Note: Descriptions are shown in the official language in which they were submitted.
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PROCESS TUBE AND CARRIER TRAY
Background
Field of the Development
[0001] The technology described herein generally relates to process
tubes used in
amplification processes and the carrier trays in which the process tubes are
securely stored for
transport and processing, as well as methods of making and using the same.
Description of the Related Art
[0002] The medical diagnostics industry is a critical element of today's
healthcare
infrastructure. At present, however, in vitro diagnostic analyses, no matter
how routine, have
become a bottleneck in patient care. Understanding that diagnostic assays of
biological samples
may break down into several key steps, it is often desirable to automate one
or more steps. For
example, a biological sample, such as those obtained from a patient, can be
used in nucleic acid
amplification assays, in order to amplify a target nucleic acid (e.g., DNA,
RNA, or the like) of
interest. Polymerase chain reaction (PCR), conducted in a thermal cycler
device, is one such
amplification assay used to amplify a sample of interest.
[0003] Once amplified, the presence of a target nucleic acid, or
amplification product
of a target nucleic acid (e.g., a target amplicon) can be detected, wherein
the presence of a
target nucleic acid and/or target amplicon is used to identify and/or quantify
the presence of a
target (e.g., a target pathogen, genetic mutation or alteration, or the like).
Often, nucleic acid
amplification assays involve multiple steps, which can include nucleic acid
extraction and
preparation, nucleic acid amplification, and target nucleic acid detection.
[0004] In many nucleic acid-based diagnostic assays, the biological,
environmental,
or other samples to be analyzed, once obtained, are mixed with reagents for
processing. Such
processing can include combining extracted nucleic acids from the biological
sample with
amplification and detection reagents, such as probes and fluorophores.
Processing samples for
amplification is currently a time-consuming and labor intensive step.
[0005] Processing samples for amplification often occurs in dedicated
process tubes,
used to hold the extracted DNA samples prior to and during the amplification
process. In some
instances, the process tubes arc placed directly in a thermal cycler for
amplification. In some
instances, to simplify the procedure, process tubes are first placed in a tube
rack for pre-
amplification processing (such as filling up the tubes with the amplification
reagents, drying the
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reagents, and marking the tubes by hot stamping them). The process tubes are
often removed
from the tube rack by a lab technician and placed individually and separately
in contact with a
heater unit of the thermal cycler. Placing the process tubes individually in
the thermal cycler is
inefficient, time consuming, and can be difficult to automate. Further, such
processes are
susceptible to human error.
[0006] In some instances, racks containing the process tubes can be
placed directly
in the thermal cycler. However, this approach too has drawbacks because the
process tubes may
shift in the rack during handling and transport and consequently will likely
not line up correctly
with the heaters of the thermal cycler. Additional intervention by a lab
technician is required
align the tubes and fit them into the heaters of the thermal cycler.
Furthermore, if the process
tubes are not securely connected to the rack, the process may become dislodged
during marking
of the process tubes, being pulled up and out of the rack by the stamping
apparatus.
[0007] Much of the difficulty with the handling and transport of process
tubes in a
rack stems from the shape of the tubes generally used in amplification
processes. Process tubes
are often conical in shape, having an outside diameter larger at the top of
the process tube than
at the bottom of the process tube. Some process tubes are cylindrical in
shape, having a constant
diameter from top to bottom. The ports of the rack in which the process tubes
are placed must
be of a greater diameter than the largest outside diameter of the process
tubes (at the top of the
process tube). To address the tolerances associated with manufacturing the
process tubes and
the rack, the ports in the rack are often appreciably larger than the outside
diameter of the
process tubes, allowing the tubes to move around in the rack and potentially
fall out. Without a
secure fit in the rack, the process tube may tilt to one side or another. With
multiple process
tubes in a rack, the tilting process tubes may bump into each other and break
and/or cause loss
of sample and/or reagents stored therein. Furthermore, it can be very
difficult to line up the
differently tilted process tubes into the rigid heaters of the thermal cycler.
[0008] Thus, there is a need for process tubes and a tray that fit
securely together to
allow for safe and efficient handling and transport of the process tubes prior
to and during
amplification. Furthermore, there is a need for process tubes that still have
an ability to adjust or
float within the tray in order to facilitate alignment with the heaters of a
thermal cycler.
[0009] The discussion of the background herein is included to explain
the context of
the inventions described herein. This is not to be taken as an admission that
any of the material
referred to was published, known, or part of the common general knowledge as
at the priority
date of any of the claims.
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Summary
[0010] Certain embodiments disclosed herein contemplate a process tube
having a
securement region that includes an annular ledge, a protrusion, and a neck
between the ledge
and the protrusion. The process tube also includes a body extending below the
protrusion and a
top ring extending vertically up from the annular ledge which defines an
opening to the tube.
[0011] In certain embodiments, an outside surface of the neck can be
parallel to a
longitudinal axis through the process tube. The protrusion can include an
apex, an upper slope
from the apex to the neck, and a lower slope from the apex to the body. The
angle of the upper
slope on the protrusion can be steeper than the angle of the lower slope on
the protrusion. The
annular ledge of the process tube can have an upper surface, a lower surface,
and an outside
surface. The protrusion can have a larger outside diameter than the outside
diameter of the neck.
The annular ledge can have a larger outside diameter than the outside diameter
of the protrusion.
The process tube can further include a base below the body which defines a
bottom of the
process tube.
100121 Certain embodiments disclosed herein include a process tube strip
having a
plurality of process tubes. The plurality of process tubes is connected by a
tab adjoining the
annular ledges of the plurality of tubes.
[0013] Certain embodiments contemplate a process tube having an annular
ledge
extending laterally from the tube, the annular ledge comprising an upper
surface, a lower
surface, and an outer surface. The process tube can include a top ring
extending vertically up
from the upper surface of the annular ledge which defines an opening to the
process tube. The
process tube can further include an annular protrusion extending laterally
from the process tube,
at a location on the tube below the annular ledge. The protrusion can have an
apex, an upper
slope, and a lower slope. The process tube can include a neck between the
annular ledge and the
protrusion, a body below the protrusion, and a base which defines a bottom of
the tube.
[0014] Embodiments of the process tube disclosed can be configured to
securely fit
in a carrier tray. The carrier tray can have a shelf and a base, such that the
shelf has a plurality
of ports through a top of the shelf, and the ports having an interior wall. In
certain
embodiments, the protrusion of the process tube disclosed can have a larger
outside diameter
than the diameter of the port in the carrier tray. The neck of the process
tube can have a smaller
outside diameter than the diameter of the port in the carrier tray. The
process tube can be
securely fit into a port of the carrier tray.
[0015] In certain embodiments of the process tube, the lower surface of
the annular
ledge of the process tube can rest on an exterior of the shelf top and the
upper slope of the
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protrusion can rest on a bottom edge of the interior wall of the port. A gap
can exist between the
neck of the process tube and the interior wall of the port and the gap can
allow the process tube to
tilt or adjust within the port of the carrier tray.
[0016] Further embodiments of the disclosure contemplate a system
having a
carrier tray with a plurality of ports therethrough and a process tube having
a securement region.
The securement region of the process tube can include an annular ledge, a
neck, and a protrusion.
