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WO1998050147A1 - Chambres de reaction microfabriquees a effet peltier pour cyclage thermique - Google Patents

Chambres de reaction microfabriquees a effet peltier pour cyclage thermique Download PDF

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Publication number
WO1998050147A1
WO1998050147A1 PCT/US1998/009488 US9809488W WO9850147A1 WO 1998050147 A1 WO1998050147 A1 WO 1998050147A1 US 9809488 W US9809488 W US 9809488W WO 9850147 A1 WO9850147 A1 WO 9850147A1
Authority
WO
WIPO (PCT)
Prior art keywords
reaction chamber
silicon
peltier
heat pump
sleeve
Prior art date
Application number
PCT/US1998/009488
Other languages
English (en)
Inventor
M. Allen Northrup
Barton V. Beeman
William J. Benett
Dean R. Hadley
Phoebe Landre
Stacy L. Lehew
Peter A. Krulevitch
Original Assignee
The Regents Of The University Of California
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by The Regents Of The University Of California filed Critical The Regents Of The University Of California
Priority to AU74773/98A priority Critical patent/AU7477398A/en
Publication of WO1998050147A1 publication Critical patent/WO1998050147A1/fr

Links

Classifications

    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • B01L3/502—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
    • B01L3/5027—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J19/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J19/0093—Microreactors, e.g. miniaturised or microfabricated reactors
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L7/00—Heating or cooling apparatus; Heat insulating devices
    • B01L7/52—Heating or cooling apparatus; Heat insulating devices with provision for submitting samples to a predetermined sequence of different temperatures, e.g. for treating nucleic acid samples
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00049—Controlling or regulating processes
    • B01J2219/00051—Controlling the temperature
    • B01J2219/00132—Controlling the temperature using electric heating or cooling elements
    • B01J2219/00137—Peltier cooling elements
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00781—Aspects relating to microreactors
    • B01J2219/00783—Laminate assemblies, i.e. the reactor comprising a stack of plates
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00781—Aspects relating to microreactors
    • B01J2219/00819—Materials of construction
    • B01J2219/00824—Ceramic
    • B01J2219/00828—Silicon wafers or plates
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00781—Aspects relating to microreactors
    • B01J2219/00873—Heat exchange
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00—Additional constructional details
    • B01L2300/18—Means for temperature control
    • B01L2300/1805—Conductive heating, heat from thermostatted solids is conducted to receptacles, e.g. heating plates, blocks
    • B01L2300/1822—Conductive heating, heat from thermostatted solids is conducted to receptacles, e.g. heating plates, blocks using Peltier elements
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • B01L3/502—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
    • B01L3/5027—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip
    • B01L3/502707—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip characterised by the manufacture of the container or its components

