U.S. patent application number 17/410060 was filed with the patent office on 2022-02-10 for systems and methods for a thermal cycler heated cover.
This patent application is currently assigned to LIFE TECHNOLOGIES CORPORATION. The applicant listed for this patent is LIFE TECHNOLOGIES CORPORATION. Invention is credited to Kuan Moon (Bernard) BOO, Siew Yin LEE, Wuh Ken LOH, Zeqi TAN.
Application Number | 20220040700 17/410060 |
Document ID | / |
Family ID | 1000005929129 |
Filed Date | 2022-02-10 |
United States Patent
Application |
20220040700 |
Kind Code |
A1 |
TAN; Zeqi ; et al. |
February 10, 2022 |
SYSTEMS AND METHODS FOR A THERMAL CYCLER HEATED COVER
Abstract
A thermal cycler system for use with a sample holder configured
to receive a plurality of samples includes a sample block
configured to receive the sample holder, a cover lid configured to
move in a direction toward the sample block from an open position
to a closed position, a heated cover operatively coupled to the
cover lid and configured to move in a direction toward the sample
block from a raised position to a first lowered position, in which
the heated cover contacts the sample holder when the sample holder
is received by the sample block, and a drive assembly including a
motion guide configured to move in a direction toward the sample
block from a first position, wherein the cover lid is in the open
position and the heated cover is in the raised position, to a
second position, wherein the cover lid is in the closed
position.
Inventors: |
TAN; Zeqi; (Singapore,
SG) ; LOH; Wuh Ken; (Singapore, SG) ; LEE;
Siew Yin; (Singapore, SG) ; BOO; Kuan Moon
(Bernard); (Singapore, SG) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
LIFE TECHNOLOGIES CORPORATION |
Carlsbad |
CA |
US |
|
|
Assignee: |
LIFE TECHNOLOGIES
CORPORATION
Carlsbad
CA
|
Family ID: |
1000005929129 |
Appl. No.: |
17/410060 |
Filed: |
August 24, 2021 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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16515533 |
Jul 18, 2019 |
11110462 |
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17410060 |
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15387631 |
Dec 21, 2016 |
10384208 |
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16515533 |
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62270695 |
Dec 22, 2015 |
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Current U.S.
Class: |
1/1 |
Current CPC
Class: |
B01L 2300/0663 20130101;
B01L 2300/0609 20130101; B01L 2300/18 20130101; G01N 35/026
20130101; B01L 2300/041 20130101; B01L 2200/143 20130101; B01L
2200/025 20130101; B01L 2300/045 20130101; B01L 2300/046 20130101;
B01L 2300/1827 20130101; B01L 7/52 20130101 |
International
Class: |
B01L 7/00 20060101
B01L007/00; G01N 35/02 20060101 G01N035/02 |
Claims
1. A thermal cycler system for use with a sample holder configured
to receive a plurality of samples, the system comprising: a sample
block configured to receive the sample holder; a heated cover
configured to move in a direction toward the sample block from a
raised position to a first lowered position when the sample holder
is received by the sample block, and from the first lowered
position to a second lowered position when the sample holder is
removed from the sample block; and a first sensor configured to
detect whether the heated cover is in the first lowered position,
wherein, in the first lowered position, the heated cover is in
contact with the sample holder in the first lowered position, and
wherein, in the second lowered position, the heated cover is in a
position intermediate of the first lowered position and the sample
block.
2. The thermal cycler system of claim 1, wherein, when the sample
holder is received by the sample block and the heated cover is in
the first lowered position, the heated cover is configured to apply
a force to the sample holder.
3. The thermal cycler system of claim 2, wherein the heated cover
is configured to apply a predetermined force to the sample
holder.
4. The thermal cycler system of claim 3, the system further
comprising: a pressure bar coupled to the heated cover, wherein,
when the heated cover is applying the predetermined force to the
sample holder, the pressure bar and the heated cover are spaced
apart by a predetermined distance and the first sensor is
configured to detect whether the pressure bar and the heated cover
are spaced apart by the predetermined distance.
5. The thermal cycler system of claim 1, further comprising: a
second sensor configured to detect whether the heated cover is in
the second lowered position.
6. The thermal cycler system of claim 5, further comprising: a
motion guide configured to move in a direction toward the sample
block from a first position to a second position when the sample
holder is removed from the sample block, wherein, in the first
position of the motion guide, the heated cover is in the raised
position in the first position of the motion guide, wherein, in the
second position of the motion guide, the heated cover is in the
second lowered position, wherein the second sensor is configured to
detect whether the motion guide is in the second position.
