Temperature control apparatus

• US 6,602,473 B1
• Filed: 04/07/2000
• Issued: 08/05/2003
• Est. Priority Date: 06/20/1995
• Status: Expired due to Term

• Current Assignee: Lawrence Livermore National Security LLC (Government of the United States of America)
• Original Assignee: Regents of the University of California (University of California)
• Inventors: Northrup, M. Allen
• Primary Examiner(s): Warden, Jill
• Assistant Examiner(s): SIEFKE, SAMUEL P
• Application Number:
  US09/545,440
• Time in Patent Office: 1,215 Days
• Field of Search: 422/52, 422/58, 422/82.05, 422/82.09, 422/102, 422/129, 422/240, 422/241, 422/131, 422/82.01, 435/285.1, 435/292.1, 435/287.1, 435/288.3, 935/88
• US Class Current: 422/547
• CPC Class Codes: B01J 19/0046 Sequential or parallel reactions, e.g. for the synthesis of polypeptides or polynucleotides; Apparatus and devices for combinatorial chemistry or for making molecular arrays synthesis methods per se C40B50/00
• CPC Class Codes: B01J 19/0093 Microreactors, e.g. miniaturised or microfabricated reactors laboratory containers with capillary fluid transport in microfabricated channels or chambers B01L3/5027
• CPC Class Codes: B01J 2219/00783 Laminate assemblies, i.e. the reactor comprising a stack of plates
• CPC Class Codes: B01J 2219/00822 Metal
• CPC Class Codes: B01J 2219/00824 Ceramic
• CPC Class Codes: B01J 2219/00828 Silicon wafers or plates
• CPC Class Codes: B01J 2219/00853 Employing electrode arrangements
• CPC Class Codes: B01J 2219/00873 Heat exchange
• CPC Class Codes: B01J 2219/00889 Mixing
• CPC Class Codes: B01J 2219/00891 Feeding or evacuation
• CPC Class Codes: B01J 2219/00912 by electrophoresis
• CPC Class Codes: B01J 2219/00936 UV-radiations
• CPC Class Codes: B01J 2219/00945 Infrared light
• CPC Class Codes: B01J 2219/00952 Sensing operations
• CPC Class Codes: B01L 2200/027 for microfluidic devices
• CPC Class Codes: B01L 2200/028 Modular arrangements
• CPC Class Codes: B01L 2200/10 Integrating sample preparation and analysis in single entity, e.g. lab-on-a-chip concept
• CPC Class Codes: B01L 2200/12 Specific details about manufacturing devices
• CPC Class Codes: B01L 2300/0645 Electrodes
• CPC Class Codes: B01L 2300/0654 Lenses; Optical fibres
• CPC Class Codes: B01L 2300/0867 : Multiple inlets and one sample wells, e.g. mixing, dilution
• CPC Class Codes: B01L 2300/087 : Multiple sequential chambers
• CPC Class Codes: B01L 2300/1822 : using Peltier elements
• CPC Class Codes: B01L 2300/1827 : using resistive heater
• CPC Class Codes: B01L 2400/0415 : electrical forces, e.g. electrokinetic
• CPC Class Codes: B01L 2400/0421 : electrophoretic flow
• CPC Class Codes: B01L 2400/0439 : ultrasonic vibrations, vibrating piezo elements
• CPC Class Codes: B01L 2400/0487 : fluid pressure, pneumatics
• CPC Class Codes: B01L 3/5027 : 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 B01L3/5023 takes precedence; micromixers B01F33/30; microreactors for synthesis B01J19/0093; microcapillary devices in general B81B1/00
• CPC Class Codes: B01L 3/502707 : characterised by the manufacture of the container or its components by shaping or joining plastic parts B29C59/00, B29C65/00; by laminating B32B37/00; manufacture of microstructural devices in general B81C
• CPC Class Codes: B01L 7/52 : with provision for submitting samples to a predetermined sequence of different temperatures, e.g. for treating nucleic acid samples amplification or hybridisation processes per se C12Q1/68; controlling sequential reactions for synthesis B01J19/0046
• CPC Class Codes: B01L 9/527 : for microfluidic devices, e.g. used for lab-on-a-chip
• CPC Class Codes: B81C 3/00 : Assembling of devices or systems from individually processed components
• CPC Class Codes: G01N 2021/0346 : Capillary cells; Microcells
• CPC Class Codes: G01N 21/0332 : with temperature control control of temperature G05D23/00; cryostats F17C3/08
• CPC Class Codes: G01N 21/05 : Flow-through cuvettes G01N21/09 takes precedence; handling fluid samples G01N1/10
• CPC Class Codes: G01N 21/69 : specially adapted for fluids , e.g. molten metal
• CPC Class Codes: G01N 21/76 : Chemiluminescence; Bioluminescence

