 seconds of
collection of the sample from the subject.
[00478] As used herein, a "sample receiving site" is a place where a
transported
sample may be received, and wherein one or more steps may be performed with
the sample.
For example, a sample which arrives at a sample receiving site may be
processed, analyzed,
or handled at the sample receiving site, for example, as part of a test or
assay with the sample.
A sample may be transported, for example, in any vessel or device as described
herein. In
embodiments, a sample receiving site may contain one or more sample processing
devices,
which may be used for processing or analyzing the sample. A sample processing
device may
be as described in, for example, U.S. Pat. App. Ser. No. 13/244,947 filed
Sept. 26, 2011, or as
in any other document incorporated by reference elsewhere herein. During the
transport of a
sample from a sample collection site to a sample receiving site, the sample
may pass through
any number of locations. In embodiments, a first location may be a sample
collection site
and a second location may be a sample receiving site.
[00479] Referring now to Figure 44, one embodiment of bodily fluid sample
collection
and transport will now be described. Figure 44 shows a bodily fluid sample B
on a skin
surface S of the subject. In the non-limiting example of Figure 44, the bodily
fluid sample B
can be collected by one of a variety of devices. By way of non-limiting
example, collection
device 3530 may be but is not limited to those described in U.S. Patent
Application Ser. No.
61/697,797 filed September 6, 2012, which is fully incorporated herein by
reference for all
purposes. In the present embodiment, the bodily fluid sample B is collected by
one or more
capillary channels and then directed into sample vessels 3540. By way of non-
limiting
example, at least one of the sample vessels 3540 may have an interior that is
initially under a
partial vacuum that is used to draw bodily fluid sample into the sample vessel
3540. Some
embodiments may simultaneously draw sample from the sample collection device
into the
sample vessels 3540 from the same or different collection channels in the
sample collection
device. Optionally, some embodiments may simultaneous draw sample into the
sample
vessels
[00480] In the present embodiment after the bodily fluid sample is inside
the sample
vessels 3540, the sample vessels 3540 in their holder 3542 (or optionally,
removed from their
holder 3542) are loaded into the transport container 3500. In this embodiment,
there may be
one or more slots sized for the sample vessel holder 3542 or slots for the
sample vessels in
the transport container 3500. By way of non-limiting example, they may hold
the sample
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vessels in an arrayed configuration and oriented to be vertical or some other
pre-determined
orientation. It should be understood that some embodiments of the sample
vessels 3540 are
configured so that they hold different amount of sample in each of the
vessels. By way of
non-limiting example, this can be controlled based on the amount of vacuum
force in each of
the sample vessels, the amount of sample collected in the sample collection
channel(s) of the
collection device, and/or other factors. Optionally, different pre-treatments
such as but not
limited to different anti-coagulants or the like can also be present in the
sample vessels.
1004811 As seen in Figure 44, the sample vessels 3540 are collecting
sample at a first
location such as but not limited to a sample collection site. By way of non-
limiting example,
the bodily fluid samples are then transported in the transport container 3500
to a second
location such as but not limited to a receiving site such as but not limited
to an analysis site.
The method of transport may be by courier, postal delivery, or other shipping
technique. In
many embodiments, the transport may be implemented by having a yet another
container that
holds the transport container therein. In one embodiment, the sample
collection site may be a
point-of-care. Optionally, the sample collection site is a point-of-service.
Optionally, the
sample collection site is remote from the sample analysis site.
1004821 Although the present embodiment of Figure 44 shows the collection
of bodily
fluid sample from a surface of the subject, other alternative embodiments may
use collection
techniques for collecting sample from other areas of the subject, such as by
venipuncture, to
fill the sample vessel(s) 3540. Such other collection techniques are not
excluded for use as
alternative to or in conjunction with surface collection. Surface collection
may be on exterior
surfaces of the subject. Optionally, some embodiments may collect from
accessible surfaces
on the interior of the subject. Presence of bodily fluid sample B on these
surfaces may be
naturally occurring or may occur through wound creation or other techniques to
make the
bodily fluid surface accessible.
1004831 Referring now to Figure 45, yet another embodiment is described
herein
wherein bodily fluid sample can be collected from an interior of the subject
versus collecting
sample that is pooled on a surface of the subject. This embodiment of Figure
45 shows a
collection device 3550 with a hypodermic needle 3552 that is configured to
collect bodily
fluid sample such as but not limited to venous blood. In one embodiment, the
bodily fluid
sample may fill a chamber 3554 in the device 3550 at which time sample
vessel(s) 3540 may
be engaged to draw the sample into the respective vessel(s). Optionally, some
embodiments
may not have a chamber 3554 but instead have very little void space other than
channel(s),
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pathway(s), or tube(s) used to direct sample from the needle 3552 to the
sample vessel(s)
3540. For bodily fluid samples such as blood, the pressure from within the
blood vessel is
such that the blood sample can fill the chamber 554 without much if any
assistance from the
collection device. Such embodiments may optionally include one or more vents,
such as but
not limited to a port, to allow air escape as the channels in the collection
device are filled
with sample.
[00484] At least some or all of the embodiments can have a fill indicator
such as but
not limited to a view window or opening that shows when sample is present
inside the
collection device and thus indicate that it is acceptable to engage the sample
vessel(s) 3540.
Optionally, embodiments that do not have a fill indicator are not excluded.
The filled sample
vessel(s) 3540 may be disconnected from the sample collection device after a
desired fill
level is reached. Optionally, additional sample vessel(s) 3540 can be engaged
to the sample
collection device 3550 (or 530) to collect additional amounts of bodily fluid
sample.
[00485] Figure 46 shows a still further embodiment of a sample collection
device
3570. This embodiment described herein has a tissue penetrating portion 3572
such as but
not limited to a hypodermic needle with a handling portion 3574. The handling
portion 3574
can facilitate positioning of the tissue penetrating portion 3572 to more
accurately enter the
patient to a desired depth and location. In the present embodiment, the sample
collection
vessel(s) 3540 are in a carrier 3576 that is not in direct physical contact
with the tissue
penetration portion 3572. A fluid connection pathway 3578 such as but not
limited to a
flexible tube can be used to connect the tissue penetrating portion 3572 with
the sample
collection vessel(s) 3540. Some embodiments have the sample vessel(s) 3540
configured to
be slidable to only be in fluid communication with the tissue penetrating
portion 3572 upon
control of the user. At least some or all of the embodiments can have a fill
indicator such as
but not limited to a view window or opening that shows when sample is present
inside the
collection device and thus indicate that it is acceptable to engage the sample
vessel(s) 3540.
Optionally, embodiments that do not have a fill indicator are not excluded.
Some
embodiments may optionally include one or more vents, such as but not limited
to a port, to
allow air escape as the channels in the collection device are filled with
sample. In most
embodiments, the filled sample vessel(s) 3540 may be disconnected from the
sample
collection device after a desired fill level is reached. Optionally,
additional sample vessel(s)
3540 can be engaged to the sample collection device 3570 to collect additional
amounts of
bodily fluid sample.
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Sample Processing
[00486] Referring now to Figure 47, a system view is shown of the
transport container
3500 having its contents unloaded after arriving at a destination location by
unloading
assembly 3600. In one embodiment, after the lid 3502 is positioned in an open
position, the
sample vessels in the vessel 3500 can be removed from therein. By way of non-
limiting
example, the removal may occur by removing an entire tray of the sample
vessels, removing
holders of multiple sample vessels from the tray, and/or by removing the
sample vessels
individually. Some embodiments may use a robotically controlled structure 3602
that can
move vertically as indicated by arrow 3604 and/or horizontally as indicated by
arrow 3606
along a gantry 3608 to remove sample vessels from the transport container
3500. A
programmable process 3610 can be used to control the position of the structure
3602 that is
used to manipulate the sample vessels. In one embodiment, the structure 3602
includes a
magnet for engaging the retention mechanisms to remove the tray from the
structure 3602.
Other embodiments using robotic arms and/or other types of programmable
manipulators can
be configured for use herein and are not excluded.
[00487] In embodiments, upon the arrival of a sample vessel containing a
sample at a
location for processing or analysis of the sample, the sample may be removed
from the
sample vessel. The sample vessel may processed (e.g. shaken, rotated, mixed,
or centrifuged)
before the sample is removed from the sample vessel. Sample may be removed
from the
sample vessel by any appropriate mechanism, such as aspiration (e.g. by a
fluid handling
system or pipette), pouring, or mechanical force (e.g. by forcing the sample
from the vessel
by reducing the dimensions of the interior region of the sample vessel). In
embodiments,
upon the removal of the sample from the sample vessel, little or no sample
remains behind in
the vessel (e.g. as mechanical / transfer loss). For example, after the
removal of sample from
the vessel, less than or equal to 50 [11, 40 1, 30 td, 20 j.tl, 15 j.tl, 10
ill, 5 Ill, 4 1, 3 j.tl, 2 1, 1
IA, or 0111 of sample may remain in the sample vessel.
1004881 By way of non-limiting example, the samples in the sample vessels
can then
be processed using systems such as that described in U.S. Patent Application
Ser. No.
13/244,947 filed September 26, 2011, fully incorporated herein by reference
for all purposes.
The analysis system can be configured in a CLIA compliant manner as described
in U.S.
Patent Application Ser. No. 13/244,946 filed September 26, 2011, fully
incorporated herein
by reference for all purposes. In embodiments, a sample transported according
to systems or
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methods provided herein may be divided into two or more smaller portions upon
arrival at
location for processing or analysis, and various assays may be performed with
the sample.
For example, in embodiments, at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 20, 30,
40, or 50 assays may
be performed with a sample transported according to systems or methods
provided herein.
The assays may include assays of different types (e.g. to assay for protein,
nucleic acid, or
cells), and use one or more detection methods (e.g. cytometry, luminescence,
or
spectrophotometer-based). In embodiments, two or more sample vessels
containing sample
from a single subject may be transported, wherein the two or more sample
vessels contain at
least two different anticoagulants mixed with the sample (e.g. one sample
vessel contains
EDTA-sample and one sample vessel contains heparin-sample). Sample from the
EDTA-
sample vessel may then be used for one or more assays that are heparin-
sensitive or EDTA-
insensitive. Similarly, sample from the heparin-sample vessel may then be used
for one or
more assays that are EDTA-sensitive or heparin-insensitive. In embodiments, a
sample
transported according to systems and methods provided herein may be divided
into two or
more portions upon arrival at a destination, and analyzed on 1, 2, 3, 4, 5, 6,
7, 8, 9, 10 or
more different sample analyzers.
[00489]
Referring now to Figures 49 to 51, it should be understood that at least any
two of the tests on the list (Figures 49 to 51) can be performed using a
sample from a subject
prepared or transported according to a system or method provided herein. For
example, at
least two tests on the list may be performed using a bodily fluid sample from
a subject,
wherein the total volume of bodily fluid sample used to perform the test is no
more than 300
microliters, and the total volume of bodily fluid sample from the subject is
transported in
liquid form a sample vessel having an interior volume of 400 microliters or
less. In another
example, at least two tests on the list may be performed using a bodily fluid
sample from a
subject, wherein the total volume of bodily fluid sample used to perforrh the
tests is no more
than 300 microliters, and the total volume of bodily fluid sample from the
subject is
transported in liquid form in a first sample vessel and a second sample
vessel, each vessel
having an interior volume of 200 microliters or less, the first sample vessel
containing bodily
fluid sample mixed with a first anticoagulant and the second sample vessel
containing bodily
fluid sample mixed with a second anticoagulant. In embodiments, at least 2, 3,
4, 5, 6, 7, 8,
9, 10, 11, 12, 13, 14, 15, 20, 25, 30, 35, 40, 50, or 60 of the tests on the
list (Figures 49 to 51)
may be performed using a bodily fluid sample from a subject having a total
volume of no
greater than or equal to 5 ml, 4 ml, 3 ml, 2 ml, 1.5 ml, 1 ml, 750 .1, 500
1, 400 ?Al, 300 I,
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200 I, 150 1, 100 1, 75 IA, 50 1, 40 1, 30 1, 20 I, 10 1, 5 1 or 1
1. The total volume
of the bodily fluid sample may be stored or transported from a collection site
to an analysis or
processing location in a single sample vessel, or it may be divided between 2,
3, 4, 5, 6, 7, 8,
9, 10, 11, 12, 13, 14, 15, 20, 25, or more sample vessels. When the total
volume of a bodily
fluid sample from a single subject is divided into two or more sample vessels,
the sample
portions in some or each of the sample vessels may contain a different
anticoagulant or other
additive. In an example, no more than a total volume of 300 microliters of
bodily fluid
sample from a subject may be used for performing two or more of the tests,
wherein at least
one portion of the no more than 300 microliter sample is mixed with first anti-
coagulant and a
second portion of the no more than 300 microliter sample is mixed with a
second anti-
coagulant different from the first. Optionally, each portion of the no more
than 300
microliter sample is in its own sample vessel. Optionally, two or more of the
tests may be
performed, wherein all of the no more than 300 microliter sample is
transported in a single
vessel and contains a single anti-coagulant. Optionally, at least any three of
the tests on that
list can be conducted using no more than a total volume of 300 microliters of
blood from a
subject for all of the tests. Optionally, at least any five of the tests on
that list can be
conducted using no more than a total volume of 300 microliters of blood from a
subject for
all of the tests. Optionally, at least any seven of the tests on that list can
be conducted using
no more than a total volume of 300 microliters of blood from a subject for all
of the tests.
Optionally, at least any ten of the tests on that list can be conducted using
no more than a
total volume of 300 microliters of blood from a subject for all of the tests.
Optionally, at least
any fifteen of the tests on that list can be conducted using no more than a
total volume of 300
microliters of blood from a subject for all of the tests. Optionally, at least
any twenty of the
tests on that list can be conducted using no more than a total volume of 300
microliters of
blood from a subject for all of the tests. For any of the above, in at least
some embodiments,
at least one portion is of a first anti-coagulant and a second portion is of a
second anti-
coagulant different from the first.
1004901 Referring now to Figure 52, yet another embodiment is shown of a
device for
bodily fluid sample collection. Figure 52 shows a bodily fluid sample B on the
subject being
collected by a collection device 3710. As seen in Figure 52, the collection
device 3710 may
include a collection portion 3712 such as but not limited to capillary tube or
other collection
structure. The collection portion 3712 draws fluid therein, eventually
directing it towards an
inner cavity 3714 of the device 3710. After the collection portion 3712 has
collected a
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desired amount, the entire device 3710 can be oriented as shown in Figure 52
so that gravity
can then draw the sample into the cavity 3714. After all the sample B has been
moved into
the cavity 3714, the collection portion 3712 can be removed from device 3710.
In one
embodiment, the cap and the collection portion 3712 is removed and replaced
with a closed
cap 3718. In one non-limiting example, the cap 3718 can be one without any
openings
thereon. Optionally, some may have a septa or other closable opening in the
cap, wherein the
collection portion 3712 can be removed without having to replace the cap with
a new one of a
different configuration.