The securement region of the process tube can fit securely in a port of the
carrier tray. In this
system, the annular ledge and protrusion of the process tube can have outside
diameters that are
larger than the diameter of the port of the carrier tray and the neck of the
process tube can have an
outside diameter that is smaller than the diameter of the port. When the
process tube is securely fit
in the port of the carrier tray, the process tube can tilt or adjust within
the port of the carrier tray.
[0016a] According to an aspect of the invention is a process tube
that snaps securely
into a port of a carrier tray, the process tube comprising:
a securement region on the exterior of the process tube, the securement region
comprising an annular ledge, a protrusion, and a neck between the ledge and
the protrusion,
wherein an outside diameter of the protrusion at an apex of the protrusion is
larger than an
outside diameter of the neck and a diameter of the port;
a body extending below the protrusion, wherein the protrusion comprises an
apex,
an upper slope from the apex to the neck, and a lower slope from the apex to
the body, and
wherein the angle of the upper slope on the protrusion is steeper than the
angle of the lower
slope on the protrusion, and wherein the angle of the upper slope of the
protrusion and the
angle of the lower slope of the protrusion are each non-orthogonal with
respect to the
longitudinal axis of the process tube; and
a top ring extending vertically up from the annular ledge and defining an
opening
to the tube, wherein the process tube undergoes maximum strain and is
maximally flexed
as the apex slides through the port of the carrier tray, and wherein the
strain in the process
tube is released and the process tube snaps securely into place when the apex
breaches a
bottom edge of the port.
[0016b] According to a further aspect of the invention is a process
tube that snaps
securely into a port of a carrier tray, the process tube comprising:
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an annular ledge extending laterally from the process tube, the annular ledge
comprising an upper surface, a lower surface, and an outer surface;
a top ring extending vertically up from the upper surface of the annular ledge
and
defining an opening to the process tube;
an annular protrusion extending laterally from the exterior of the process
tube at a
location on the process tube below the annular ledge, the protrusion having an
apex, an
upper slope, and a lower slope, wherein the angle of the upper slope on the
protrusion is
steeper than the angle of the lower slope on the protrusion, wherein the angle
of the upper
slope of the protrusion and the angle of the lower slope of the protrusion are
each non-
orthogonal with respect to the longitudinal axis of the tube;
a neck between the annular ledge and the protrusion, wherein an outside
diameter
of the protrusion at the apex is larger than an outside diameter of the neck;
a body below the protrusion; and
a base defining a bottom of the process tube, wherein the process tube
undergoes
maximum strain and is maximally flexed as the apex slides through the port of
the carrier
tray, and wherein the strain in the process tube is released and the process
tube snaps
securely into place when the apex breaches a bottom edge of the port.
[0016c] According to a further aspect of the invention is a system
comprising:
a carrier tray comprising a plurality of elliptical ports therethrough, each
port
having a top edge, a bottom edge, an interior wall, and a length diameter that
is larger than
a width diameter;
a process tube comprising a securement region on the exterior of the tube, the
securement region comprising an annular ledge, an annular protrusion, and a
neck between
the ledge and the protrusion, wherein the protrusion comprises an apex, an
upper slope
from the apex to the neck, and a lower slope from the apex to the body,
wherein the angle
of the upper slope on the protrusion is steeper than the angle of the lower
slope on the
protrusion, wherein the process tube securely fits in an elliptical port of
the plurality of
elliptical ports of the carrier tray such that a bottom surface of the ledge
rests on a top
surface of the carrier tray and the upper slope of the protrusion contacts the
bottom edge of
the port, wherein a diameter of the neck is less than the length diameter and
the width
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diameter of the port, wherein a diameter of the protrusion at the apex is
larger than the
width diameter of the port, and wherein a cross-section of the process tube is
circular; and
a heater assembly comprising a plurality of heater wells, each heater well
comprising an inner wall and a well bottom, wherein the process tube is
received in a heater
well of the plurality of heater wells such that the body of the process tube
contacts the inner
wall of the heater well and a gap is formed between a base of the process tube
and the well
bottom of the heater well, the gap configured to prevent the process tube from
bottoming
out in the heater well.
[0016d] According to a further aspect of the invention is a system
comprising:
a carrier tray comprising a plurality of elliptical ports therethrough, each
port having a top
edge, a bottom edge, an interior wall, and a length diameter that is larger
than a width diameter;
and
a process tube configured to removably snap into an elliptical port of the
plurality of ports
of the carrier tray, the process tube comprising a securement region on the
exterior of the tube, the
securement region comprising an annular ledge, an annular protrusion, and a
neck between the
ledge and the protrusion, wherein the protrusion comprises an apex, an upper
slope from the apex
to the neck, and a lower slope from the apex to the body, wherein the angle of
the upper slope on
the protrusion is steeper than the angle of the lower slope on the protrusion,
wherein a diameter of
the neck is less than the length diameter and the width diameter of the port,
wherein a diameter of
the protrusion at the apex is larger than the width diameter of the port,
wherein a cross-section of
the process tube is circular, and wherein, when the process tube is removably
snapped into the
elliptical port, a gap is formed between the neck and the elliptical port, a
bottom surface of the
ledge rests on a top surface of the carrier tray, and the upper slope of the
protrusion contacts the
bottom edge of the port.
Brief Description of the Drawings
[0017] Fig. 1A shows an isometric view of an exemplary process tube
strip as
described herein.
[0018] Fig. 1B is a side plan view of the process tube strip of
Fig. 1A.
[0019] Fig. 1C is a top view of the process tube strip of Fig. 1A.
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[0020] Fig. 1D shows an isometric view of another exemplary process
tube strip as
described herein.
[0021] Fig. lE shows an isometric view of another exemplary process
tube strip as
described herein.
[0022] Fig. 2A is an isometric view of an exemplary, single process
tube as
described herein.
[0023] Fig. 2B is a cross-sectional view of the process tube of
Fig. 2A taken along
line 2B in Fig. 1C.
[0024] Fig. 3A shows an exemplary carrier tray, as described
herein.
[0025] Fig. 3B shows a plurality of exemplary process tube strips
in the carrier tray
of Fig. 3 A.
[0026] Fig. 4 is a cross-sectional view of 12 process tubes
positioned in the carrier
tray prior to securing the process tubes in the carrier tray.
[0027] Fig. 5 is a cross-sectional view of two exemplary process
tubes positioned
in the carrier tray prior to securing the process tubes in the carrier tray.
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[0028] Fig. 6A is a cross-sectional view, taken along line 6A in Fig.
3B, of the 12
process tubes of Fig. 4 after securing the process tubes in the carrier tray.
[0029] Fig. 6B is a cross-sectional view, taken along line 6B in Fig.
3B, of a process
tube strip positioned in the carrier tray after securing the process tubes in
the carrier tray.
[0030] Fig. 7 is a cross-sectional view of the process tubes of Fig. 5
positioned in the
carrier tray after securing the process tubes in the carrier tray.
[0031] Fig. 8 is an isometric view of an exemplary heater assembly of a
thermal
cycler.
[0032] Fig. 9 is a cross-sectional view of exemplary process tubes
positioned in
heater wells of a heater assembly, as described herein.
Detailed Description
[0033] Before the embodiments are further described, it is to be
understood that this
invention is not limited to particular embodiments described, as such may,
vary. It is also to be
understood that the terminology used herein is for the purpose of describing
particular
embodiments only, and is not intended to be limiting.
