Microfabricated sleeve devices for chemical reactions

• US 6,524,532 B1
• Filed: 12/11/1996
• Issued: 02/25/2003
• 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): LUDLOW, JAN M
• Application Number:
  US08/763,465
• Time in Patent Office: 2,267 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. In a microfabricated chemical reactor, the improvement comprising:

a sleeve reaction chamber constructed of silicon-based or nonsilicon-based materials;

said sleeve reaction chamber including a slot therein for insertion of reaction fluid.

2. The improvement of claim 1, wherein said slot is constructed for insertion of reaction fluid into said sleeve reaction chamber directly, via a tube, or via an insert containing the reaction fluid.

3. The improvement of claim 1, wherein said sleeve reaction chamber materials are selected from the group consisting of silicon, glass, ceramics, metal, metallic alloys, polymers, composites, and combinations thereof.

4. The improvement of claim 3, wherein said chamber material consists of ceramics selected from the group consisting of crystalline, non-crystalline, silicate, and non-silicate based ceramics.

5. The improvement of claim 3, wherein said chamber material consists of polymer material comprising at least one polymer containing a dopant to increase thermal conduction.

6. The improvement of claim 1, wherein said sleeve reaction chamber is provided with at least one optical window.

7. The improvement of claim 1, additionally including at least one via, channel, or hole in said reaction chamber for placement of a detection system.

8. The improvement of claim 7, additionally including at least one integrated optical lens located in said at least one via, channel, or hole to provide optical access to reaction chamber liners located in said reaction chamber.

9. The improvement of claim 1, wherein said sleeve reaction chamber is composed of a plurality of bonded members.

10. The improvement of claim 9, wherein said bonded members are constructed of polysilicon and bulk silicon.

11. The improvement of claim 3, wherein said sleeve reaction chamber is composed of a first material, and including a liner in said reaction chamber and constructed of a second material.

12. The improvement of claim 11, wherein said sleeve reaction chamber is composed of material selected from the group consisting of silicon and metal, and wherein said liner is composed of a polymer passivation layer.

13. The improvement of claim 12, wherein said polymer passivation layer is composed of teflon or polypropylene.

14. The improvement of claim 11, wherein said sleeve reaction chamber is composed of a material selected from the group consisting of silicon, metal, and ceramic, and wherein said liner is composed of a material selected from the group consisting of polymer, glass, and metal.

15. The improvement of claim 1, wherein said sleeve reaction chamber is constructed of a first material and includes a heating means composed of a second material.

16. The improvement of claim 1, additionally including heating and cooling means for said reaction chamber composed of a thermal electric film.

17. The improvement of claim 1, wherein said reaction chamber additionally includes electroactive films for electrical control of electrically active reagents.

18. The improvement of claim 1, wherein said reaction chamber additionally include films for control of magnetic and paramagnetic reagents.

19. The improvement of claim 15, wherein said sleeve reaction chamber includes a plurality of windows and a heating means located adjacent each window.

20. The improvement of claim 15, wherein said reaction chamber is composed of material selected from the group of silicon, polymer, and ceramic, and said heating means is composed of polysilicon or metal.

21. The improvement of claim 1, additionally including an insert adapted to be inserted into said slot, said insert containing reaction fluids.

22. The improvement of claim 1, wherein said sleeve reaction chamber is provided with a plurality of slots therein, each slot having at least one window.

23. The improvement of claim 22, wherein at least one of said windows is provided with a test strip.

24. The improvement of claim 22, additionally including an insert adapted to be inserted into at least one of said slots, said at least one insert including at least one window therein.

25. The improvement of claim 1, wherein said sleeve reaction chamber is constructed and is adapted to be inserted into a hand-held, battery-operated instrument.

26. The improvement of claim 1, wherein said sleeve reaction chamber is constructed and is adapted to be inserted into an instrument constructed to contain an array of such reaction chambers.

27. The improvement of claim 26, wherein said instrument containing an array of such reaction chambers is operatively connected via an array of microinjectors to a microelectrophoresis array.

28. The improvement of claim 26, wherein said instrument containing an array of such reaction chambers is connected directly to a microelectrophoresis array.

29. The improvement of claim 27, wherein said array of such reaction chambers are constructed of silicon, metals and ceramic, and wherein said microelectrophoresis array is constructed of glass, polymer and ceramic.

30. The improvement of claim 6, additionally including an optical detector positioned adjacent said optical window.

31. The improvement of claim 30, additionally including a data readout system operatively connected to said optical detector, and an instrument controller operatively connected to said data readout system and said reaction chamber.

32. The improvement of claim 27, wherein each of said reaction chambers include a liner composed of polymer, glass, or other compatible material.

33. The improvement of claim 1, additionally including multiple detection systems.

34. The improvement of claim 1, additionally including at least one detection system.

35. The improvement of claim 34, wherein said at least one detection system is selected from the group consisting of optical, electochemical, electrocheminescence, magnetic and capacitive.

36. The improvement of claim 1, wherein said reaction chamber additionally includes microfabricated elements for providing detection of reaction fluid in said sleeve reaction chamber.

37. The improvement of claim 1, comprising an array of said sleeve reaction chambers interconnected via tubing to an array of reaction chambers, and control elements providing a flow-through reaction system.

38. The improvement of claim 1, comprising an array of said sleeve reaction chambers containing an array of adjacent detection systems, said detection systems including means for providing feedback control of a reaction process in said reaction chambers.