Modular Sample Collection Device
[00491] Referring now to Figures 53A-53C, although the embodiments herein
typically describe sample collection device as having an adapter portion 3750
for connecting
the sample collection portion 3740 with the sample storage vessels 3760, it
should be
understood that embodiments without such configurations are not excluded.
[00492] By way of non-limiting example in Figure 53A, one or more adapter
portion
3750 may be discrete elements not initially in direct fluid communication with
either the
collection portion 3740 or the sample storage vessels 3760. Herein the
collection portion
3740 may connect to the vessel 3760 by way of relative motion between one or
more of the
collection portion, the adapter portion 3750, or the vessel(s) 3760
(sequentially or
simultaneously) to create a fluid pathway from the collection channels through
the one or
more adapter channels into the vessels.
[00493] By way of non-limiting example in Figure 53B, as previously
suggested
herein, some embodiments may be without a discrete, separate adapter portion
3750. Herein
the collection portion 3740 may connect directly to the vessel 3760 by way of
relative motion
between one or both of those elements as indicated by the arrow 3770. As seen
in Figure
53B, there may be a fluid flow feature 3780 that with relative motion between
one or both of
those elements as indicated by the arrow 3782. In one non-limiting example,
this fluid flow
feature 3780 can be a cap that engages one end of the collection portion 3740
to encourage
fluid flow in to the vessel 3760. Optionally, the fluid flow feature 3780 may
be a cap that has
a front surface shaped to engage the collection portion 3740. Optionally, the
fluid flow
feature 3780 may be a plunger, a rod, and/or other device to encourage flow
towards the
sample storage vessel 3760. Optionally, the fluid flow feature 3780 is not
fully engaged until
the sample collection portion 3740 is ready to engage the vessel 3760.
Optionally, some
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embodiments may be configured so that the flow from collection portion 3740 to
sample
storage vessel 3760 is without the use of the fluid flow feature 3780, but is
instead based on a
different motive force, such as but not limited to gravity, vacuum suction, or
blowing force
provided at the appropriate end of the collection portion 3740.
[00494] By way of non-limiting example in Figure 53C, one or more
embodiment may
use the collection portion 3740 as the storage vessel. Some embodiments may
simply cap
both ends with caps 3790 and 3792 once the desired fill level is reached. As
seen in Figure in
Figure 53C, the caps 3790 and 3792 can hold the fluid therein, even when the
portion 3740 is
in a vertical orientation.
[00495] There may be variations and alternatives to the embodiments
described herein
and that no single embodiment should be construed to encompass the entire
invention. For
example, there can be two or more capillary tubes in the collection portion
3740. Optionally,
they can be each formed as discrete tubes or channels. Optionally, some may
have a common
initial portion but separate exits ports such as but not limited to a Y
configuration. It should
be understood that any of the embodiments herein could be modified to include
the features
recited in the description for Figures 53A-53C.
[00496] Referring now to Figure 54, after a sample vessel 3800 arrives at
a desired
processing destination, the sample in the vessel 3800 can be appropriately
prepared. In one
embodiment, the vessel 3800 is similar to that of vessel 3710. As seen in
Figure 54, the
sample can be processed to aliquot one portion into a processing device such
as but not
limited to an inlet on a cartridge 3802 and to another inlet on another
cartridge 3804. In one
embodiment, both of the cartridges 3802 are microfluidic discs that process
sample for blood
chemistry testing such as but not limited to Comprehensive Metabolic Panel
(ALB, ALP,
ALT, AST, BUN, Ca, Cl-, CRE, GLU, K+, Na+, TBIL, tCO2, TP), Basic Metabolic
Panel
(BUN, Ca, CRE, eGFR, GLU, Cl-, K+, Na+, tCO2) Lipid Panel (CHOL, HDL,
CHOL/HDL,
LDL, TRIG, VLDL, nHDLc); Lipid Panel Plus (tCHOL, HDL, CHOL/HDL Ratio, LDL,
TRIG, VLDL, GLU, ALT, AST, nHDLc); Liver Panel Plus (ALB, ALP, ALT, AST, AMY,
TBIL, TP, GGT); Electrolyte Panel (C1-, K+, Na+, tCO2); General Chemistry
(ALB, ALP,
ALT, AMY, AST, BUN, Ca, CRE, eGFR, GGT, GLU, TBIL, TP, UA); General Chemistry
6
(ALT, AST, CRE, eGFR, GLU, BUN, GGT) Renal Function Panel (ALB, BUN, Ca, CRE,
eGFR, GLU, Cl-, K+, Na+, tCO2 PHOS); Metlyte (C1-, K+, Na+, tCO2, BUN, CK,
CRE,
eGFR, GLU); Kidney Function (BUN, CRE, eGFR; Hepatic Function Panel (ALB, ALP,
ALT, AST, DBIL, TBIL, TP); Basic Metabolic Panel (BUN, Ca, CRE, eGFR, GLU, Cl-
, K+,
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Na+, tCO2, Mg, LDH); MetLyte Plus CRP (C1-, K+, Na+, tCO2, BUN, CK, CRE, eGFR,
GLU, CRP); BioChemistry Panel Plus (ALB, ALP, ALT, AMY, AST, BUN, Ca, CRE,
eGFR, CRP, GGT, GLU, TP, UA); MetLac (ALB, BUN, Ca, Cl-, CRE, GLU, K+, LAC,
Mg,
Na+, Phos, tCO2). It should be understood that other fluid handling
technologies that may be
developed in the future can also be adapted for use in at least one of the
embodiments herein.
In some embodiments, the sample can be delivered to a general chemistry
microfluidic/centrifugal cartridge(s) 3802 (and/or 3804) using tubing to carry
the fluid to a
destination such as but not limited to fluid receiving port on the cartridge.
At least one or
more other cartridges, such as but not limited to an open-fluid movement type
cartridge as
described in the applications incorporated by reference herein, can also be
used to improve
the types of testing available. Although at least two destination cartridges
are shown, it
should be understood that embodiment with more than two are not excluded (as
shown by the
additional cartridge shown in phantom). Fluid transport may be by way of
pipette, by fluidic
tubing, microfluidics, or by other fluid handling technologies that may be
developed in the
future.
[00497] Referring now to Figure 55A, it should be understood that some
embodiments
can use a sample handling system with pipette(s) or the like the extract the
sample in a
tubeless manner from the vessel 3800. Although pipette(s) are described in
this embodiment,
it should be understood that other fluid handling technologies that may be
developed in the
future can also be adapted for use in at least one of the embodiments herein.
Figure 55A
shows that an automated system can be used to aliquot the sample. It should
also be
understood that in some embodiments, prior to, during, or after aliquoting,
there can be
sample dilution to increase the liquid volume of the sample. This can be
beneficial for
various purposes. Figure 55A also shows that in some embodiments, the sample
can be
delivered to a general chemistry microfluidic/centrifugal cartridge(s) 3802
(and/or 3804). At
least one or more other cartridges, such as but not limited to an open-fluid
movement type
cartridge as described in the applications incorporated by reference herein,
can also be used
to improve the types of testing available. Although at least two destination
cartridges are
shown, it should be understood that embodiment with more than two are not
excluded (as
shown by the additional cartridge shown in phantom). Fluid transport may be by
way of
pipette, by fluidic tubing, microfluidics, or by other fluid handling
technologies that may be
developed in the future. Some embodiments may use the same techniques to move
sample to
the cartridges or other destination(s), or optionally, some may use a
combination of one or
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more of the techniques to move the sample. By way of example and not
limitation, testing
may involve using other detection techniques such as but not limited to ELISA,
nucleic acid
amplification, microscopy, spectrophotometry, electrochemistry and/or other
detection
techniques to augment the types of analysis that can be done, in addition to
the general
chemistry testing using the cartridge 3802. Optionally, it should be
understood that more
than one cartridge 3802 and/or individual unit cartridge 3806 can be used
herein with the
system of aliquoting from the vessel 3800.
1004981 Referring now to Figures 55B, a still further embodiment is shown
wherein a
vessel 3800 is shown having a sample fluid therein. In one example, the sample
fluid therein
may be "neat" or undiluted. Optionally, some embodiments may be configured so
that
sample may have been pre-processed at the collection site and/or at the
receiving site to dilute
the sample and/or provide certain chemical material into the sample. As seen
in Figure 55B,
a fluid handling system may use a pipette 3602 to aliquot sample from vessel
3800 to one or
more other vessels 3810, 3812, and/or 3814. By way of non-limiting example,
these vessels
3810, 3812, or 3814 may be the same vessel as that of vessel 3800. Optionally,
they may be
different type of vessel. Based on bar code or other information about the
sample, the
processor programmed to determine at least a desired sample dilution for a
sample and at
least a desired number of aliquot(s). In this non-limiting example, the
aliquots are each
transported to one sample processing unit 3820, 3822, and 3824. These may all
be the same
type of processing unit, each may be a type different from the other, or some
may be the same
and some different. In at least one non-limiting example, the sample
processing unit can be
single sample processor or a batch processor that can handle a plurality of
sample
simultaneously.
[00499] Figure 55C shows a still further embodiment wherein a sample is
collected at
a collection site and then transported to a second site while sample remains
in liquid form.
Figure 55C shows that a plurality of vessels having sample can be collected
from a single
wound on the subject. This allows the subject to provide multiple samples that
can be treated
by different types of chemicals in each of the vessels. Figure 55C shows a
courier that can
transport a transport container that may include samples from only one subject
or multiple
samples from multiple subjects to a receiving site. Although a human courier
is shown, it
should be understood that robotic transports, drones, or other transport
techniques, systems,
or devices that may be developed in the future are not excluded (including but
not limited to
transport of "virtual" version(s) of the sample). In this non-limiting
example, the receiving
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site may load one or more vessels 1504 from the transport container into a
cartridge having
independently movable reagent units and/or assay units. This cartridge can
then be loaded
into one or more processing modules 701 to 707. These units may be identical
modules.
Optionally, at least one of the modules is different from the others. Similar
to Figure 55B,
some embodiments may include a processor 3830 that may coordinate dilution
and/or
aliquoting of sample from vessel 1504 (based on vessel ID or other associated
information)
prior to loading the vessel 1504 or other vessel(s) that contain the sample
and/or pre-diluted
sample into the cartridge. In at least one embodiment herein, each of the
modules can receive
at least one cartridge and at least one sample vessel. Optionally, more than
one sample vessel
can be placed in each cartridge. Optionally, the sample vessels may contain
different types of
sample so that cartridge can have more than one type of sample loaded into it.
Optionally,
some embodiments may have modules with at least one receiving area for a
cartridge and at
least one receiving area for a sample.
[00500] Optionally, some embodiments may have only one location for
receiving a
cartridge which then also contains at least one sample. In this manner, a user
has decreased
risk of having to load separate items into the module. Once loaded, at least
one embodiment
herein is configured so that there is no more user manipulation of the sample
once it is
inserted in the module. This non-limiting example can be used minimize error
associated
with human factors once the sample is being processed in the module.
[00501] It should also be understood that some embodiments may handle a
plurality of
sample simultaneously using centrifugal or other force to bring the sample
down to a settled
level inside the sample vessels. In one non-limiting example, this can be
achieved by way of
a tray centrifuge such as but not limited to a 384 well plate centrifuge.
[00502] FIG. 55C shows a system 700 having a plurality of modules 701-706
and a
cytometry station 707, in accordance with an embodiment of the invention. The
plurality of
modules include a first module 701, second module 702, third module 703,
fourth module
704, fifth module 705 and sixth module 706.
[00503] The cytometry station 707 is operatively coupled to each of the
plurality of
modules 701-706 by way of a sample handling system 708. The sample handling
system 708
may include a pipette, such as a positive displacement, air displacement or
suction-type
pipette, as described herein.
[00504] The cytometry station 707 includes a cytometer for performing
cytometry on a
sample, as described above and in other embodiments of the invention. The
cytometry
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station 707 may perform cytometry on a sample while one or more of the modules
701-706
perform other preparation and/or assaying procedure on another sample. In some
situations,
the cytometry station 707 performs cytometry on a sample after the sample has
undergone
sample preparation in one or more of the modules 701-706.
[00505] The system 700 includes a support structure 709 having a plurality
of bays (or
mounting stations). The plurality of bays is for docking the modules 701-706
to the support
structure 709. The support structure 709, as illustrated, is a rack.
[00506] Each module is secured to rack 709 with the aid of an attachment
member. In
an embodiment, an attachment member is a hook fastened to either the module or
the bay. In
such a case, the hook is configured to slide into a receptacle of either the
module or the bay.
In another embodiment, an attachment member includes a fastener, such as a
screw fastener.
In another embodiment, an attachment member is formed of a magnetic material.
In such a
case, the module and bay may include magnetic materials of opposite polarities
so as to
provide an attractive force to secure the module to the bay. In another
embodiment, the
attachment member includes one or more tracks or rails in the bay. In such a
case, a module
includes one or more structures for mating with the one or more tracks or
rails, thereby
securing the module to the rack 709. Optionally, power may be provided by the
rails.
[00507] An example of a structure that may permit a module to mate with a
rack may
include one or more pins. In some cases, modules receive power directly from
the rack. In
some cases, a module may be a power source like a lithium ion, or fuel cell
powered battery
that powers the device internally. In an example, the modules are configured
to mate with the
rack with the aid of rails, and power for the modules comes directly from the
rails. In another
example, the modules mate with the rack with the aid of attachment members
(rails, pins,
hooks, fasteners), but power is provided to the modules wirelessly, such as
inductively (i.e.,
inductive coupling). In some embodiments, a module mating with a rack need not
require
pins. For example, an inductive electrical communication may be provided
between the
module and rack or other support. In some instances, wireless communications
may be used,
such as with the aid of ZigBee communications or other communication protocols
or
protocols that may be developed in the future.
[00508] Each module may be removable from the rack 709. In some
situations, one
module is replaceable with a like, similar or different module. In an
embodiment, a module
is removed from the rack 709 by sliding the module out of the rack. In another
embodiment,
a module is removed from the rack 709 by twisting or turning the module such
that an
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attachment member of the module disengages from the rack 709. Removing a
module from
the rack 709 may terminate any electrical connectivity between the module and
the rack 709.
[00509] In an embodiment, a module is attached to the rack by sliding the
module into
the bay. In another embodiment, a module is attached to the rack by twisting
or turning the
module such that an attachment member of the module engages the rack 709.
Attaching a
module to the rack 709 may establish an electrical connection between the
module and the
rack. The electrical connection may be for providing power to the module or to
the rack or to
the device from the module and/or providing a communications bus between the
module and
one or more other modules or a controller of the system 700.
[00510] Each bay of the rack may be occupied or unoccupied. As illustrated,
all bays
of the rack 709 are occupied with a module. In some situations, however, one
or more of the
bays of the rack 709 are not occupied by a module. In an example, the first
module 701 has
been removed from the rack. The system 700 in such a case may operate without
the
removed module.