[0034] Where a range of values is provided, it is understood that each
intervening
value, to the tenth of the unit of the lower limit unless the context clearly
dictates otherwise,
between the upper and lower limit of that range and any other stated or
intervening value in that
stated range is encompassed within the embodiments. The upper and lower limits
of these
smaller ranges may independently be included in the smaller ranges and are
also encompassed
within the embodiments, subject to any specifically excluded limit in the
stated range. Where
the stated range includes one or both of the limits, ranges excluding either
both of those included
limits are also included in the embodiments.
[0035] Unless defined otherwise, all technical and scientific terms used
herein have
the same meaning as commonly understood by one of ordinary skill in the art to
which the
embodiments belong. Although any methods and materials similar or equivalent
to those
described herein may also be used in the practice or testing of the
embodiments, the preferred
methods and materials are now described.
[0036] It must be noted that as used herein and in the appended claims,
the singular
forms "a," "and," and "the" include plural referents unless the context
clearly dictates otherwise.
Thus, for example, reference to "a method" includes a plurality of such
methods and equivalents
thereof known to those skilled in the art, and so forth.
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[0037] Throughout the description and claims of the specification the
word
"comprise" and variations thereof, such as "comprising" and "comprises," is
not intended to
exclude other additives, components, integers or steps.
[0038] The process tubes and carrier tray described herein can be used
together to
provide a safe and efficient system of preparing, storing, and transporting
the process tubes prior
to use in a thermal cycler and also for positioning the process tubes
accurately and securely in
the thermal cycler during amplification.
[0039] Fig. lA shows an isometric view of an exemplary process tube
strip 100
according to the embodiments described herein. Fig. 1B is a side plan view of
the process tube
strip of Fig. 1A. Fig. 1C is a top view of the process tube strip of Figure
1A. As shown in Figs.
1A-1C, the process tube strip 100 is a collection of process tubes 102,
connected together by a
connector tab 104. The exemplary process tube strip 100 can also include a top
end tab 106, as
shown in Figures 1A-1C, indicating the top of the process tube strip 100 and a
bottom end tab
108 indicating the bottom of the process tube strip 100. The process tube
strip 100 shown in
Figures 1A-1C includes eight process tubes 102 connected together in the
process tube strip 100.
One skilled in the art will immediately appreciate however, that in other
embodiments, the
process tube strip 100 can include, for example any other number of process
tubes, e.g., 40, 30,
20, 19, 18, 17, 16, 15, 14, 13, 12, 11, 10, 9, 7, 6, 5, 4, 3, or 2 process
tubes 102 connected in the
process tube strip 100. An embodiment of the process tube strip 100 can
include an insignia or
indication on the upper surface of the top and bottom end tabs 106, 108. In
one embodiment, the
top end tab 106 can be marked with an "A" indicating the top of the process
tube strip 100 and
the bottom end tab 108 can be marked with the letter of the alphabet
corresponding to the
number of process tubes 102 in the process tube strip 100 (for example, an "H"
would be
marked on the bottom end tab 108 of the process tube strip 100 for a process
tube strip 100
having eight process tubes 102 connected together in the process tube strip
100). The skilled
artisan will readily appreciate, however, that various other characters, e.g.,
alphanumeric
characters, such as "1" and "8" can also be readily used in marking the top
and bottom end tabs
of process tube strip 100, to achieve the same purpose. Thus, the top and
bottom end tabs 106,
108 can be used to indicate the top and bottom of a process tube 102 and the
number of process
tubes 102 in a process tube strip 100. In addition, the end tabs 106, 108 can
be marked with a
color marking, a barcode, or some other designation to identify, for example,
the contents of the
process tubes 102, the assay type being performed in the process tube strip
100, and the date and
location of manufacture of the process tube strip 100.
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[0040] Fig. ID is another embodiment of the process tube strip 100 that
includes a
ledge extension 110 on each of the process tubes 102. Fig. lE is an additional
embodiment of
the process tube strip 100 that includes a tube tag 112 positioned on the
ledge extension 110 of
each process tube 102. These embodiments will be discussed in further detail
below.
[0041] Process tubes 102 can be receptacles for, or house, solids or
liquids. For
example, process tubes 102 can hold reagents and/or samples, e.g., nucleic
acid samples to be
used in amplification assays. The process tubes 102 can be circular in cross-
section, but other
cross sections are possible and consistent herewith. The process tubes 102 can
be manufactured
via a unitary construction, although in certain instances the process tubes
may be constructed
from two or more parts fused or otherwise joined together as applicable.
Typically, the process
tubes 102 have an opening that is configured to accept/receive a pipette tip
for deposit and/or
retrieval of fluids within the process tube 102.
[0042] In some embodiments, the process tubes 102 can be constructed
from
polypropylene or other thermoplastic polymers known to those skilled in the
art. Alternatively,
process tubes 102 can be constructed from other appropriate materials, such as
polycarbonate or
the like. In some embodiments, the polypropylene is advantageously
supplemented with a
pigment, such as titanium dioxide, zinc oxide, zirconium oxide, or calcium
carbonate, or the
like. Preferably, the process tubes 102 are manufactured using materials such
that they do not
fluoresce and thus do not interfere with detection of the amplified nucleic
acid in the process
tubes 102.
[0043] Figs. 2A and 2B show, respectively, an isometric and a cross-
sectional view
of an exemplary single process tube 102. Connector tabs 104 are shown in Fig.
2A, connecting
the process tube 102 to other process tubes 102 on either side of the process
tube 102. In Fig.
2B, the shown connector tab 104 includes a connector recess 232 on the
underside of the
connector tab. In some embodiments, the connector recess 232 provides a
separation point to
easily break apart different process tubes 102 connected as part of a process
strip 100. The
process tubes 102 can be broken apart by the end user in order to mix and
match different
process tubes 102 having different dried reagents, and rearranging the process
tubes in the
carrier tray 300 to match the necessary operation of the amplification assay
in the thermal
cycler. A connector tab 104 can also be positioned between the process tube
102 at the end of a
process tube strip 100 and the top or bottom end tab 106, 108. Such a
connector tab 104 allows
the end process tube 102 to be removed easily and also mixed and matched with
process tubes
102 from other process tube strips 100 or to be used individually in a thermal
cycler.
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[0044] As shown in Figs. 2A and 2B, the process tube 102 can have a top
ring 202,
the top ring 202 defining an opening 226 at the top of the process tube 102.
The top ring 202
extends around the circumference of the opening 226. As part of the process
tube 102, an
annular ledge 204 extends laterally out from the side of the process tube 102
below the top ring
202. In this manner, the top ring 202 extends upwards from an upper surface
206 of the annular
ledge 204. In addition to the upper surface 206, the annular ledge 204 is also
defined by an
outer surface 208 and a lower surface 210. Below the annular ledge 204 is a
neck 228 of the
process tube 102, which extends vertically from the annular ledge 204,
parallel to the
longitudinal axis 230 of the process tube 102. As shown in Fig. 2B, the
exterior of the process
tube 102 at the neck 228 can be parallel to a longitudinal axis 230 running
vertically through the
process tube 102. In another embodiment, the exterior neck 228 can be at an
angle to the
longitudinal axis 230 to aid in removal of the process tube 102 from an
injection mold during
the manufacturing process.