7. The thermal cycler system of claim 5, further comprising: a
third sensor configured to detect whether the heated cover is in
the raised position.
8. The thermal cycler system of claim 7, further comprising: a
cover lid configured to move in a direction toward the sample block
from an open position to a closed position; and a third sensor
configured to detect whether the cover lid is in the open position,
wherein, in the open position of the cover lid, the heated cover is
in the raised position.
9. A thermal cycler system comprising: a sample block comprising a
sample holder receiving surface configured to receive the sample
holder; and a cover assembly moveable in a first direction parallel
to the sample holder receiving surface between an open position and
a closed position relative to the sample holder receiving surface,
wherein the cover assembly covers the sample holder receiving
surface in the closed position and exposes the sample holder
receiving surface in the open position, wherein the cover assembly
comprises: a platen moveable, in the closed position of the cover
assembly, in a second direction perpendicular to the first
direction between a raised position and a lowered position relative
to the sample holder receiving surface, a cover lid over the
platen, the cover lid having a first range of motion in the first
direction from an initial position to a final position of the cover
lid, an actuatable linkage coupled to and extending transversely
across the platen in a direction perpendicular to the first
direction, the actuatable linkage moveable in the second direction
between a raised position and a lowered position, and the
actuatable linkage being movable in the first direction with the
cover lid through the first range of motion of the cover lid, and
an elastically deformable member between the actuatable linkage and
the platen, the elastically deformable member arranged to exert a
compressive force against the platen in the lowered position of the
platen and the actuatable linkage.
10. The system of claim 9, wherein the platen is configured to be
heated.
11. The system of claim 9, further comprising a drive assembly
operably coupled to the cover assembly, the drive assembly
configured to impart a drive force on the cover assembly in the
first direction.
12. The system of claim 11, further comprising a motion guide
coupled to the cover assembly and the drive assembly, the motion
guide positioned to transfer the drive force from the drive
assembly to the cover assembly, the motion guide and the cover
assembly moving together over the first range of motion in the
first direction in response to the drive force.
13. The system of claim 12, wherein the platen is moveable over a
second range of motion in the second direction in response to
movement of the motion guide relative to the cover assembly.
14. The system of claim 9, further comprising imparting a drive
force on the cover assembly in the first direction using a drive
assembly operably coupled to the cover assembly.
15. The system of claim 14, further comprising transferring the
drive force from the drive assembly to the cover assembly using a
motion guide coupled to the cover assembly and the drive assembly,
the motion guide and the cover assembly moving together over the
first range of motion.
16. The system of claim 15, wherein the platen is moved over a
second range of motion in response to movement of the motion guide
relative to the cover assembly.
17. A method of operating a thermal cycler, the method comprising:
moving a cover assembly in a first direction parallel to a sample
holder receiving surface between an open position and a closed
position relative to the sample holder receiving surface, wherein
the cover assembly covers the sample holder receiving surface in
the closed position and exposes the sample holder receiving surface
in the open position, wherein the cover assembly comprises a
platen, a cover lid located over the platen, an actuatable linkage,
and an elastically deformable member; moving the platen, in the
closed position of the cover assembly, in a second direction
perpendicular to the first direction between a raised position and
a lowered position relative to the sample holder receiving surface;
moving the cover lid over a first range of motion in the first
direction from an initial position to a final position of the cover
lid; moving the actuatable linkage in the second direction between
a raised position and a lowered position; and moving the actuatable
linkage being in the first direction with the cover lid through the
first range of motion of the cover lid.
18. The method of claim 17, wherein the actuatable linkage is
coupled to and extends transversely across the platen in a
direction perpendicular to the first direction.
19. The method of claim 17, further comprising exerting a
compressive force against the platen in the lowered position of the
platen and the actuatable linkage.
20. The method of claim 19, wherein the compressive force is
exerted using an elastically deformable member between the
actuatable linkage and the platen.
Description
CROSS REFERENCE TO RELATED APPLICATIONS
[0001] This application is a continuation of U.S. application Ser.
No. 16/515,533, filed Jul. 18, 2019, which is a divisional of U.S.
application Ser. No. 15/387,631, filed Dec. 21, 2016 (now U.S. Pat.
No. 10,384,208), which claims the benefit under 35 U.S.C. .sctn.