[00511] In some situations, a bay may be configured to accept a subset of
the types of
modules the system 700 is configured to use. For example, a bay may be
configured to
accept a module capable of running an agglutination assay but not a cytometry
assay. In such
a case, the module may be "specialized" for agglutination. Agglutination may
be measured
in a variety of ways. Measuring the time-dependent change in turbidity of the
sample is one
method. One can achieve this by illuminating the sample with light and
measuring the
reflected light at 90 degrees with an optical sensor, such as a photodiode or
camera. Over
time, the measured light would increase as more light is scattered by the
sample. Measuring
the time dependent change in transmittance is another example. In the latter
case, this can be
achieved by illuminating the sample in a vessel and measuring the light that
passes through
the sample with an optical sensor, such as a photodiode or a camera. Over
time, as the
sample agglutinates, the measured light may reduce or increase (depending, for
example, on
whether the agglutinated material remains in suspension or settles out of
suspension). In
other situations, a bay may be configured to accept all types of modules that
the system 700 is
configured to use, ranging from detection stations to the supporting
electrical systems.
[00512] Each of the modules may be configured to function (or perform)
independently from the other modules. In an example, the first module 701 is
configured to
perform independently from the second 702, third 703, fourth 704, fifth 705
and sixth 706
modules. In other situations, a module is configured to perform with one or
more other
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modules. In such a case, the modules may enable parallel processing of one or
more samples.
In an example, while the first module 701 prepares a sample, the second module
702 assays
the same or different sample. This may enable a minimization or elimination of
downtime
among the modules.
[00513] The support structure (or rack) 709 may have a server type
configuration. In
some situations, various dimensions of the rack are standardized. In an
example, spacing
between the modules 701-706 is standardized as multiples of at least about 0.5
inches, or 1
inch, or 2 inches, or 3 inches, or 4 inches, or 5 inches, or 6 inches, or 7
inches, or 8 inches, or
9 inches, or 10 inches, or 11 inches, or 12 inches.
[00514] The rack 709 may support the weight of one or more of the modules
701-706.
Additionally, the rack 709 has a center of gravity that is selected such that
the module 701
(top) is mounted on the rack 709 without generating a moment arm that may
cause the rack
709 to spin or fall over. In some situations, the center of gravity of the
rack 709 is disposed
between the vertical midpoint of the rack and a base of the rack, the vertical
midpoint being
50% from the base of the rack 709 and a top of the rack. In an embodiment, the
center of
gravity of the rack 709, as measured along a vertical axis away from the base
of the rack 709,
is disposed at least about 0.1%, or 1%, or 10%, or 20%, or 30%, or 40%, or
50%, or 60%, or
70%, or 80%, or 90%, or 100% of the height of the rack as measured from the
base of the
rack 709.
[00515] A rack may have multiple bays (or mounting stations) configured to
accept
one or more modules. In an example, the rack 709 has six mounting stations for
permitting
each of the modules 701-706 to mount the rack. In some situations, the bays
are on the same
side of the rack. In other situations, the bays are on alternating sides of
the rack.
[00516] In some embodiments, the system 700 includes an electrical
connectivity
component for electrically connecting the modules 701-706 to one another. The
electrical
connectivity component may be a bus, such as a system bus. In some situations,
the electrical
connectivity component also enables the modules 701-706 to communicate with
each other
and/or a controller of the system 700.
[00517] In some embodiments, the system 700 includes a controller (not
shown) for
facilitating processing of samples with the aid of one or more of the modules
701-706. In an
embodiment, the controller facilitates parallel processing of the samples in
the modules 701-
706. In an example, the controller directs the sample handling system 708 to
provide a
sample in the first module 701 and second module 702 to run different assays
on the sample
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at the same time. In another example, the controller directs the sample
handling system 708
to provide a sample in one of the modules 701-706 and also provide the sample
(such as a
portion of a finite volume of the sample) to the cytometry station 707 so that
cytometry and
one or more other sample preparation procedures and/or assays are done on the
sample in
parallel. In such fashion, the system minimizes, if not eliminates, downtime
among the
modules 701-706 and the cytometry station 707.
[00518] Each individual module of the plurality of modules may include a
sample
handling system for providing samples to and removing samples from various
processing and
assaying modules of the individual module. In addition, each module may
include various
sample processing and/or assaying modules, in addition to other components for
facilitating
processing and/or assaying of a sample with the aid of the module. The sample
handling
system of each module may be separate from the sample handling system 708 of
the system
700. That is, the sample handling system 708 transfers samples to and from the
modules 701-
706, whereas the sample handling system of each module transfers samples to
and from
various sample processing and/or assaying modules included within each module.
[00519] In the illustrated example of FIG. 55C, the sixth module 706
includes a sample
handling system 710 including a suction-type pipette 711 and positive
displacement pipette
712. The sixth module 706 includes a centrifuge 713, a spectrophotometer 714,
a nucleic
acid assay (such as a polymerase chain reaction (PCR) assay) station 715 and
PMT 716. An
example of the spectrophotometer 714 is shown in FIG. 55C (see below). The
sixth module
706 further includes a cartridge 717 for holding a plurality of tips for
facilitating sample
transfer to and from each processing or assaying module of the sixth module.
[00520] In an embodiment, the suction type pipette 711 includes 1 or more,
or 2 or
more, or 3 or more, or 4 or more, or 5 or more, or 6 or more, or 7 or more, or
8 or more, or 9
or more, or 10 or more, or 15 or more, or 20 or more, or 30 or more, or 40 or
more, or 50 or
more heads. In an example, the suction type pipette 711 is an 8-head pipette
with eight
heads. The suction type pipette 711 may be as described in other embodiments
of the
invention.
[00521] In some embodiments, the positive displacement pipette 712 has a
coefficient
of variation less than or equal to about 20%, 15%, 12%, 10%, 9%, 8%, 7%, 6%,
5%, 4%, 3%,
2%, 1%, 0.5%, 0.3%, or 0.1% or less. The coefficient of variation is
determined according to
D 0 0, wherein 'D' is the standard deviation and D' D is the mean across
sample
measurements.
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[00522] In an embodiment, all modules are identical to one another. In
another
embodiment, at least some of the modules are different from one another. In an
example, the
first, second, third, fourth, fifth, and sixth modules 701-706 include a
positive displacement
pipette and suction-type pipette and various assays, such as a nucleic acid
assay and
spectrophotometer. In another example, at least one of the modules 701-706 may
have assays
and/or sample preparation stations that are different from the other modules.
In an example,
the first module 701 includes an agglutination assay but not a nucleic acid
amplification
assay, and the second module 702 includes a nucleic acid assay but not an
agglutination
assay. Modules may not include any assays.
[00523] In the illustrated example of FIG. 55C, the modules 701-706
include the same
assays and sample preparation (or manipulation) stations. However, in other
embodiments,
each module includes any number and combination of assays and processing
stations
described herein.
[00524] The modules may be stacked vertically or horizontally with respect
to one
another. Two modules are oriented vertically in relation to one another if
they are oriented
along a plane that is parallel, substantially parallel, or nearly parallel to
the gravitational
acceleration vector. Two modules are oriented horizontally in relation to one
another if they
are oriented along a plane orthogonal, substantially orthogonal, or nearly
orthogonal to the
gravitational acceleration vector.
[00525] In an embodiment, the modules are stacked vertically, i.e., one
module on top
of another module. In the illustrated example of FIG. 55C, the rack 709 is
oriented such that
the modules 701-706 are disposed vertically in relation to one another.
However, in other
situations the modules are disposed horizontally in relation to one another.
In such a case, the
rack 709 may be oriented such that the modules 701-706 may be situated
horizontally
alongside one another.
[00526] In yet another embodiment of a system 730 is shown with a
plurality of
modules 701 to 704. This embodiment shows a horizontal configuration wherein
the modules
701 to 704 are mounted to a support structure 732 on which a transport device
734 can move
along the X, Y, and/or optionally Z axis to move elements such as but not
limited sample
vessels, tips, cuvettes, or the like within a module and/or between modules..
By way of non-
limiting example, the modules 701-704 are oriented horizontally in relation to
one another if
they are oriented along a plane orthogonal, substantially orthogonal, or
nearly orthogonal to
the gravitational acceleration vector.
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[00527] It should be understood that, like the embodiment of FIG. 55C,
modules 701-
704 may all be modules that are identical to one another. In another
embodiment, at least
some of the modules are different from one another. In an example, the first,
second, third,
and/or fourth modules 701-704 may be replaced by one or more other modules
that can
occupy the location of the module being replaced. The other modules may
optionally provide
different functionality such as but not limited to a replacing one of the
modules 701-704 with
one or more cytometry modules 707, communications modules, storage modules,
sample
preparation modules, slide preparation modules, tissue preparation modules, or
the like. For
example, one of the modules 701-704 may be replaced with one or more modules
that
provide a different hardware configuration such as but not limited to provide
a thermal
controlled storage chamber for incubation, storage between testing, and/or
storage after
testing. Optionally, the module replacing one or more of the modules 701-704
can provide a
non-assay related functionality, such as but not limited to additional
telecommunication
equipment for the system 730, additional imaging or user interface equipment,
or additional
power source such as but not limited to batteries, fuel cells, or the like.
Optionally, the
module replacing one or more of the modules 701-704 may provide storage for
additional
disposables and/or reagents or fluids. It should be understood that although
some
embodiments show only four modules mounted on the support structure, other
embodiments
having fewer or more modules are not excluded from this horizontal mounting
configuration.
It should also be understood that configurations may also be run with not
every bay or slot
occupied by a module, particularly in any scenario wherein one or more types
of modules
draw more power that other modules. In such a configuration, power otherwise
directed to an
empty bay can be used by the module that may draw more power than the others.
[00528] It should be understood that, like the embodiment of FIG. 55C,
modules 701-
706 may all be modules that are identical to one another. In another
embodiment, at least
some of the modules are different from one another. In an example, the first,
second, third,
and/or fourth modules 701-706 may be replaced by one or more other modules
that can
occupy the location of the module being replaced. The other modules may
optionally provide
different functionality such as but not limited to a replacing one of the
modules 701-706 with
one or more cytometry modules 707, communications modules, storage modules,
sample
preparation modules, slide preparation modules, tissue preparation modules, or
the like.
[00529] It should be understood that although some embodiments show only
six
modules mounted on the support structure, other embodiments having fewer or
more modules
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are not excluded from this horizontal and vertical mounting configuration. It
should also be
understood that configurations may also be run with not every bay or slot
occupied by a
module, particularly in any scenario wherein one or more types of modules draw
more power
that other modules. In such a configuration, power otherwise directed to an
empty bay can be
used by the module that may draw more power than the others.
[00530] Some embodiments may provide a system with a plurality of modules
701,
702, 703, 704, 706, and 707. Such an embodiment may have an additional module
that can
with one or more modules that provide a different hardware configuration such
as but not
limited to provide a thermal controlled storage chamber for incubation,
storage between
testing, or storage after testing. Optionally, the module replacing one or
more of the modules
701-704 can provide a non-assay related functionality, such as but not limited
to additional
telecommunication equipment for the system, additional imaging or user
interface equipment,
or additional power source such as but not limited to batteries, fuel cells,
or the like.
Optionally, the module replacing one or more of the modules 701-707 may
provide storage
for additional disposables and/or reagents or fluids.
[00531] It should be understood that although Fig. 55C shows seven modules
mounted
on the support structure, other embodiments having fewer or more modules are
not excluded
from this mounting configuration. It should also be understood that
configurations may also
be run with not every bay or slot occupied by a module, particularly in any
scenario wherein
one or more types of modules draw more power that other modules. In such a
configuration,
power otherwise directed to an empty bay can be used by the module that may
draw more
power than the others.
[00532] In some embodiments, the modules 701-706 are in communication with
one
another and/or a controller of the system 700 by way of a communications bus
("bus"), which
may include electronic circuitry and components for facilitating communication
among the
modules and/or the controller. The communications bus includes a subsystem
that transfers
data between the modules and/or controller of the system 700. A bus may bring
various
components of the system 700 in communication with a central processing unit
(CPU),
memory (e.g., internal memory, system cache) and storage location (e.g., hard
disk) of the
system 700.
[00533] A communications bus may include parallel electrical wires with
multiple
connections, or any physical arrangement that provides logical functionality
as a parallel
electrical bus. A communications bus may include both parallel and bit-serial
connections,
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and can be wired in either a multidrop (i.e., electrical parallel) or daisy
chain topology, or
connected by switched hubs. In an embodiment, a communications bus may be a
first
generation bus, second generation bus or third generation bus. The
communications bus
permits communication between each of the modules and other modules and/or the
controller. In some situations, the communications bus enables communication
among a
plurality of systems, such as a plurality of systems similar or identical to
the system 700.
[00534] The system 700 may include one or more of a serial bus, parallel
bus, or self-
repairable bus. A bus may include a master scheduler that control data
traffic, such as traffic
to and from modules (e.g., modules 701-706), controller, and/or other systems.
A bus may
include an external bus, which connects external devices and systems to a main
system board
(e.g., motherboard), and an internal bus, which connects internal components
of a system to
the system board. An internal bus connects internal components to one or more
central
processing units (CPUs) and internal memory.
[00535] In some embodiments, the communication bus may be a wireless bus.
The
commuincations bus may be a Firewire (IEEE 1394), USB (1.0, 2.0, 3.0, or
others),
Thunderbolt, or other protocols (current or developed in the future).
[00536] In some embodiments, the system 700 includes one or more buses
selected
from the group consisting of Media Bus, Computer Automated Measurement and
Control
(CAMAC) bus, industry standard architecture (ISA) bus, USB bus, Firewire,
Thunderbolt,
extended ISA (EISA) bus, low pin count bus, MBus, MicroChannel bus, Multibus,
NuBus or
IEEE 1196, OPTi local bus, peripheral component interconnect (PCI) bus,
Parallel Advanced
Technology Attachment (ATA) bus, Q-Bus, S-100 bus (or IEEE 696), SBus (or IEEE
1496),
SS-50 bus, STEbus, STD bus (for STD-80 [8-bit] and STD32 [16-/32-bit]),
Unibus, VESA
local bus, VMEbus, PC/104 bus, PC/104 Plus bus, PC/104 Express bus, PCI-104
bus, PCIe-
104 bus, 1-Wire bus, HyperTransport bus, Inter-Integrated Circuit (I2C) bus,
PCI Express (or
PCIe) bus, Serial ATA (SATA) bus, Serial Peripheral Interface bus, UNI/O bus,
SMBus, 2-
wire or 3-wire interface, self-repairable elastic interface buses and variants
and/or
combinations thereof.
