Microfluidic devices and methods

• US 7,007,710 B2
• Filed: 04/21/2003
• Issued: 03/07/2006
• Est. Priority Date: 04/21/2003
• Status: Expired due to Fees

• Current Assignee: Vern Norviel
• Original Assignee: Predicant Biosciences, Inc. (Response Genetics, Inc)
• Inventors: Heller, Jonathan, Zhao, Mingqi, Bousse, Luc, Stults, John, Srinivasan, Uthara
• Primary Examiner(s): CHAMBERS, A MICHAEL
• Application Number:
  US10/421,677
• Publication Number:
  US 20040206399A1
• Time in Patent Office: 1,051 Days
• Field of Search: 137/827, 137/833, 137/807, 137/15.01, 204/601, 250/288, 422/100, 436/177, 436/180, 251/368
• US Class Current: 137/15.01
• CPC Class Codes: H01J 49/0018 Microminiaturised spectrometers, e.g. chip-integrated devices, Micro-Electro-Mechanical Systems [MEMS]
• CPC Class Codes: H01J 49/165 Electrospray ionisation
• CPC Class Codes: Y10T 137/0402 Cleaning, repairing, or assembling
• CPC Class Codes: Y10T 137/2082 Utilizing particular fluid
• CPC Class Codes: Y10T 137/2191 By non-fluid energy field affecting input [e.g., transducer]
• CPC Class Codes: Y10T 137/2224 Structure of body of device
• CPC Class Codes: Y10T 137/7036 Jacketed
• CPC Class Codes: Y10T 436/2575 Volumetric liquid transfer

Abstract

Microfluidic devices provide substances to a mass spectrometer. The microfluidic devices include first and second surfaces, at least one microchannel formed by the surfaces, and an outlet at an edge of the surfaces which is recessed back from an adjacent portion of the edge. Hydrophilic surfaces and/or hydrophobic surfaces guide substances out of the outlet. A source of electrical potential can help move substances through the microchannel, separate substances and/or provide electrospray ionization.

Claims

1. A method of making a microfluidic device for providing one or more substances to a mass spectrometer for analysis of the substances, the method comprising:

fabricating a substrate comprising;

at least one microchannel having a microfabricated surface; and

an outlet in fluid communication with the microchannel and disposed along an edge surface of the substrate, the outlet recessed into the substrate relative to an adjacent portion of the edge surface; and

applying a cover to the substrate.

2. A method for making a microfluidic device for providing one or more substances to a mass spectrometer for analysis of the substances, the method comprising:

fabricating a microfluidic body comprising;

first and second major surfaces with an edge surface therebetween;

at least one microchannel disposed between the first and second major surfaces, the microchannel having a microfabricated surface; and

an outlet in fluid communication with the microchannel and disposed along the edge surface, the outlet recessed into the microfluidic body relative to an adjacent portion of the edge surface.

3. A method for providing at least one substance from a microfluidic device into a mass spectrometer, the method comprising:

moving the at least one substance through at least one microchannel in the microfluidic device; and

causing the at least one substance to pass from the microchannel out of an outlet at a recessed edge of the microfluidic device.

4. A method as in claim 3, wherein providing the at least one substance comprises providing at least one substance in the form of ions.

5. A method as in claim 3, wherein the at least one substance is moved through at least one microchannel by applying an electrical potential to the substance.

6. A method as in claim 5, further including using the electrical potential to separate one or more substances.

7. A method as in claim 5, wherein applying the electrical potential to the substance does not generate a significant amount of bubbles in the substance.

8. A method as in claim 3, wherein the at least one substance is moved through at least one microchannel via pressure.

9. A method as in claim 3, wherein causing the substance to pass from the microchannel out of the outlet comprises directing the substance with at least one hydrophobic surface, and directing the substance with at least one surface of the microfluidic device selected from the group consisting of a hydrophilic surface and a surface that minimizes protein binding.

10. A method as in claim 3, wherein causing the substance to pass from the microchannel out of the outlet comprises directing the substance out of the outlet in a direction approximately parallel to a longitudinal axis of the at least one microchannel.

11. A method as in claim 3, wherein causing the substance to pass from the microchannel out of the outlet comprises directing the substance out of the outlet in a direction non-parallel to a longitudinal axis of the at least one microchannel.

12. A method as in claim 3, wherein causing the substance to pass from the microchannel out of the outlet comprises directing the substance out of the outlet in the form of a spray.

