Note: Descriptions are shown in the official language in which they were submitted.
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CENTRIFUGAL FILLING OF SAMPLE PROCESSING DEVICES
Field of the Invention
The present invention relates to the field of sample processing devices. More
particularly, the present invention relates to sample processing devices and
methods of
distributing sample material in sample processing devices.
Background
Many different chemical, biochemical, and other reactions are performed on a
variety of sample materials. Although it may be possible to process samples
individually
and obtain accurate sample-to-sample results, individual processing of samples
can be time-
consuming and expensive.
One approach to reducing the time and cost of processing multiple samples is
to use
a device including multiple chambers in which diil'erent portions of one
sample or different
samples can be processed simultaneously. This approach, however, presents
several issues
related to distribution of sample materials to the multiple chambers in the
devices. Other
problems may be encountered in the migration of materials between chambers
during
processing, which may lead to erroneous test results due to cross-chamber
contamination.
SummarX of the Invention
The present invention provides methods and devices for distributing sample
material
to a plurality of process chambers in a sample processing device by rotating
the device
about an axis of rotation. The process chambers are located along conduits
extending from
a loading chamber and, together, the loading chamber, conduits, and process
chambers
form process arrays that are aligned along a length of the sample processing
devices. The
process arrays are unvented, i.e., access to the interior volume of the
process arrays is
available only through the loading chamber.
In other aspects, the present invention may provide sample processing devices
including conduits that can be sealed by deforming one or both sides of the
sample
processing device to restrict or completely close offthe conduit. It may be
advantageous if
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the sample processing device includes a pressure sensitive adhesive located
between two
major sides of the device to assist in sealing of the conduit during and after
deformation.
Other aspects of the sample processing devices may include, for example,
elongated processing chambers, feeder conduits leading to the process chambers
that form
feeder conduit angles with the main conduit of less than 90 degrees, etc.
The process arrays in sample processing devices of the present invention may
be
capable of customization by selective opening and/or closing of fluid paths in
the process
arrays.
In some methods of centrifugal loading, it may be desirable to compress the
sample
processing devices during rotation to significantly reduce or eliminate
leakage from the
conduits and/or process chambers as a result of the centrifugal forces.
Compression may
be particularly helpful when used in connection with centrifugal loading of
sample
processing devices constructed using pressure sensitive adhesives.
The present invention also includes, in some aspects, an assembly of a carrier
and a
sample processing device attached to the carrier. The carrier may integral
with the sample
processing device, i.e., it may be provided as a single use article, or the
carrier may be
reusable. The carriers may advantageously include rails to support the main
conduits of
process arrays on the sample processing device, openings to allow for
monitoring of
process chambers on the sample processing devices, and other features.
In one aspect, the present invention provides a method of distributing sample
material in a sample processing device by providing a sample processing device
with first
and second opposing ends and at least one unvented process array including a
loading
chamber located proximate the first end, a main conduit extending towards the
second end,
and a plurality of process chambers distributed along the main conduit,
wherein the main
conduit is in fluid communication with the loading chamber and the plurality
of process
chambers. The method further includes loading sample material in the loading
chamber of
each of the process arrays, and transporting the sample material to at least
some of the
process chambers by rotating the sample processing device about an axis of
rotation
located proximate the first end of the sample processing device, wherein the
process
chambers are located further from the axis of rotation than the loading
chambers.
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In another aspect, the present invention provides a sample processing assembly
including a sample processing device with first and second opposing ends and
at least one
unvented process array comprising a loading chamber located proximate the
first end, a
main conduit extending towards the second end, and a plurality of process
chambers
distributed along the main conduit, wherein the main conduit is in fluid
communication
with the loading chamber and the plurality of process chambers; and a carrier
attached to a
first major side of the sample processing device, the carrier including a
carrier body spaced
from at least a portion of the first major side of the sample processing
device.
In another aspect, the present invention provides a sample processing device
including first and second opposing ends; a plurality of unvented process
arrays, each of
the process arrays including a loading chamber located proximate the first
end; a main
conduit extending towards the second end; and a plurality of process chambers
distributed
along the main conduit, wherein the main conduit is in fluid communication
with the
loading chamber and the plurality of process chambers; and wherein each of the
process
chambers is in fluid communication with one of the main conduits through a
feeder
conduit, and wherein the feeder conduits form feeder conduit angles with the
main
conduits that are less than 90 degrees.
These and other features and advantages of the present invention are described
below in connection with various illustrative embodiments of the devices and
methods of
the present invention.
Brief Description of the Drawings
Figure 1 is a plan view of one sample processing device.
Figure 2 is an enlarged partial cross-sectional view of one process array on a
sample processing device.