[00537] In some situations, the system 700 includes a Serial Peripheral
Interface (SPI),
which is an interface between one or more microprocessors and peripheral
elements or I/0
components (e.g., modules 701-706) of the system 700. The SPI can be used to
attach 2 or
more, or 3 or more, or 4 or more, or 5 or more, or 6 or more, or 7 or more, or
8 or more, or 9
or more, or 10 or more or 50 or more or 100 or more SPI compatible I/0
components to a
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microprocessor or a plurality of microprocessors. In other instances, the
system 700 includes
RS-485 or other standards.
1005381 In an embodiment, an SPI is provided having an SPI bridge having a
parallel
and/or series topology. Such a bridge allows selection of one of many SPI
components on an
SPI I/0 bus without the proliferation of chip selects. This is accomplished by
the application
of appropriate control signals, described below, to allow daisy chaining the
device or chip
selects for the devices on the SPI bus. It does however retain parallel data
paths so that there
is no Daisy Chaining of data to be transferred between SPI components and a
microprocessor.
1005391 In some embodiments, an SPI bridge component is provided between a
microprocessor and a plurality of SPI I/0 components which are connected in a
parallel
and/or series (or serial) topology. The SPI bridge component enables parallel
SPI using
MISO and MOSI lines and serial (daisy chain) local chip select connection to
other slaves
(CSL/). In an embodiment, SPI bridge components provided herein resolve any
issues
associated with multiple chip selects for multiple slaves. In another
embodiment, SPI bridge
components provided herein support four, eight, sixteen, thirty two, sixty
four or more
individual chip selects for four SPI enabled devices (CS1/ ¨ CS4/). In another
embodiment,
SPI bridge components provided herein enable four times cascading with
external address
line setting (ADRO ¨ ADR1). In some situations, SPI bridge components provided
herein
provide the ability to control up to eight, sixteen, thirty two, sixty four or
more general output
bits for control or data. SPI bridge components provided herein in some cases
enable the
control of up to eight, sixteen, thirty two, sixty four or more general input
bits for control or
data, and may be used for device identification to the master and/or
diagnostics
communication to the master.
[005401 One embodiment may use an SPI bridge scheme having master and
parallel-
series SPI slave bridges, in accordance with an embodiment of the invention.
The SPI bus is
augmented by the addition of a local chip select (CSL/), module select
(MOD_SEL) and
select data in (DIN SEL) into a SPI bridge to allow the addition of various
system features,
including essential and non-essential system features, such as cascading of
multiple slave
devices, virtual daisy chaining of device chip selects to keep the module-to-
module signal
count at an acceptable level, the support for module identification and
diagnostics, and
communication to non-SPI elements on modules while maintaining compatibility
with
embedded SPI complaint slave components. FIG. 41B shows an example of an SPI
bridge, in
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accordance with an embodiment of the invention. The SPI bridge includes
internal SPI
control logic, a control register (8 bit, as shown), and various input and
output pins.
[00541] Each slave bridge is connected to a master (also "SPI master" and
"master
bridge" herein) in a parallel-series configuration. The MOSI pin of each slave
bridge is
connected to the MOSI pin of the master bridge, and the MOSI pins of the slave
bridges are
connected to one another. Similarly, the MISO pin of each slave bridge is
connected to the
MISO pin of the master bridge, and the MISO pins of the slave bridges are
connected to one
another.
[00542] Each slave bridge may be a module (e.g., one of the modules 701-
706 of FIG.
55C) or a component in a module. In an example, the First Slave Bridge is the
first module
701, the Second Slave Bridge is the second module 702, and so on. In another
example, the
First Slave Bridge is a component of a module.
[00543] At least one non-limiting example may use a module component
diagram with
interconnected module pins and various components of a master bridge and slave
bridge, in
accordance with an embodiment of the invention. Slave bridges may be connected
to a
master bridge, in accordance with an embodiment of the invention. The MISO pin
of each
slave bridge is in electrical communication with a MOSI pin of the master
bridge. The MOSI
pin of each slave bridge is in electrical communication with a MISO pin of the
master bridge.
The DIN SEL pin of the first slave bridge (left) is in electrical
communication with the
MOSI pin of the first slave bridge. The DOUT_SEL pin of the first slave bridge
is in
electrical communication with the DIN SEL of the second slave (right).
Additional slave
bridges may be connected as the second slave by bringing the DIN_SEL pins of
each
additional slave bridge in electrical communication with a DOUT_SEL pin of a
previous
slave bridge. In such fashion, the slave bridge are connected in a parallel-
series
configuration.
1005441 In some embodiments, CLK pulses directed to connected SPI-Bridges
capture
the state of DIN SEL Bits shifted into the Bridges at the assertion of the
Module Select Line
(MOD SEL). The number of DIN SEL bits corresponds to the number of modules
connected together on a parallel-series SPI-Link. In an example, if the two
modules are
connected in a parallel-series configuration (e.g. RS486), the number of
DIN_SEL is equal to
two.
[00545] In an embodiment, SPI-Bridges which latch a '1' during the module
selection
sequence become the 'selected module' set to receive 8 bit control word during
a following
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element selection sequence. Each SPI-Bridge may access up to 4 cascaded SPI
Slave
devices. Additionally, each SPI-Bridge may have an 8-Bit GP Receive port and 8-
Bit GP
Transmit Port. An 'element selection' sequence writes an 8 bit word into the
'selected
module' SPI-Bridge control register to enable subsequent transactions with
specific SPI
devices or to read or write data via the SPI-Bridge GPIO port.
1005461 In an embodiment, element selection takes place by assertion of
the local chip
select line (CSL/) then clocking the first byte of MOSI transferred data word
into the control
register. In some cases, the format of the control register is C54 C53 C52 CS1
AD1 ADO
R/W N. In another embodiment, the second byte is transmit or receive data.
When CSL/ is
de-asserted, the cycle is complete.
1005471 In an SPI transaction, following the element selection sequence,
subsequent
SPI slave data transactions commence. The SPI CS/ (which may be referred to as
SS/) is
routed to one of 4 possible bridged devices, per the true state of either CS4,
CS3, C52 or
CS1. Jumper bits ADO, ADlare compared to ADO, AD1 of the control register
allow up to
four SPI-Bridges on a module.
1005481 One embodiment shows a device having a plurality of modules
mounted on a
SPI link of a communications bus of the device, in accordance with an
embodiment of the
invention. Three modules are illustrated, namely Module 1, Module 2 and Module
3. Each
module includes one or more SPI bridges for bringing various components of a
module in
electrical connection with the SPI link, including a master controller
(including one or more
CPU's) in electrical communication with the SPI link. Module 1 includes a
plurality of SPI
slaves in electrical communication with each of SPI Bridge 00, SPI Bridge 01,
SPI Bridge 10
and SPI Bridge 11. In addition, each module includes a Receive Data
controller, Transmit
Data controller and Module ID jumpers.
1005491 In other embodiments, the modules 701-706 are configured to
communicate
with one another and/or one or more controllers of the system 700 with the aid
of a wireless
communications bus (or interface). In an example, the modules 701-706
communicate with
one another with the aid of a wireless communications interface. In another
example, one or
more of the modules 701-706 communicate with a controller of the system 700
with the aid
of a wireless communications bus. In some cases, communication among the
modules 701-
706 and/or one or more controllers of the system is solely by way of a
wireless
communications bus. This may advantageously preclude the need for wired
interfaces in the
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bays for accepting the modules 701-706. In other cases, the system 700
includes a wired
interface that works in conjunction with a wireless interface of the system
700.
[00550] Although the system 700, as illustrated, has a single rack, a
system, such as the
system 700, may have multiple racks. In some embodiments, a system has at most
1, or 2, or
3, or 4, or 5, or 6, or 7, or 8, or 9, or 10, or 20, or 30, or 40, or 50, or
100, or 1000, or 10,000
racks. In an embodiment, the system has a plurality of racks disposed in a
side-by-side
configuration.
1005511 In some embodiments, a user provides a sample to a system having
one or
more modules, such as the system 700 of FIG. 55C. The user provides the sample
to a
sample collection module of the system. In an embodiment, the sample
collection module
includes one or more of a lancet, needle, microneedle, venous draw, scalpel,
cup, swab, wash,
bucket, basket, kit, permeable matrix, or any other sample collection
mechanism or method
described elsewhere herein. Next, the system directs the sample from the
sample collection
module to one or more processing modules (e.g., modules 701-706) for sample
preparation,
assaying and/or detection. In an embodiment, the sample is directed from the
collection
module to the one or more processing modules with the aid of a sample handling
system,
such as a pipette. Next, the sample is processed in the one or more modules.
In some
situations, the sample is assayed in the one or more modules and subsequently
put through
one or more detection routines.
[00552] In some embodiments, following processing in the one or more
modules, the
system communicates the results to a user or a system (e.g., server) in
communication with
the system. Other systems or users may then access the results to aid in
treating or
diagnosing a subject.
= [00553] In an embodiment, the system is configured for two-way
communication with
other systems, such as similar or like systems (e.g., a rack, such as that
described in the
context of FIG. 55C) or other computers systems, including servers.
[00554] Devices and methods provided herein, by enabling parallel
processing, may
advantageously decrease the energy or carbon footprint of point of service
systems. In some
situations, systems, such as the system 700 of FIG. 55C, has a footprint that
is at most 10%,
or 15%, or 20%, or 25%, or 30%, or 35%, or 40%, or 45%, or 50%, or 55%, or
60%, or 65%,
or 70%, or 75%, or 80%, or 85%, or 90%, or 95%, or 99% that of other point of
service
systems.
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[00555] In some embodiments, methods are provided for detecting analytes.
In an
embodiment, a processing routine includes detecting the presence or absence of
an analyte.
The processing routine is facilitated with the aid of systems and devices
provided herein. In
some situations, analytes are associated with biological processes,
physiological processes,
environmental conditions, sample conditions, disorders, or stages of
disorders, such as one or
more of autoimmune disease, obesity, hypertension, diabetes, neuronal and/or
muscular
degenerative diseases, cardiac diseases, and endocrine diseases.
[00556] In some situations, a device processes one sample at a time.
However,
systems provided herein are configured for multiplexing sample processing. In
an
embodiment, a device processes multiple samples at a time, or with overlapping
times. In an
example, a user provides a sample to a device having a plurality of modules,
such as the
system 700 of FIG. 55C. The device then processes the sample with the aid of
one or more
modules of the device. In another example, a user provides multiple samples to
a device
having a plurality of modules. The device then processes the samples at the
same time with
the aid of the plurality of modules by processing a first sample in a first
module while
processing a second sample in second module.
1005571 The system may process the same type of sample or different types
of
samples. In an embodiment, the system processes one or more portions of the
same sample at
the same time. This may be useful if various assaying and/or detection
protocols on the same
sample are desired. In another embodiment, the system processes different
types of samples
at the same time. In an example, the system processes a blood and urine sample
concurrently
in either different modules of the system or a single module having processing
stations for
processing the blood and urine samples.
[00558] In some embodiments, a method for processing a sample with the aid
of a
point of service system, such as the system 700 of FIG. 55C, comprises
accepting testing
criteria or parameters and determining a test order or schedule based on the
criteria. The
testing criteria is accepted from a user, a system in communication with the
point of service
system, or a server. The criteria are selectable based on a desired or
predetermined effect,
such as minimizing time, cost, component use, steps, and/or energy. The point
of service
system processes the sample per the test order or schedule. In some
situations, a feedback
loop (coupled with sensors) enables the point of service system to monitor the
progress of
sample processing and maintain or alter the test order or schedule. In an
example, if the
system detects that processing is taking longer than the predetermined amount
of time set
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forth in the schedule, the system speeds up processing or adjusts any parallel
processes, such
as sample processing in another module of the system. The feedback loop
permits real-time
or pseudo-real time (e.g., cached) monitoring. In some situations, the
feedback loop may
provide permit reflex testing, which may cause subsequent tests, assays,
preparation steps,
and/or other processes to be initiated after starting or completing another
test and/or assay or
sensing one or more parameter. Such subsequent tests, assays, preparation
steps, and/or other
processes may be initiated automatically without any human intervention.
Optionally, reflex
testing is performed in response to an assay result. Namely by way of non-
limiting example,
if a reflex test is ordered, a cartridge is pre-loaded with reagents for assay
A and assay B.
Assay A is the primary test, and assay B is the reflexed test. If the result
of assay A is meets
a predefined criteria initiating the reflex test, then assay B is run with the
same sample in the
device. The device protocol is planned to account for the possibility of
running the reflex
test. Some or all protocol steps of assay B can be performed before the
results for assay A
are complete. For example, sample preparation can be completed in advance on
the device. It
is possible also to run a reflex test with a second sample from the patient.
In some
embodiments, devices and systems provided herein may contain components such
that
multiple different assays and assay types may be reflex tested with the same
device. In some
embodiments, multiple tests of clinical significance may be performed in a
single device
provided herein as part of a reflex testing protocol, where the performance of
the same tests
with known systems and methods requires two or more separate devices.
Accordingly,
systems and devices provided herein may permit, for example, reflex testing
which is faster
and requires less sample than known systems and methods. In addition, in some
embodiments, for reflex testing with a device provided herein, it is not
necessary to know in
advance which reflexed tested will be performed.
1005591 In some embodiments, the point of s.ervice system may stick to a
pre-
determined test order or schedule based on initial parameters and/or desired
effects. In other
embodiments, the schedule and/or test order may be modified on the fly. The
schedule
and/or test order may be modified based on one or more detected conditions,
one or more
additional processes to run, one or more processes to no longer run, one or
more processes to
modify, one or more resource/component utilization modifications, one or more
detected
error or alert condition, one or more unavailability of a resource and/or
component, one or
more subsequent input or sample provided by a user, external data, or any
other reason.
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[00560] In some examples, one or more additional samples may be provided
to a
device after one or more initial samples are provided to the device. The
additional samples
may be from the same subject or different subjects. The additional samples may
be the same
type of sample as the initial sample or different types of samples (e.g.,
blood, tissue). The
additional samples may be provided prior to, concurrently with, and/or
subsequent to
processing the one or more initial samples on the device. The same and/or
different tests or
desired criteria may be provided for the additional samples, as opposed to one
another and/or
the initial samples. The additional samples may be processed in sequence
and/or in parallel
with the initial samples. The additional samples may use one or more of the
same
components as the initial samples, or may use different components. The
additional samples
may or may not be requested in view of one or more detected condition of the
initial samples.
[00561] In some embodiments, the system accepts a sample with the aid of a
sample
collection module, such as a lancet, scalpel, or fluid collection vessel. The
system then loads
or accesses a protocol for performing one or more processing routines from a
plurality of
potential processing routines. In an example, the system loads a
centrifugation protocol and
cytometry protocol. In some embodiments, the protocol may be loaded from an
external
device to a sample processing device. Alternatively, the protocol may already
be on the
sample processing device. The protocol may be generated based on one or more
desired
criteria and/or processing routines. In one example, generating a protocol may
include
generating a list of one or more subtasks for each of the input processes. In
some
embodiments, each subtask is to be performed by a single component of the one
or more
devices. Generating a protocol may also include generating the order of the
list, the timing
and/or allocating one or more resources.