[0045] Below the neck 228 of the exemplary process tube 102 shown in
Figures 2A-
2B, is a protrusion 212 extending laterally from the side of the process tube
102. The protrusion
212 is defined by an upper slope 214 when extends from the neck 228 to an apex
215 of the
protrusion 212. The apex 215 of the protrusion 212 has the largest outside
diameter of the
protrusion 212 and then the protrusion 212 includes a lower slope 216 which
extends from the
apex 215 down the exterior of the process tube 102. The upper slope 214 of the
protrusion 212
slopes away from the longitudinal axis 230 and the lower slope 216 slopes back
towards the
longitudinal axis 230. In some embodiments, as shown in Figures 2A-2B, the
angle of the upper
slope 214 on the protrusion is steeper than the angle of the lower slope 216
on the protrusion
212. The lower slope 216 of the protrusion 212 meets a longer body portion 218
of the process
tube 102. The body 218, like the lower slope 216 of the protrusion 212, slopes
towards the
longitudinal axis 230, but has a less steep angle than the lower slope 215 of
the protrusion 212.
The body 218 extends to a base 220 of the process tube 102. The base 220
includes an annular
bottom ring 224 on the bottom of the process tube 102, defined by a divot 222
in the bottom of
the process tube 102. In this embodiment, the top ring 202, the annular ledge
204, the neck
228, the protrusion 212, and the body 218 are coaxial with the longitudinal
axis 230.
[0046] The annular ledge 204, neck 228, and protrusion 212 together
define a
securement region 200 of the process tube 102. As will be explained in detail
below, the
securement region 200 provides a way to easily and securely attach the process
tube 102 ( or
plurality of process tubes 102 in the form of a process strip 100) to a
carrier tray for transport
and later processing in the heater of an thermal cycler.
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[0047] As described above, the process tubes 102 can be manufactured as
a strip 100
of tubes 102 connected together by a connector tab 104. Multiple process tube
strips 100 can
then be inserted securely in a carrier tray 300. Fig. 3A shows an exemplary
carrier tray 300. As
seen in Fig. 3A, the carrier tray 300 can house a plurality of ports 306 in a
shelf 302 of the
carrier tray 300. The plurality of ports 306 can be configured to receive the
individual process
tubes 102, and the number of ports 306 in a column of the carrier tray 300 can
be
advantageously designed to fit the length of the process tube strips 100.
Thus, the number of
ports 306 in the y-direction can be designed to correspond to the number of
process tubes 102 in
a process tube strip 100. In one embodiment, the carrier tray 300 can have
eight ports 306 in the
y-direction such that a process tube strip 100 consisting of eight process
tubes 102 can be
inserted and secured in the ports 306 of the carrier tray 300 in the y-
direction.
[0048] In one embodiment, the ports 306 in the carrier tray 300 are
elliptical in
shape, having a larger cross-sectional diameter in the y-direction. In this
manner, the larger
diameter cross-sections of the elliptical ports 306 are lined up in the same
direction as the
process tube strips 100 when inserted in the carrier tray 300.
[0049] Fig. 3B shows a plurality of process tube strips 100 securely fit
in an
exemplary carrier tray 300. Once the process tubes 102 are inserted securely
in the carrier tray
300, assay reagents, e.g., amplification and detection reagents, can be added
to the process tubes
102 in an automated manner. In some embodiments, liquid reagents can be
pipetted into the
individual process tubes 102 and then the carrier tray 300 can optionally be
placed in a drier to
dry the liquid reagents in the bottom of the process tubes as a solid mass
formed to the shape of
the internal base 220 of the process tube 102. In some embodiments, liquid
reagents are not
dried down in the process tubes 102. In some embodiments, each process tube
102 in a carrier
tray 300 can be deposited with identical reagents. In other embodiments, some
or each of the
process tubes 102 in process tube strip 100 can be filled with differing
reagents or samples.
100501 Once filled with the desired reagents, e.g., following drying of
the reagents
in embodiments wherein the reagents are dried, or simply following deposition
of the reagents in
embodiments wherein the reagents are not dried, the process tubes 102 can be
marked with an
indicator to identify the contents (for example, the specific reagents) of the
process tubes 102.
In some embodiments, marking of the process tubes 102 can be accomplished by
hot stamping
the top ring 202 of the process tubes 102 with a specific color indicating the
contents (e.g.,
reagents) of the process tubes 102. The top ring 202 also provides a surface
to which an
adhesive seal can be applied to seal the opening 226 of the process tube 102.
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[0051] As described above, Fig. 1D shows a process tube strip 100
wherein each
process tube 100 includes a ledge extension 110 extending from one side of the
annular ledge
204 of the process tube 100. The ledge extension 110 provides additional
surface area on the
annular ledge 204 for marking of the individual process tubes 102. In one
embodiment, the
ledge extension 110 can be pre-marked with an alphanumeric identifier (e.g.,
A, B, C, etc, or 1,
2, 3, etc.) to identify an individual process tube 102 within a process tube
strip 100. In one
embodiment, as an alternative to hot stamping the top ring 202, the ledge
extension 110 of the
process tubes 102 can be hot stamped, or otherwise marked, to identify the
contents (e.g.,
reagents) of the process tubes 102 following the deposit of the reagents in
the process tubes 102.
Furthermore, a 2-D bar code (ink or laser) can be printed directly on the
ledge extension 110.
[0052] As shown in Fig. IF, the individual process tubes 102 of the
process tube
strip 100 can include a tube tag 112 affixed to the top of the ledge extension
110. The tag 112
can be used in addition to, or in conjunction with, marking (e.g., hot
stamping) the top ring 202
of the process tubes 102 to identify the contents, such as reagents, in a
particular process tube
102. The tag 112 can be a 2-dimensional matrix bar code (for example, a QR
code or Aztec
code) encoded with data identifying the contents of the associated process
tube 102. In using a
tag 112 to indicate the contents of the process tube 102, a camera (e.g., a
CCD camera) can be
used to scan and verify the contents of the process tube 102 and ensure the
correct amplification
assays are being performed with the associated reagents. The camera can
efficiently and quickly
verify the contents of each process tube 102 by reading the tag 112, thus
avoiding the possibility
of user error in pairing incorrect reagents with a specific amplification
assay required for a given
polynucleotide sample.
100531 In some instances, identical reagents can be added to each
process tube in a
carrier tray 300. In one example, each tube strip 100 can include eight
process tubes 102 and
then 12 tube strips can be securely fit into a 96-port carrier tray 300.
Identical reagents can then
be added to each of the 96 process tubes in the carrier tray 300. If all
process tubes 102 are
provided with identical reagents, all process tubes 102 in the entire carrier
tray 300 can be hot
stamped with the same color. A number of carrier trays 300 can be stacked and
sent together to
the end user. In some embodiments, each or some of the process tubes 102 in
tube strip 100 can
include different reagents. In such instances, process tubes 102 that contain
identical reagents
can be marked with the same color. Different colors can be used to identify
process tubes 102
containing different reagents.