Figure 3 is an enlarged partial cross-sectional view of the process array of
Figure 2
depicting one method of sealing the main conduit.
Figure 4 is a plan view of one centrifuge system for rotating sample
processing
devices.
Figure 5 is a plan view of a portion of an alternative process array.
Figure 6 is a cross-sectional view taken along line 6-6 in Figure 5.
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Figure 7 is a cross-sectional view taken along line 7-7 in Figure 6.
Figure 8 depicts an alternative set of process arrays for a sample processing
device.
Figure 9 depicts an alternative set of process arrays for a sample processing
device.
Figure 10 is a perspective view of a sample processing device in which the
loading
chambers are being separated from the remainder of the sample processing
device.
Figure 11 is a perspective view of the sample processing device of Figure 10
after
sealing.
Figure 12 is a plan view of another sample processing device.
Figure 13 is a side view of the sample processing device of Figure 12 after
folding
the device along a line separating the loading chambers from the process
chambers.
Figure 14 depicts a sample processing device located within a compression
device.
Figure 15 is a plan view of an alternative compression device.
Figure 16 is a cross-sectional view taken along line 16-16 in Figure 15.
Figure 17 is an exploded perspective view of an assembly including a sample
processing device and a carrier.
Figure 18 is a perspective view of the carrier of Figure 18 taken from the
side of
the carrier facing the sample processing device.
Figure 19 is a partial cross-sectional view of a sample processing device and
carrier
including an optical element.
Detailed Description of Illustrative Embodiments of the Invention
The present invention provides a sample processing device that can be used in
the
processing of liquid sample materials (or sample materials entrained in a
liquid) in
multiple process chambers to obtain desired reactions, e.g., PCR
amplification, ligase
chain reaction (LCR), self sustaining sequence replication, enzyme kinetic
studies,
homogeneous ligand binding assays, and other chemical, biochemical, or other
reactions
that may, e.g., require precise and/or rapid thermal variations. More
particularly, the
present invention provides sample processing devices in which sample material
is
delivered to the process chambers by rotating the devices. The methods may
also include
sealing of the sample processing devices after sample material distribution.
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Although various constructions of illustrative embodiments are described
below,
sample processing devices of the present invention may be manufactured
according to the
principles described in U.S. Provisional Patent Application Serial No.
60/214,508 filed on
June 28, 2000 and titled THERMAL PROCESSING DEVICES AND METHODS; U.S.
Provisional Patent Application Serial No. 60/214,642 filed on June 28, 2000
and titled
SAMPLE PROCESSING DEVICES, SYSTEMS AND METHODS; and U.S. Provisional
Patent Application Serial No. 60/237,072 filed on October 2, 2000 and titled
SAMPLE
PROCESSING DEVICES, SYSTEMS AND METHODS.
The documents identified above all disclose a variety of different
constructions of
sample processing devices that could be used to manufacture sample processing
devices
according to the principles of the present invention. For example, although
many of the
sample processing devices described herein are attached using adhesives (e.g.,
pressure
sensitive adhesives), devices of the present invention could be manufactured
using heat
sealing or other bonding techniques.
One illustrative sample processing device manufactured according to the
principles
of the present invention is illustrated in Figures 1 and 2. The sample
processing device 10
includes at least one, and preferably a plurality of process arrays 20. Each
of the process
arrays 20 extends from proximate a first end 12 towards the second end 14 of
the sample
processing device 10.
The process arrays 20 are depicted as being substantially parallel in their
arrangement on the sample processing device 10. Although this arrangement may
be
preferred, it will be understood that any arrangement of process arrays 20
that results in
their substantial alignment between the first and second ends 12 and 14 of the
device 10 is
sufficient.
Alignment of the process arrays 20 between the first and second ends 12 and 14
is
important because sample materials are distributed throughout the sample
processing
device by rotation about an axis of rotation proximate the first end 12 of the
device 10.
When so rotated, any sample material located proximate the first end 12 is
driven toward
the second end 14 by centrifugal forces developed during the rotation.
Each of the process arrays 20 includes at least one loading chamber 30, at
least one
main conduit 40, and a plurality of process chambers 50 located along each
main conduit
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40. It may be preferred that each of the process arrays include only one
loading chamber
30 and only one main conduit 40. The process chambers 50 are in fluid
communication
with the main conduit 40 through feeder conduits 42. As a result, the loading
chamber 30
in each of the process arrays 20 is in fluid communication with each on the
process
chambers 50 located along the main conduit 40 leading to the loading chamber
30. Each
of the process arrays 20 depicted in Figure 1 also includes an optional drain
chamber 22
located at the end of the main conduit 40.