[00562] In an embodiment, a protocol provides processing details or
specifications that
are specific to a sample or a component in the sample. For instance, a
centrifugation protocol
may include rotational velocity and processing time that is suited to a
predetermined sample
density, which enables density-dependent separation of a sample from other
material that
may be present with a desirable component of the sample.
[00563] A protocol is included in the system, such as in a protocol
repository of the
system, or retrieved from another system, such as a database, in communication
with the
system. In an embodiment, the system is in one-way communication with a
database server
that provides protocols to the system upon request from the system for one or
more
processing protocols. In another embodiment, the system is in two-way
communication with
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a database server, which enables the system to upload user-specific processing
routines to the
database server for future use by the user or other users that may have use
for the user-
specific processing routines.
[00564] Referring now to Figures 56A and 56B, the transport container 4000
may be
configured to contain therein a plurality of bodily fluid samples from a
plurality of subjects
such as patients. In some embodiments there are multiple vessels of sample
from each
subject. Optionally, at least two of the samples from the same subject have
had different
chemical pre-treatment, such as but not limited to different anti-coagulant in
each vessel.
Optionally, some embodiments may use a vessel that has two or more separate
chambers,
wherein each chamber is configured to hold a portion of the fluid sample
separate from fluid
sample in another chamber. Some embodiments may include samples from a subject
in
single chamber vessels and/or multi-chamber vessels.
[00565] As seen in Figures 56A and 56B, various views of one embodiment of
the
transport container 4000 wherein the lid 4010 has a least a mesa portion 4012
that is sized to
fit into a recess 4020 on the bottom of the transport container4000 as seen in
Figure 57A so
that the vessels 4000 may be stackable. The transport container4000 may have
any of the
features described herein for other embodiments of transport containers
described herein.
1005661 Figure 57B shows that there may be a tray 4030 in the transport
container4000
that is fixed and/or removable from the transport container4000. In one
embodiment, the tray
4030 is held in place by a fixture device such as but not limited to magnetic
or metal portions
4032 that align with metal or magnetic portions in the chassis of the
transport container4000
to form a magnetic connection. In some embodiments, the length-to-width aspect
ratio is in
the range of about to 128:86 to 127:85. Optionally, the length-to-width aspect
ratio is in the
range of about to 130:90 to 120:80. Optionally, the length of the tray is in
the range of about
to 130mm to 120mm and the width is in the range of about 90mm to 80mm. In some
embodiments, the height or thickness of the tray is in the range of about 14
to 20 mm. The
aspect ratio and/or size is configured to hold a tray that is sized to fit a
slot, recess, or other
holder on a plate centrifuge. In this manner, the entire tray 4030 can be
centrifuged to
prepare a plurality of the samples therein.
[00567] As seen in Figures 57B and 58B, the tray 4030 has a plurality of
slots 4034,
wherein the slots 4034 are sized to hold at least one of the sample storage
vessels. At least
one portion 4040 of the slot 4034 has a first shape and at least a second
portion 4042 having a
second shape different from the first shape, wherein the shapes are keyed in a
manner that the
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sample vessel can only be inserted into the slot 4034 in a desired
orientation. As seen in
Figure 58B, one end is semi-circular while the other is asymmetrically shaped.
The tray 4030
can also be shaped to have cut outs 4036 or other shapes so that the tray 4030
can only be
inserted in one orientation into the transport container 4000. It should also
be understood that
the tray 4030 can be held in the tray so that a user cannot remove it using
their fingers from
the vessel 4000 without the use of a tool or other tray extraction device.
This minimizes the
risk of user tampering. The tray 4030 can be configured to be held in the
transport container
4000 even when the transport container4000 is upside down and can resist the
pull of earth
gravity.
[00568] Figures 59A and 59B show yet another embodiment wherein there a
plurality
of slots 4100 in a tray 4102. The tray has a different aspect ratio (closer to
square) and has a
plurality of shaped slots in the tray to hold the sample vessels.
[00569] In at least some embodiments, a medical provider (or their staff
when
appropriate) can be the sample collector, test result recipient, and/or both.
For example, in
one embodiment, a healthcare professional such as but not limited to a dentist
can collect a
sample as part of or separate from a dental procedure. Optionally, some
embodiments may
have the sample collected from suctioned blood and/or saliva from the
subject's dental
procedure. The collected sample can be processed in the dental office and/or
shipped to a
receiving location that receives a plurality of samples for processing.
[00570] In embodiments, a bodily fluid sample used in a system, device, or
method
provided herein may be diluted. In embodiments, a bodily fluid sample may be
diluted
before it is transported from a first location to a second location. In
embodiments, a bodily
fluid sample may be diluted after it is transported from a first location to a
second location.
In embodiments, a bodily fluid sample may be diluted both before and after it
is transported
from a first location to a second location. In embodiments, the bodily fluid
sample may be
diluted after it is transported from a first location to a second location and
before it is used for
performing one or more steps of a laboratory test at the second location. An
original bodily
fluid sample may be diluted, for example, at least 2, 3, 4, 5, 6, 7, 8, 9, 10,
15, 20, 50, 100,
200, 300, 400, 500, 1000, 5,000, 10,000, 50,000, or 100,000-fold. As used
herein, an "n-
fold" dilution refers to a ratio by which an original sample is diluted ¨ e.g.
an original sample
which is diluted 5-fold contains, after dilution, original sample at 1/5 of
its original
concentration (i.e. the diluted sample contains sample at 1/5 of the
concentration of sample in
the original sample); similarly, an original sample which is diluted 500-fold
contains, after
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dilution, original sample at 1/500 of its original concentration. Thus, for
example, if an
original sample contains 5 mg protein / microliter, and it is diluted 2-fold,
the diluted sample
contains 2.5 mg protein / microliter. A bodily fluid sample may be divided
into any number
of portions, and the various portions may be diluted to varying degrees of
dilution, such that
an original bodily fluid sample may be processed to yield multiple diluted
samples, each
having a different degree of dilution. Thus, for example, an original bodily
fluid sample may
be divided into 5 portions, with one portion being diluted 8-fold, another
portion being
diluted 12-fold, another portion being diluted 3-fold, another portion being
diluted 400-fold,
and another portion being diluted 2,000-fold. Dilution of a sample may be
performed serially
or in a single step. For a single-step dilution, a selected quantity of sample
may be mixed
with a selected quantity of diluent, in order to achieve a desired dilution of
the sample. For a
serial dilution, two or more separate sequential dilutions of the sample may
be performed in
order to achieve a desired dilution of the sample. For example, a first
dilution of the sample
may be performed, and a portion of that first dilution may be used as the
input material for a
second dilution, to yield a sample at a selected dilution level.
[00571] For dilutions described herein, an "original sample" or the like
refers to the
sample that is used at the start of a given dilution process. Thus, while an
"original sample"
may be a sample that is directly obtained from a subject (e.g. whole blood),
it may also
include any other sample (e.g. sample that has been processed or previously
diluted in a
separate dilution procedure) that is used as the starting material for a given
dilution
procedure.
[00572] In some embodiments, a serial dilution of a sample may be
performed as
follows. A selected quantity (e.g. volume) of an original sample may be mixed
with a
selected quantity of diluent, to yield a first dilution sample. The first
dilution sample (and
any subsequent dilution samples) will have: i) a sample dilution factor (e.g.
the amount by
which the original sample is diluted in the first dilution sample) and ii) an
initial quantity (e.g.
the total quantity of the first dilution sample present after combining the
selected quantity of
original sample and selected quantity of diluent). For example, 10 microliters
of an original
sample may be mixed with 40 microliters of diluent, to yield a first dilution
sample having a
5-fold sample dilution factor (as compared with the original sample) and an
initial quantity of
50 microliters. Next, a selected quantity of the first dilution sample may be
mixed with a
selected quantity of diluent, to yield a second dilution sample. For example,
5 microliters of
the first dilution sample may be mixed with 95 microliters of diluent, to
yield a second
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dilution sample having an 100-fold dilution factor (as compared with the
original sample) and
an initial quantity of 100 microliters. For each of the above dilution steps,
the original
sample, dilution sample(s), and diluent may be stored or mixed in fluidically
isolated vessels.
Sequential dilutions may continue in the preceding manner for as many steps as
needed to
reach a selected sample dilution level / dilution factor. In embodiments, a
sample may be
diluted as described in, for example, U.S. Pat. App. Ser. No. 13/769,820,
filed February 18,
2013, or any other document incorporated by reference elsewhere herein.
[00573] As used herein, a reagent that is, or may be used as, a "diluent"
is one which
is, e.g., useful for increasing the volume of a sample, or portion of a
sample, or is useful for
the preparation of a liquid formulation, such as a formulation reconstituted
after
lyophilization, or for adding to a sample, solution, or material for any other
reason. In
embodiments, a diluent may be buffered (e.g., to have a pH near pH 7, or near
pH 7.4, or
other desired pH), and may be pharmaceutically acceptable (safe and non-toxic
for
administration to a human). A diluent typically does not react with, or bind
to, an analyte in a
sample. Water may be a diluent, as may be an aqueous saline solution, a
buffered solution, a
solution containing a surfactant, or any other solution. Exemplary diluents
include sterile
water, bacteriostatic water for injection (BWFI), a pH buffered solution (e.g.
phosphate-
buffered saline), sterile saline solution, Ringer's solution or dextrose
solution. In
embodiments, diluents can include aqueous solutions of salts or buffers.
[00574] In embodiments, a bodily fluid sample or portion thereof which has
been, for
example, collected from a subject, processed, or transported according to a
system or method
provided herein may be divided into at least 2, 3, 4, 5, 6, 7, 8, 9, 10, 15,
20, 25, 30, 35, 40, 50,
100, 200, 300, 400, 500, 1000, 5,000, 10,000 or more different portions. For
descriptions of
division of a sample into multiple portions provided herein, an "original
sample" or the like
refers to the sample that is used at the start of a given sample division
process. Thus, while
an "original sample" may be, for example, a sample that was directly obtained
from a subject
(e.g. whole blood), it may also include any other sample (e.g. sample that has
been processed
or previously divided in a separate sample division procedure) that is used as
the starting
material for a given sample division procedure. In embodiments, an "original
sample" may
be subject to both sample division and dilution steps; in such circumstances,
reference to the
"original sample" refers to a starting material that is used for the
combination sample dilution
/ sample division procedure. When a sample is divided into different portions,
the different
portions may contain different amounts of the original sample. For instance,
if an original
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sample having of volume of 100 microliters is divided into 5 portions, one
portion may
contain 50 microliters original sample, another portion may contain 25
microliters original
sample, another portion may contain 15 microliters original sample, another
portion may
contain 8 microliters original sample, and the last portion may contain 2
microliters original
sample. Likewise, when a sample is both diluted and divided into different
portions, the
different portions may have different degrees of dilution relative to the
original sample. For
example, if an original sample is divided into three portions, one portion may
be diluted 5-
fold relative to the original sample, another portion may be diluted 20-fold
relative to the
original sample, and the third portion may be diluted 200-fold relative to the
original
sample.
[00575] Thus, in an example, a bodily fluid sample may be collected from a
subject at
a first location (e.g. a sample collection site). The bodily fluid sample as
first collected from
the subject may be considered an "original sample". Such an "original sample"
may be, for
example, a small quantity (e.g. less than 400, 300, 200, or 100 microliters)
of whole blood
from the subject. Shortly after or concurrent with the collection of the
"original sample"
from the subject, the "original sample" may be divided into at least a first
portion and a
second portion, after which the first portion is transferred into a first
vessel and the second
portion is transferred into a second vessel. In embodiments, the first vessel
may contain a
first anticoagulant (e.g. EDTA) and the second vessel may contain a second
anticoagulant
(e.g. heparin). The first and second vessels may be transported according to a
system or
method provided herein from the first location to a second location. In
embodiments, at the
second location, the sample in one or both of the vessels or portions thereof
may be subject to
further processing or analysis steps. For example, the sample in one or both
of the vessels or
portions thereof may be divided into additional portions, diluted, and/or used
for performing
one or more tests.
[00576] In another example, a bodily fluid sample may be shipped in a
vessel from a
first location to a second location according to systems and methods provided
herein. The
bodily fluid sample in the vessel may be the entirety of a sample that was
collected from a
subject, or a portion thereof. At the second location, at least some of the
bodily fluid sample
in the vessel may be removed from the vessel and used for a sample division
and/or dilution
procedure. The sample that is removed from vessel and used for the sample
division and/or
dilution procedure may be considered an "original sample". That original
sample may be, for
example, whole blood, plasma, serum, saliva, or urine, and may constitute the
entirety of the
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sample that was transported in the vessel, or a portion thereof That original
sample may be
divided into any number of portions; the various portions may have different
degrees of
dilution relative to the original sample. For example, the original sample
removed from a
transported vessel may have a volume of less than or equal to 400, 300, 250,
200, 150, 100,
90, 80, 70, 60, 50, 40, 30, 25, 20, 15, 10, 9, 8, 7, 6, 5, 4, 3, 2, or 1
microliter. The original
sample removed from a transported vessel may then be divided into at least 2,
3, 4, 5, 6, 7, 8,
9, 10, 15, 20, 25, 30, 35, 40, 50, 100, 200, 300, 400, 500, 1000, 5,000,
10,000 or more
different portions. In embodiments, the different portions may have different
degrees of
dilution relative to the original sample. For example, the different portions
may have at least
2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25, 30, 35, 40, 50, 100, 200, 300, 400,
500, 1000, or 5,000
different degrees of dilution relative to the original sample, with the
condition that the
number of portions having different degrees of dilution does not exceed the
total number of
portions prepared from the original sample. The different portions may have
any type of
dilution relative to the original sample, including, for example, no dilution,
at least 2-fold
dilution, at least 3-fold dilution, at least 5-fold dilution, at least 10-fold
dilution, at least 20-
fold dilution, at least 50-fold dilution, at least 100-fold dilution, at least
500-fold dilution, at
least 1000-fold dilution, at least 5000-fold dilution, at least 10,000-fold
dilution, at least
50,000-fold dilution, or at least 100,000-fold dilution. In embodiments, one
or more different
portions of an original sample may be used for a laboratory test. In
embodiments, one
portion of an original sample may be used for one laboratory test. A portion
of an original
sample used for a laboratory test may be a diluted sample.
[00577] In
embodiments, an original sample may be a whole blood sample obtained
from a subject. The original sample may be obtained from a subject's digit.