119(e) of U.S. Provisional Patent Application No. 62/270,695 filed
on Dec. 22, 2015 (now expired), which are hereby incorporated by
reference in their entireties.
TECHNICAL FIELD
[0002] The present invention relates generally to thermal cycler
systems and methods of using same.
BACKGROUND
[0003] Testing of biological or chemical samples often requires a
device for repeatedly subjecting multiple samples though a series
of temperature cycles. To prepare, observe, test, and/or analyze an
array of biological samples, one example of an instrument that may
be utilized is a thermal cycler or thermocycling device, such as an
end-point polymerase chain reaction (PCR) instrument or a
quantitative, or real-time, PCR instrument. Such devices are used
to generate specific temperature cycles, i.e. to set predetermined
temperatures in the reaction vessels to be maintained for
predetermined intervals of time.
[0004] Generally, it is desirable to increase the efficiency and
output of the PCR process. Advances in automated biological sample
processing instruments allow for quicker and more efficient
analysis of samples. However, such automated systems often must be
capable of integrating with other automated laboratory systems.
Eliminating user interaction increases efficiency but requires the
development of feedback controls to cue the main instrument
controller that the next stage in the process is ready to occur.
For example, the system must be sure that a sample holder is in
place within the biological analysis system before activating the
thermal cycling routine. In an automated system where there are no
user interventions, it is desirable to cue the main instrument
controller that the sample holder is in place based on feedback by
the lab automation system.
[0005] A potential method to detect that the consumer plate in
position is the use of an imaging system integrated into the main
lab automation system. The imaging system may capture an image and,
through complex algorithms, determine the presence of a sample
holder on the sample block of the PCR system. Such a method is
complex, costly, and tedious to implement. Other methods include
the embedding of a sensitive load cell on the sample block module
or the use of a barcode reader, which can detect the presence of
the plate through a weight change or a barcode on the sample
holder, respectively. However, such methods are costly to
implement.
[0006] There is an increasing need to provide improved thermal
cycler systems that address one or more of the above drawbacks.
SUMMARY
[0007] In accordance with one embodiment, a thermal cycler system
for use with a sample holder configured to receive a plurality of
samples includes a sample block configured to receive the sample
holder, a cover lid, a heated cover operatively coupled to the
cover lid, and a drive assembly for moving the cover lid and the
heated cover. The cover lid is configured to move in a direction
toward the sample block from an open position to a closed position.
The heated cover is configured to move in a direction toward the
sample block from a raised position to a first lowered position, in
which the heated cover contacts the sample holder when the sample
holder is received by the sample block. The drive assembly includes
a motion guide operatively coupled to the cover lid and to the
heated cover. The motion guide is configured to move in a direction
toward the sample block from a first position, wherein the cover
lid is in the open position and the heated cover is in the raised
position, to a second position, wherein the cover lid is in the
closed position.
[0008] In accordance with another embodiment, a thermal cycler
system for use with a sample holder configured to receive a
plurality of samples includes a sample block configured to receive
the sample holder, a heated cover, and a first sensor. The heated
cover is configured to move in a direction toward the sample block
from a raised position to a first lowered position, wherein the
heated cover is in contact with the sample holder when the sample
holder is received by the sample block, and from the first lowered
position to a second lowered position when the sample holder is
removed from the sample block, wherein the heated cover is in
contact with the sample block. The first sensor is configured to
detect whether the heated cover is in the first lowered
position.
[0009] Various additional features and advantages of the invention
will become more apparent to those of ordinary skill in the art
upon review of the following detailed description of the
illustrative embodiments taken in conjunction with the accompanying
drawings.
BRIEF DESCRIPTION OF THE DRAWINGS
[0010] The accompanying drawings, which are incorporated in and
constitute a part of this specification, illustrate embodiments of
the invention and, together with a general description of the
invention given above, and the detailed description given below,
serve to explain the invention.
[0011] FIG. 1 is a perspective view of a thermal cycler system
according to one embodiment showing the cover lid in an open
position.
[0012] FIG. 2 is a perspective view of the thermal cycler system of
FIG. 1 showing the cover lid in a closed position.
[0013] FIG. 3 is a front perspective view of the thermal cycler
system of FIG. 1 with an outer housing removed.
[0014] FIG. 4 is a rear perspective view of the thermal cycler
system of FIG. 1 with the outer housing removed.