Abstract

A silicon-based sleeve type chemical reaction chamber that combines heaters, such as doped polysilicon for heating, and bulk silicon for convection cooling. The reaction chamber combines a critical ratio of silicon and non-silicon based materials to provide the thermal properties desired. For example, the chamber may combine a critical ratio of silicon and silicon nitride to the volume of material to be heated (e.g., a liquid) in order to provide uniform heating, yet low power requirements. The reaction chamber will also allow the introduction of a secondary tube (e.g., plastic) into the reaction sleeve that contains the reaction mixture thereby alleviating any potential materials incompatibility issues. The reaction chamber may be utilized in any chemical reaction system for synthesis or processing of organic, inorganic, or biochemical reactions, such as the polymerase chain reaction (PCR) and/or other DNA reactions, such as the ligase chain reaction, which are examples of a synthetic, thermal-cycling-based reaction. The reaction chamber may also be used in synthesis instruments, particularly those for DNA amplification and synthesis.

Claims

1. An apparatus for controlling the temperature of a reaction mixture contained in a tube or insert, the apparatus comprising:

a) a reaction sleeve comprising at least two substrates defining a slot between them for receiving the insert, wherein the substrates are constructed of a material selected from the group consisting of ceramics, polymers, metals, metallic alloys, composites, or combinations thereof; and

b) a resistive heater deposited on at least one of the substrates.

2. The apparatus of claim 1, wherein at least one of the substrates comprises a ceramic material, and wherein the heater comprises a film deposited on the ceramic material.

3. The apparatus of claim 1, wherein each of the substrates comprises a ceramic material, and wherein the apparatus includes at least one heater deposited on each of the ceramic substrates.

4. The apparatus of claim 1, wherein each of the substrates has a thickness in the range of 0.1 to 1.0 mm.

5. The apparatus of claim 1, wherein the ratio of the cross sectional area of the reaction sleeve to the cross sectional area of the slot is less than 5:

1.

6. The apparatus of claim 1, wherein the ratio of the cross sectional area of the reaction sleeve to the cross sectional area of the slot is less than 3:

1.

7. The apparatus of claim 1, wherein the ratio of the cross sectional area of the reaction sleeve to the cross sectional area of the slot is less than 2:

1.

8. The apparatus of claim 1, wherein the sleeve includes a first optical window, the insert includes a second optical window which is aligned with the first window when the insert is positioned in the sleeve, and the apparatus further comprises an optical detector for detecting a product in the reaction mixture through the windows.

9. The apparatus of claim 8, wherein the second window includes a test strip.

10. The apparatus of claim 8, further comprising:

a) a data readout system connected to the detector; and

b) an instrument controller connected to the data readout system.

11. The apparatus of claim 10, wherein each of the substrates comprises a ceramic material, and wherein the apparatus includes at least one heater deposited on each of the ceramic substrates.

12. The apparatus of claim 11, wherein each of the ceramic substrates has a thickness in the range of 0.1 to 1.0 mm.

13. The apparatus of claim 1, wherein the heater comprises a thermoelectric film.

14. The apparatus of claim 11, further comprising an electroactive film coupled to at least one of the substrates for controlling an electrically active reagent in the reaction mixture.

15. The apparatus of claim 11, further comprising a magnetic film coupled to at least one of the substrates for controlling a magnetic or paramagnetic reagent in the reaction mixture.

16. The apparatus of claim 1, further comprising a hand-held, battery-operated instrument into which the sleeve is inserted, wherein the instrument includes electronics for controlling the heater.

17. The apparatus of claim 1, further comprising an array of such reaction sleeves and an instrument for holding the sleeves, wherein the instrument includes control elements for individually controlling the operation of each sleeve.

18. The apparatus of claim 1, further comprising an array of such reaction sleeves and an array of adjacent detectors for providing feedback control of a reaction process in the sleeves.

19. An apparatus for controlling the temperature of a reaction mixture, the apparatus comprising:

a. a reaction sleeve defining a chamber for receiving the mixture, wherein the sleeve has at least one open end for insertion of the mixture into the chamber, and wherein the sleeve is constructed of a material selected from the group consisting of ceramics, polymers, metals, metallic alloys, composites, or combinations thereof; and

b. at least one resistive heater deposited on the sleeve for heating the mixture contained in the chamber, wherein the ratio of the cross sectional area of the sleeve to the cross sectional area of the chamber is less than 5;

1.