13. A method as in claim 12, wherein the spray has a desired spray geometry.

14. A method of making microfluidic devices for providing one or more substances to a mass spectrometer for analysis of the substances, the method comprising:

forming at least one microchannel on a first substrate;

forming a recessed edge on the first substrate and a second substrate;

providing a layer of film having at least one tip and at least one alignment feature;

aligning the layer of film between the first and second substrates; and

bonding the layer of film between the first and second substrates.

15. A microfluidic device for providing one or more substances to a mass spectrometer for analysis of the substances, the microfluidic device comprising:

a microfluidic body having first and second major surfaces and at least one edge surface;

at least one microchannel disposed between the first and second major surfaces, the microchannel having a microfabricated surface; and

at least one outlet in fluid communication with the microchannel and disposed along the edge surface, the outlet recessed into the microfluidic body relative to an adjacent portion of the edge surface.

16. A microfluidic device as in claim 15, wherein at least part of the microfabricated surface comprises a surface that minimizes protein binding.

17. A microfluidic device as in claim 16, wherein the surface that minimizes protein binding comprises a part of the microfabricated surface adjacent the outlet.

18. A microfluidic device as in claim 16, wherein the surface that minimizes protein binding is disposed along the entire length of the microfabricated surface.

19. A microfluidic device as in claim 16, wherein the surface that minimizes protein binding comprises at least one of a coated surface, a gel matrix, a polymer, a sol-gel monolith and a chemically modified surface.

20. A microfluidic device as in claim 19, wherein a coating on the coated surface comprises a material selected from the group consisting of cellulose polymer, polyacrylamide, polydimethylacrylamide, acrylarmide-based copolymer, polyvinyl alcohol, polyvinylpyrrolidone, plyethylene oxide, Pluronic™

polymers, poly-N-hydroxyethylacrylamide, Tween™

, dextran, a sugar, hydroxyethyl methacrylate and indoleacetic acid.

21. A microfluidic device as in claim 19, wherein the chemically modified surface has been modified by at least one of gas plasma treatment, plasma polymerization, corona discharge treatment, UV/ozone treatment, and an oxidizing solution.

22. A microfluidic device as in claim 15, wherein at least part of the microfabricated surface comprises a hydrophilic surface.

23. A microfluidic device as in claim 22, wherein the hydrophilic surface comprises a part of the microfabricated surface adjacent the outlet.

24. A microfluidic device as in claim 22, wherein the hydrophilic surface is disposed along the entire length of the microfabricated surface.

25. A microfluidic device as in claim 22, wherein the hydrophilic surface comprises at least one of a coated surface, a gel matrix, a polymer, a sol-gel monolith and a chemically modified surface.

26. A microfluidic device as in claim 25, wherein a coating on the coated surface comprises a material selected from the group consisting of cellulose polymer, polyacrylamide, polydimethylacrylamide, acrylamide-based copolymer, polyvinyl alcohol, polyvinylpyrrolidone, plyethylene oxide, Pluronic™

polymers, poly-N-hydroxyethylacrylamide, Tween™

, dextran, a sugar, hydroxyethyl methacrylate and indoleacetic acid.

27. A microfluidic device as in claim 25, wherein the chemically modified surface has been modified by at least one of gas plasma treatment, plasma polymerization, corona discharge treatment, UV/ozone treatment, and an oxidizing solution.

28. A microfluidic device as in claim 15, wherein at least one of the first major surface, the second major surface and the edge surface comprises, at least in part, a hydrophobic surface.

29. A microfluidic device as in claim 28, wherein the at least one hydrophobic surface is disposed adjacent the outlet.

30. A microfluidic device as in claim 15, wherein at least one of the first and second major surfaces comprises a material selected from the group consisting of glass, silicon, ceramic, polymer, copolymer, silicon dioxide, quartz, silica and a combination thereof.

31. A microfluidic device as in claim 30, wherein the polymer comprises a material selected from the group consisting of cyclic polyolefin, polycarbonate, polystyrene, PMMA, acrylate, polyimide, epoxy, polyethylene, polyether, polyethylene terephtalate, polyvinyl chloride, polydimethylsiloxane, polyurethane, polypropylene, phenol formaldehyde, polyacrylonitrile, Mylar™

and Teflon™

.

32. A microfluidic device as in claim 15, further comprising at least one protrusion extending from at least one surface of the microchannel beyond the outlet, the protrusion recessed into the microfluidic body relative to the adjacent portion of the edge surface.

33. A microfluidic device as in claim 32, wherein the at least one protrusion comprises at least one surface that minimizes protein binding.

34. A microfluidic device as in claim 32, wherein the at least one protrusion comprises at least one hydrophilic surface.