[0015] FIGS. 5A-5D are rear perspective views of a portion of the
thermal cycler system of FIG. 1 showing a cover lid, a motion
guide, and a heated cover in various positions.
[0016] FIGS. 6A-6C are cross-sectional views of a portion of the
thermal cycler system taken generally along line 6B-6B of FIG. 5C
showing the heated cover in various positions relative to a sample
holder positioned on the sample block.
[0017] FIG. 7 is a cross-sectional view of a portion of the thermal
cycler system taken generally along line 7-7 of FIG. 5D showing the
heated cover positioned on the sample block without a sample
holder.
[0018] FIG. 8 is a cross-sectional view of a portion of the thermal
cycler system taken generally along line 8-8 of FIG. 4 showing the
guides.
DETAILED DESCRIPTION
[0019] Referring to FIGS. 1-4, a thermal cycler system 10 is shown
constructed in accordance with an illustrative embodiment of the
present invention. The thermal cycler system 10 includes an outer
housing 12 and a sample block 14 configured to receive a sample
holder 16. The sample block 14 includes a plurality of cavities 18
and is configured to be loaded with the correspondingly shaped
sample holder 16 containing a plurality of biological or
biochemical samples located in a plurality of wells 20, as shown
best in FIG. 8. The thermal cycler system 10 further includes a
heated cover or platen 22 operatively coupled to a pressure bar 24
(shown in FIG. 5A) and a cover lid 26. The heated cover 22 is
configured to provide a downward force to the sample holder 16. The
downward force provides vertical compression between the sample
holder 16, sample block 14, and the other components of a thermal
block assembly (not shown), which improves thermal contact between
the sample block 14 and the sample holder 16 to heat and cool the
samples in the wells 20. As shown in FIGS. 3 and 4, the thermal
cycler system 10 also includes a drive assembly 28 for moving the
cover lid 26 from an open position (FIG. 1) to a closed position
(FIG. 2) and for moving the heated cover 22 from a raised position
(FIG. 6A) to a lowered position (FIGS. 6C and 7). The drive
assembly 28 includes a belt drive system 30 and a motion guide 32.
The thermal cycler system 10 further includes a sensor assembly for
sensing various positions of the heated cover 22 and the motion
guide 32 as described in greater detail below.
[0020] The thermal cycler system 10, unless otherwise indicated, is
described herein in the exemplary embodiment using a reference
frame in which the sample block 14 is located in the front or
forward portion of the thermal cycler system 10, the belt drive
system 30 is located in the back or rearward portion of the thermal
cycler system 10, and the cover lid 26 is located above the sample
block 14 when the cover lid 26 is in the closed position.
Consequently, as used herein, terms such as forward, backward,
downward, upward, lateral, and vertical used to describe the
exemplary thermal cycler system 10 are relative to the chosen
reference frame. The embodiments of the present invention, however,
are not limited to the chosen reference frame and descriptive
terms. For example, the belt drive system 30 may be located in the
front or forward portion of the thermal cycler system 10 and be
within the scope of the invention. Those of ordinary skill in the
art will recognize that the descriptive terms used herein may not
directly apply when there is a change in reference frame.
Nevertheless, the relative terms used to describe embodiments of
the thermal cycler system 10 are to merely provide a clear
description of the exemplary embodiments in the drawings. As such,
the relative terms forward, backward, downward, upward, lateral,
and vertical are in no way limiting the present invention to a
particular location or orientation.
[0021] With reference to FIGS. 3 and 4, the belt drive system 30 is
shown in more detail. The belt drive system 30 is configured to
move the motion guide in a lateral direction forward toward the
sample block 14 and backward away from the sample block 14. The
belt drive system 30 includes a belt 34 looped about a pair of
spaced apart pulleys 36, 38 and a screw 40. The belt drive system
30 may also include an electric drive motor and a transmission,
such as a gear box, that transfers motive power from the drive
motor to the pulley 36 for moving the belt 34 about the pulleys 36,
38. A first end 42 of the screw 40 is coupled to the pulley 38. As
the belt 34 rotates around the pulleys 36, 38, the screw 40
rotates. A second end 44 of the screw 40 is operatively coupled to
the motion guide 32. More particularly, the second end 44 of the
screw 40 extends through a cylindrical tube 46, which is coupled to
the motion guide 32 by a bracket 48. The cylindrical tube 46
includes threads (not shown) that cooperate with threads 50 of the
screw 40. Thus, as the screw 40 rotates, the engagement of threads
50 with the corresponding threads in the tube 46 provides an
axially directed sliding motion of the tube 46 and, thus, the
motion guide 32 toward or away from the sample block 14.