20. The apparatus of claim 19, further comprising an insert for holding the mixture, wherein the insert is constructed of a material that is substantially inert with respect to the mixture, and wherein the insert is sized to be inserted into the chamber.

21. The apparatus of claim 20, wherein the sleeve includes a first optical window, the insert includes a second optical window which is aligned with the first window when the insert is positioned in the chamber, and the apparatus further comprises an optical detector for detecting a product in the reaction mixture through the windows.

22. The apparatus of claim 21, further comprising:

a. a data readout system connected to the detector; and

b. an instrument controller connected to the data readout system.

23. The apparatus of claim 19, further comprising a liner inside the sleeve, wherein the liner comprises a material that is substantially inert with respect to the reaction mixture.

24. The apparatus of claim 19, wherein the sleeve comprises a ceramic material, and wherein the heater comprises a film deposited on the ceramic material.

25. The apparatus of claim 19, wherein the sleeve comprises at least two substrates defining the chamber between them, and wherein the apparatus includes at least one heater deposited on each of the substrates.

26. The apparatus of claim 25, wherein each of the substrates has a thickness in the range of 0.1 to 1.0 mm.

27. The apparatus of claim 25, wherein each of the substrates comprises a ceramic material.

28. The apparatus of claim 19, wherein the ratio of the cross sectional area of the sleeve to the cross sectional area of the chamber is less than 3:

1.

29. The apparatus of claim 19, wherein the ratio of the cross sectional area of the sleeve to the cross sectional area of the chamber is less than 2:

1.

30. The apparatus of claim 19, further comprising a hand-held, battery-operated instrument into which the sleeve is inserted, wherein the instrument includes electronics for controlling the heater.

31. The apparatus of claim 19, further comprising an array of such reaction sleeves and an instrument for holding the sleeves, wherein the instrument includes control elements for controlling the operation of the sleeves.

32. The apparatus of claim 31, further comprising a microelectrophoresis array, wherein the array of reaction sleeves is connected to the microelectrophoresis array.

33. The apparatus of claim 32, further comprising at least one array of microinjectors connecting the array of reaction sleeves to the microelectrophoresis array.

34. The apparatus of claim 19, wherein the heater comprises at least one film.

35. The apparatus of claim 19, further comprising an electroactive film coupled to the sleeve for controlling an electrically active reagent in the reaction mixture.

36. The apparatus of claim 19, further comprising a magnetic film coupled to the sleeve for controlling a magnetic or paramagnetic reagent in the reaction mixture.

37. The apparatus of claim 19, further comprising an array of such reaction sleeves and tubes connecting the chambers of the sleeves to each other to provide a flow-through reaction system.

38. The apparatus of claim 37, further comprising an array of detectors for providing feedback control of a reaction process in the sleeves.

39. An apparatus for controlling the temperature of a reaction mixture contained in a tube or insert, the apparatus comprising:

a. a reaction steere comprising at least two substrates defining a slot between them for receiving the insert, wherein the substrates are constructed of a material selected from the group consisting of ceramics, polymers, metals, metallic alloys, composites, or combinations thereof, and wherein each of the substrates has a thickness in the range of 0.1 to 1 mm; and

b. a heater coupled to at least one of the substrates for heating the mixture contained in the insert.

40. The apparatus of claim 39, wherein each of the substrates comprises a ceramic material, and wherein the apparatus includes at least one resistive heater deposited on each of the ceramic substrates.

41. The apparatus of claim 40, wherein each of the heaters comprises a film.

42. The apparatus of claim 39, wherein the steere comprises a first optical window, the insert includes a second optical window which is aligned with the first window when the insert is positioned in the sleeve, and the apparatus further comprises an optical detector for detecting a product in the reaction mixture through the windows.

43. The apparatus of claim 42, further comprising:

a. a data readout system connected to the detector; and

b. an instrument controller connected to the data readout system.

44. In a microfabricated chemical reactor, the improvement comprising:

a. an insert for holding a reaction fluid; and

b. a sleeve reaction chamber comprising at least two substrates defining a slot between them for receiving the insert;

wherein the substrates are constructed of a material selected from the group consisting of ceramics, polymers, metals, metallic alloys, composites, or combinations thereof; and

the sleeve reaction chamber includes at least one heating element for heating the reaction fluid.

45. The improvement of claim 44, wherein the sleeve reaction chamber comprises a ceramic material, and wherein the heating element comprises a resistor coupled to the ceramic material.

46. The improvement of claim 44, wherein the insert includes an optical window, and wherein the chemical reactor further comprises an optical detector positioned adjacent the optical window.