Microfabricated reactor

• US 7,169,601 B1
• Filed: 07/24/1997
• Issued: 01/30/2007
• Est. Priority Date: 08/31/1992
• Status: Expired due to Fees

• Current Assignee: Regents of the University of California (University of California)
• Original Assignee: Regents of the University of California (University of California)
• Inventors: Northrup, M. Allen, White, Richard M.
• Primary Examiner(s): FREDMAN, JEFFREY NORMAN
• Application Number:
  US08/900,735
• Time in Patent Office: 3,477 Days
• Field of Search: 435/6, 435/91.1, 435/91.2, 435/183, 435/287.2, 435/270, 422/50, 422/63, 422/68.1, 422/82.05, 422/99, 422/103
• US Class Current: 435/287.2
• CPC Class Codes: B01F 31/86 with vibration of the receptacle or part of it
• CPC Class Codes: B01F 33/30 Micromixers
• 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 2219/00828 Silicon wafers or plates
• CPC Class Codes: B01J 2219/00831 Glass
• CPC Class Codes: B01J 2219/00873 Heat exchange
• CPC Class Codes: B01J 2219/00889 Mixing micromixers B01F33/30
• CPC Class Codes: B01J 2219/00891 Feeding or evacuation
• CPC Class Codes: B01J 2219/0093 Electric or magnetic energy
• CPC Class Codes: B01J 2219/00932 Sonic or ultrasonic vibrations
• CPC Class Codes: B01J 2219/00934 Electromagnetic waves
• CPC Class Codes: B01J 2219/00952 Sensing operations
• CPC Class Codes: B01L 2300/1827 using resistive heater
• CPC Class Codes: B01L 2400/0406 capillary forces
• CPC Class Codes: B01L 2400/0436 acoustic forces, e.g. surface acoustic waves [SAW]
• 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 3/50273 characterised by the means or forces applied to move the fluids micropumps F04B19/006, of the membrane type F04B43/043
• 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 7/525 with physical movement of samples between temperature zones
• CPC Class Codes: B01L 9/527 for microfluidic devices, e.g. used for lab-on-a-chip
• CPC Class Codes: G01N 2035/00237 : Handling microquantities of analyte, e.g. microvalves, capillary networks
• CPC Class Codes: G01N 2035/00554 : using ultrasound
• CPC Class Codes: G01N 2291/02466 : Biological material, e.g. blood
• CPC Class Codes: G01N 2291/0256 : Adsorption, desorption, surface mass change, e.g. on biosensors
• CPC Class Codes: G01N 2291/0421 : Longitudinal waves
• CPC Class Codes: G01N 29/022 : Fluid sensors based on microsensors, e.g. quartz crystal-microbalance [QCM], surface acoustic wave [SAW] devices, tuning forks, cantilevers, flexural plate wave [FPW] devices microdevices per se B81B
• CPC Class Codes: G01N 35/00 : Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
• CPC Class Codes: G01N 35/1079 : with means for piercing stoppers or septums
• CPC Class Codes: Y10S 73/04 : Piezoelectric

Abstract

An integrated microfabricated instrument for manipulation, reaction and detection of microliter to picoliter samples. The instrument is suited for biochemical reactions, particularly DNA-based reactions such as the polymerase chain reaction, that require thermal cycling since the inherently small size of the instrument facilitates rapid cycle times. The integrated nature of the instrument provides accurate, contamination-free processing. The instrument may include reagent reservoirs, agitators and mixers, heaters, pumps, and optical or electromechanical sensors. Ultrasonic Lamb-wave devices may be used as sensors, pumps and agitators.

Claims

1. An apparatus for controlling a chemical reaction, comprising:

a) an array of chambers including;

a reaction chamber configured to contain a chemical reaction;

at least one reactant chamber configured to receive one or more reactants;

at least one channel interconnecting said reaction and reactant chambers;

b) a heater configured to heat reactants in the reaction chamber;

c) a temperature controller coupled to the heater and configured to control the temperature of a reaction in the reaction chamber; and

d) a product analysis chamber coupled to the reaction chamber and adapted to analyze reaction products contained in the product analysis chamber.