[0022] With reference to FIG. 5A, the heated cover 22 and the
pressure bar 24 are shown in more detail. The heated cover 22 is
coupled to the pressure bar 24 via springs 52a, 52b. The springs
52a, 52b may be compression springs or die springs, for example.
The dimensions of a die spring may be smaller than a compression
spring capable of handling the same load. Die springs may also have
a longer service cycle and may be able to withstand high heat. A
die spring may be used when higher loads need to be taken or when
higher temperatures need to be withstood. In one embodiment, the
springs 52a, 52b may be TL16-36 die springs available from Tokyo
Hatsujyo Manufacturing Co., Ltd. The pressure bar 24 is engaged
with the motion guide 32, and, thus, the heated cover 22 is
operatively coupled with the motion guide 32. To that end, ends 54,
56 of the pressure bar 24 include projections 62a, 62b, and side
walls 58, 60 of the motion guide 32 include slots 64a, 64b. The
projections 62a, 62b extend through the slots 64a, 64b. The slots
64a, 64b are slanted allowing longitudinal motion of the motion
guide 32 along a horizontal axis to translate into simultaneous
vertical motion of the pressure bar 24 along a vertical axis and,
consequently, the heated cover 22. The vertical motion of the
pressure bar 24 may be guided by guides 66a, 66b, which are
described in greater detail below. When the pressure bar 24 moves
in a vertical direction toward the sample block 14, the springs
52a, 52b exert a force on the heated cover 22. Accordingly, the
heated cover 22 moves in a vertical direction toward the sample
block 14 until it contacts the sample holder 16 when it is received
by the sample block 14. When the heated cover 22 is in contact with
the sample holder 16, further downward movement is prevented. If
the pressure bar 24 continues to move vertically downward, the
springs 52a, 52b will compress and the heated cover 22 will exert a
force on the sample holder 16.
[0023] Referring still to FIG. 5A, the cover lid 26 and the housing
12 are shown in more detail. The housing 12 has shoulders 68a, 68b
(shown in phantom) that engage the cover lid 26. More specifically,
the cover lid 26 includes ledges 70a, 70b that engage the
undersides of the shoulders 68a, 68b, respectively. As the cover
lid 26 moves from the opened position to the closed position, the
ledges 70a, 70b move along the shoulders 68a, 68b. The underside of
the shoulders 68a, 68b includes projections 72a, 72b at an end of
the shoulders 68a, 68b. When the cover lid 26 reaches the closed
position, the projections 72a, 72b prevent further movement of the
cover lid 26 in a direction away from the belt drive system 30.
[0024] With further reference to FIG. 5A, the cover lid 26 and the
motion guide 32 are shown in more detail. The cover lid 26 includes
a front wall 74, opposed side walls 76, 78, and a rear wall 80. The
cover lid 26 is configured to be moved longitudinally from the open
position to the closed position by the motion guide 32. In the
illustrative embodiment, the cover lid 26 and the motion guide 32
are engaged in various manners. To that end, the rear wall 80 of
the cover lid 26 is coupled to a cross-bar 82 of the motion guide
32 by springs 84a, 84b. In one embodiment, the springs 84a, 84b may
be compression springs, such as type SSC-028-12 coil springs
available from Shincoil Spring Pte Ltd. Additionally, the cover lid
26 is engaged with the motion guide 32 via the pressure bar 24. In
that regard, the side walls 76, 78 of the cover lid 26 include
vertical channels 86a, 86b through which the ends 54, 56 of the
pressure bar 24 extend. Thus, when the projections 62a, 62b of the
pressure bar 24 move through the slots 64a, 64b of the motion guide
32, the ends 54, 56 of the pressure bar 24 move vertically through
the channels 86a, 86b of the cover lid 26. The channels 86a, 86b
aid the guides 66a, 66b in preventing relative longitudinal motion
between the pressure bar 24 and the cover lid 26. The cover lid 26
further includes troughs 88a, 88b. Each of the troughs 88a, 88b are
shown as being discontinuous in the particular embodiment
illustrated within FIG. 5A, although the invention is not so
limited. The bottoms edges of the side walls 58, 60 of the motion
guide 32 are engaged in the troughs 88a, 88b. When the motion guide
32 moves relative to the cover lid 26, the side walls 58, 60 of the
motion guide 32 move through the troughs 88a, 88b,
respectively.