[0054] The end user may need different stamped process tubes 102 to run
different
amplification assays with the different reagents provided. In some instances
the end user may
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need to use different reagents in an amplification assay, so a carrier tray
300 having process
tubes 102 of all the same reagents could not be used. In this case, the end
user can remove one
or more process tube strips 100 from a single-color carrier tray 300 and
exchange them with
differently colored process tube strips 100 in a different carrier tray 300 to
achieve the desired
number and type of reagents for a given amplification assay. It is also
contemplated that the
manufacturer could provide the end user with a carrier tray 300 having
different colored process
tube strips 100.
[0055] The end user can further refine the collection of different
reagents in an
amplification assay by breaking apart an individual process tube strip 100 at
the connector
recess 232 between process tubes 102. For example, an eight-tube process tube
strip 100 can be
broken into smaller collections of process tubes 102 having 1, 2, 3, 4, 5, 6,
or 7 process tubes
102. Breaking apart the process tube strips 100 allows the end user to include
process tubes 102
of different reagents in the same column of the carrier tray 300.
[0056] As described above, Fig. 3B provides an illustration of the
process tubes 102
when the process tubes are already securely fit into the carrier tray 300.
Fig. 4 is a cross-
sectional view of 12 process tubes 102 positioned in the carrier tray 300
prior to securing the
process tubes 102 in the carrier tray 300. This view is analogous to the cross-
sectional view 6A
shown in Fig. 3, but shows the process tubes 102 resting in the ports 306 of
the carrier tray 300
prior to securing the process tubes 102 in the carrier tray 300. As shown in
Fig. 3B and Fig. 4,
the carrier tray 300 has a base 304 and a shelf 302, the base 304 being wider
and longer than the
shelf 302 and, thus, having a larger planar surface area than shelf 302. The
shelf 302 of the
carrier tray 300 includes a shelf side 308 and a shelf top 310. The shelf top
310 is the
horizontal, planar portion of the shelf 302 and covers the top of the carrier
tray 300. The shelf
top 310 includes an exterior surface 312 and an interior surface 314. As the
base 304 of the
carrier tray 300 is wider and longer than the shelf 302, the base 304 includes
a bridge 320
running horizontally connecting the shelf side 308 and a base side 305. The
bridge 320 includes
an interior side 322. The shelf side 308 of the shelf 302 on the carrier tray
300 extends down
from the shelf top 310 and joins the base 304 of the carrier tray 300 at the
bridge 320. As shown
in Fig. 4, the process tubes 102 of a process tube strip 100 can be positioned
in the ports 306 in
the shelf 302 of the carrier fray 300.
[0057] Fig. 5 is a close-up, cross-sectional view of two exemplary
process tubes 102
positioned in an exemplary carrier tray 300, prior to securing the process
tubes 102 in the carrier
tray 300. Prior to securing a process tube 102 in the carrier tray 300, the
process tube 102 is
able to rest in the port 306 of the carrier tray 300. The outside diameter of
the body 218 of the
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process tube 102 is smaller than the diameter of the port 306, thus, the body
218 of the process
tube 102 can be inserted through the port 306. The protrusion 212 on the
process tube 102 has a
larger diameter than at least one diameter of the port 306. For example, in
the instance of the
port 306 being elliptical, the smaller diameter of the port 306 (for example
the width diameter in
the x-direction of Figs. 3A and 3B) is smaller than the diameter of the
protrusion 212. In some
embodiments, the larger diameter of the port 306 (for example the length
diameter in the y-
direction of Figs. 3A and 3B) can be larger than the diameter of the
protrusion 212. Thus, when
the body 218 of the process tube 102 is inserted into the port 306, the body
218 enters the
underside area of the carrier tray 300, but a top portion of the process tube
102, including the
securement region 200 (comprising the protrusion 212, the neck 228, and the
annular ledge 204)
and the top ring 202, is prevented from entering the port 306. In this manner,
the protrusion 212
comes to rest on a top edge 318 of the port 306. More specifically, the lower
slope 216 of the
protrusion 212 comes to rest on the port top edge 318.
[0058] In some embodiments, the apex 212 of the protrusion 212 is
circular, having a
constant outside diameter. For an elliptical port 306, in one embodiment, the
port 306 can have
a length diameter larger than the width diameter. In this embodiment, the
diameter of the port
306 width (in the x direction) can be less than the diameter of the apex 215
of the protrusion
212. Thus, the process tube 102 comes to rest, at the protrusion 212, on the
top edge 318 of the
port 306. In one embodiment, the length diameter (in the y direction) of the
port 306 can be
greater than the diameter of the apex 215 of the protrusion 212. Thus, a small
gap on two ends
(in the y-direction) of the port 306 is provided that facilitates easier
securement of the process
tube 102 in the port 306 and also facilitates easier removal of the process
tube 102 from the port
306, if needed. In other embodiments, the port 306 can be round, having a
constant diameter.
[0059] As the process tube 102 rests in the port 306 against the port
top edge 318, a
force can be applied to the top of the process tube 102 to press the process
tube 102 further into
the port 306 to secure the process tube 102 in the port 306 of the carrier
tray 300. The force to
secure the process tube 102 into the port 306 can be applied to the top ring
202 of the process
tube 102 or the force can be applied to the upper surface 206 of the annular
ledge 204.
[0060] Securing the process tube 102 in the port 306 initially involves
applying
sufficient force to the top of the process tube 102 to force the lower slope
216 of the protrusion
212 into the port 306. The lower slope 216 is angled towards the longitudinal
axis 230 of the
process tube 102. As continued pressure is applied to the top of the process
tube 102, the lower
slope 216 of the protrusion 212 slides down along the port top edge 318 until
the apex 215 of the
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protrusion 212 reaches the port top edge 318. The port top edge 318 can be
rounded or sloped to
facilitate the travel of the protrusion 212 through the port 306.
[0061] As the process tube 102 is pushed into the port 306, the portions
of the lower
slope 216 of the protrusion 212 that have passed into the port 306 do not
contact the port interior
wall 316 because the lower slope 216 is angled towards the longitudinal axis
230. The lower
slope 216 of the protrusion 212 gradually widens (the outside diameter
increases) as the lower
slope 216 extends upwards towards the apex 215 of the protrusion 212. The
wider the diameter
of the lower slope 216, the greater resistance to pushing the process tube 102
into the port 306.
Thus, a resistive force is generated which counters the force applied to push
the process tube
102 into the port 306. The resistive force against the process tube 102
increases (and the force
necessary to push the process tube 102 increases), the farther down the
process tube 212 travels
into the port 306. The resistive force against the process tube 102 continues
to increase until the
apex 215 of the protrusion 212 reaches the port top edge 318.
[0062] In an embodiment of the carrier tray 300 having elliptical ports
306, the larger
diameter of the port 306 in the y direction may more easily allow the process
tube 102 to be
pushed into the port 306 and secured in the carrier tray 300, thus reducing
the force required to
secure the process tube. An elliptical port 306 can provide extra space (e.g.,
a gap) between the
protrusion 212 of the process tube 102 and the port interior 316 on two ends
that allows the
process tube 102 to flex and elongate in the y direction and compress in the x
direction.
