U.S. patent application number 10/987931 was filed with the patent office on 2006-05-18 for thermal cycler with protection from atmospheric moisture.
This patent application is currently assigned to BIO-RAD LABORATORIES, INC.. Invention is credited to Sunand Banerji, David A. Cohen, Michael J. Denninger.
Application Number | 20060101830 10/987931 |
Document ID | / |
Family ID | 36384705 |
Filed Date | 2006-05-18 |
United States Patent
Application |
20060101830 |
Kind Code |
A1 |
Cohen; David A. ; et
al. |
May 18, 2006 |
THERMAL CYCLER WITH PROTECTION FROM ATMOSPHERIC MOISTURE
Abstract
Localized temperature control in a thermal cycler is achieved by
thermoelectric modules that are protected from exposure to
atmospheric moisture by a pair of loop-shaped gaskets that seal off
an enclosure formed by the sample block, the heat sink, and a
support frame to which the components are secured. The heat sink is
a block with a plurality of fins and is secured to the
thermoelectric modules by one or more clamping bars that fit
between the fins and are arranged to eliminate interference with
the fin geometry and with the functional surface area of the fins.
Electric leads are embedded in a molded retainer element, each lead
being in the shape of a "U" with two exposed legs joined by a bar
at one end, one of the leads extending into the region sealed from
the atmosphere and the other extending outside the region.
Inventors: |
Cohen; David A.; (Dedham,
MA) ; Banerji; Sunand; (Stoneham, MA) ;
Denninger; Michael J.; (Belmont, MA) |
Correspondence
Address: |
TOWNSEND AND TOWNSEND AND CREW, LLP
TWO EMBARCADERO CENTER
EIGHTH FLOOR
SAN FRANCISCO
CA
94111-3834
US
|
Assignee: |
BIO-RAD LABORATORIES, INC.
Hercules
CA
a corporation of the state of Delaware
|
Family ID: |
36384705 |
Appl. No.: |
10/987931 |
Filed: |
November 12, 2004 |
Current U.S.
Class: |
62/3.3 ;
62/371 |
Current CPC
Class: |
B01L 3/50851 20130101;
B01L 7/52 20130101; B01L 2300/0829 20130101; B01L 2300/0838
20130101; B01L 2300/1822 20130101; B01L 2300/1894 20130101; F25B
21/04 20130101; B01L 2200/025 20130101; B01L 2200/0689 20130101;
F25B 2321/023 20130101 |
Class at
Publication: |
062/003.3 ;
062/371 |
International
Class: |
F25B 21/02 20060101
F25B021/02; F25D 3/08 20060101 F25D003/08 |
Claims
1. Apparatus for controlling temperature in a plurality of samples,
said apparatus comprising: a multi-receptacle sample block, a
thermoelectric module, and a heat sink block, all shaped to be
capable of arrangement in a stacked configuration in which said
sample block is in thermal contact with said thermoelectric module
and said thermoelectric module is in thermal contact with said heat
sink block, a support frame sized to receive said sample block,
said thermoelectric module, and said heat sink block in said
stacked configuration, a first loop-shaped gasket sized to encircle
said sample block along a peripheral surface thereof and thereby
form a seal between said sample block and said support frame, and a
second loop-shaped gasket sized to encircle said heat sink block
along a peripheral surface thereof and thereby form a seal between
said heat sink block and said support frame, said sample block,
said heat sink block, said support frame, and said loop-shaped
gaskets thereby together forming a sealed enclosure surrounding
said thermoelectric module and protecting said thermoelectric
module from atmospheric moisture.
2. The apparatus of claim 1 further comprising a first groove in
said peripheral surface of said sample block to receive said first
loop-shaped gasket and a second groove in said peripheral surface
of said heat sink block to receive said second loop-shaped gasket,
and wherein said support frame has flat surfaces where said support
frame contacts said first and second loop-shaped gaskets.
