Controlled fluid transport in microfabricated polymeric substrates

• US 6,409,900 B1
• Filed: 09/19/2000
• Issued: 06/25/2002
• Est. Priority Date: 04/16/1996
• Status: Expired due to Term

• Current Assignee: Caliper Technologies Corp (Revvity, Inc.)
• Original Assignee: Caliper Technologies Corp (Revvity, Inc.)
• Inventors: Knapp, Michael R., Bousse, Luc, Chow, Calvin Y. H., Parce, John Wallace
• Primary Examiner(s): Phasge, Arun S.
• Application Number:
  US09/664,847
• Time in Patent Office: 644 Days
• Field of Search: 204/450, 204/600, 204/601, 156/500
• US Class Current: 204/450
• 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 2219/00833 Plastic
• CPC Class Codes: B01J 2219/00853 Employing electrode arrangements
• CPC Class Codes: B01J 2219/00952 Sensing operations
• CPC Class Codes: B01J 2219/00995 Mathematical modeling
• CPC Class Codes: B01L 2200/0689 Sealing
• CPC Class Codes: B01L 2200/12 Specific details about manufacturing devices
• CPC Class Codes: B01L 2200/147 Employing temperature sensors
• CPC Class Codes: B01L 2300/0816 Cards, e.g. flat sample carriers usually with flow in two horizontal directions
• CPC Class Codes: B01L 2300/0887 Laminated structure
• CPC Class Codes: B01L 2300/12 Specific details about materials
• CPC Class Codes: B01L 2400/0418 electro-osmotic flow [EOF]
• 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: G01N 27/44791 Microapparatus sample containers with integrated microfluidic structures B01L3/5027
• CPC Class Codes: Y10S 366/03 Micromixers: variable geometry from the pathway influences mixing/agitation of non-laminar fluid flow
• CPC Class Codes: Y10T 137/2224 Structure of body of device
• CPC Class Codes: Y10T 29/49229 Prime mover or fluid pump making

Abstract

Microfluidic devices are provided for the performance of chemical and biochemical analyses, syntheses and detection. The devices of the invention combine precise fluidic control systems with microfabricated polymeric substrates to provide accurate, low cost miniaturized analytical devices that have broad applications in the fields of chemistry, biochemistry, biotechnology, molecular biology and numerous other fields.

Claims

1. A microfluidic device, comprising:

a body structure comprising at least one polymeric material, the body structure having at least a first microchannel disposed therein, which at least first microchannel comprises at least a first fluidic material, which first fluidic material is electroosmotically flowed through the at least first microchannel at a mobility of at least about 1×

10<sup>−

5</sup> cm²V<sup>−

1</sup>s<sup>−

1</sup>.

2. The microfluidic device of claim 1, wherein the first fluidic material comprises a sodium borate buffer having an ionic strength between about 1 and about 100 mM and a pH from about 6 to about 9.

3. The microfluidic device of claim 2, wherein the first fluidic material has an ionic strength between about 1 and about 10 mM and a pH from about 7 to about 9.

4. The microfluidic device of claim 1, wherein the at least first microchannel has a zeta potential associated therewith, which zeta potential supports electroosmotic flow of the first fluidic material in the at least first microchannel.

5. The microfluidic device of claim 1, further comprising at least a second microchannel intersecting the first microchannel within the polymeric body structure.

6. The microfluidic device of claim 1, further comprising at least one well fluidly connected to the first microchannel.

7. The microfluidic device of claim 1, further comprising:

at least one well fluidly connected to the first microchannel, wherein an electrode is disposed within the well.

8. The microfluidic device of claim 1, further comprising a well fluidly connected to the first microchannel, which well comprises at least a portion of the first fluidic material, the device further comprising a voltage controller in electrical contact with the first fluidic material in the well or a pressure source fluidly coupled to the well.

9. The microfluidic device of claim 1, further comprising:

a well fluidly connected to at least the first microchannel;

a voltage controller in electrical contact with a fluid in the well;

a computer operably linked to the voltage controller; and

,

a detector mounted proximal to the at least one microchannel for viewing an analyte in the microchannel.

10. The microfluidic device of claim 9, wherein the detector provides data to the computer.

11. The microfluidic device of claim 1, wherein the body structure is fabricated by bonding a first polymeric substrate to a second polymeric substrate, wherein at least the first microchannel is formed between the first polymeric substrate and the second polymeric substrate.