Each of the loading chambers 30 includes an inlet port 32 for receiving sample
material into the loading chamber 30. The sample material may be delivered to
port 32 by
any suitable technique and/or equipment. A pipette 11 is depicted in Figure 1,
but is only
one technique for loading sample material into the loading chambers 30. The
pipette 11
may be operated manually or may be part of an automated sample delivery system
for
loading the sample material into loading chambers 30 a sample processing
device 10.
Each of the process arrays 20 in the sample processing devices 10 of the
present
invention are preferably unvented. As used in connection with the present
invention, an
"unvented" process array is a process array in which the only ports leading
into the volume
of the process array are located in a loading chamber of the process array. In
other words,
to reach the process chambers within an unvented process array, sample
materials must be
delivered to the loading chamber through a port located in the loading
chamber. Similarly,
any air or other fluid located within the process array before loading with
sample material
must also escape from the process array through a port or ports located in the
loading
chamber. In contrast, a vented process array would include at least one
opening outside of
the loading chamber. That opening would allow for the escape of any air or
other fluid
located within the process array before loading during distribution of the
sample material
within the process array.
As seen in Figure 2, the process chamber 50 defining a volume 52 that may
include
a reagent 54. It may be preferred that at least some, and preferably all, of
the process
chambers 50 in the devices 10 of the present invention contain at least one
reagent before
any sample material is distributed. The reagent 54 may be fixed within the
process
chamber 50 as depicted in Figure 2. The reagent 54 is optional, i.e., sample
processing
devices 10 of the present invention may or may not include any reagents 54 in
the process
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chambers 50. In another variation, some of the process chambers 50 may include
a reagent
54, while others do not. In yet another variation, different process chambers
50 may
contain different reagents.
Other features depicted in the sample processing device 10 are a first major
side 16
and a second major side 18, between which the volume 52 of process chamber 50
is
formed. Also depicted in Figure 2 is a portion of feeder conduit 42 used to
deliver sample
material to the process chamber 50. The major sides 16 and 18 of the device 10
may be
manufactured of any suitable material or materials. Examples of suitable
materials include
polymeric materials (e.g., polypropylene, polyester, polycarbonate,
polyethylene, etc.),
metals (e.g., metal foils), etc.
It may be preferred that at least one of the first and second major sides 16
and 18
be constructed of a material or materials that substantially transmit
electromagnetic energy
of selected wavelengths. For example, it may be preferred that one of the
first and second
major sides 16 and 18 be constructed of a material that allows for visual or
machine
monitoring of fluorescence or color changes within the process chambers 50.
It may also be preferred that at least one of the first and second major sides
16 and
18 be in the form of a metallic foil. The metallic foil may include a
passivation layer on
the surfaces that face the interiors of the loading chambers 30, main conduits
40, feeder
conduits 42, and/or process chambers 50 to prevent contamination of the sample
materials.
In the illustrative embodiment of the sample processing device depicted in
Figures 1 and 2, the first major side 16 is preferably manufactured of a
polymeric film
(e.g., polypropylene) that is formed to provide structures such as the loading
chambers 30,
main conduit 40, feeder conduits 42, and process chambers 50. The second major
side 18
is preferably manufactured of a' metallic foil, e.g., an aluminum or other
metal foil. The
metallic foil is preferably deformable as discussed in more detail below.
The first and second major sides 16 and 18 may be attached by any suitable
technique or techniques, e.g., heat sealing, ultrasonic welding, etc. It may,
however, be
preferred that the first and second major sides 16 and 18 be attached using
adhesive. As
depicted in Figure 2, the adhesive may preferably be provided in the form of a
layer of
adhesive 19. It may be preferred that the adhesive layer 19 be provided as a
continuous,
unbroken layer over the surface of at least one of the first and second major
sides 16 and
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18. It may, for example, be preferred that the adhesive layer 19 be provided
on the
metallic foil of major side 18.
A variety of adhesives may be used, although any adhesive selected should be
capable of withstanding the forces generated during processing of any sample
materials
located in the process chambers 50. Those forces may be large where, e.g., the
processing
involves thermal cycling as in, e.g., polymerase chain reaction and similar
processes. The
adhesives may include, e.g., hot melt adhesives, curable adhesives, pressure
sensitive
adhesives, etc.
Among the pressure sensitive adhesives that may be used in connection with the
sample processing devices of the present invention are those that are
resistant to high
temperatures and humidity. It may, for example, be preferred to use silicone
pressure
sensitive adhesives. Examples of some suitable silicone-based pressure
sensitive
adhesives are silicone-polyurea compositions as described in, e.g., U.S.
Patents 5,461,134
and 6,007,914 or International Publication No. WO 96/35458 that contain a
sufficient level
of tackifying resin to provide the desired tackiness to the composition.