[0063] Once the entirety of the lower slope 216 passes through the port
top edge 318,
and the apex 215 of the protrusion passes through the port top edge 318, the
apex 215 of the
protrusion 212 comes into contact with the port interior wall 316. The apex
215 is the widest
portion (largest outside diameter) of the protrusion 212. As the apex 215 is
being fit through the
port 306 and pressed against the port interior wall 316, the process tube 102
undergoes
maximum strain and is maximally flexed. As continued force is applied to the
top of the process
tube 102, the apex 215 is forced to slide down the port interior wall 316
until it completely
passes through the port 306 at the bottom edge 319 of the port 306. Once the
apex 215 breaches
the bottom edge 319, the strain on the process tube 102 is released and the
process tube 102
"snaps" securely into place in the port 306 and becomes secured in the carrier
tray 300. The
force necessary to secure each process tube 102 of the process tube strips 100
in a carrier tray
300 can range from approximately 0.7 lbs. force to approximately 1.7 lbs.
force. In one
embodiment, the force necessary to insert and secure process tube 102 in a
port 306 can be
approximately 1 lb. force. In one embodiment, the force necessary to secure a
process tube 102
in a port 306 can be approximately 1.18 lbs. force.
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[0064] The carrier tray 300 can be advantageously designed for efficient
stacking
and transport of the carrier trays 300. The carrier tray 300 can be
constructed from
polycarbonate resin thermoplastic. Referring to Figs. 3, 4, and 5, the carrier
tray 300 can
include a bridge 320 at the top of the base 220. The bridge 320 provides a
platform on which
the bottom surface 326 of another empty carrier tray 300 can positioned. When
two carrier trays
300 are stacked on top of each other, the bridge interior 322 of a top carrier
tray 300 comes to
rest on the shelf top 310 of a bottom carrier tray 300 and the bottom surface
326 of the top
carrier tray 300 comes to rest on the bridge 320 of the bottom carrier tray
300.
[0065] When the carrier trays 300 are populated with the process tube
strips 100,
they can be efficiently stacked in a similar manner. The body 218 of the
process tubes 102 in a
top carrier tray 300 can be placed in the opening 226 of the process tubes 102
in a bottom carrier
tray 300. Likewise, the process tubes 102 in the top carrier tray 300 can
further receive the body
218 of the process tubes 102 in another carrier tray 300 to be stacked on top
of it.
[0066] Fig. 6A is a cross-sectional view, taken along line 6A in Fig.
3B, of the 12
process tubes 102 shown in Fig. 4. Fig. 6A shows the process tubes 102 now
secured in the
carrier tray 300. The direction of cross-section 6A in Fig. 3B provides a view
of 12 process
tubes 102, each from a different process tube strip 100. Fig. 6B is a cross-
sectional view, taken
along line 6B in Fig. 3B, of an entire process tube strip 100 positioned in
the carrier tray 300
after securing the process tubes 102 in the carrier tray 300. As shown in Fig.
6B, the cross-
sectional diameter of the elliptical port 306 in the y direction can be larger
than the diameter of
the protrusion 212.
[0067] Fig. 7 is a close-up view of two of the process tubes 102 shown
in Fig. 6A
and corresponds to the process tubes 102 of Fig. 5 after securing the process
tubes 102 in the
carrier tray 300. As shown in Fig. 7, the cross-sectional diameter of the
elliptical port in the x
direction can be smaller than the diameter of the protrusion 212. When the
apex 215 of the
protrusion 212 breaches the bottom edge 319, the upper slope 214 of the
protrusion 212 comes
into contact with, and lodges against, the bottom edge 319 of the port 306, at
the bottom of the
securement region 200. Also, when the apex 215 breaches the bottom edge 319,
the lower
surface 210 of the annular ledge 204 comes into contact with, and lodges
against, the shelf top
exterior 312 of the shelf 302, at the top of the securement region 200. At the
top of the
securement region 200, the annular ledge 204 is sufficiently wide at at least
two points around
the port 306 that the annular ledge 204 cannot pass through the port 306. In
one embodiment,
the annular ledge 204 can have a sufficiently large diameter to cover all
points around the port
306. For example, the annular ledge 204 can have a larger diameter than the
width and length
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diameters of the port 306. The height of the securement region 200 (from the
lower surface 210
of the annular ledge 204 to a location on the upper slope 214 of the
protrusion 212) corresponds
approximately to the height of the port 306, between the port top edge 318 and
the port bottom
edge 319.
[0068] As shown in Fig. 7, the neck 228 of the process tube 102 can have
a smaller
outside diameter than the diameter of the port 306, creating a gap 324 between
the process tube
102 and the port interior wall 314. In one embodiment, the outside diameter of
the neck 228 can
be a fixed circular diameter. As the port 306 can be elliptical in shape and
have a larger length
diameter on one side and a smaller width diameter on the other side, the width
of the gap 324
can vary between the length side (y direction) and width side (x direction) of
the port 306. For
example, the size of the gap 324 on each length side of the port 306 can be
approximately twice
the size of the gap on each width side of the port 306.
[0069] The gap 324 provides a point of adjustment for the process tube
102 in the
securement region 200. The gap 324 exists primarily between the neck 228 of
the process tube
102 and the port interior wall 316, but the gap 324 also exists along a
portion of the upper slope
214 of the protrusion 212 and along a portion of the lower surface 210 of the
annular ledge 204.
The gap 324 is enlarged slightly at the top portion of the securement region
200 because the
rounded corners of the port top edge 318 provide additional distance between
the port 306 and
the neck 228 of the process tube 102. The gap 324 can provide the process tube
102 some
degree of freedom of movement within the port 306 of the carrier tray 300,
even when the
process tube 102 is secured in the port 306.
[0070] The process tube 102 can be adjusted in the port 306 while being
maintained
securely in the port 306 because the point of contact between the upper slope
214 of the
protrusion 212 and the port bottom edge 319 can adjust as the process tube 102
needs to tilt.
When a process tube 102 tilts, the locations of the points of contact between
the securement
region 200 of the process tube 102 and the port 306 of the carrier tray 300
will adjust. For
example, when the process tube tilts to one side, a point of contact on one
side of the process
tube 102 between the upper slope 214 and port bottom edge 319 moves near the
top of the upper
slope 214; on the other side of the tube, another point of contact moves to be
near the bottom of
the upper slope 214 (near the apex 215). Similar adjustment is possible at the
top of the
securement region 200, such that the neck 228 can be tilted towards the
rounded port top edge
318 on one side of the process tube 102 and can be tilted away from the port
top edge 318 on the
other side of the process tube 102.
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NOM The gap 324 allows the process tube 102 to adjust when placing a
plurality of
process tubes into the carrier tray 100 as part of a process tube strip 100.
Because of possible
manufacturing variations of the carrier trays 300 and the process tubes 102,
each carrier tray 300
may be sized slightly differently and each process tube 102 may fit in the
carrier trays 300
differently. Given that the process tubes 102 are often attached together as
part of a process
tube strip 102 when inserted in the carrier tray 300, it is possible that,
without mitigating
considerations, the manufacturing variations of the carrier tray 300 and
process tubes 102 could
prevent accurate placement of an entire process tube strip 100 in a carrier
tray 300. For
example, accurate insertion of a process tube 102 at one end of a process tube
strip 100 into the
carrier tray 300 could prevent accurate insertion of the process tubes 102 at
the other end of the
process tube strip 100 into the carrier tray 300 because the process tubes 102
could be
misaligned in either the x direction (lateral) or y direction (front to back).
Even if a rigid
process tube strip 100 is forced into the ports 306 of a carrier tray 300
despite being misaligned,
the rigid attachment of the process tubes 102 would prevent the process tubes
102 from lying
flat on the carrier tray 300 which could inhibit the hot stamping process.