Definitions

  • the present invention relates to chemical reaction chambers, particularly to a chemical reaction chamber combined with means for augmenting heat/ cooling using the Peltier effect, and more particularly to a micromachined silicon or high thermal conductivity reaction chamber in combination with devices such as doped polysilicon for heating, bulk silicon for convective cooling, and thermoelectric coolers to augment the heating and cooling rates of such chambers.
  • Instruments generally used for performing chemical synthesis through thermal control and cycling are very large (table-top size) and inefficient. They typically work by heating and cooling a large thermal mass (e.g. an aluminum block) that has inserts for test tubes.
  • a large thermal mass e.g. an aluminum block
  • Recently, efforts have been directed to miniaturize these instruments by designing and constructing reaction chambers out of silicon and silicon- based materials (e.g., silicon nitride, polycrystalline silicon) that have integrated heaters and cooling via convection through the silicon.
  • silicon and silicon- based materials e.g., silicon nitride, polycrystalline silicon
  • the present invention is a chemical reaction chamber that combines doped polysilicon for heating, bulk silicon for convective cooling, and thermoelectric devices to augment the heating and cooling rates of the chamber.
  • the combination of the reaction chamber with the thermoelectric device enables the heat contained in the thermally conductive areas to be used/reused to heat the device, thereby conserving energy and expediting the heating/ cooling rates.
  • the chemical reaction chamber may be composed of micromachined silicon or any high thermal conductivity material.
  • the thermoelectric mechanism comprises, for example, a Peltier device.
  • An object of the present invention is to provide reaction chambers for thermal cycling.
  • a further object of the invention is to provide a Peltier- assisted microfabricated reaction chamber for thermal cycling.
  • a further object of the invention is to combine a microfabricated reaction chamber with an additional device for augmented heating/cooling using the Peltier effect.
  • Another object of the invention is to provide a chemical reaction chamber constructed of silicon-based or non-silicon-based materials in combination with a thermoelectric cooling mechanism.
  • Another object of the invention is to combine a microfabricated chemical reaction chamber with a Peltier type heating /cooling mechanism.
  • Another object of the invention is to combine a sleeve-type micromachined silicon reaction chamber with a Peltier effect device for augmented heating/cooling, which enables use of the reaction chamber in extreme high or low temperature environments.
  • the invention involves a silicon-based or non-silicon-based microfabricated reactor with a thermoelectric (i.e. Peltier effect) cooler/heater to augment the thermal cycling rates.
  • the reaction chamber may be constructed of silicon or silicon-based materials (e.g., silicon nitride, polycrystalline silicon) or non-silicon-based, high thermal conductivity materials (e.g., copper, aluminum, etc.).
  • the Peltier effect thermoelectric heater/coolers are used to rapidly cycle the temperature of the micro reaction chamber.
  • the reaction chamber system may be constructed to include an array of individual chambers located in a sleeve-type silicon-based reaction chamber arrangement.
  • the illustrated embodiment has been experimentally utilized as a thermal cycling instrumentation for the polymerase chain reaction and other chemical reactions. By these experiments the invention has been shown to be superior to present commercial instruments on thermally- driven chemical reactions.
  • the single figure is a perspective view of an embodiment of a Peltier-assisted microfabricated reaction chamber system made in accordance with the present invention.
  • the present invention involves Peltier-assisted microfabricated reaction chambers for thermal cycling.
  • the microfabricated reactor may be constructed of silicon or silicon-based materials, such as silicon nitride and polycrystalline silicon, or of non- silicon-based, high thermal conductivity materials, such as copper, aluminum, etc., used in combination with a thermo-electric (TE) cooling mechanism, such as a Peltier device.
  • TE thermo-electric
  • the disclosed embodiment involves silicon-based sleeve-type reaction chambers with a specific arrangement of the TE device such that the TE device functions as a TE heater/cooler wherein the heat contained in the thermally conductive portion thereof can be used/reused to heat the reaction chambers, thereby conserving energy and expediting the heating/cooling rates.
  • the disclosed embodiment of the invention combines a micromachined silicon reaction chamber with an additional module (TE heater/cooler) for augmented heating/cooling using the Peltier effect.
  • This additional module is particularly useful in extreme temperature environments where augmented heating/cooling would speed up the thermal cycling rates.
  • the silicon-based micro-reactor chambers may be constructed as described in above-referenced copending application Serial No. 08/492,678 and the fabrication process thereof is incorporated herein.
  • Peltier heat pumps have become commercially available.
  • This invention uses off-the-shelf Peltier coolers (heat pumps) to rapidly cycle the temperature of the silicon-based micro chamber array.
  • Peltier heat pumps are semiconductor devices typically with two planner surfaces. When a direct current (dc) source is applied to the heat pump, heat is moved from one surface to the other. If the polarity is reversed the heat is pumped in the opposite direction.
  • dc direct current
  • the rapid thermal cycling is accomplished by shuttling the heat from a thermal reservoir, such as a copper block, to the reaction chamber(s) and then back to the thermal reservoir using one or more Peltier heat pumps.
  • the cycle starts by pumping the heat from the reservoir into the test device (reaction chamber) to heat it to the desired temperature.
  • Using the heat from the reservoir to heat the device lowers the temperature of the reservoir thereby increasing the ⁇ T between the chamber and the reservoir.
  • the polarity of the heat pump is reversed the heat is pumped from the device back to the reservoir. Because the ⁇ T between the device and the reservoir has been increased the thermal transfer occurs much faster.
  • the active thermal system can be insulated from the ambient temperature and no external source of heat is required.
  • the system can be speeded up by thermally biasing the temperature of the entire thermal system to be near the center of the range of the temperature cycle.
  • good temperature uniformly can be accomplished by applying heat pumps and thermal reservoirs to both planner surfaces of the test device (chamber array).
  • a more cube-like configured test device might require heat pumps on four or five surfaces to achieve rapid cycling and good uniformity.
  • the single figure illustrates an embodiment of the system of the invention using a planner type test device or reaction chamber array with a Peltier type device and a thermal reservoir positioned on opposite sides of the reaction chamber array.
  • the system generally indicated at 10 comprises a test device 11 which includes three reaction chambers 12, 13, and 14 into which material to be tested is inserted as known in the art.
  • the device 11 may have a length of 1.0cm, width of 1.0cm, and thickness of 2mm.
  • Peltier heat pumps 15 and 16 are positioned adjacent opposite sides of the test device 11 with electrical leads or contacts 17-18 and 19-20, respectively, extending therefrom.
  • heat pumps 15 and 16 may be constructed of bismuth tellurium with a thickness of 2mm.
  • Thermal reservoirs 21 and 22 are positioned adjacent the Peltier heat pumps.
  • the Peltier heat pumps 15 and 16 are secured to test device 11 and to thermal reservoirs 21 and 22 by bonding, pressure fit, or clamping, indicated at 23-24 and 25- 26, or other means using material which is highly thermally conductive, such as thermal epoxy, so as to minimize heat loss during transfer from the reservoirs to or from the test device.
  • thermal reservoirs may be constructed of copper, aluminum, silicon, or other highly thermal conductive materials such as aluminum-based ceramics or cermets with a thickness of 5mm.
  • the electrical leads or contacts 17-20 are connected to an appropriate power supply and switching arrangement schematically illustrated at 27 and 28.
  • the present invention provides a system including a reaction chamber having augmented heating/ cooling capabilities whereby the system can be utilized in extreme (hot and cold) temperature environments, and the Peltier effect heating/cooling arrangement provides rapid thermal cycling.
  • the system can be used for synthesis or processing or organic, inorganic, or biochemical reactions.
  • the additional power required for the TE heater/cooler is not prohibitive, particularly for operation in more extreme environments.