It may be preferred that all features, e.g., loading chambers 30, main conduit
40,
feeder conduit 42, process chambers 50, and drain chambers 22, be formed in
the first
major side 16 while the second major side 18 is substantially flat. By
locating all of the
features in one side of the sample processing device 10, the need for aligning
the two sides
together before attaching them may be eliminated. Furthermore, a flat second
major side
18 may promote intimate contact with, e.g., a thermal block such as that used
in thermal
cycling equipment. Alternatively, however, it will be understood that features
may be
formed in both sides 16 and 18 of sample processing devices according to the
present
invention.
Another potential feature of the sample processing devices of the invention is
isolation of the process chambers 50 by closing the fluid pathways in the
devices 10.
Referring now to Figures 2 and 3, the process chambers 50 may be isolated
after
distribution of any sample materials by deforming the second major side 18
such that it
extends into one or both of the main conduits 40 or the feeder conduits 42 in
each of the
process arrays 20. Figure 3 illustrates one such closure method where the
second major
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side 18 is deformed into the main conduit 40, with the adhesive layer 19
located between
the two sides.
The desire to hermetically seal fluid pathways in the sample processing
devices 10
of the present invention may lead towards the use of pressure sensitive
adhesive for the
adhesive layer 19. Where a pressure sensitive adhesive is present between the
first and
second major sides 16 and 18 of the device, deformation of the second major
side 18 may
result in adhesion between the first and second major sides 16 and 18 in the
deformed area.
That adhesion may enhance any sealing or closure produced by the deformation.
The need
for hermetic sealing may be more acute when the sample processing devices are
to be used
in thermal processing reactions such as, e.g., polymerase chain reaction, in
which any
liquids in the devices can exert high pressures on the seals due to thermal
expansion.
After distribution of sample materials into the process chambers 50 is
completed, it
may be desirable to isolate the process chambers 50 from each other. Isolation
may be
accomplished in a variety of manners. For example, isolation of the process
chambers 50
may involve deformation of the feeder conduits 42 and/or main conduits 40
within each of
the process arrays 20.
For those sample processing devices that include a metallic layer, isolation
of the
process chambers 50 may involve plastic deformation of the metallic layer to
close the
main conduits 40 and/or feeder conduits 42. If, for example, a pressure
sensitive adhesive
19 is used to attach the first and second major sides 16 and 18 of the sample
processing
device together, that same pressure sensitive adhesive may improve the sealing
of main
conduits 40 and/or feeder conduits 42 by adhering the deformed first and
second major
sides 16 and 18 together.
It should be understood, however, that complete sealing of the deformed
portions
of the sample processing device 10 may not be required. For example, it may
only be
required that the deformation restrict flow, migration or diffusion through a
conduit or
other fluid pathway sufficiently to provide the desired isolation.
In one method in which the process arrays 20 are closed after distribution of
sample materials into process chambers 50, it may be necessary to deform only
a portion
of the main conduit 40 or, alternatively, the entire length of the
distribution channel 40.
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Where only a portion of the main conduit 40 is deformed, it may be preferred
to deform
that portion of the main conduit 40 located proximate the loading chamber 30.
Sealing all of the main conduit 40 by forcing the sides 16 and 18 together
along the
length of the conduit 40 may provide advantages such as driving any fluid
located in the
main conduit 40 back into the loading chamber 30. One potential advantage,
however, of
sealing only a portion of the main conduit 40 is that either none or only a
small amount of
any fluid material located in the main conduit 40 would be returned to the
loading chamber
30.
Methods of distributing sample materials by rotating a sample processing
device
according to the present invention will now be described with reference to
Figure 4. After
providing a sample processing device 10' that includes first and second
opposing ends 12'
and 14' with at least one process array 20' aligned between the ends 12' and
14' of the
device 10', sample material may be delivered to the process chambers 50'of the
process
array 20' by rotating. It should be noted that the sample processing device
10' includes
only one process array 20' with a single loading chamber 30' connected to the
process
chambers 50' along two main conduits 40'.
The amount of sample material delivered to each of the loading chambers on the
devices 10' may vary. It may, however, be preferred that the volume of sample
material
delivered to each of the loading chambers is no greater than the combined
volumes of any
main conduits, feeder conduits, and process chambers in fluid communication
with the
loading chamber. Where an optional drain chamber (see, e.g., Figure 1) is
located at the
distal and of the process array, the amount of sample material delivery to
each of the
loading chambers may be increased to compensate for the additional volume of
the process
array downstream from the loading chamber.
After the loading chambers contain the desired sample material, that sample
material must be transported to the process chambers within each of the
process arrays.