3. The apparatus of claim 1 comprising a plurality of
thermoelectric modules arranged edge to edge in a planar array, and
wherein in said stacked configuration said sample block is in
thermal contact with said planar array, and said planar array is in
thermal contact with said heat sink block.
4. The apparatus of claim 1 wherein said sealed enclosure defines a
gap between edges of said thermoelectric module and said support
frame.
5. The apparatus of claim 1 wherein said support frame is a unitary
molded piece with electric leads partially embedded therein.
6. The apparatus of claim 5 wherein said sealed enclosure defines a
gap between edges of said thermoelectric module and said support
frame and said electric leads have exposed ends extending into said
gap.
7. The apparatus of claim 5 wherein each electric lead consists of
first and second legs joined by a cross-bar in a U-shape, said
cross-bar embedded in said molded piece and said first and second
legs exposed, said first leg extending inside said sealed enclosure
and said second leg extending outside said sealed enclosure.
8. A molded housing for an electronic instrument, said housing
comprising a sealed enclosure comprising: a molded partition
separating an interior from atmospheric exposure, and a U-shaped
electric lead defined by first and second legs joined by an end
cross-bar, said end cross-bar embedded in said partition with said
first leg extending to one side of said partition and said second
leg extending to another side of said partition.
9. Apparatus for controlling temperature in a plurality of samples,
said apparatus comprising: a multi-receptacle sample block, a
thermoelectric module, and a finned heat sink block, all shaped to
be capable of arrangement in a stacked configuration in which said
sample block is in thermal contact with said thermoelectric module
and said thermoelectric module is in thermal contact with said heat
sink block, a support frame sized to receive said sample block,
said thermoelectric module, and said finned heat sink block in said
stacked configuration, and a bar greater in length than said fins
of said finned heat sink block and sized to fit between adjacent
fins of said finned heat sink block, and spring-loaded fasteners
affixing said bar to said support frame to secure said finned heat
sink block against said thermoelectric module when in said stacked
configuration, one such fastener at each end of said bar.
10. (canceled)
11. (canceled)
12. Apparatus for controlling temperature in a plurality of
samples, said apparatus comprising: a multi-receptacle sample
block, a thermoelectric module, and a finned heat sink block, all
shaped to be capable of arrangement in a stacked configuration in
which said sample block is in thermal contact with said
thermoelectric module and said thermoelectric module is in thermal
contact with said heat sink block, a support frame sized to receive
said sample block, said thermoelectric module, and said finned heat
sink block in said stacked configuration, and exactly two bars
sized to fit between adjacent fins of said finned heat sink block,
and a pair of spring-loaded fasteners positioned on opposing ends
of said fins, each said fastener engaging both bars.
Description
BACKGROUND OF THE INVENTION
[0001] 1. Field of the Invention
[0002] This invention resides in the field of laboratory apparatus
for performing procedures that require simultaneous temperature
control in a multitude of samples in a multi-receptacle sample
block. In particular, this invention addresses concerns arising
with the use of thermoelectric modules for temperature modulation
and control.
[0003] 2. Description of the Prior Art
[0004] The polymerase chain reaction (PCR) is one of many examples
of chemical processes that require precise temperature control of
reaction mixtures with rapid temperature changes between different
stages of the procedure. PCR is a process for amplifying DNA, i.e.,
producing multiple copies of a DNA sequence from a single copy. PCR
is typically performed in instruments that provide reagent
transfer, temperature control, and optical detection in a multitude
of reaction vessels such as wells, tubes, or capillaries. The
process includes a sequence of stages that are
temperature-sensitive, different stages being performed at
different temperatures and the temperature being cycled through
repeated temperature changes. In the typical PCR process, each
sample is heated and cooled to three different target temperatures
where the sample is maintained for a designated period of time. The
first target temperature is about 95.degree. C. which is the
temperature required to separate double strands. This is followed
by cooling to a target temperature of 55.degree. C. for
hybridization of the separated strands, and then heating to a
target temperature of 72.degree. C. for reactions involving the
polymerase enzyme. The cycle is then repeated to achieve multiples
of the product DNA, and the time consumed by each cycle can vary
from a fraction of a minute to two minutes, depending on the
equipment, the scale of the reaction, and the degree of automation.