The original
sample may have a volume of no greater than 400, 300, 200, 150, 100, 90, 80,
70, 60, 50, 40,
30, 25, 20, 15, 10, 9, 8, 7, 6, 5, 4, 3, 2, or 1 microliters. The original
sample may be divided
into multiple portions. Division of the sample into multiple portions may
occur before, after,
or a combination of before and after the sample is transported from a first
location to a
second location according to a system or method provided herein. In
embodiments, the
original sample may be divided into at least 2, 3, 4, 5, 6, 7, 8, 9, 10, 15,
20, 25, 30, 35, 40, 50,
100, 200, 300, 400, 500, 1000, 5,000, 10,000 or more different portions, and
the different
portions are used to perform at least 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25,
30, 35, 40, 50, 100,
200, 300, 400, 500, 1000, 5,000, 10,000 different laboratory tests. The
different portions of
the original sample may have diluted original sample. In embodiments, no more
than 10, 9,
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8, 7, 6, 5, 4, 3, 2, 1, 0.9, 0.8, 0.7, 0.6, 0.5, 0.4, 0.3, 0.2, 0.1, 0.05, or
0.01 microliter of the
original sample is used per each laboratory test.
[00578] In embodiments, an original sample may be plasma or serum obtained
from
whole blood sample obtained from a subject. The whole blood may be obtained
from a
subject's digit. The whole blood sample from which the plasma or serum is
obtained may
have a volume of no greater than 400, 300, 200, 150, 100, 90, 80, 70, 60, 50,
40, 30, 25, 20,
15, 10, 9, 8, 7, 6, 5, 4, 3, 2, or 1 microliters. The plasma or serum original
sample may have a
volume of no greater than 300, 200, 150, 100, 90, 80, 70, 60, 50, 40, 30, 25,
20, 15, 10, 9, 8,
7, 6, 5, 4, 3, 2, or 1 microliters. The original sample may be divided into
multiple portions.
Division of the sample into multiple portions may occur before, after, or a
combination of
before and after the sample is transported from a first location to a second
location according
to a system or method provided herein. In embodiments, the original sample may
be divided
into at least 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25, 30, 35, 40, 50, 100,
200, 300, 400, 500, 1000,
5,000, 10,000 or more different portions, and the different portions are used
to perform at
least 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25, 30, 35, 40, 50, 100, 200, 300,
400, 500, 1000, 5,000,
10,000 different laboratory tests. The different portions of the original
sample may have
diluted original sample.
[00579] In embodiments, the equivalent of no more than 10, 9, 8, 7, 6, 5,
4, 3, 2, 1, 0.9,
0.8, 0.7, 0.6, 0.5, 0.4, 0.3, 0.2, 0.1, 0.05, or 0.01 microliter of an
original sample is used for a
laboratory test. For example, if an original sample is whole blood, and the
original sample is
divided into multiple portions, and at least one of the portions contains a
diluted sample
which contains original sample which has been diluted 100-fold, and 5
microliters of that
diluted sample is used to perform a laboratory test, then the equivalent of
0.05 microliters of
the original sample (e.g. whole blood) is used for that test (5 microliters x
1/100 dilution). In
another example, an original sample may be whole blood. That whole blood may
be
processed to yield plasma [e.g. by separating the liquid components of the
blood from the
solid components of blood (e.g. cells]. A certain volume of plasma may be
obtained from a
certain volume of whole blood - e.g. the volume of plasma that may be obtained
from a
volume of whole blood may be, for example, at least or about 30%, 40%, 50%,
60%, or 70%
of the volume of whole blood. Thus, for example, if the volume of plasma from
whole blood
is 50%, from 2 nil whole blood, 1 ml plasma may be obtained. The plasma from
whole blood
may be further diluted, and one or more diluted portions of the plasma may be
used to
perform one or more laboratory tests. In another example, an original sample
may be whole
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blood. The whole blood may be processed to yield plasma, where the volume of
plasma from
the whole blood is 60% of the whole blood (e.g. from 100 microliters whole
blood, 60
microliters plasma is obtained). The plasma may be diluted 10-fold. 2
microliters of the
diluted plasma may be used to perform a laboratory test. Thus, for that
laboratory test, the
equivalent of about 0.33 microliters original sample (whole blood) is used to
perform the test
(2 microliters x 1/10 dilution x 100/60 whole blood/plasma conversion). In
another example,
an original sample may be plasma, and the original sample may be divided into
multiple
portions, and at least one of the portions contains a diluted sample which
contains original
sample which has been diluted 50-fold, and 4 microliters of that diluted
sample is used to
perform a laboratory test, then the equivalent of 0.08 microliters of the
original sample (e.g.
plasma) is used for that test (4 microliters x 1/50 dilution).
1005801 In embodiments, an original sample may be divided into at least 2,
3, 4, 5, 6,
7, 8, 9, 10, 15, 20, 25, 30, 35, 40, 50, 100, 200, 300, 400, 500, 1000, 5,000,
10,000 or more
different portions, and the different portions may be used to perform at least
2, 3, 4, 5, 6, 7, 8,
9, 10, 15, 20, 25, 30, 35, 40, 50, 100, 200, 300, 400, 500, 1000, 5,000,
10,000 different
laboratory tests. In some embodiments, at least as many portions of sample are
prepared as
laboratory tests are performed with portions of a sample (e.g. in order to
perform 10
laboratory tests with an original sample, the original sample may be divided
into at least 10
portions, with at least 1 portion being used per test). In certain other
embodiments, more than
one laboratory test may be performed with a single sample. For instance, in
embodiments, an
optical property of a sample may be measured (e.g. cell count in a blood
sample), and then
the same sample may be used to assay for an analyte in the blood. Thus, in
some
embodiments, more laboratory tests may be performed with an original sample
than the
number of portions which are prepared from the same original sample (e.g. 10
laboratory
tests may be performed from an original sample which is divided into only 8
portions).
1005811 When an original sample is divided into multiple portions, and the
multiple
portions are used to perform two or more laboratory tests, the laboratory
tests may be of the
same type of laboratory test, or they may be of different types of laboratory
test. For
instance, if an original sample is divided into 10 portions, and the 10
portions are each used
for a laboratory test, the laboratory test with each of the portions may be an
immunoassay. In
another example, if an original sample is divided into 5 portions, and the 5
portions are each
used for .a laboratory test, the laboratory test with each of the portions may
be a nucleic acid
amplification-based test.
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[00582] In other situations, when an original sample is divided into
multiple portions,
and the multiple portions are used to perform two or more laboratory tests, at
least two of the
laboratory tests may be of different types of laboratory test. For instance,
if an original
sample is divided into 5 portions, and the 5 portions are each used for a
laboratory test, 2 of
the portions may be used for an immunoassay (e.g. ELISA) and 3 of the portions
may be used
for a nucleic acid amplification-based test.
[00583] A bodily fluid sample or portion thereof transported according to
a system or
method provided herein may be used in various types of laboratory test, such
as an
immunoassay, nucleic acid amplification assay, general chemistry assay, or
cytometry assay.
In embodiments, a bodily fluid sample or portion thereof transported according
to a system or
method provided herein may be used in any type of assay or laboratory test as
described in,
for example, U.S. Pat. App. Ser. No. 13/769,820, filed February 18, 2013, or
any other
document incorporated by reference elsewhere herein.
[00584] In some embodiments, a bodily fluid sample or portion thereof
transported
according to a system or method provided herein may be used in an immunoassay.
As used
herein, an "immunoassay" refers to any assay which involves probing for an
analyte with an
antibody which has affinity for the analyte. Immunoassays may include, for
example,
enzyme-linked immunosorbent (ELISA) assays and may include competitive and non-
competitive based-assays. The term "antibody" as used herein refers to
immunoglobulin
molecules and immunologically active portions of immunoglobulin molecules,
i.e., molecules
that comprise an antigen-binding unit ("Abu" or plural "Abus") which
specifically binds
("immunoreacts with") an antigen. Structurally, the simplest naturally
occurring antibody
(e.g., IgG) comprises four polypeptide chains, two heavy (H) chains and two
light (L) chains
inter-connected by disulfide bonds. The immunoglobulins represent a large
family of
molecules that include several types of molecules, such as IgD, IgG, IgA, IgM
and IgE. The
term "immunoglobulin molecule" includes, for example, hybrid antibodies, or
altered
antibodies, and fragments thereof. Antigen-binding unit can be broadly divided
into "single-
chain" ("Sc") and "non-single-chain" ("Nsc") types based on their molecular
structures.
[00585] Also encompassed within the terms "antibodies" and "antigen-
binding unit"
are immunoglobulin molecules and fragments thereof that may be human, nonhuman
(vertebrate or invertebrate derived), chimeric, or humanized. For a
description of the
concepts of chimeric and humanized antibodies see Clark et al., 2000 and
references cited
therein (Clark, (2000) Immunol. Today 21:397-402). In embodiments,
"immunoassays" as
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provided herein may also include assays in which the analyte to be measured in
the assay is
an antibody, and the antibody is probed for with a molecule to which the
antibody has affinity
(e.g. a target molecule of the antibody).
[00586] In
some embodiments, a bodily fluid sample or portion thereof transported
according to a system or method provided herein may be used in a nucleic acid
amplification
assay. As used herein, a "nucleic acid amplification assay" refers to an assay
in which the
copy number of a target nucleic acid may be increased. Nucleic acid
amplification assays
may include both isothermal and temperature-variable amplification techniques,
and include,
for example, techniques such as polymerase chain reaction (PCR) and loop-
mediated
isothermal amplification (LAMP). Typically, a nucleic acid amplification assay
includes at
least i) a nucleic acid polymerase, ii) primers which can bind to a target
nucleic acid
sequence, and iii) free nucleotides which may be incorporated into synthesized
nucleic acid
by a polymerase. Amplification of a target nucleic acid may be detected in
various ways,
such as measuring the fluoresecence or turbidity of a reaction over a period
of time.
[00587] In
some embodiments, a bodily fluid sample or portion thereof transported
according to a system or method provided herein may be used in a general
chemistry assay.
General chemistry assays may include, for example, assays of a Basic Metabolic
Panel
[glucose, calcium, sodium (Na), potassium (K), chloride (C1), CO2 (carbon
dioxide,
bicarbonate), creatinine, blood urea nitrogen (BUN)], assays of an Electrolyte
Panel [sodium
(Na), potassium (K), chloride (C1), CO2 (carbon dioxide, bicarbonate)], assays
of a Chem 14
Panel / Comprehensive Metabolic Panel [glucose, calcium, albumin, total
protein, sodium
(Na), potassium (K), chloride (C1), CO2 (carbon dioxide, bicarbonate),
creatinine, blood urea
nitrogen (BUN), alkaline phosphatase (ALP), alanine aminotransferase
(ALT/GPT), aspartate
aminotransferase (AST/GOT), total bilirubin] assays of a Lipid Profile / Lipid
Panel [LDL
cholesterol, HDL cholesterol, total cholesterol, and triglycerides], assays of
a Liver Panel /
Liver Function [alkaline phosphatase (ALP), alanine aminotransferase
(ALT/GPT), aspartate
aminotransferase (AST/GOT), total bilirubin, albumin, total protein, gamma-
glutamyl
transferase (GGT), lactate dehydrogenase (LDH), prothrombin time (PT)],
alkaline
phosphatase (APase), hemoglobin, VLDL cholesterol, ethanol, lipase, pH, zinc
protoporphyrin, direct bilirubin, blood typing (ABO, RHD), lead, phosphate,
hemagglutination inhibition, magnesium, iron, iron uptake, fecal occult blood,
and others,
individually or in any combination.
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1005881 In general chemistry assays provided herein, in some examples, the
level of an
analyte in a sample is determined through one or more assay steps involving a
reaction of the
analyte of interest with one or more reagents, leading to a detectable change
in the reaction
(e.g. change in the turbidity of the reaction, generation of luminescence in
the reaction,
change in the color of the reaction, etc.). In some examples, a property of a
sample is
determined through one or more assay steps involving a reaction of the sample
of interest
with one or more reagents, leading to a detectable change in the reaction
(e.g. change in the
turbidity of the reaction, generation of luminescence in the reaction, change
in the color of
the reaction, etc.). Typically, as used herein, "general chemistry" assays do
not involve
amplification of nucleic acids, imaging of cells on a microscopy stage, or the
determination
of the level of an analyte in solution based on the use of a labeled antibody
/ binder to
determine the level of an analyte in a solution. In some embodiments, general
chemistry
assays are performed with all reagents in a single vessel ¨ i.e. to perform
the reaction, all
necessary reagents are added to a reaction vessel, and during the course of
the assay,
materials are not removed from the reaction or reaction vessel (e.g. there is
no washing step;
it is a "mix and read" reaction). General chemistry assays may also be, for
example,
colorimetric assays, enzymatic assays, spectroscopic assays, turbidimetric
assays,
agglutination assays, coagulation assays, and/or other types of assays. Many
general
chemistry assays may be analyzed by measuring the absorbance of light at one
or more
selected wavelengths by the assay reaction (e.g. with a spectrophotometer). In
some
embodiments, general chemistry assays may be analyzed by measuring the
turbidity of a
reaction (e.g. with a spectrophotometer). In some embodiments, general
chemistry assays
may be analyzed by measuring the chemiluminescence generated in the reaction
(e.g. with a
PMT, photodiode, or other optical sensor). In some embodiments, general
chemistry assays
may be performed by calculations, based on experimental values determined for
one or more
other analytes in the same or a related assay. In some embodiments, general
chemistry assays
may be analyzed by measuring fluorescence of a reaction (e.g. with a detection
unit
containing or connected to i) a light source of a particular wavelength(s)
("excitation
wavelength(s)"); and ii) a sensor configured to detect light emitted at a
particular
wavelength(s) ("emission wavelength(s)"). In some embodiments, general
chemistry assays
may be analyzed by measuring agglutination in a reaction (e.g. by measuring
the turbidity of
the reaction with a spectrophotometer or by obtaining an image of the reaction
with an optical
sensor). In some embodiments, general chemistry assays may be analyzed by
imaging the
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reaction at one or more time points (e.g. with a CCD or CMOS optical sensor),
followed by
image analysis. Optionally, analysis may involve prothrombin time, activated
partial
thromboplastin time (APTT), either of which may be measured through a method
such as but
not limtied to turbidimetry. In some embodiments, general chemistry assays may
be
analyzed by measuring the viscosity of the reaction (e.g. with a
spectrophotometer, where an
increase in viscosity of the reaction changes the optical properties of the
reaction). In some
embodiments, general chemistry assays may be analyzed by measuring complex
formation
between two non-antibody reagents (e.g. a metal ion to a chromophore; such a
reaction may
be measured with a spectrophotometer or through colorimetry using another
device). In some
embodiments, general chemistry assays may be analyzed by non-ELISA or
cytometry-based
methods for assaying cellular antigens (e.g. hemagglutination assay for blood
type, which
may be measured, for example, by turbidity of the reaction). In some
embodiments, general
chemistry assays may be analyzed with the aid of electrochemical sensors (e.g.
for carbon
dioxide or oxygen). Additional methods may also be used to analyze general
chemistry
assays.
[005891 In some embodiments, a spectrophotometer may be used to measure a
general
chemistry assay. In some embodiments, general chemistry assays may be measured
at the
end of the assay (an "end-point" assay) or at two or more times during the
course of the assay
(a "time-course" or "kinetic" assay).