Referring to Figure 4, the distribution of sample material is effected by
rotating the sample
processing device 10' about an axis of rotation 15' located proximate the
first end 12' of
the sample processing device 10'. Rotation of the device 10' about the axis of
rotation
15'when so oriented will result in centrifugal forces on any sample materials
located
within the loading chamber 30'. The centrifugal forces will drive the sample
material out
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of the loading chamber 30' and into the main conduits 40' for delivery to the
process
chambers 50' .
The sample processing device 10' is oriented such that the process chambers
50'
are located further from the axis of rotation 15'than the loading chamber 30'.
The sample
processing device 10' is located on a platter 17' that rotates about the axis
15'. The platter
17' may preferably be capable of accepting more than one sample processing
device 10'
for simultaneous rotation about axis 15' .
The orientation of the sample processing devices relative to the axis of
rotation 15'
is not critical, provided that the process chambers are located further from
the axis of
rotation 15' than the loading chambers. For example, where the sample
processing device
10' is in the form of a substantially flat card-like article, the edge of the
first end 12' of the
sample processing device 10' may be oriented substantially perpendicular to
the axis of
rotation as depicted in Figure 4. Alternatively, the axis of rotation 15' may
be
substantially aligned with (e.g., parallel to) the edge of the first end 12'
of the sample
processing device 10. A multitude of orientations of the first end 12'
relative to the axis
15' can be envisioned between parallel and perpendicular, all of which are
acceptable as
long as the process chambers are distal from the axis 15'relative to the
loading chambers
on the devices.
Because the process arrays of sample processing devices according to the
present
invention are preferably unvented as described above, distribution of sample
materials to
the process chambers may be difficult due to the air or other fluids trapped
within the
process chambers. Among the techniques that may be used to assist in
distribution of the
sample materials are selection of the materials used to construct the sample
processing
device, the addition of materials to the sample material (e.g., the addition
of a surfactant to
reduce surface tension in the sample material), manipulation of the viscosity
of the sample
material (e.g., by heating), etc.
One advantage of centrifugal loading of sample materials into process chambers
is
the ability to rotate the sample processing device and inspect the device
after an initial
period of rotation to determine whether sample material has been adequately
distributed to
the process chambers. If distribution is not satisfactory, the sample
processing device can
be rotated again until satisfactory sample material distribution is obtained.
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In addition to, or in place of, a sequential rotate-inspect-rotate approach,
the
methods of the present invention may also employ two or more
acceleration/deceleration
cycles to assist in distribution of sample materials from the loading chambers
to the
process chambers. Alternating acceleration and deceleration of the device
during rotation
may essentially burp the sample materials through main conduit and feeder
conduits (if
any) into process chambers. It may also be helpful if the acceleration and/or
deceleration
are rapid. The rotation may also preferably only be in one direction or it may
be in
opposite directions.
The actual acceleration and deceleration rates may vary based on a variety of
factors such as temperature, size of the sample processing device, size of the
conduits and
chambers, distance of the sample material from the axis of rotation, materials
used to
manufacture the devices, properties of the sample materials (e.g., viscosity),
etc. one
example of a useful acceleration/deceleration cycle may include an initial
acceleration to
about 4000 revolutions per minute (rpm), followed by deceleration to about
1000 rpm over
period of about 1 second, with oscillations in rotational speed of the device
between
1000 rpm and 4000 rpm at 1 second intervals until a sample materials are
distributed.
In addition to constant speed rotation and acceleration/deceleration cycling
during
rotation, the methods of the present invention may also include vibration of
the sample
processing device to assist in the distribution of sample materials into
process chambers.
Vibration, such as tapping, high frequency oscillations, etc., may assist in
removal of
entrapped air bubbles located within the conduits or process chambers.
Vibration of the
sample processing device may be employed before or after rotation, or it may
be employed
during rotation of the sample processing device about the axis of rotation.
Although the process chambers illustrated in device 10 of Figure 1 appear
substantially circular in shape, it should be understood that the process
chambers used in
sample processing devices of the present invention may take any suitable
shape. One
example of an alternative shape is depicted in Figure 5 in which the process
chambers 150
are in the form of oval shapes that are elongated along axis 151. The axis 151
is preferably
generally aligned with the main conduit 140. As a result, the axis 151 will
generally
extend from the first end of the sample processing device to its second end,
with the oval
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shapes of process chambers 150 having their largest dimension aligned between
the first
and second ends of the sample processing device.
Figure 5 also depicts feeder conduits 142 that are preferably angled off of
the main
conduit 140 and adjoin the process chambers 150 at one end. It may be further
preferred
that the feeder conduits 142 meet the process chambers 150 at the end closest
to the first
end of the sample processing device (which is, therefore, the end of the
process chamber
that is closest to the axis of rotation during loading). Entry of the feeder
conduits 142 into
the process chambers 150 at the end may facilitate removal of air within the
chambers 150
during loading.