[0072] The present disclosure addresses these issues in a number of
ways, including
allowing the process tubes 102 to tilt and adjust in the port 306 when the
process tube strip 100
is being maneuvered and inserted in the carrier tray 300. The process tubes
102 can tilt and
adjust in the port 306 because the gaps 324 allow for such motion. The
elliptical shape of the
ports 306 also enhances the adjustment available in the y direction. Also, the
connector tabs 104
connecting the process tubes 102 are thin and pliable enough to allow
maneuverability and
adjustment between the individual process tubes 102 when inserting them in the
carrier tray 300.
In addition, the connector recess 232 (seen in Fig. 2B) on the connector tab
104 allows increased
flexibility between the individual process tubes 102 when inserting them in
the ports 306. In
this manner, the gaps 324, the elliptical-shaped ports 306, and the connector
tabs 104 afford the
process tube 102 the capacity to adjust and always lay flat on the carrier
tray 300 when inserting
a process tube strip 100 into the carrier tray 300. Furthermore, the capacity
of a process tube 102
to tilt or adjust in the carrier tray 300 facilities insertion of the process
tube 102 into a heater of
the thermal cycler, as discussed below in more detail.
[0073] When the process tubes 102 are secured in the ports 306 of the
carrier tray
300, the process tubes 102 can undergo processing in preparation for use in a
thermal cycler.
Liquid reagents can be inputted into the secured process tubes 102. The
process tubes 102 in the
carrier tray 300 can be subjected to heat or other processes for drying or
lyophilization in order
to dry the liquid reagents in the process tubes 102. While secured in the
carrier tray 300, the
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process tubes 102 can also be hot stamped to mark the process tubes 102,
indicating the type of
reagents added to the process tubes 102. The hot stamping can be in the form
of a color stamped
on the top ring 202 and/or the annular ledge 204.
[0074] The process of applying force to securing the process tubes 102
in the ports
306 of the carrier tray 300, the process of inputting liquid reagents into the
secured process tubes
102, the process of drying the liquid reagents in the process tubes 102, and
the process of hot
stamping the process tubes 102 in carrier tray 300 can all be automated and
performed at the site
of manufacture and assembly of the process tubes 102 and carrier trays 300.
The assembled
carrier trays 300 containing the prepared process tubes 102 can then be
shipped to the end user
for additional processing such as depositing extracted nucleic acid samples in
the process tubes
102 prior to running amplification assays on the samples the process tubes 102
in a thermal
cycler. The addition of the extracted nucleic acid samples to the process
tubes 102 acts to
reconstitute the dried reagents to allow the reagents to associate with the
nucleic acid samples in
the reconstituted solution.
100751 As described above, an end user can remove one or more process
tube strips
100 from a single-color carrier tray 300 and exchange them with differently
colored process tube
strips 100 in a different carrier tray 300 to achieve the desired number and
type of reagents for a
given amplification assay. The force necessary to remove the process tube
strip 100 can be
approximately half of the force required to insert it. In one embodiment, the
insertion force for a
process tube strip 100 can have a range of approximately 0.7 lbs. force to 1.7
lbs. force and the
removal force for the process tube strip 100 can have a range of approximately
0.3 lbs. force to
0.8 lbs force. In one embodiment, the insertion force for a process tube strip
100 can be
approximately 1 lb. force and the removal force for the process tube strip 100
can be
approximately 0.5 lb. force. In one embodiment, the force necessary to secure
a process tube
strip 100 in the ports 306 can be approximately 1.18 lbs. force and the force
necessary to remove
the process tube strip is 0.60 lbs. force. The insertion and removal forces
prescribed for the
process tube strips 100 insure that a process tube strip 100 is not overly
difficult to insert or
remove from the carrier tray 300 and also prevent the process tube strips 100
from falling out of
the carrier tray under normal handling conditions.
[0076] It is of note that the same carrier tray 300 (housing the process
tubes 102) in
which the mixing of reagents and nucleic acid samples occurs can be input
directly into the
thermal cycler. Thus, the end user is not required to do the mixing of
reagents and nucleic acid
in one tube and then transport that mixed solution to another tube, or even
move the first tube to
another tray. In the present disclosure, the process tubes 102 containing the
reagents and
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secured in the carrier tray 300 can receive the samples, e.g., nucleic acid
samples, and, then
without removing the process tubes 102 from the carrier tray 300, can be input
into the thermal
cycler for amplification assays.
[0077] It is also contemplated that solid reagents may be added to the
process tubes
102 in addition to, or instead of, the liquid reagents. It is also
contemplated that empty process
tubes 102 and carrier trays 300 can be supplied to the end user and the end
user can deposit the
solid or liquid reagents in the process tubes 102 prior to adding the nucleic
acid samples.
[0078] The securement force, the force necessary to push the process
tube 102
securely into the port 306, can be applied simultaneously to multiple (or all)
process tubes 102
in the carrier tray 300. Alternatively, the securement force can be applied
separately to
individual process tubes 102 one at a time, as needed. The securement force
can be applied in
an automated manner and can be conducted concurrently along with the automated
steps of
filling the process tubes 102 with reagents and hot stamping the process tubes
102. In some
instances, the same apparatus can be used to hot stamp and apply the
securement force to the
process tubes 102. Alternatively, separate apparatuses can be used for hot
stamping and
applying the securement force.
[0079] When a separate securement force device and a hot stamping device
are used,
the securement force can first be applied to secure the process tubes 102 in
the ports 306 of the
carrier tray 300 prior to hot stamping the top ring 202 of the process tubes
102. In some
instances, the automated hot stamping apparatus may stick to the top ring 202
of the process
tubes 102 when applying pressure to the top ring 202. Because of the novel way
in which the
process tubes 102 are secured in the carrier tray 300 in the embodiments
described herein, a
process tubes 102 are not pulled up and out of the carrier tray 300 when the
hot stamping
apparatus pulls apart from the process tube 102 being stamped. Furthermore,
because the
process tubes 102 are secured in the carrier tray 300, the process tubes 102
can be transported
without risk of the process tubes 102 falling out of the carrier tray 300. The
embodiments
disclosed herein also advantageously overcome other issues that present in
other PCR tube trays,
such as bunching of tubes on one side of the tray or tubes falling out of
alignment in the tray.
[0080] Fig. 8 is an isometric view of an exemplary heater assembly 400
to be used in
a thermal cycler (not shown). Amplification assays (such as PCR or isothermal
amplification)
can be performed in the thermal cycler. The heater assembly 400 is part of
temperature cycling-
subsystem of the thermal cycler and can work in conjunction with other
subsystems of the
thermal cycler, such as a detection subsystem. The exemplary heater assembly
400 shown in
Fig. 8 is a 96-well assembly containing 96 heater wells 402, although other
assemblies are
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contemplated (e.g., 48-well assemblies, etc.). The heater assembly 400
includes a flat top
surface 404 between the heater wells 402, and a side surface 410. Each heater
well 402 is
conical in shape and is comprised of an interior wall 406and a well bottom
412. The heater
wells 402 in the heater assembly 400 are arranged in an array of 8 rows and 12
columns to
correspond to the spatial arrangement of process tubes 102 in a carrier tray
300.