12. The microfluidic device of claim 1, wherein said polymeric material is selected from:

polydimethylsiloxane (PDMS), polyurethane, polyvinylchloride (PVC), polystyrene, polysulfone, polycarbonate, polymethylmethacrylate (PMMA), and polytetrafluoroethylene.

13. The microfluidic device of claim 1, the body structure comprising at least about 50% polymeric materials.

14. The microfluidic device of claim 1, the body structure comprising a polymeric substrate and a cover layer, the polymeric substrate comprising the first microchannel embossed therein, the cover layer disposed over at least a portion of the first microchannel.

15. The microfluidic device of claim 14, wherein the cover layer is laminated to the polymeric substrate.

16. The microfluidic device of claim 14, wherein the cover layer is laminated to the polymeric substrate by one or more of:

adhesive bonding, sonic welding, pressure bonding, thermal bonding, and thermal bonding under pressure.

17. The microfluidic device of claim 14, wherein the cover layer and the polymeric substrate are fused.

18. The microfluidic device of claim 14, wherein the cover layer is substantially fabricated from glass or a polymer or a combination thereof.

19. The microfluidic device of claim 14, wherein the first microchannel is embossed as at least one groove in a substantially planar portion of the polymeric substrate and wherein the cover layer overlays the at least one groove, thereby forming a closed microchannel.

20. The microfluidic device of claim 1, the first fluidic material having an electroosmotic mobility of at least about 5×

10<sup>−

5</sup> cm²V<sup>−

1</sup>s<sup>−

1</sup> in the first microchannel.

21. The microfluidic device of claim 1, the first fluidic material having an electroosmotic mobility of at least about 1×

10<sup>−

4</sup> cm²V<sup>−

1</sup>s<sup>−

1</sup> in the first microchannel.

22. The microfluidic device of claim 1, wherein the first microchannel comprises a surface coating.

23. The microfluidic device of claim 1, wherein the first microchannel comprises a surface coating, which coating is provided to the first microchannel by a process selected from:

exposure to a fluorinated modifier compound, exposure to a detergent, exposure to a material having charged functional groups associated therewith, and exposure to a fluorocarbon.

24. The microfluidic device of claim 1, wherein the at least one microchannel comprises a glass or quartz detection window.

25. The microfluidic device of claim 1, the body structure comprising at least two intersecting microchannels disposed therein, each of the at least two intersecting microchannels comprising a fluid having an electroosmotic mobility of at least about 1×

10<sup>−

5</sup> cm²V<sup>−

1</sup>s<sup>−

1</sup>.

26. The microfluidic device of claim 25, wherein said fluid comprises a sodium borate buffer having an ionic strength between about 1 and about 100 mM and a pH from about 6 to about 9.

27. The microfluidic device of claim 26, wherein said fluid comprises a sodium borate buffer having an ionic strength between about 1 and about 10 mM and a pH from about 7 to about 9.

28. The microfluidic device of claim 25, the body structure further comprising at least first, second, third and fourth ports in fluid communication with the at least two intersecting microchannels.

29. The microfluidic device of claim 1, wherein the first microchannel has a dimension between about 0.1 μ

m and about 500 μ

m.

30. The microfluidic device of claim 1, further comprising one or more of:

a sampling system for introducing the at least first fluidic material into the first microchannel;

a detection system for detecting one or more analytes in the first microchannel;

a data storage system;

a fluid control system for controlling fluid transport and direction in the first microchannel;

a temperature detector for detecting the temperature of a portion of the body structure; and

,

a current detector for detecting current in the first microchannel.

31. The microfluidic device of claim 1, further comprising a fluid direction system, which fluid direction system electroosmotically transports the first fluidic material through the at least first microchannel at a mobility of at least about 1×

10<sup>−

5</sup> cm²V<sup>−

1</sup>s<sup>−

1</sup>.

32. The microfluidic device of claim 31, wherein the fluid direction system comprises one or more of:

an electrokinetic controller and one or more electrodes.