[0025] With reference to FIGS. 5A-5D, the operation of the drive
assembly 28 is shown in detail. FIGS. 5A and 5B show the movement
of the cover lid 26 in a direction toward the sample block 14 from
the open position to the closed position. As shown in FIG. 5A, when
the motion guide 32 is in a first position, the cover lid 26 is in
the open position and the heated cover 22 is in a raised position.
When the cover lid 26 is in the open position, the sample holder 16
may be loaded on the sample block 14 by, for example, a robotic arm
(not shown). After the sample block 14 receives the sample holder
16, the belt drive system 30 may be engaged. As the belt drive
system 30 rotates the screw 40, the motion guide 32 moves in a
direction toward the sample holder 16. The forward movement of the
motion guide 32 causes the cover lid 26 to move longitudinally in a
direction toward the sample holder 16 due at least in part to the
engagement between the ends 54, 56 of the pressure bar 24 and the
channels 86a, 86b of the cover lid 26. When the cover lid 26 moves
forward from the open to the closed position, the cover lid 26 and
the motion guide 32 move as one unit. In other words, the relative
positions of the cover lid 26 and the motion guide 32 generally
remain unchanged. With reference to FIG. 5B, the cover lid 26 is
shown in a closed position relative to the sample block 14, and the
motion guide 32 is shown in a second position forward of the first
position relative to the sample block 14. At this point, further
movement of the cover lid 26 in a direction away from the belt
drive system 30 is prevented by projections 72a, 72b of the outer
housing 12.
[0026] With reference to FIGS. 5C and 5D, the movement of the
heated cover 22 and the pressure bar 24 in a direction toward the
sample block 14 from the raised position is shown. After the cover
lid 26 reaches the closed position and as the screw 40 continues to
rotate, the motion guide 32 continues to move in a longitudinal
direction toward the sample block 14. Because the cover lid 26 is
prevented from moving further forward, the springs 84a, 84b
compress as the space between the cross-bar 82 of the motion guide
32 and the rear wall 80 of the cover lid 26 decreases. Accordingly,
the side walls 58, 60 and, thus, the slots 64a, 64b of the motion
guide 32 move laterally along the side walls 76, 78 of the cover
lid 26 of the motion guide 32 in a direction toward the sample
block 14. Because the pressure bar 24 is laterally constrained by
the channels 86a, 86b of the cover lid 26, the projections 62a, 62b
move through the slanted slots 64a, 64b. Additionally, as the
motion guide 32 moves relative to the cover lid 26, the side walls
58, 60 of the motion guide 32 move through the troughs 88a, 88b,
respectively. In one embodiment, the projections 62a, 62b are
rotatable so that, when the pressure bar 24 moves relative to the
motion guide 32, the projections 62a, 62b rotate through the
slanted slots 64a, 64b. When the projections 62a, 62b move through
the slanted slots 64a, 64b, the pressure bar 24 moves in a vertical
direction toward the sample block 14. As shown in FIG. 5C, the
heated cover 22 moves to a first lowered position in which the
heated cover 22 contacts the sample holder 16 when the sample
holder 16 is received by the sample block 14. When the heated cover
22 is in the first lowered position, the motion guide 32 is in a
third position forward of the second position relative to the
sample block 14. As shown in FIG. 5D, when the sample holder 16 is
removed from the sample block 14, the heated cover 22 is configured
to move to a second lowered position in which the heated cover 22
is in a position intermediate of the first lowered position and the
sample block 14. When the heated cover 22 is in the second lowered
position, the motion guide 32 is in a fourth position forward of
the third position relative to the sample block 14. In the
illustrated embodiment, the motion guide 32 will not move to the
fourth position when the sample holder 16 is received by the sample
block 14.