The feeder conduit angle 13, i.e., the included angle formed between the
feeder
conduits 142 and the main conduit 140, may also enhance filling of the process
chambers
150 by promoting the removal of the air. It may, for example, be preferred
that the feeder
conduit angle be less than 90 degrees, more preferably less than 75 degrees.
The feeder
conduit angle will always be measured between the side of the feeder conduit
142 facing
away from the first end of the device and the main conduit 140.
Another potentially advantageous optional feature illustrated in Figure 5 is
the
longitudinal offset of the feeder conduits 142 on opposing sides of the main
conduit 140
(as opposed to the cross-conduit alignment of the feeder conduits 42 in Figure
1). That
offset between the points at which the opposing feeder conduits 142 join the
main conduit
140 may assist in preventing cross-chamber contamination during filling and/or
processing.
Figures 6 and 7, in conjunction with Figure 5, illustrate yet another optional
feature
of the sample processing devices of the present invention. Figure 6 is a cross-
sectional
view of Figure 5 taken along line 6-6 in Figure 5 and Figure 7 is a cross-
sectional view of
Figure 6 taken along line 7-7 in Figure 6. The figures illustrate the smaller
cross-sectional
area of the feeder conduit 142 as compared to the main conduit 140. The
different cross-
sectional area of the conduits 140 and 142 is achieved, in the illustrated
embodiment, by
different heights and widths in the two conduits. Providing conduits with
different cross-
sectional areas may limit diffusion of sample material from the process
chambers 150 into
the main conduit 140 after and/or during filling. By limiting diffusion, cross-
chamber
contamination may also be reduced.
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Figure 8 is a schematic diagram illustrating another arrangement for process
arrays
220 useful in sample processing devices of the invention. Among the features
depicted in
connection with process arrays 220 are the staggered relationship between
loading
chambers 230. Such a staggered relationship may improve the density or spacing
between
process chambers 250.
Each of the loading chambers 230 also includes a loading port 232 and a vent
port
234 which may facilitate rapid filling of the loading chambers 230 by
providing a pathway
separate from the loading port 232 for air to escape during filling of the
loading chamber
230.
Another feature depicted in Figure 8 is the serial relationship between the
process
chambers 250 located along each of the main conduits 240. Each pair of
successive
process chambers 250 is in fluid communication with each other along main
conduit 240.
As a result, if any reagents or other materials are to be located within
process chambers
250 before distribution of the sample material, then some mechanism or
technique for
preventing removal of those materials during distribution of the sample
material must be
provided. For example, the reagents may be contained in a wax or other
substance within
each of the process chambers 250.
Figure 9 is a schematic diagram illustrating yet another arrangement of
process
arrays 320 that may be used in connection with sample processing devices of
the present
invention. Each of the process arrays 320 includes a loading chamber 330 that,
in turn,
includes a loading port 332 and a vent port 334. The loading chambers 330 are
in fluid
communication with a plurality of process chambers 350 through main conduits
340.
One feature illustrated in connection with Figure 9 is the addition of valves
344
along the main conduits 340. Each of the main conduits 340 bifurcates to an
individual
subset of process chambers 350. By selectively opening or closing the valves
344 (which
may be either closed or open when manufactured) the delivery of sample
material to each
subset of process chambers 350 may be enabled or prevented. For example, if
one of the
valves 344 is open while the other valve 344 is closed, delivery of sample
material will be
effected only to one subset of process chambers 350 (through the open valve
344).
It may be possible to achieve the same result, i.e., enabling or preventing
delivery
of sample material to a subset of process chambers 350, by sealing the main
conduit 340 at
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an appropriate location after the bifurcation point. The use of valves 344
may, however,
provided the ability for automated control or customization of the sample
processing
device including process arrays 320. The valves 344 may take any suitable
form, some
examples of which are described in the patent applications identified above.
By using customizable process arrays 320, it may be possible to provide sample
processing devices that are tailored at the point of use for particular
testing needs. Other
advantages may be found in the ability to reduce the volume of sample material
needed by
reducing the number of process chambers 350 to which that sample material may
be
delivered. Alternatively, where a higher level of confidence is required, the
valves 344
may be opened to increase the number of process chambers 350 to which sample
material
is delivered, thereby increasing the number of tests performed.