[0081] Each
heater well 402 can receive a process tube 102. The carrier tray 300 can
be placed directly over the heater assembly 400 in the thermal cycler in order
to place all
process tube 102 in the carrier tray 300 into the heater assembly 400
simultaneously. Not
shown in Fig. 8 is the casing around the heater assembly 400 or the necessary
circuitry to
provide heat to the heater wells 402.
[0082]
Because of possible manufacturing variations of the carrier trays 300 and the
process tubes 102, each carrier tray 300 may be sized slightly differently and
each process tube
102 may fit in the carrier trays 300 differently. If the process tubes 102
were rigidly attached to
the carrier tray 300, the manufacturing tolerances could prevent all of the
process tubes in a 96-
tube carrier tray 300 from accurately being placed in the heater wells 402.
For example, fitting a
process tube 102 in a heater well 402 on one side of the heater assembly 400
may prevent a
process tube 102 on the other side of the heater assembly 400 from being
accurately and
securely placed into its respective heater well 402. As described above, the
process tubes 102
are able to float or adjust slightly when secured in the carrier tray 300
because of the gap 324
between the port interior wall 316 and the securement region 200 of the
process tube 102. The
connector recess 232 (seen in Fig. 2B) on the connector tab 104 also allows
flexibility between
the individual process tubes 102 when inserting them in the heater wells 402.
Allowing the
process tubes 102 to float within ports 306 of the carrier tray 300 permits
the process tubes 102
to adjust position to fit accurately and securely into the heater wells 402 of
the heater assembly
400.
[0083] Fig.
9 is a cross-sectional view of two exemplary process tubes 102
positioned in heater wells 402 of the heater assembly 400. When the process
tube 102 is placed
in the heater well 402, the body 218 of the process tube 102 comes in physical
contact with, and
is mated to, the interior wall 406 of the heater well 402. In some
embodiments, the heater well
402 is deeper than the body 218 of the process tube 102, such that when the
process tube 102 is
secured in a port 306 of the carrier tray 300 and the carrier tray 300 is
positioned over the heater
assembly 400, the base 220 of the process tube 102 does not extend to the well
bottom 412. In
this manner, a gap 414 is created between the base 220 of the process tube 102
and the well
bottom 412. The gap 414 ensures that the body 218 of the process tube 102
remain in physical
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contact with the well interior wall 406; if the base 220 of the process tube
102 were to bottom
out in the heater well bottom 412 first, before the body 218 contacts the well
interior wall 406, a
gap could exist between the wall 406 and the body 218 of the process tube 102
and cause poor
heat transfer between the heater well 402 and the process tube 102. Thus, the
gap 414 below the
process tube 102 ensures that a gap does not exist between the wall 406 and
the body 218 of the
process tube 102. The heater well 402 can surround the body 218 of the process
tube 102 and
provide uniform heating to the contents of the process tube 102 during the
thermal cycling steps
of the amplification assay. When the process tube 102 is placed in the heater
well 402, the
heater well 402 can surround the body 218 of the process tube to a location
just below the lower
slope 216 of the protrusion 212.
100841 The
above description discloses multiple methods and systems of the
embodiments disclosed herein. The
embodiments disclosed herein are susceptible to
modifications in the methods and materials, as well as alterations in the
fabrication methods and
equipment. Such modifications will become apparent to those skilled in the art
from a
consideration of this disclosure or practice of the invention disclosed
herein. Consequently, it is
not intended that the embodiments disclosed herein be limited to the specific
embodiments
disclosed herein, but that it cover all modifications and alternatives coming
within the true scope
and spirit of the invention.
Example 1
[0085] This
example illustrates a specific process for preparing a carrier tray 300
with process tubes 102 to be provided to an end user.
1. Manufacturing 12 process tube strips containing eight connected process
tubes
formed from polypropylene.
2. Manufacturing a carrier tray from polycarbonate having 96 ports in an 8 x
12 array. .
3. The 12 process tube strips are placed in the carrier tray.
4. The process tubes of the process tube strips are secured in the ports of
the carrier tray
by applying a force to the top ring of the process tube.
5. Each process tube in the carrier tray is filled with the same specific
liquid reagents.
6. The carrier tray is heated to dry the reagents in the process tubes.
7. The process tubes are hot stamped with specific colors to indicate the
assay for which
they will be used.
8. The carrier tray is stacked and packaged with other carrier trays having
the same or
different reagents and shipped to the end user.
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9. The end user can use the entire carrier tray as is, or may depopulate the
carrier tray
and repopulate the carrier tray or trays with a mix of individual process tube
strips or
tubes of various reagent types.
Example 2
[0086] This example describes the test procedure and results of a test
to determine
the force necessary to secure the process tube strips 100 in the ports 306 of
the carrier tray 300
and the force necessary to subsequently remove the process tube strips 100
from the ports 306.
[0087] An Amtek AccuForce Cadet Force Gage, (0-5 lbs) was used to
measure the
force necessary to secure and remove the process tubes 102 in the ports 306.
Test Procedure
1. Lay one strip of tubes in a column of the carrier tray. (Not yet secured
in the carrier
tray)
2. Turn on the gage.
3. Zero the gage with the gage in the upright position.
4. Clear the gage.
5. Slowly press down on each tube within the strip starting at the "A" row
with the gage
at a slight angle ¨ 2-3 degrees from vertical on each tube until all the tubes
snap into
place.
6. Record the force value on the gauge and the column number as insertion
values.
7. Press the clear button to clear the memory.
8. Lay the second strip of tubes in the second column. Repeat steps 5-7.
9. Repeat steps 5-7 for the remaining strips 3-12.
10. Turn the carrier tray upside down and starting with the first strip slowly
press the
tubes out of the carrier starting at the "A" row.
11. Record the force value and the column number as removal values.
12. Press the clear button to clear the memory.
13. Repeat steps 10, 11 and 12 for the remaining process tube strips.
14. Rearrange the 12 process tube strips in the carrier tray and repeat steps
3-13.
Results
[0088] The results of the force testing are provided in Table 1. Table 1
shows the
force necessary to insert and secure all the process tubes 102 of a process
tube strip 100 in a
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carrier tray 300. As shown, the average insertion force to secure the process
tube strips 100 in
the carrier tray 300 was 1.18 lbs force and the average removal force was 0.60
lbs force.
Table 1 - Process Tube Insertion and Removal Testing
Tube Strips
1st Round 1 2 3 4 5 6
Insertion 0.708 1.084 1.137 1.467 0.945 1.476
Removal 0.313 0.478 0.573 0.589 0.520 0.518
3.5t Round 7 8 9 10 11 12 Avg
Insertion 0.866 1.075 1.408 0.969 1.025 1.217 1.115
Removal 0.553 0.978 0.767 0.388 0.602 0.485 0.564
2nd Round -tube strips randomly rearranged
1 2 3 4 5 6
Insertion 0.668 0.904 1.661 1.727 1.677 1.296
Removal 0.439 0.534 0.699 0.630 0.584 0.652
2nd Round -tube strips randomly rearranged
7 8 9 10 11 12 Avg
Insertion 1.536 1.051 1.280 1.056 1.012 0.983 1.238 Average
Insertion 1.18
Removal 0.723 0.675 0.778 0.750 0.619 0.514 0.633 Average
Removal 0.60
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