35. A microfluidic device as in claim 32, wherein the at least one protrusion comprises at least one metallic surface.

36. A microfluidic device as in claim 32, wherein the at least one protrusion comprises at least one hydrophobic surface.

37. A microfluidic device as in claim 32, wherein the at least one protrusion comprises a pointed tip.

38. A microfluidic device as in claim 32, wherein the at least one protrusion comprises a semi-circular tip having a radius of less than 40 micrometers.

39. A microfluidic device as in claim 15, further comprising a source of pressure coupled with the device to move the substances through the microchannel.

40. A microfluidic device as in claim 15, further comprising a source of potential coupled with the device to move the substances through the microchannel by electrokinetic mobility.

41. A microfluidic device as in claim 15, further comprising a source of electrokinetic potential coupled with the device to move the substances through the microchannel.

42. A microfluidic device as in claim 15, further comprising an electrical potential source coupled with the device to move the substances through the microchannel.

43. A microfluidic device as in claim 42, wherein the electrical potential source comprises an electrical potential microchannel in fluid communication with the microchannel, the electrical potential microchannel containing at least one electrically conducting substance.

44. A microfluidic device as in claim 42, wherein the electrical potential source comprises an electrical potential microchannel which exits the microfluidic device immediately adjacent the microchannel, the electrical potential microchannel containing at least one electrically charged substance.

45. A microfluidic device as in claim 42, wherein the electrical potential source comprises at least one electrode on the microfluidics device.

46. A microfluidic device as in claim 45, wherein the at least one electrode provides potential for effecting at least one of electrophoretic separation of the substances and electrospray ionization.

47. A microfluidic device as in claim 45, wherein the at least one electrode provides potential for effecting at least one of electrokinetic movement of the substances in the microchannel and electrospray ionization.

48. A microfluidic device as in claim 45, wherein the electrode comprises at least one of copper, nickel, conductive ink, silver, silver/silver chloride, gold, platinum, palladium, iridium, aluminum, titanium, tantalum, niobium, carbon, doped silicon, indium tin oxide, other conductive oxides, polyanaline, sexithiophene, polypyrrole, polythiophene, polyethylene dioxythiophene, carbon black, carbon fibers, conductive fibers, and other conductive polymers and conjugated polymers.

49. A microfluidic device as in claim 45, wherein the at least one electrode generates the electrical potential without producing a significant quantity of bubbles in the one or more substances.

50. A microfluidic device as in claim 15, wherein the outlet has a cross-sectional dimension of between about 0.1 micron and about 500 microns.

51. A microfluidic device as in claim 15, wherein the outlet has a cross-sectional dimension of between about 50 microns and about 150 microns.

52. A microfluidic device as in claim 15, wherein the outlet has a cross-sectional dimension of between about 1 micron and about 5 microns.

53. A microfluidic device as in claim 15, wherein the outlet has a cross-sectional dimension of between about 5 microns and about 50 microns.

64. A microfluidic device as in claim 25, wherein the chemically modified surface has been modified by at least one of gas plasma treatment, plasma polymerization, corona discharge treatment, UV/ozone treatment, and an oxidizing solution.

54. A microfluidic device for providing one or more substances to a mass spectrometer for analysis of the substances, the microfluidic device comprising:

a microfluidic body having first and second major surfaces and at least one edge surface;

at least one microchannel disposed between the first and second major surfaces, the microchannel having a microfabricated surface;

at least one outlet in fluid communication with the microchannel and disposed along the edge surface, the outlet recessed into the microfluidic body relative to an adjacent portion of the edge surface; and

at least one protruding tip separated from the outlet and disposed in a path of fluid flow from the outlet, the protruding tip recessed into the microfluidic body relative to the adjacent portion of the edge surface.

55. A microfluidic device as in claim 54, wherein at least one of the microfabricated surface and the protruding tip comprises a surface that minimizes protein binding.

56. A microfluidic device as in claim 55, wherein the surface that minimizes protein binding is disposed adjacent the outlet.

57. A microfluidic device as in claim 55, wherein the surface that minimizes protein binding comprises at least one of a coated surface, a gel matrix, a polymer, a sol-gel monolith and a chemically modified surface.

58. A microfluidic device as in claim 57, wherein a coating on the coated surface comprises a material selected from the group consisting of cellulose polymer, polyacrylamide, polydimethylacrylamide, acrylarmide-based copolymer, polyvinyl alcohol, polyvinylpyrrolidone, plyethylene oxide, Pluronic™

polymers, poly-N-hydroxyethylacrylamide, Tween™

, dextran, a sugar, hydroxyethyl methacrylate and indoleacetic acid.