1005901 In some embodiments, a bodily fluid sample or portion thereof
transported
according to a system or method provided herein may be used in a cytometry
assay.
Cytometry assays are typically used to optically, electrically, or
acoustically measure
characteristics of individual cells. For the purposes of this disclosure,
"cells" may encompass
non-cellular samples that are generally of similar sizes to individual cells,
including but not
limited to vesicles (such as liposomes), small groups of cells, virions,
bacteria, protozoa,
crystals, bodies formed by aggregation of lipids and/or proteins, and
substances bound to
small particles such as beads or microspheres. Such characteristics include
but are not
limited to size; shape; granularity; light scattering pattern (or optical
indicatrix); whether the
cell membrane is intact; concentration, morphology and spatio-temporal
distribution of
internal cell contents, including but not limited to protein content, protein
modifications,
nucleic acid content, nucleic acid modifications, organelle content, nucleus
structure, nucleus
content, internal cell structure, contents of internal vesicles (including
pH), ion
concentrations, and presence of other small molecules such as steroids or
drugs; and cell
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surface (both cellular membrane and cell wall) markers including proteins,
lipids,
carbohydrates, and modifications thereof By using appropriate dyes, stains, or
other labeling
molecules either in pure form, conjugated with other molecules or immobilized
in, or bound
to nano- or micro-particles, cytometry may be used to determine the presence,
quantity,
and/or modifications of specific proteins, nucleic acids, lipids,
carbohydrates, or other
molecules. Cytometric analysis may, for example, be by flow cytometry or by
microscopy.
Flow cytometry typically uses a mobile liquid medium that sequentially carries
individual
cells to an optical, electrical or acoustic detector. Microscopy typically
uses optical or
acoustic means to detect stationary cells, generally by recording at least one
magnified
image. In embodiments, a cytometry assay may involve obtaining images of one
or more
cells in a sample. In embodiments, a sample may be provided on or in a
microscope slide or
cuvette, which may permit cells in a sample to settle in a desired
configuration for imaging.
Images of cells may be obtained, for example, with a CCD or CMOS-based camera.
1005911 In some embodiments, laboratory test types may be classified based
on how
the results of the test are detected. Different types of laboratory test
result detection may
include, for example, i) luminescence detection; ii) fluorescence detection;
iii) absorbance
detection; iv) light scattering detection; and v) imaging. Each of these
detection methods are
described, for example, in U.S. Pat. App. Ser. No. 13/769,820, filed February
18, 2013,
which is hereby incorporated in its entirety for all purposes. Briefly,
luminescence may be
detected from tests which yield a measurable light signal. Such reactions may
be, for
example, chemiluminescent reactions. In order to detect the result of a
luminescent reaction,
a light detector such as a PMT or photodiode may be used to detect light from
an assay unit
containing a luminescent reaction. Fluorescence may be detected, for example,
with an
optical set up which includes a light source and a light detector. The light
source may emit
light of a particular wavelength(s). An assay unit containing the test
material may be situated
in the path of the light source, such that light of the particular
wavelength(s) reaches the
contents of the assay unit ("excitation wavelength(s)"). The assay unit may
contain a
molecule of interest which, at least under some circumstances, absorbs light
at the particular
wavelength(s) from the light source, and, subsequently, releases light of a
different
wavelength. The light detector may be configured to detect light released by
the molecule of
interest ("emission wavelength(s)"). The light source and/or light detector
may include a
band-pass filter after the light source or before the light detector, in order
to restrict the
wavelength(s) of light from the light source or reaching the light detector.
The light source
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may be, for example, a light bulb, a laser or an LED, and the light detector
may be, for
example, a PMT or photodiode. Absorbance may be detected, for example, with an
optical
set up which includes a light source and a light detector. The light source
and light detector
may be situated in line with each other, and configured such that an assay
unit containing the
test material may be situated between the light source and light detector,
such that some light
may pass through the test material to the light detector and some light may be
absorbed.
Different amounts of light may be absorbed by the test material, based on the
outcome of the
test. Similarly, transmission of light through the test material may be
determined. For an
absorbance / transmission determination assay, the wavelength(s) of light
emitted by the light
source may be same as the wavelength(s) of light detected by the light
detector. The light
source may be, for example, a light bulb, a laser or an LED, and the light
detector may be, for
example, a PMT or photodiode. Light scattering may be detected, for example,
witkan
optical set up which includes a light source and a light detector. The light
source and light
detector may be situated at an angle relative to each other, and configured
such that an assay
unit containing the test material may be situated in line with both the light
source and light
detector, such that light from the light source may reach the assay unit and
be scattered by
test material in the assay unit, to reach the light detector. Different
amounts of light may be
scattered by the test material, based on the outcome of the test. The light
source may be, for
example, a light bulb, a laser or an LED, and the light detector may be, for
example, a PMT
or photodiode. Images of a test material may be obtained, for example, by a
detector which
includes an image sensor (e.g. a CCD or CMOS sensor). Typically the image
sensor will be
included in a camera. Images of test material may be analyzed, for example, by
automated or
manual image analysis, in order to determine test results. Bodily fluid
samples as provided
herein may also be used in laboratory tests which detect results through non-
optical based
detection methods (e.g. measurements of conductivity, radioactivity, or
temperature).
[00592] In embodiments, in order to perform an assay / test with a portion
of a bodily
fluid sample, the portion of the bodily fluid sample may be transferred into
an assay unit for
at least one step of the assay / test. Assay units may have various form
factors, such as a
pipette tip, a tube, or a microscope slide. Steps of an assay that may occur
in an assay unit
may include, for example, an analyte in the sample binding to a binder (e.g.
an antibody) for
the analyte, a target nucleic acid in the sample being amplified in a nucleic
acid amplification
reaction, a sample coagulating based on the addition of one or more reagents
to the sample, or
a sample adopting a configuration for optical analysis (e.g. cells settling on
a surface of a
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microscope slide in order to facilitate obtaining one or more images of the
cells). As used
herein, the terms "assay" and "test" may be used interchangeably, unless the
context clearly
dictates otherwise.
Examples
[00593] The following examples are offered for illustrative purposes only,
and are not
intended to limit the present disclosure in any way.
[00594] Example 1
[00595] A whole blood sample was obtained from a subject. The whole blood
sample
was centrifuged in a vessel, in order to separate the whole blood into
pelleted cells and a
plasma supernatant. The centrifuged vessel was moved to an argon-purged glove
box.
Plasma was aspirated from the centrifuged vessel and then aliquoted into 5
separate sample
vessels as provided herein, wherein the sample vessels each had an interior
volume of no
greater than 100 microliters, wherein no greater than 95 microliters plasma
was aliquoted into
each sample vessel, and wherein each of the sample vessels was of the same
size and
received the same volume of plasma. The vessels each had a removable butyl
rubber cap.
The 5 sample vessels were associated with the labels "0 hour", "1 hour", "2
hours", "8
hours", and "24 hours". At the respective time period associated with each
sample vessel, the
sample in each vessel was assayed for bicarbonate. The results of the assays
are provided
below in Table 1.
[00596] Table 1
Time (hours) 0 1 2 8 24
Concentration 32.7 30.4 29.8 31.6 31.1
Bicarbonate
(mM)
[00597] As shown in Table 1, the bicarbonate in the sample was stable for
at least 24
hours in a sample vessel provided herein.
[00598] Example 2
[00599] A whole blood sample was obtained from a subject. EDTA was mixed
with
the whole blood sample. Eighty microliters of the EDTA-containing blood was
aliquoted
into each of 10 sample vessels as provided herein, wherein each sample vessel
had an interior
volume of no greater than 100 microliters, and was of the same size. The
sample vessels
were associated with labeled for analysis as follows: Real-time: Day 1, 2, 3,
4, 5, and 7; Pre-
centrifuged: Day 1, 2, 4, and 7. Each of the "pre-centrifuged" vessels were
centrifuged at the
time of aliquoting the sample into the vessel, to generate plasma and pelleted
cells. Each of
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the "real-time" vessels was centrifuged on the respective day, to generate
plasma and pelleted
cells. After sample was aliquoted into each sample vessel, it was capped. On
the respective
day for each vessel, plasma was removed from the vessel and assayed for blood
nitrogen urea
(BUN). The BUN assay results are shown in the graph in Figure 48. As shown in
the graph,
BUN remains stable in a sample in a sample vessel provided herein for at least
7 days, in both
whole blood and plasma samples.
[00600] The publications discussed or cited herein are provided solely for
their
disclosure prior to the filing date of the present application. Nothing herein
is to be construed
as an admission that the present invention is not entitled to antedate such
publication by
virtue of prior invention. Further, the dates of publication provided may be
different from the
actual publication dates which may need to be independently confirmed. All
publications
mentioned herein are incorporated herein by reference to disclose and describe
the structures
and/or methods in connection with which the publications are cited. The
following
applications are fully incorporated herein by reference for all purposes: in
U.S. Provisional
Patent Application No. 61/435,250, filed January 21, 2011 ("SYSTEMS AND
METHODS
FOR SAMPLE USE MAXIMIZATION"), and U.S. Patent Publication No. 2009/0088336
("MODULAR POINT-OF-CARE DEVICES, SYSTEMS, AND USES THEREOF"). The
following applications are also fully incorporated herein by reference for all
purposes: U.S.
Patent Publication 2005/0100937, U.S. Patent 8,380,541; U.S. Pat. App. Ser.
No. 61/766,113,
filed February 18, 2013; U.S. Pat. App. Ser. No. 13/769,798, filed February
18, 2013; U.S.
Pat. App. Ser. No. 13/769,779, filed February 18, 2013; U.S. Pat. App. Ser.
No. 13/769,820,
filed February 18, 2013; U.S. Pat. App. Ser. No. 13/244,947 filed Sept. 26,
2011;
PCT/US2012/57155, filed September 25, 2012; U.S. Application Serial No.
13/244,946, filed
September 26, 2011; U.S. Patent Application 13/244,949, filed September 26,
2011; and U.S.
Application Serial No. 61/673,245, filed September 26, 2011, the disclosures
of which
patents and patent applications are all hereby incorporated by reference in
their entireties.
EMBODIMENTS
[00601] In one embodiment described herein, a device for collecting a
bodily fluid
sample from a subject is provided comprising: at least two sample collection
pathways
configured to draw the bodily fluid sample into the device from a single end
of the device in
contact with the subject, thereby separating the fluid sample into two
separate samples; a
second portion comprising a plurality of sample vessels for receiving the
bodily fluid sample
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collected in the sample collection pathways, the sample vessels operably
engagable to be in
fluid communication with the sample collection pathways, whereupon when fluid
communication is established, the vessels provide a motive force to move a
majority of the
two separate samples from the pathways into the vessels.
[00602] In another embodiment described herein, a device for collecting a
bodily fluid
sample is provided comprising: a first portion comprising at least one fluid
collection location
leading to at least two sample collection pathways configured to draw the
fluid sample
therein via a first type of motive force; a second portion comprising a
plurality of sample
vessels for receiving the bodily fluid sample collected in the sample
collection pathways, the
sample vessels operably engagable to be in fluid communication with the sample
collection
pathways, whereupon when fluid communication is established, the vessels
provide a second
motive force different from the first motive force to move a majority of the
bodily fluid
sample from the pathways into the vessels; wherein at least one of the sample
collection
pathways comprises a fill indicator to indicate when a minimum fill level has
been reached
and that at least one of the sample vessels can be engaged to be in fluid
communication with
at least one of the sample collection pathways.
[00603] In another embodiment described herein, a device for collecting a
bodily fluid
sample is provided comprising a first portion comprising at least two sample
collection
channels configured to draw the fluid sample into the sample collection
channels via a first
type of motive force, wherein one of the sample collection channels has an
interior coating
designed to mix with the fluid sample and another of the sample collection
channels has
another interior coating chemically different from said interior coating; a
second portion
comprising a plurality of sample vessels for receiving the bodily fluid sample
collected in the
sample collection channels, the sample vessels operably engagable to be in
fluid
communication with the collection channels, whereupon when fluid communication
is
established, the vessels provide a second motive force different from the
first motive force to
move a majority of the bodily fluid sample from the channels into the vessels;
wherein
vessels are arranged such that mixing of the fluid sample between the vessels
does not occur.
[00604] In another embodiment described herein, a device for collecting a
bodily fluid
sample is provided comprising: a first portion comprising a plurality of
sample collection
channels, wherein at least two of the channels are configured to
simultaneously draw the fluid
sample into each of the at least two sample collection channels via a first
type of motive
force; a second portion comprising a plurality of sample vessels for receiving
the bodily fluid
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sample collected in the sample collection channels, wherein the sample vessels
have a first
condition where the sample vessels are not in fluid communication with the
sample collection
channels, and a second condition where the sample vessels are operably
engagable to be in
fluid communication with the collection channels, whereupon when fluid
communication is
established, the vessels provide a second motive force different from the
first motive force to
move bodily fluid sample from the channels into the vessels.
[00605] In another embodiment described herein, a sample collection device
is
provided comprising: (a) a collection channel comprising a first opening and a
second
opening, and being configured to draw a bodily fluid sample via capillary
action from the
first opening towards the second opening; and (b) a sample vessel for
receiving the bodily
fluid sample, the vessel being engagable with the collection channel, having
an interior with a
vacuum therein, and having a cap configured to receive a channel; wherein the
second
opening is defined by a portion the collection channel configured to penetrate
the cap of the
sample vessel, and to provide a fluid flow path between the collection channel
and the sample
vessel, and the sample vessel has an interior volume no greater than ten times
larger than the
interior volume of the collection channel.
100606] In another embodiment described herein, a sample collection device
is
provided comprising: (a) a collection channel comprising a first opening and a
second
opening, and being configured to draw a bodily fluid sample via capillary
action from the
first opening towards the second opening; (b) a sample vessel for receiving
the bodily fluid
sample, the vessel being engagable with the collection channel, having an
interior with a
vacuum therein, and having a cap configured to receive a channel; and (c) an
adaptor channel
configured to provide a fluid flow path between the collection channel and the
sample vessel,
having a first opening and a second opening, the first opening being
configured to contact the
second opening of the collection channel, the second opening being configured
to penetrate
the cap of the sample vessel..
[00607] In another embodiment described herein, a sample collection device
is
provided comprising: (a) a body, containing a collection channel , the
collection channel
comprising a first opening and a second opening, and being configured to draw
a bodily fluid
via capillary action from the first opening towards the second opening; (b) a
base, containing
a sample vessel for receiving the bodily fluid sample, the sample vessel being
engagable with
the collection channel, having an interior with a vacuum therein, and having a
cap configured
to receive a channel; and (c) a support, wherein, the body and the base are
connected to
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opposite ends of the support, and are configured to be movable relative to
each other, such
that sample collection device is configured to have an extended state and a
compressed state,
wherein at least a portion of the base is closer to the body in the extended
state of the device
than in the compressed state, the second opening of the collection channel is
configured to
penetrate the cap of the sample vessel, in the extended state of the device,
the second opening
of the collection channel is not in contact with the interior of the sample
vessel, and in the
compressed state of the device, the second opening of the collection channel
extends into the
interior of the sample vessel through the cap of the vessel, thereby providing
fluidic
communication between the collection channel and the sample vessel.