Referring now to Figure 10, another optional feature of the present invention
is
separation of the loading chambers 430 from the remainder of the sample
processing
device 410. Separation of the loading portion of the sample processing device
410 from
the portion containing the process chambers 450 may provide advantages such
as, for
example, reducing the size of the sample processing device 410, reducing the
thermal mass
of the sample processing device 410, removing any sample materials that may
remain
within the loading chambers 430 after distribution to process chambers 450,
etc.
Separation of the loading chambers 430 from the sample processing device 410
may involve, for example, cutting the sample processing device 410 along the
separation
line 413 as depicted in Figure 10. Where the loading chambers 430 are to be
physically
separated from the remainder of the sample processing device 410, it is
typically preferable
that the main conduits 440 be sealed across at least the separation line 413
to prevent
leakage of the sample materials during and after the separation process.
The use of a pressure sensitive adhesive within the main conduits 440 (see,
e.g.,
Figures 2 and 3) may be particularly helpful to ensure adequate sealing of the
main
conduits. In addition to, or in place of, pressure sensitive adhesives within
the conduits
440, it may be desirable to further seal the main conduits 440 by, e.g., the
application of
heat and/or pressure to bond the conduit closed.
If additional sealing is required, it may also be helpful to cover the ends of
the main
conduits with a seal 444 as illustrated in Figure 11. The seal may be
provided, e.g., in the
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form of an adhesive coated foil or other material. Alternatively or in
addition to the use of
an adhesive to secure the seal 444, it may be desirable to, e.g., heat seal
the seal 444 in
place on the sample processing device 410.
Referring now to Figures 12 and 13, one alternative to physical separation of
the
loading chambers 530 from the remainder of the sample processing device 510
may
include folding the sample processing device 510 along, e.g., separation line
513. That
folding process may also close the main conduit 540 across the separation line
513 by
crimping the main conduits 540, such that a desired level isolation may be
achieved
between the process chambers 550 without further deformation of any of the
main
conduits 540 or the feeder conduits 542.
It may be desirable to provide crimping areas 546 located at the intersections
of the
main conduits 540 with the folding line 513 that are wider and shallower than
the
surrounding portions of conduits 540 to facilitate crimping of the conduits
540 during
folding. The wider, shallower crimping areas 546 do, however, preferably
provide a cross-
sectional area for fluid flow that is similar to the cross-sectional fluid
flow area of the
surrounding portions of the main conduits 540.
The centrifugal forces developed during rotation of the sample processing
devices
to deliver the sample materials to process chambers may challenge the sealing
of the
process chambers and other fluid pathways in each of the process arrays. The
challenges
may be especially acute when the sample processing device is constructed using
an
adhesive to attach to layers together.
To assist with the sealing of the process chambers and other fluid pathways on
the
sample processing devices during rotation, it may be advantageous to compress
the major
sides of the sample processing devices together during rotation. Referring to
Figure 14,
the sample processing device 610 may, for example, be located within a
compression
device 660 (e.g., in the form of a clamshell or other suitable structure) that
compresses the
major sides of the sample processing device 610 together during rotation. The
compression device 660 may, for example, include conformable material 662 in
contact
with one side of the sample processing device 610. The conformable material
662 may,
for example be a resilient foam or similar composition.
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Also included in the compression device 660 is a base 664 in contact with the
opposing side of the sample processing device 610. As the conformable material
662 and
the base 664 axe biased toward each other, the major sides of the sample
processing device
610 are compressed. That compression may significantly reduce or prevent
leakage of any
sample materials out of the process chambers or other fluid pathways during
rotation of the
sample processing device 610.
The conformable material 662 is preferably located in contact with the side of
the
device 610 that includes any structures such as process chambers or conduits
protruding
therefrom to avoid damaging those structures. The base 664 may be formed of
any
suitable material which may be rigid where no structures are protruding from
the side of
the device 610 facing the base 664.
A portion of an alternative compression device is depicted in Figures 15 and
16 in
connection with a process chamber 650' and portion of a feeder conduit 642'.
The
alternative compression device is designed to provide pressure. The
compression device
includes a shaped compression die 662' that applies pressure along a discrete
area or areas
located about the periphery of the process chamber 650' and the feeder conduit
642'. The
compression die 662' preferably acts against a base 664' located on the
opposite side of
the sample processing device. Departing from the design of the compression
device
depicted in Figure 14, the compression die 662' may preferably be formed of a
substantially rigid material
Figure 17 is an exploded perspective view of an assembly including a sample
processing device 710 of the present invention and a carrier 780. Because, in
many
instances, the sample processing devices 710 are manufactured from materials
that are
relatively thin, it may be desirable to attach the device 710 to a carrier 780
for a variety of
reasons. Among those reasons are the need to provide an assembly having
sufficient
thickness to be processed in existing thermal processing equipment with a
minimum of
modification to that equipment.