This thermal cycling is critical to the successful performance of
the process, and is an important feature of any process that
requires close control of temperature and a succession of stages at
different temperatures. Many of these processes involve the
simultaneous processing of large numbers of samples, each of a
relatively small size, often on the microliter scale. In some
cases, the procedure requires that certain samples maintained at
one temperature while others are maintained at another. Laboratory
equipment known as thermal cyclers have been developed to allow
these procedures to be performed in an automated manner.
[0005] One of the methods for achieving temperature control over a
multitude of samples in a thermal cycler or in any planar array,
and also for placing segregated groups of samples at different
temperatures, is by the use of thermoelectric modules. These
modules are semi-conductor-based electronic components that
function as small heat pumps through use of the Peltier effect, and
can cause heat to flow in either direction, depending on the
direction of current through the component. The many uses of
thermoelectric modules include small laser diode coolers, portable
refrigerators, and liquid coolers.
[0006] Thermoelectric modules are of particular interest in thermal
cyclers in view of the localized temperature effect, electronic
control, and rapid response that the modules offer. The modules are
typically arranged edge-to-edge in a planar array to provide
heating or cooling of a multitude of samples over a wide area,
particularly when the samples are contained in a sample block,
which is a unitary piece that has a flat undersurface and a number
of wells or receptacles formed in its upper surface in a
standardized geometrical arrangement. In the typical arrangement,
the modules are placed under the sample block, and a heat sink,
typically finned, is placed under the modules.
[0007] While the modules are highly effective and versatile, their
efficiency can be compromised by a variety of factors in the
construction of the cycler. The temperature changes can cause
condensation on the module surfaces, for example, and the clamping
apparatus that assures that the components are in full thermal
contact can interfere with the heat sink fins. These and other
concerns are addressed by the present invention.
SUMMARY OF THE INVENTION
[0008] In accordance with the present invention, the thermoelectric
modules in a thermal cycler are placed inside an enclosure that is
formed by the sample block, the heat sink and a support frame, and
that is sealed against the intrusion of atmospheric moisture by
gaskets, one of which is compressed between the sample block and
the support frame and the other between the heat sink and the
support frame. The gaskets allow for rapid assembly of the
components and do not require manual positioning or alignment.
Sealing can be achieved by simply placing the sample block,
modules, and heat sink in the frame and securing these parts
together.
[0009] This invention further resides in a construction for
securement of a finned heat sink to the thermoelectric modules in a
manner that does not compromise the fins of the heat sink in terms
of the surface area of the fins or the access of the fins to air
flowing past them. Securement is achieved by way of one or more
clamping bars that are sufficiently thin to fit between the fins
and of substantially smaller depth than the fins so that the most
of the surface of each adjacent fin remains exposed. Preferably,
the bars extend the full length of the adjacent fins, and most
preferably, are in fact longer than the fins so that the ends of
the bars will protrude beyond the fins to be secured to the
remaining components of the assembly.
[0010] A still further innovation present by this invention is a
novel configuration of an electric lead in a molded part that
serves as a partition dividing a region sealed against atmospheric
exposure from a neighboring region. The electric lead has two legs
joined at one end by a cross-bar to form a "U" shape. The cross-bar
is embedded in the molded part and both legs are exposed and
available for electrical connections, one leg extending into the
sealed region and the other leg extending into the neighboring
region. The "U" shape facilitates the molding of the part around
the lead, and the part with the lead thus embedded is useful in any
electronic device or instrument that contains electronic components
that require an environment in which they are protected from
exposure to atmospheric moisture. One such instrument is a thermal
cycler, where one leg of the lead is electrically connected to the
thermoelectric module inside the enclosure and the other leg is
electrically connected to external electrical components such as a
power supply, a controller, or any such component that feeds or
regulates current to the module.