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  • Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Clinical Laboratory Science (AREA)
  • General Health & Medical Sciences (AREA)
  • Biochemistry (AREA)
  • Molecular Biology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Organic Chemistry (AREA)
  • Dispersion Chemistry (AREA)
  • Analytical Chemistry (AREA)
  • Hematology (AREA)
  • Apparatus Associated With Microorganisms And Enzymes (AREA)

Abstract

L'invention concerne un système de chambre de réaction chimique (10) combinant des dispositifs tels que du silicium polycristallin dopé pour le chauffage, du silicium brut pour le refroidissement convectif, et des refroidisseurs thermo-électriques (TE) (15, 16) pour accroître les vitesses de chauffage et de refroidissement de la ou des chambres de réaction (12, 13, 14). De plus, le système comporte des chambres de réaction ne fonctionnant pas au silicium (12, 13, 14), telles que tout matériau à haute conductivité thermique utilisé en combinaison avec un mécanisme de refroidissement thermo-électrique (15, 16) (c.-à-d. un dispositif à effet Peltier). La chaleur contenue dans la partie conductrice de chaleur du système peut être utilisée/réutilisée pour chauffer le dispositif, ce qui permet de conserver l'énergie et d'activer les vitesses de chauffage/refroidissement. Le système combine une chambre de réaction au silicium micro-usinée (12, 13, 14), par exemple, avec un module/dispositif (15, 16) supplémentaire permettant d'accroître le chauffage/refroidissement par l'effet Peltier. Ce module supplémentaire est particulièrement utile dans des environnements extrêmes (très chauds ou extrêmement froids) où un chauffage/refroidissement accru est utile pour accélérer les vitesses de cyclage thermique. Le système de chambre de réaction chimique (10) offre diverses applications en vue d'une synthèse ou d'un traitement de réactions organiques, inorganiques ou biochimiques, y compris la réaction de polymérisation en chaîne (PCR) et/ou d'autres réactions d'ADN, telle la réaction de ligation répétitive d'oligonucléotides.
PCT/US1998/009488 1997-05-09 1998-05-08 Chambres de reaction microfabriquees a effet peltier pour cyclage thermique WO1998050147A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
AU74773/98A AU7477398A (en) 1997-05-09 1998-05-08 Peltier-assisted microfabricated reaction chambers for thermal cycling

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US85328297A 1997-05-09 1997-05-09
US08/853,282 1997-05-09

Publications (1)

Publication Number Publication Date
WO1998050147A1 true WO1998050147A1 (fr) 1998-11-12

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