[0027] Referring again to FIGS. 5A-5D, the sensor assembly is shown
in detail. The sensor assembly includes a first sensor 90 and a
second sensor 92. In one embodiment, the sensors 90, 92 may be deep
gap slotted optical switches, such as type OPB820W sensors
available from OPTEK Technology. The exemplary sensors 90, 92
include two spaced apart arms 94 and are configured to detect when
a locating pin is positioned between the arms 94. The motion guide
32 includes a locating pin 96. The first sensor 90 is configured to
detect if the cover lid 26 is in the open position, as shown in
FIG. 5A. To that end, when the cover lid 26 is in the open
position, the locating pin 96 of the motion guide 32 is located
between the arms 94 of the first sensor 90 so that the sensor 90
detects the presence of the locating pin 96. The second sensor 92
is configured to detect if the cover lid 26 is closed and the
sample holder 16 is removed from the sample block 14 (i.e., the
motion guide is in the fourth position). In such a case, when the
motion guide 32 is in the fourth position, the locating pin 96 is
located between the arms 94 of the second sensor 92 so that the
second sensor 92 detects the presence of the locating pin 96. When
the second sensor 92 detects the presence of the locating pin 96,
the drive system may be configured to disengage because the motion
guide 32 is in the forward-most position (i.e., the fourth
position). As discussed above, if the sample holder 16 is received
by the sample block 14, the motion guide 32 will move to the third
position but not to the fourth position. Thus, the second sensor 92
will not detect the location of the motion guide 32 if the sample
holder 16 is received by the sample block 14 because the locating
pin 96 will not be located within the arms 94 of the second sensor
92.
[0028] With reference to FIGS. 6A-6C and FIG. 7, the movement of
the heated cover 22 and the pressure bar 24 is shown in more
detail. FIGS. 6A-6C show the movement of the heated cover 22 from a
raised position to a first lowered position when the sample holder
16 is received by the sample block 14. In FIG. 6A, the heated cover
22 is shown in the raised position. When the pressure bar 24 moves
in a vertical direction towards the sample block 14, the heated
cover 22 moves downward to the first lowered position and contacts
the sample holder 16, as shown in FIG. 6B. After the heated cover
22 contacts the sample holder 16, the sample holder 16 prevents the
heated cover 22 from moving further in a direction toward the
sample block 14. Therefore, as shown in FIG. 6C, the springs 52a,
52b begin to compress due to the continued downward movement of the
pressure bar 24. In this manner, the heated cover 22 exerts a force
on the sample holder 16. In one embodiment, the heated cover 22 may
be configured to exert a predetermined force on the sample holder
16. When the predetermined force is reached, the drive assembly 28
may be configured to stop moving the motion guide 32 and, thus, the
pressure bar 24, so that the predetermined force is not exceeded.
In one embodiment, the heated cover 22 may be configured to exert a
force of 96 lbf on the sample holder 16. If the sample holder 16 is
removed from the sample block 14, as shown in FIG. 7, the heated
cover 22 moves to the second lowered position.
[0029] Referring again to FIGS. 6A-6C and FIG. 7, the sensor
assembly further includes a third sensor 98 coupled to the pressure
bar 24 via an arm 100. The third sensor 98 is configured to detect
if the cover lid 26 is in the closed position and the sample holder
16 is received by the sample block 14. More particularly, the third
sensor 98 may be configured to detect whether the heated cover 22
is exerting a predetermined force on the sample holder 16. When the
third sensor 98 detects that the heated cover 22 is exerting a
predetermined force on the sample holder 16, the thermal cycler
system 10 may be configured to disengage the drive assembly 28 to
prevent exceeding the predetermined force. In the illustrated
embodiment, the thermal cycler system 10 includes a flexible
connector 102, as illustrated previously in FIGS. 5A-5D. The
flexible connector 102 may connect the heated cover 22 and, for
example, the third sensor 98. In one embodiment, the flexible
connector 102 may also connect to a printed circuit board (not
shown). After the heated cover 22 is exerting a predetermined force
on the sample holder 16, the thermal cycler system 10 may then
proceed to the next step of the PCR process. In the illustrated
embodiment, the third sensor 98 is configured to detect a locating
pin 104 coupled to the heated cover 22 when the pressure bar 24 and
the heated cover 22 are spaced apart by a predetermined distance.
The predetermined distance is based on the predetermined force to
be exerted on the sample holder 16 and depends at least in part on
the characteristics of the springs 52a, 52b. In that regard, the
compressed length of the springs 52a, 52b depends on the pressure
bar 24 and the force being exerted by the heated cover 22.
Therefore, the distance between the pressure bar 24 and the heated
cover 22 when the predetermined force is being exerted on the
sample holder 16 may be determined based on the characteristics of
the springs 52a, 52b. Accordingly, when the heated cover 22 is
exerting the predetermined force on the sample holder 16, the
locating pin 104 is located within the arms 94 of the third sensor
98 so that the sensor 92 detects the presence of the locating pin
96. Consequently, as shown in FIG. 7, the pressure bar 24 and the
heated cover 22 will be spaced apart by a distance greater than the
predetermined distance and the locating pin 96 is not located
between the arms 94 such that the third sensor 98 will not detect
the presence of the locating pin 96. Therefore, the third sensor 98
does not detect when the heated cover 22 is in the second lowered
position. At this point, however, the second sensor 92 will detect
that the motion guide 32 is in the fourth position and the drive
assembly 28 may be disengaged.