BRIEF DESCRIPTION OF THE DRAWINGS
[0011] FIG. 1 is an exploded perspective view of a thermal cycler
assembly in accordance with the present invention.
[0012] FIG. 2 is a cross section of the thermal cycler assembly of
FIG. 1 in the plane indicated by the line 2-2 of FIG. 1.
[0013] FIG. 3 is a cross section of the thermal cycler assembly of
FIG. 1 in the plane indicated by the line 3-3 of FIG. 1.
DETAILED DESCRIPTION OF THE INVENTION AND PREFERRED EMBODIMENTS
[0014] Each of the several different aspects of the present
invention is susceptible to a wide range of variation in terms of
the configurations of each component, the arrangements of the
components in the assembly, the particular instrument or apparatus
in which they are incorporated, and the function that the
instrument is designed to perform. A detailed review of one
particular embodiment however will provide an understanding of the
function and operation of the invention in each of its many
embodiments. The figures hereto depict a thermal cycler for a PCR
instrument as one such embodiment.
[0015] The components shown in the exploded perspective view of
FIG. 1 include a sample block 11, thermoelectric modules 12, and a
finned heat sink 13. These three components are shaped to allow
them to be stacked in a configuration that places the broad faces
on the upper and lower sides of the thermoelectric modules in
thermal contact with the sample block and the heat sink,
respectively. The terms "thermal contact" and "thermal interface"
are used herein to indicate physical contact that allows free flow
of thermal energy between two components along the entire area of
contact of each component. The sample block 11 can be a unitary
molded, cast, or machined component with a flat undersurface 14 and
sample wells 15 on its upper side. The sample block shown has 48
sample wells arranged in a regularly spaced two-dimensional array.
The thermoelectric modules 12 are beneath the sample block and in
thermal contact with the undersurface 14 of the sample block. Four
thermoelectric modules are shown. As in various other features of
this invention, neither the number of sample wells nor the number
of thermoelectric modules are critical, and each can vary widely.
The heat sink 15 is positioned beneath the thermoelectric modules
and includes a row of fins 16 extending away from the
thermoelectric modules. On the upper surface of the heat sink is a
thin layer 17 of heat conductive material to provide an enhanced
thermal interface between the heat sink and the thermoelectric
modules. The heat sink 15 is also referred to herein as a "heat
sink block" since it is typically a unitary (single-piece)
component.
[0016] The remaining components shown in FIG. 1 serve to secure the
sample block, thermoelectric modules, and heat sink together, and
to provide electrical connections for controlling the
thermoelectric modules. These components are as follows: [0017] a
mounting skirt 21 that joins the entire assembly to the remainder
of the thermal cycler instrument of which the assembly itself is a
component; [0018] a pair of clamping bars 22, 23 that fit between
the fins 16 of the heat sink 15 to press the heat sink against the
underside of the thermoelectric modules to achieve full thermal
contact; [0019] an inner circuit board 24 that provides electrical
connections directly to the thermoelectric modules; [0020] an outer
circuit board 25 that provides electrical connections to components
of the thermal cycler that are external to the assembly; [0021] a
retainer element 26 that serves as a mount or support frame for the
other components shown in the Figure, and that aligns the
components and provides threaded bosses and other fastener
connections that hold the components together; [0022] a loop-shaped
gasket 31 to encircle the sample block 11 and seal the sample block
against an inward-facing surface of the retainer element; and
[0023] a second loop-shaped gasket 32 to encircle the heat sink 15
and seal the heat sink against another inward-facing surface of the
retained element.
[0024] Components that are not shown in FIG. 1 include common
fastening elements such as screws, washers, and the like that hold
the parts together. The screws are received by threaded holes or
bosses in the retainer element 26.