By providing a carrier 780 that is separate from the sample processing device
710,
the thermal mass of the sample processing device 710 can be minimally affected
as
compared to manufacturing the entire sample processing device 710 with a
thickness
suitable for processing in conventional equipment. Another potential advantage
of a
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carrier 780 is that the sample processing devices 710 may exhibit a tendency
to curl or
otherwise deviate from a planar configuration. Attaching the device 710 to a
rigid carrier
780 can retain the sample processing device in a planar configuration for
processing.
The carrier 780 may be attached to the sample processing device 710 in a
manner
that allows for the carrier 780 to be reused with many different sample
processing devices
710. Alternatively, each carrier 780 may be permanently attached to a single
sample
processing device 710 such that, after use, both the sample processing device
710 and the
carrier 780 are discarded together.
The sample processing device 710 may be manufactured as described above. The
carrier 780 may include various features such as carrier openings 782 that are
preferably
aligned with the plurality of process chambers 750 in the device 710. By
providing carrier
openings 782, the process chambers 750 can be viewed from the side of the
sample
processing device 710 facing the carrier 780. One alternative to providing the
plurality of
carrier openings 782 is to manufacture the carrier 780 of a material (or
materials)
transmissive to electromagnetic radiation in the desired wavelengths. As a
result, it may
be possible to use a carrier 780 that is contiguous over the surface of the
sample processing
device 710, i.e., the carrier provides no openings for access to the process
chambers 750.
The carrier 780 illustrated in Figures 17 and 18 may also provide advantages
in the
sealing or isolation of the process chambers 750 after loading. Figure 18
illustrates the
rails 783 in the carrier 780 that extend along the length of the main conduits
740 in the
associated sample processing device 710. The rails 783 may, for example,
provide a
surface against which the main conduits 740 of the sample processing device
710 may be
pressed while the conduit is deformed to isolate the process chambers 750
and/or seal the
conduits 740 prior to separating the loading chambers 730 from the device 710.
In addition to their use during deformation of the main conduits 740, the
rails 783
a may also be relied on during, e.g., thermal processing to apply pressure to
the conduits 740
(thereby potentially improving the seals formed along the main conduits 740).
Furthermore, the use of rails 783 also provides an additional advantage in
that they provide
for significantly reduced contact between the sample processing device 710 and
the carrier
780 while still providing the necessary support for sealing of the main
conduits 740 on
device 710. The importance of reducing contact between the carrier 780 and
device 710
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may be particularly important when the assembly is to be used in thermal
processing of
sample materials (e.g., polymerase chain reaction, etc.). As such, the carrier
780 may be
characterized including a carrier body that is spaced from the sample
processing device
710 between the main conduits 740 when the rails 783 are aligned with the main
conduits
740. The voids formed between the carrier body and the sample processing
device 710
may be occupied by air or by, e.g., a resilient andlor thermally insulating
material.
Various alignment features are also illustrated in Figures 17 and 18,
including
structures that align the sample processing device 710 relative to the carrier
780, as well as
structures that align the assembly of sample processing device 710 and carrier
780 relative
to, e.g., a thermal processing system used to thermally cycle materials in the
sample
process chambers 750. Alignment may also be used in connection with a
detection system
for detecting the presence or absence of a selected analyte in the process
chambers 750.
It may be preferred that the sample processing device 710 be aligned relative
to the
carrier 780 proximate a center of both of those articles (center 781 of
carrier 780 being
indicated in Figure 17). To prevent rotation of the sample processing device
710 relative
to the carrier 780, at least two points of registration or contact are
required. Because the
device 710 and carrier 780 may be subjected to temperature extremes during
processing, it
may be desirable, for example, that the sample processing device 710 be
fixedly connected
to carrier 780 in the center of the two articles, while any additional points
of attachment
provide for differential expansion/contraction between the device 710 and
carrier 780.
The alignment structures used to align the assembly as a whole to, e.g.,
thermal
cycling and/or detection equipment, include protrusions 774 that are
preferably designed to
extend through alignment openings 776 in the sample processing device 710. As
a result,
alignment of the assembly is based on structures found in carrier 780. One
advantage to
relying on the carrier 780 for alignment structures is that its construction
will typically
being more dimensionally stable and accurate as compared to the sample
processing
device 710.
Figure 19 illustrates yet another optional feature of carriers used in
connection with
the present invention. The carrier 880 is depicted with an optical element
888, e.g., a lens,
that may assist in focusing electromagnetic energy directed into the process
chamber 850
or emanating from the process chamber 850. The optical element 888 is depicted
as
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integral with the carrier 880, although it should be understood that the
optical element 888
may be provided as a separate article that is attached to the carrier 880.
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