[0030] Advantageously, the configuration of the sensor assembly
allows for the thermal cycler system 10 to be compatible with
sample holders 16 that vary in design, such as the design of a deck
106 of the sample holder 16. For example, the deck thickness of
commercially available sample holders varies. Accordingly, when the
heated cover 22 is in the first lowered position, the distance of
the heated cover 22 from the sample block 14 may vary depending on
the thickness of the particular sample holder 16. However, the
thickness of the deck 106 does not affect the detection of the
presence of the sample holder 16 because the third sensor 98
indirectly detects the presence of the sample holder 16 based on
the predetermined force. Thus, the heated cover 22 may be
configured to exert the same predetermined force on sample holders
16 having varying deck thicknesses.
[0031] With reference to FIG. 8, the guides 66a, 66b are shown in
more detail. The guides 66a, 66b are coupled to the cover lid 26.
More particularly, the guides 66a, 66b are secured in bores 108a,
108b of the cover lid 26. The guides 66a, 66b extend from the cover
lid 26 in a direction toward the sample block 14 and into
through-holes 110a, 110b in the pressure bar 24. The guides 66a,
66b are slidable through the through-holes 110a, 110b. Thus, as the
pressure bar 24 moves in a direction toward the sample block 14,
the through-holes 110a, 110b slide in a downward direction along
the guides 66a, 66b. The guides 66a, 66b aid in preventing
horizontal or lateral movement of the pressure bar 24 and, thus,
the heated cover 22. Advantageously, preventing horizontal or
lateral movement of the heated cover 22 reduces potential shear
stress on the sample holder 16 that results from the heated cover
22 being lowered at an angle towards the sample holder 16.
[0032] Still referring to FIG. 8, the sample block 14 and the
sample holder 16 are shown in more detail. As discussed above, in
various embodiments, the sample block 14 may have a plurality of
cavities 18 configured to receive a plurality of correspondingly
shaped wells 20 of the sample holder 16. The wells 20 are
configured to receive a plurality of samples, wherein the wells 20
may be sealed within the sample holder 16 via a lid, cap, sealing
film or other sealing mechanism between the wells 20 and the heated
cover. In the illustrative embodiment, there are 96 cavities 18 in
the sample block 14. In such an embodiment, the sample holder 16
may be a 96-well microtiter plate. It should be recognized that the
sample block 14 and the sample holder 16 may have alternate
configurations. For example, the sample holder 16 may be, but is
not limited to, any size multi-well plate, card or array including,
but not limited to, a 32-well microtiter plate, a 50-well
microtiter plate, a 384-well microtiter plate, a 484-well
microtiter plate, a microcard, a through-hole array, or a
substantially planar holder, such as a glass or plastic slide. The
wells 20 in various embodiments of a sample holder 16 may include
depressions, indentations, ridges, and combinations thereof,
patterned in regular or irregular arrays formed on the surface of
the sample holder 16. Sample or reaction volumes can also be
located within wells or indentations formed in a substrate, spots
of solution distributed on the surface a substrate, or other types
of reaction chambers or formats, such as samples or solutions
located within test sites or volumes of a microfluidic system, or
within or on small beads or spheres. Samples held within the wells
20 may include one or more of at least one target nucleic acid
sequence, at least one primer, at least one buffer, at least one
nucleotide, at least one enzyme, at least one detergent, at least
one blocking agent, or at least one dye, marker, and/or probe
suitable for detecting a target or reference nucleic acid
sequence.
[0033] While the present invention has been illustrated by the
description of specific embodiments thereof, and while the
embodiments have been described in considerable detail, it is not
intended to restrict or in any way limit the scope of the appended
claims to such detail. The various features discussed herein may be
used alone or in any combination. Additional advantages and
modifications will readily appear to those skilled in the art. The
invention in its broader aspects is therefore not limited to the
specific details, representative apparatus and methods and
illustrative examples shown and described. Accordingly, departures
may be made from such details without departing from the scope or
spirit of the general inventive concept.
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