Microfluidic devices and uses thereof in biochemical processes

• US 7,015,030 B1
• Filed: 07/28/2000
• Issued: 03/21/2006
• Est. Priority Date: 07/28/1999
• Status: Expired due to Fees

• Current Assignee: Serono Genetics Institute S.A. (Merck & Co., Inc.)
• Original Assignee: Commissariat a L'Energie Atomique (AES Corporation), Genset SA
• Inventors: Vauchier, Claude, Fouillet, Yves, Clerc, Jean-Frederic, Peponnet, Christine
• Primary Examiner(s): Sisson, Bradley L.
• Application Number:
  US09/627,647
• Time in Patent Office: 2,062 Days
• Field of Search: 435/6, 435/91.1, 435/91.2, 435/183, 435/287.2, 536/23.1, 536/24.33
• US Class Current: 435/287.1
• CPC Class Codes: B01L 2200/0673 Handling of plugs of fluid surrounded by immiscible fluid
• 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 2300/0816 Cards, e.g. flat sample carriers usually with flow in two horizontal directions
• CPC Class Codes: B01L 2300/0845 Filaments, strings, fibres, i.e. not hollow
• 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 2300/1805 Conductive heating, heat from thermostatted solids is conducted to receptacles, e.g. heating plates, blocks
• CPC Class Codes: B01L 2300/1822 using Peltier elements
• CPC Class Codes: B01L 2300/1827 using resistive heater
• CPC Class Codes: B01L 2300/1838 using fluid heat transfer medium
• CPC Class Codes: B01L 2300/1883 using thermal insulation
• CPC Class Codes: B01L 2400/0418 electro-osmotic flow [EOF]
• CPC Class Codes: B01L 2400/0421 electrophoretic flow
• CPC Class Codes: B01L 2400/0487 fluid pressure, pneumatics
• CPC Class Codes: B01L 3/5025 for parallel transport of multiple samples
• 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 7/02 Water baths; Sand baths; Air baths
• 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 7/5255 by moving sample containers
• CPC Class Codes: F28F 2260/02 : having microchannels
• CPC Class Codes: G01N 35/08 : using a stream of discrete samples flowing along a tube system, e.g. flow injection analysis

Abstract

Provided is a microfluidic device comprising a microfluidic substrate comprising at least one pathway for sample flow; and at least one thermal transfer member which is capable of cycling between at least two temperatures. The thermal transfer member is adapted to heat at least a portion of the sample pathway while a sample is flowing along said at least a portion of said sample pathway. Provided also are methods of carrying out biochemical protocols using such a device.

Claims

1. A device comprising:

a microfluidic substrate comprising at least one sample pathway for sample flow; and

said microfluidic substrate further comprising at least one temperature regulated zone that cycles between at least two different and predetermined temperatures, said at least one temperature regulated zone being adapted to bring at least a portion of said sample pathway to said at least two temperatures while a sample is unidirectionally flowing along said at least a portion of said sample pathway and said at least one temperature regulated zone comprising a metal bar in fluid communication with a plurality of water sources containing water at said at least two temperatures, said metal bar being in thermal communication with said at least a portion of said sample pathway and wherein a sample is cycled between said at least two different and predetermined temperatures while in said at least one temperature regulated zone.

2. The device of claim 1, further comprising a force supplying member operably linked to said at least one pathway for sample flow wherein said force supplying member applies a force to said sample such that said sample travels along said at least one pathway.

3. The device of claim 1, wherein said microfluidic substrate consists essentially of silicon.

4. The device of claim 1, further comprising a detector for measuring a physicochemical property of a biological sample.

5. The device of claim 1, wherein said device comprises a microfluidic substrate comprising at least one temperature regulated zone which is capable of cycling between at least two temperatures, and at least one constant temperature zone.

6. The device of claim 1, wherein said device comprises a microfluidic substrate comprising several temperature regulated zones capable of cycling between at least two temperatures.

7. The device of claim 1, wherein said flowing sample goes through a plurality of temperature cycles as it travels through the temperature regulated zone.

8. The device of claim 1, wherein said device comprises one temperature regulated zone.

9. The device of claim 1, wherein said device further comprises at least one thermostatting means that cycles said temperature regulated zone between said at least two different and predetermined temperatures.

10. The device of claim 1, wherein said at least one temperature regulated zone cycles between −

5°

C. and 150°

C.

11. The device of claim 1, wherein said at least one temperature regulated zone cycles between 20°

C. and 40°

C.

12. The device of claim 1, wherein said at least one temperature regulated zone cycles between 57°

C., 72°

C., and 94°

C.

13. The device of claim 1, wherein said at least one temperature regulated zone cycles between 37°

C. and 94°

C.

14. The device of claim 1, wherein said at least one temperature regulated zone cycles between 55°

C. and 94°

C.

15. The device of claim 1, wherein said at least one temperature regulated zone cycles between 65°

C. and 94°

C.

16. The device of claim 1, wherein said at least one of temperature regulated zone cycles at 25°

C. and 42.5°

C.

17. The device of claim 1, wherein said device further comprises temperature sensors in each temperature regulated zone.

18. The device of claim 17, wherein said temperature sensors are two thermocouples and a platinum sensor.

19. The device of claim 2, wherein the force generated by said force supplying member is pressure.

20. The device of claim 19, further comprising a sample supplier which supplies a sample to said at least one pathway.

21. The device of claim 20, further comprising at least one inlet basin positioned at a first end of said at least one pathway such that said sample supplier supplies said sample to said inlet basin and said sample travels from said inlet basin to said at least one pathway.

22. The device of claim 21, further comprising at least one outlet basin positioned at a second end of said pathway.

23. The device of claim 22, further comprising at least one reagent supplier positioned between said inlet basin and said outlet basin.

24. The device of claim 23, wherein said device comprises a plurality of said pathways.

25. The device of claim 24, wherein said pathways comprise channels arranged in parallel, and wherein said channels are fed in series with different samples separated from each other by separators.

26. The device of claim 25 wherein the portion of the channel which crosses the temperature regulated zone is rectilinear.

27. The device of claim 19, wherein said microfluidic substrate consists essentially of silicon.

28. The device of claim 19, further comprising a detector for measuring a physicochemical property of a biological sample.

29. The device of claim 19, wherein said device comprises a microfluidic substrate comprising at least one temperature regulated zone which is capable of cycling between at least two temperatures, and at least one constant temperature zone.

30. The device of claim 19, wherein said device comprises a microfluidic substrate comprising more than one temperature regulated zone capable of cycling between at least two temperatures.

31. The device of claim 19, wherein said flowing sample goes through a plurality of temperature cycles as it travels through the temperature regulated zone.

32. The device of claim 2, further comprising a sample supplier which supplies a sample to said at least one pathway.

33. The device of claim 32, further comprising at least one inlet basin positioned at a first end of said at least one pathway such that said sample supplier supplies said sample to said inlet basin and said sample travels from said inlet basin to said at least one pathway.

34. The device of claim 33, further comprising at least one outlet basin positioned at a second end of said pathway.

35. The device of claim 34, further comprising at least one reagent supplier positioned between said inlet basin and said outlet basin.

36. The device of claim 35, wherein said device comprises a plurality of said pathways.

37. The device of claim 36, wherein said pathways comprise channels arranged in parallel.

38. The device of claim 37, wherein the force generated by said force supplying member is pressure.

39. The device of claim 37, wherein said channels are fed in series with different samples separated from each other by separators.

40. The device of claim 37 wherein the portion of the channel which crosses the temperature regulated zone is rectilinear.