[0025] The cross section of FIG. 2, whose orientation is indicated
in FIG. 1 by the line 2-2 shows each of the parts of FIG. 1. The
assembled parts form an enclosure around the thermoelectric modules
12, with the sample block 11 and a portion of the retainer element
26 forming the roof of the enclosure, the heat sink block 13
forming the floor of the enclosure, and other portions of the
retainer element 26 forming the side walls. The smaller of the two
loop-shaped gaskets 31 is lodged between the peripheral edge of the
sample block 11 and a surface 41 along the interior opening of the
retainer element 26, and the larger of the two loop-shaped gaskets
32 is lodged between the peripheral edge of the heat sink block 13
and a different surface 42 along the interior opening of the
retainer element 26. In the embodiment show, the gaskets each
reside in a groove along the peripheral edge of the sample block
and the heat sink block, respectively, and when these parts are
inside the retainer element 26, both gaskets contact flat surfaces
on the interior of the retainer element. The two gaskets seal the
enclosure and protect the thermoelectric modules from exposure to
regions outside (i.e., above, below, or lateral to) the retainer
element 26, as well as regions above the sample block 11 and
regions below the heat sink block 13. As a whole, the enclosure
protects the thermoelectric modules from exposure to atmospheric
moisture.
[0026] Also visible in FIG. 2 are the clamping bars 22, 23. The
width of each bar is smaller than the gap between adjacent fins 16,
thereby allowing each bar to fit easily between the fins. The depth
of each bar is likewise less than the depth of each fin, thereby
producing minimal interference with the exposure of the fin surface
to air or any flowing coolant medium that might be used to
dissipate the heat from the fins. In preferred constructions, each
bar has two raised sections on its upper edge at locations inward
from the ends of the bars. These raised sections contact the
underside of the heat sink, thereby allowing greater contact of the
heat sink with air, better control of the pressure exerted on the
thermoelectric modules, and minimization of the stresses in the
bars.
[0027] The profile of the retainer element 26 has a section that is
T-shaped with a vertical section 43 and a horizontal section 44 at
one end of the vertical section. The vertical section 43 serves as
a partition that separates the sealed enclosure from the external
regions. The horizontal section 44 serves as a mounting surface for
the fastening screws referred to above (shown only in FIG. 3 and
discussed below), with threaded holes and bosses (also shown in
FIG. 3).
[0028] Also shown in FIG. 2 is an electrical lead 45 that joins the
inner circuit board 24 with the outer circuit board 25. The lead is
U-shaped with two legs 46, 47 joined by a cross-bar 48. The two
legs are connected to the inner and outer circuit boards,
respectively, while the cross-bar is embedded in the retaining
element. As noted above, the U-shaped lead has applications in
instruments in general that require the sealing of internal
components in an interior region of the instrument from the
environment or from other portions of the instrument. In all such
applications, the lead is partially embedded in the molded part,
with the cross-bar section of the lead fully embedded and the two
legs exposed to allow them to be used for electrical connections.
The lead can be embedded in any molded housing that serves as a
partition between sealed and unsealed regions. In the embodiment
shown in FIG. 2, the enclosure referred to above is formed by a gap
49 between the thermoelectric elements 12 and the retainer element
wall 43. The inner exposed leg of the electric lead extends into
this gap.
[0029] The orientation of the cross section of FIG. 3 is indicated
in FIG. 1 by the line 3-3 and is transverse to the orientation of
the cross section of FIG. 2. FIG. 3 shows each of the parts of FIG.
1 except the skirt 21 and the inner and outer circuit boards 24,
25. In addition to the parts that are also shown in FIG. 1, FIG. 3
shows the fastener components that engaged the clamping bars 22, 23
and secure together the sample block 11, thermoelectric modules 14,
and heat sink block 15. By virtue of the orientation of the cross
section, FIG. 3 shows a broad surface of one fin 16 and the broad
surface of one clamping bar 23. The fastener is a spring-loaded
fastener, and its components include a boss 51 on the undersurface
of the retainer element 26, a bolt 52, a flat washer 24, and
several spring washers 25. The boss 51 is internally threaded to
mate with threads on the bolt. The bolt 52 fits between the two
clamping bars, and the flat washer 24 is wide enough to contact
both bars and press the bars against the heat sink block. Both bars
are thus engaged by the single fastener. The spring washers 25 are
shown in a compressed condition, and their effect is to apply
pressure to the clamping bars in a manner that is consistent and
reproducible.