[00608] In another embodiment described herein, a sample collection device
is
provided comprising: (a) a body, containing a collection channel , the
collection channel
comprising a first opening and a second opening, and being configured to draw
a bodily fluid
via capillary action from the first opening towards the second opening; (b) a
base, containing
a sample vessel for receiving the bodily fluid sample, the sample vessel being
engagable with
the collection channel, having an interior with a vacuum therein and having a
cap configured
to receive a channel; (c) a support, and (d) an adaptor channel, having a
first opening and a
second opening, the first opening being configured to contact the second
opening of the
collection channel, and the second opening being configured to penetrate the
cap of the
sample vessel, wherein, the body and the base are connected to opposite ends
of the support,
and are configured to be movable relative to each other, such that sample
collection device is
configured to have an extended state and a compressed state, wherein at least
a portion of the
base is closer to the body in the extended state of the device than in the
compressed state, in
the extended state of the device, the adaptor channel is not in contact with
one or both of the
collection channel and the interior of the sample vessel, and in the
compressed state of the
device, the first opening of the adaptor channel is in contact with the second
opening of the
collection channel, and the second opening of the adaptor channel extends into
the interior of
the sample vessel through the cap of the vessel, thereby providing fluidic
communication
between the collection channel and the sample vessel.
[00609] In another embodiment described herein, a device for collecting a
fluid sample
from a subject is provided comprising: (a) a body containing a collection
channel, the
collection channel comprising a first opening and a second opening, and being
configured to
draw a bodily fluid via capillary action from the first opening towards the
second opening;
(b) a base, engagable with the body, wherein the base supports a sample
vessel, the vessel
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being engagable with the collection channel, having an interior with a vacuum
therein, and
having a cap configured to receive a channel; wherein the second opening of
the collection
channel is configured to penetrate the cap of the sample vessel, and to
provide a fluid flow
path between the collection channel and the sample vessel.
[00610] In another embodiment described herein, a device for collecting a
fluid sample
from a subject is provided comprising: (a) a body containing a collection
channel, the
collection channel comprising a first opening and a second opening, and being
configured to
draw a bodily fluid via capillary action from the first opening towards the
second opening;
(b) a base, engagable with the body, wherein the base supports a sample
vessel, the sample
vessel being engagable with the collection channel, having an interior with a
vacuum therein
and having a cap configured to receive a channel; and (c) an adaptor channel,
having a first
opening and a second opening, the first opening being configured to contact
the second
opening of the collection channel, and the second opening being configured to
penetrate the
cap of the sample vessel.
[00611] It should be understood that one or more of the following features
may be
adapted for use with any of the embodiments described herein. By way of non-
limiting
example, the body may comprise of two collection channels. Optionally, the
interior of the
collection channel(s) are coated with an anticoagulant. Optionally, the body
comprises a first
collection channel and a second collection channel, and the interior of the
first collection
channel is coated with a different anticoagulant than the interior of the
second collection
channel. Optionally, the first anticoagulant is ethylenediaminetetraacetic
acid (EDTA) and
the second anticoagulant is different from EDTA. Optionally, the first
anticoagulant is citrate
and the second anticoagulant is different from citrate. Optionally, the first
anticoagulant is
heparin and the second anticoagulant is different from heparin. Optionally,
one anticoagulant
is heparin and the second anticoagulant is EDTA. Optionally, one anticoagulant
is heparin
and the second anticoagulant is citrate. Optionally, one anticoagulant is
citrate and the
second anticoagulant is EDTA. Optionally, the body is formed from an optically
transmissive material. Optionally, the device includes the same number of
sample vessels as
collection channels. Optionally, the device includes the same number of
adaptor channels as
collection channels. Optionally, the base contains an optical indicator that
provides a visual
indication of whether the sample has reached the sample vessel in the base.
Optionally, the
base is a window that allows a user to see the vessel in the base. Optionally,
the support
comprises a spring, and spring exerts a force so that the device is at the
extended state when
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the device is at its natural state. Optionally, the second opening of the
collection channel or
the adaptor channel is capped by a sleeve, wherein said sleeve does not
prevent movement of
bodily fluid via capillary action from the first opening towards the second
opening.
Optionally, the sleeve contains a vent. Optionally, each collection channel
can hold a volume
of no greater than 500 uL. Optionally, each collection channel can hold a
volume of no
greater than 200 uL. Optionally, each collection channel can hold a volume of
no greater
than 100 uL. Optionally, each collection channel can hold a volume of no
greater than 70 uL.
Optionally, each collection channel can hold a volume of no greater than 500
uL. Optionally,
each collection channel can hold a volume of no greater than 30 uL.
Optionally, the internal
circumferential perimeter of a cross-section of each collection channel is no
greater than 16
mm. Optionally, the internal circumferential perimeter of a cross-section of
each collection
channel is no greater than 8 mm. Optionally, the internal circumferential
perimeter of a
cross-section of each collection channel is no greater than 4 mm. Optionally,
the internal
circumferential perimeter is a circumference. Optionally, the device comprises
a first and a
second collection channel, and the opening of the first channel is adjacent to
an opening of
said second channel, and the openings are configured to draw blood
simultaneously from a
single drop of blood. Optionally, the opening of the first channel and the
opening of the
second channel have a center-to-center spacing of less than or equal to about
5 mm.
Optionally, each sample vessel has an interior volume no greater than twenty
times larger
than the interior volume of the collection channel with which it is engagable.
Optionally,
each sample vessel has an interior volume no greater than ten times larger
than the interior
volume of the collection channel with which it is engagable. Optionally, each
sample vessel
has an interior volume no greater than five times larger than the interior
volume of the
collection channel with which it is engagable. Optionally, each sample vessel
has an interior
volume no greater than two times larger than the interior volume of the
collection channel
with which it is engagable. Optionally, establishment of fluidic communication
between the
collection channel and the sample vessel results in transfer of at least 90%
of the bodily fluid
sample in the collection channel into the sample vessel.
[00612] It should be understood that one or more of the following features
may be
adapted for use with any of the embodiments described herein. Optionally,
establishment of
fluidic communication between the collection channel and the sample vessel
results in
transfer of at least 95% of the bodily fluid sample in the collection channel
into the sample
vessel. Optionally, establishment of fluidic communication between of the
collection channel
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and the sample vessel results in transfer of at least 98% of the bodily fluid
sample in the
collection channel into the sample vessel. Optionally, establishment of
fluidic
communication between the collection channel and the sample vessel results in
transfer of the
bodily fluid sample into the sample vessel and in no more than ten uL of
bodily fluid sample
remaining in the collection channel. Optionally, establishment of fluidic
communication
between the collection channel and the sample vessel results in transfer of
the bodily fluid
sample into the sample vessel and in no more than five uL of bodily fluid
sample remaining
in the collection channel. Optionally, engagement of the collection channel
with the sample
vessel results in transfer of the bodily fluid sample into the sample vessel
and in no more than
2 uL of bodily fluid sample remaining in the collection channel.
[00613] In another embodiment described herein, a method is provided
comprising
contacting one end of a sample collection device to a bodily fluid sample to
split the sample
into at least two portions by drawing the sample into at least two collection
channels of the
sample collection device by way of a first type of motive force; establishing
fluid
communication between the sample collection channels and the sample vessels
after a desired
amount of sample fluid has been confirmed to be in at least one of the
collection channels,
whereupon the vessels provide a second motive force different from the first
motive force to
move each of the portions of bodily fluid sample into their respective
vessels.
[00614] In another embodiment described herein, a method is provided
comprising
metering a minimum amount of sample into at least two channels by using a
sample
collection device with at least two of the sample collection channels
configured to
simultaneously draw the fluid sample into each of the at least two sample
collection channels
via a first type of motive force; after a desired amount of sample fluid has
been confirmed to
be in the collection channels, fluid communication is established between the
sample
collection channels and the sample vessels, whereupon the vessels provide a
second motive
force different from the first motive force use to collect the samples to move
bodily fluid
sample from the channels into the vessels.
[00615] In another embodiment described herein, a method of collecting a
bodily fluid
sample is provided comprising (a) contacting a bodily fluid sample with a
device comprising
a collection channel, the collection channel comprising a first opening and a
second opening,
and being configured to draw a bodily fluid via capillary action from the
first opening
towards the second opening, such that the bodily fluid sample fills the
collection channel
from the first opening through the second opening; (b) establishing a fluid
flow path between
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the collection channel and the interior of a sample vessel , said sample
vessel having an
interior volume no greater than ten times larger than the interior volume of
the collection
channel and having a vacuum prior to establishment of the fluid flow path
between the
collection channel and the interior of the sample vessel, such that
establishment of the fluid
flow path between the collection channel and the interior of the sample vessel
generates a
negative pressure at the second opening of the collection channel, and the
fluidic sample is
transferred from the collection channel to the interior of the sample vessel.
[00616] In another embodiment described herein, a method of collecting a
bodily fluid
sample is provided comprising (a) contacting a bodily fluid sample with any
collection device
as described herein, such that the bodily fluid sample fills the collection
channel from the first
opening through the second opening of at least one of the collection
channel(s) in the device;
and (b) establishing a fluid flow path between the collection channel and the
interior of the
sample vessel, such that establishing a fluid flow path between the collection
channel and the
interior of the sample vessel generates a negative pressure at the second
opening of the
collection channel, and the fluidic sample is transferred from the collection
channel to the
interior of the sample vessel.
[00617] It should be understood that one or more of the following features
may be
adapted for use with any of the embodiments described herein. Optionally, the
collection
channel and the interior of the sample vessel are not brought into fluid
communication until
the bodily fluid reaches the second opening of the collection channel.
Optionally, the device
comprises two collection channels, and the collection channels and the
interior of the sample
vessels are not brought into fluidic communication until the bodily fluid
reaches the second
opening of both collection channels. Optionally, the second opening of the
collection channel
in the device is configured to penetrate the cap of the sample vessel, and
wherein a fluidic
flow path between the second opening of the collection channel and the sample
vessel is
established by providing relative movement between the second opening of the
collection
channel and the sample vessel, such that the second opening of the collection
channel
penetrates the cap of the sample vessel. Optionally, the device comprises an
adaptor channel
for each collection channel in the device, the adaptor channel having a first
opening and a
second opening, the first opening being configured to contact the second
opening of the
collection channel, and the second opening being configured to penetrate the
cap of the
sample vessel, and wherein a fluidic flow path between the collection channel
and the sample
vessel is established by providing relative movement between two or more of:
(a) the second
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opening of the collection channel, (b) the adaptor channel, and (c) the sample
vessel, such
that the second opening of the adaptor channel penetrates the cap of the
sample vessel.
[00618] In another embodiment described herein, a method for collecting a
bodily fluid
sample from a subject is provided comprising: (a) bringing a device comprising
a first
channel and a second channel into fluidic communication with a bodily fluid
from the
subject, each channel having an input opening configured for fluidic
communication with
said bodily fluid, each channel having an output opening downstream of the
input opening of
each channel, and each channel being configured to draw a bodily fluid via
capillary action
from the input opening towards the output opening; (b) bringing, through the
output opening
of each of the first channel and the second channel, said first channel and
said second channel
into fluidic communication with a first vessel and a second vessel,
respectively; and (c)
directing said bodily fluid within each of said first channel and second
channel to each of said
first vessel and second vessel with the aid of: (i) negative pressure relative
to ambient
pressure in said first vessel or said second vessel, wherein said negative
pressure is sufficient
to effect flow of said bodily fluid through said first channel or said second
channel into its
corresponding vessel, or (ii) positive pressure relative to ambient pressure
upstream of said
first channel or said second channel, wherein said positive pressure is
sufficient to effect flow
of said whole blood sample through said first channel or said second channel
into its
corresponding vessel.
[00619] In another embodiment described herein, a method of manufacturing
a sample
collection device is provided comprising forming one portion of a sample
collection device
having at least two channels configured to simultaneously draw the fluid
sample into each of
the at least two sample collection channels via a first type of motive force;
forming sample
vessels, whereupon the vessels are configured to be coupled to the sample
collection device
to the provide a second motive force different from the first motive force use
to collect the
samples to move bodily fluid sample from the channels into the vessels.
[00620] In another embodiment described herein, computer executable
instructions are
provided for performing a method comprising: forming one portion of a sample
collection
device having at least two channels configured to simultaneously draw the
fluid sample into
each of the at least two sample collection channels via a first type of motive
force.
[00621] In another embodiment described herein, computer executable
instructions for
performing a method comprising: forming sample vessels, whereupon the vessels
are
configured to be coupled to the sample collection device to provide a second
motive force
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different from the first motive force use to collect the samples to move
bodily fluid sample
from the channels into the vessels.
[00622] In yet another embodiment described herein, a device for
collecting a bodily
fluid sample from a subject, the device comprising: means for drawing the
bodily fluid
sample into the device from a single end of the device in contact with the
subject, thereby
separating the fluid sample into two separate samples; means for transferring
the fluid sample
into a plurality of sample vessels, wherein the vessels provide a motive force
to move a
majority of the two separate samples from the pathways into the vessels.
[00623] While the above is a complete description of the preferred
embodiment as
described herein, it is possible to use various alternatives, modifications
and equivalents.
Therefore, the scope of the present invention should be determined not with
reference to the
above description but should, instead, be determined with reference to the
appended claims,
along with their full scope of equivalents. Any feature, whether preferred or
not, may be
combined with any other feature, whether preferred or not. The appended claims
are not to
be interpreted as including means-plus-function limitations, unless such a
limitation is
explicitly recited in a given claim using the phrase "means for." It should be
understood that
as used in the description herein and throughout the claims that follow, the
meaning of "a,"
"an," and "the" includes plural reference unless the context clearly dictates
otherwise. Also,
as used in the description herein and throughout the claims that follow, the
meaning of "in"
includes "in" and "on" unless the context clearly dictates otherwise. Finally,
as used in the
description herein and throughout the claims that follow, the meanings of
"and" and "or"
include both the conjunctive and disjunctive and may be used interchangeably
unless the
context expressly dictates otherwise. Thus, in contexts where the terms "and"
or "or" are
used, usage of such conjunctions do not exclude an "and/or" meaning unless the
context
expressly dictates otherwise. The following US patent applications are
incorporated herein by
reference for all purposes: 61/733,886 filed 12-05-2012, 61/875,030 filed 09-
07-2013, and
61/875,107 filed 09-08-2013. This document contains material subject to
copyright
protection. The copyright owner (Applicant herein) has no objection to
facsimile
reproduction of the patent documents and disclosures, as they appear in the US
Patent and
Trademark Office patent file or records, but otherwise reserves all copyright
rights
whatsoever. The following notice shall apply: Copyright 2013 Theranos, Inc.
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