33. A method of fabricating a microfluidic device, the method comprising:

fabricating a polymeric material to form a substrate having at least one surface, which surface has at least a first channel disposed therein, which first channel has a zeta potential associated therewith, which zeta potential supports an electroosmotic mobility of at least about 1×

10<sup>−

5</sup> cm²V<sup>−

1</sup>s<sup>−

1</sup> for at least a first fluidic material, said first fluidic material comprising from about 1 mM to about 100 mM sodium borate buffer at a pH of from about 6 to about 9, said first channel having a dimension in a range from about 0.1 μ

m to about 500 μ

m; and

,

overlaying a cover layer on said at least one surface, said cover layer enclosing said first channel, and wherein said substrate and said cover layer together comprise one or more port disposed therein, which one or more port is in fluid communication with said first channel.

34. The method of claim 33, wherein said polymeric material is selected from:

polydimethylsiloxane (PDMS), polyurethane, polyvinylchloride (PVC), polystyrene, polysulfone, polycarbonate, polymethylmethacrylate (PMMA), and polytetrafluoroethylene.

35. The method of claim 33, said fabricating comprising molding said polymeric material to form said substrate.

36. The method of claim 33, said fabricating comprising injection molding said polymeric material to form said substrate.

37. The method of claim 33, said fabricating comprising embossing said at least one surface of said substrate to form said at least one channel.

38. The method of claim 33, further comprising treating said first channel to provide the zeta potential.

39. The method of claim 38, wherein said treating comprises treating said first channel with a fluorinated modifier compound.

40. The method of claim 33, wherein said polymeric material comprises PDMS and said treating comprises exposing said first channel to oxygen plasma.

41. The method of claim 33, wherein said overlaying comprises bonding said cover layer to said surface of said substrate.

42. A method of flowing a fluidic material through a microchannel in a polymeric substrate, which microchannel has a zeta potential associated therewith, the method comprising:

applying a voltage to the fluidic material in the microchannel in the polymeric substrate, thereby flowing the fluidic material through the microchannel at a mobility of at least about 1×

10<sup>−

5</sup> cm²V<sup>−

1</sup>s<sup>−

1</sup>.

43. The method of claim 42, wherein the fluidic material comprises a sodium borate buffer having an ionic strength between about 1 and about 100 mM and a pH from about 6 to about 9.

44. The method of claim 42, wherein the fluidic material has an ionic strength between about 1 and about 10 mM and a pH from about 7 to about 9.

45. The method of claim 42, wherein applying the voltage to the fluidic material in the microchannel comprises using a voltage controller, which voltage controller is in electrical contact with the fluidic material.

46. The method of claim 45, wherein the voltage controller is in electrical contact with the fluidic material in at least one well, which well is fluidly connected to the at least one microchannel and comprises an electrode disposed within the well.

47. The method of claim 42, further comprising detecting the fluidic material in the microchannel.

48. The method of claim 42, comprising detecting the fluidic material using a detector mounted proximal to the microchannel.

49. The method of claim 42, wherein the polymeric substrate is fabricated by bonding a first polymeric surface to a second polymeric surface, wherein the microchannel is formed between the first polymeric surface and the second polymeric surface.

50. The method of claim 42, wherein the polymeric substrate is fabricated from:

polydimethylsiloxane (PDMS), polyurethane, polyvinylchloride (PVC), polystyrene, polysulfone, polycarbonate, polymethylmethacrylate (PMMA), or polytetrafluoroethylene.

51. The method of claim 42, wherein the polymeric substrate comprises at least about 50% polymeric materials.

52. The method of claim 42, wherein the at least one microchannel is embossed as at least one groove in a substantially planar portion of the polymeric substrate and wherein a cover layer overlays the at least one groove, thereby forming a closed microchannel.

53. The method of claim 42, comprising flowing the fluidic material through the microchannel at an electroosmotic mobility of at least about 5×

10<sup>−

5</sup> cm²V<sup>−

1</sup>s<sup>−

1</sup>.

54. The method of claim 42, comprising flowing the fluidic material through the microchannel at an electroosmotic mobility of at least about 1×

10<sup>−

4</sup> cm²V<sup>−

1</sup>s<sup>−

1</sup>.

55. The method of claim 42, wherein the microchannel comprises a surface coating.

56. The method of claim 42, wherein the microchannel comprises a surface coating, which coating is provided to the first microchannel by a process selected from:

exposure to a fluorinated modifier compound, exposure to a detergent, exposure to a material having charged functional groups associated therewith, and exposure to a fluorocarbon.

57. The method of claim 42, further comprising flowing the fluidic material through a second microchannel at an electroosmotic mobility of at least about 1×

10<sup>−

5</sup> cm²V<sup>−

1</sup>s<sup>−

1</sup>.