[0030] While the Figure shows only the bolt, washers, and threaded
boss at one end of the clamping bars, an identical bolt, washers
and threaded boss exist at the other end in a symmetrical
arrangement with those that are shown.
[0031] The components used in the practice of this invention can be
components that were in existence at the time of filing of this
application, including those that are readily available from
suppliers. The thermoelectric modules, which are also known as
Peltier devices, are units widely used as components in laboratory
instrumentation and equipment, well known among those familiar with
such equipment, and readily available from commercial suppliers of
electrical components. Thermoelectric modules are small solid-state
devices that function as heat pumps, operating under the theory
that when electric current flows through two dissimilar conductors,
the junction of the two conductors will either absorb or release
heat depending on the direction of current flow. The typical
thermoelectric module consists of two ceramic or metallic plates
separated by a semiconductor material, of which a common example is
bismuth telluride. In addition to the electric current, the
direction of heat transport can further be determined by the nature
of the charge carrier in the semiconductor (i.e., N-type vs.
P-type). Thermoelectric modules can thus be arranged and/or
electrically connected in the apparatus of the present invention to
heat or to cool the sample block or portions of the sample block. A
single thermoelectric module can be as thin as a few millimeters
with surface dimensions of a few centimeters square, although both
smaller and larger thermoelectric modules exist and can be used. A
single thermoelectric module can be used, or two or more
thermoelectric modules can be grouped together to control the
temperature of a region of the sample block whose lateral
dimensions exceed those of a single module. Adjacent thermoelectric
modules can also be controlled to produce different rates or
directions of heat flow, thereby placing different samples or
groups of samples at different temperatures.
[0032] Further variations are also within the scope of the
invention. The loop-shaped gaskets, for example, are shown as
different sizes but the shapes of the components can be adjusted or
varied to permit the use of gaskets of the same size. The
construction shown in the Figures contains two clamping bars, but
effective securement can also be achieved with a single clamping
bar or with three or more clamping bars. As shown, the clamping
bars are greater in length than the fins, and extend beyond the
fins in both directions, leaving the ends of the bars accessible
for securement to the retainer element. Alternatively, the bars can
be equal to or less than the length of each fin, or secured to the
retainer element at only one end rather than at both ends. A
further alternative is the use of pairs of bars that extend to less
than half the distance toward the fin centers, with one bar of each
pair entering the fin area from one end of the fin array and the
other from the other end. A still further alternative is the use of
a pair of bars that are joined at both ends to form a loop to
encircle a fin or two or more fins. The spacing between the
clamping bars can also vary. In the embodiment shown, the bars are
spaced such that only one fin passes between them. Alternatively,
the spacing can be increased to allow two or more fins pass between
the bars. The heat sink shown in the Figures contains fifteen fins,
but this number can vary widely, from as few as three or four to as
many as fifty or more. A preferred range is six to twenty.
Furthermore, alternatives to the threaded bolts, such as clips or
cams, can also be used and will be readily apparent to those
skilled in the art.
[0033] The materials of construction will preferably be selected to
allow each component to serve its function in an optimal manner.
Components that are in contact with the samples, for example, will
be fabricated from inert materials, such as polycarbonate or other
plastics, and sample blocks and heat sinks that respond rapidly to
changes in the heat transfer rate induced by the thermoelectric
modules can be obtained by the use of thin materials or materials
that conduct heat readily. Still further variations will be readily
apparent to those skilled in the art of laboratory equipment
design, construction, and use.
* * * * *