2. The apparatus of claim 1, wherein said product analysis chamber is configured to perform one or more analyses selected from a group consisting of:

sequencing of target species, DNA fingerprinting, physical mapping of target species, DNA library analysis, electrochemical detection, and hybridization detection.

3. The apparatus of claim 1, wherein at least one reactant chamber is configured to contain a sample selected from a group consisting of:

intact cells, fixed cells, lysed cells, microorganism, and tissue.

4. The apparatus of claim 1, wherein at least one reactant chamber is configured to contain a sample comprising a specific nucleic acid target molecule.

5. The apparatus of claim 1, wherein at least one reactant chamber is configured to contain a sample comprising specific cell types.

6. The apparatus of claim 1, wherein said reaction and reactant chambers are constructed on a single substrate.

7. The apparatus of claim 1, wherein the temperature controller is configured to maintain said reaction at a constant temperature.

8. The apparatus of claim 7, wherein said reaction chamber is configured to contain an in vitro transcription reaction.

9. The apparatus of claim 1, wherein the temperature controller is configured to thermally cycle said reaction.

10. The apparatus of claim 9, wherein said reaction chamber is configured to contain a chain reaction.

11. The apparatus of claim 10, wherein said reaction chamber is configured to contain a polymerase chain reaction.

12. The apparatus of claim 10, wherein said reaction chamber is configured to contain a ligase chain reaction.

31. The apparatus of claim 1, wherein the array of chambers and the heater are integrated on a single substrate.

13. An apparatus for controlling a chemical reaction, comprising:

a) an array of chambers including;

a reaction chamber configured to contain a chemical reaction;

at least one reactant chamber configured to receive one or more reactants;

at least one channel interconnecting said reaction and reactant chambers;

a transferring mechanism coupled to said reaction and reactant chambers by way of said channel;

b) a heater configured to heat reactants in the reaction chamber;

c) a temperature controller coupled to the heater and configured to control the temperature of a reaction in the reaction chamber; and

d) a product analysis chamber coupled to the reaction chamber and adapted to analyze reaction products contained in the product analysis chamber.

14. The apparatus of claim 13, wherein said product analysis chamber is configured to perform one or more analyses selected from the group consisting of:

sequencing of target species, DNA fingerprinting, physical mapping of target species, DNA fingerprinting, physical mapping of target species, DNA library analysis, electrochemical detection, and hybridization detection.

15. The apparatus of claim 13 in which said product analysis chamber utilizes a predetermined array of oligonucleotides.

16. The apparatus of claim 15 in which said product analysis chamber is configured to use the array of oligonucleotides in performing hybridization techniques.

17. The apparatus of claim 13, wherein said product analysis chamber is configured to purify said reaction products.

18. The instrument of claim 17, wherein said purification is performed by electrophoresis.

19. The instrument of claim 17, wherein said purification is performed by chromatography.

20. The apparatus of claim 13, wherein at least one reactant chamber is configured to contain a sample selected from a group consisting of:

intact cells, fixed cells, lysed cells, microorganism, and tissue.

21. The apparatus of claim 20, wherein at least one reactant chamber is configure to contain a sample comprising a specific nucleic acid target molecule.

22. The apparatus of claim 13, wherein at least one reactant chamber is configured to contain a sample comprising specific cell types.

23. The apparatus of claim 13, wherein said reaction and reactant chambers are constructed on a single substrate.

24. The apparatus of claim 13, wherein the temperature controller is configured to maintain said reaction at a constant temperature.

25. The instrument of claim 24, wherein said reaction is in vitro transcription.

26. The apparatus of claim 13, wherein the temperature controller is configured to thermally cycle said reaction.

27. The apparatus of claim 26, wherein said reaction chamber is configured to contain a chain reaction.

28. The apparatus of claim 27, wherein said reaction chamber is configured to contain a polymerase chain reaction.

29. The apparatus of claim 27, wherein said reaction chamber is configured to contain ligase chain reaction.

30. The apparatus of any of claim 29, wherein at least one reactant chamber is configured to contain labeled primers for subsequent identification of reaction products.

32. The apparatus of claim 13, wherein the array of chambers and the heater are integrated on a single substrate.