59. A microfluidic device as in claim 57, wherein the chemically modified surface has been modified by at least one of gas plasma treatment, plasma polymerization, corona discharge treatment, UV/ozone treatment, and an oxidizing solution.

60. A microfluidic device as in claim 54, wherein at least one of the microfabricated surface and the protruding tip comprises a hydrophilic surface.

61. A microfluidic device as in claim 60, wherein the hydrophilic surface is disposed adjacent the outlet.

62. A microfluidic device as in claim 60, wherein the hydrophilic surface comprises at least one of a coated surface, a gel matrix, a polymer, a sol-gel monolith and a chemically modified surface.

63. A microfluidic device as in claim 62, wherein a coating on the coated surface comprises a material selected from the group consisting of cellulose polymer, polyacrylamide, polydimethylacrylamide, acrylamide-based copolymer, polyvinyl alcohol, polyvinylpyrrolidone, plyethylene oxide, Pluronic™

polymers, poly-N-hydroxyethylacrylamide, Tween™

, dextran, a sugar, hydroxyethyl methacrylate and indoleacetic acid.

65. A microfluidic device as in claim 54, wherein at least one of first major surface, the second major surface and the edge surface comprises, at least in part, a hydrophobic surface.

66. A microfluidic device as in claim 65, wherein the at least one hydrophobic surface is disposed adjacent the outlet.

67. A microfluidic device as in claim 54, wherein at least one of the first and second major surfaces comprises a material selected from the group consisting of glass, silicon, ceramic, polymer, copolymer, silicon dioxide, quartz, silica and a combination thereof.

68. A microfluidic device as in claim 67, wherein the polymer comprises a material selected from the group consisting of cyclic polyolefin, polycarbonate, polystyrene, PMMA, acrylate, polyimide, epoxy, polyethylene, polyether, polyethylene terephtalate, polyvinyl chloride, polydimethylsiloxane, polyurethane, polypropylene, phenol formaldehyde, polyacrylonitrile, Mylar™

and Teflon™

.

69. A microfluidic device as in claim 54, further comprising a source of pressure coupled with the device to move the substances through the microchannel.

70. A microfluidic device as in claim 54, further comprising a source of potential coupled with the device to move the substance through the microchannel by electrophoretic mobility.

71. A microfluidic device as in claim 54, further comprising a source of potential coupled with the device to move the substance through the microchannel by electrokinetic mobility.

72. A microfluidic device as in claim 54, further comprising an electrical potential source coupled with the device to move the substances through the microchannel.

73. A microfluidic device as in claim 72, wherein the electrical potential source comprises an electrical potential microchannel in fluid communication with the microchannel, the electrical potential microchannel containing at least one electrically charged substance.

74. A microfluidic device as in claim 72, wherein the electrical potential source comprises an electrical potential microchannel which exits the microfluidic device immediately adjacent the microchannel, the electrical potential microchannel containing at least one electrically charged substance.

75. A microfluidic device as in claim 72, wherein the electrical potential source comprises at least one electrode on the microfluidic device.

76. A microfluidic device as in claim 75, wherein the at least one electrode provides potential for effecting at least one of electrophoretic separation of the substances and electrospray ionization.

77. A microfluidic device as in claim 75, wherein the at least one electrode provides potential for effecting at least one of electrokinetic movement of the substances in the microchannel and electrospray ionization.

78. A microfluidic device as in claim 75, wherein the at least one electrode comprises at least one of copper, nickel, conductive ink, silver, silver/silver chloride, gold, platinum, palladium, iridium, aluminum, titanium, tantalum, niobium, carbon, doped silicon, indium tin oxide, other conductive oxides, polyanaline, sexithiophene, polypyrrole, polythiophene, polyethylene dioxythiophene, carbon black, carbon fibers, conductive fibers, and other conductive polymers and conjugated polymers.

79. A microfluidic device as in claim 75, wherein the at least one electrode generates the electrical potential without producing a significant quantity of bubbles in the substances.

80. A microfluidic device as in claim 54, wherein the protruding tip is selected from the group consisting of a pyramidal tip, a conical tip, a helical tip, a tubular tip, a triangular tip, a rectangular tip and a round tip.

81. A microfluidic device as in claim 54, wherein the outlet has a cross-sectional dimension of between about 0.1 micron and about 500 microns.

82. A microfluidic device as in claim 54, wherein the outlet has a cross-sectional dimension of between about 50 microns and about 150 microns.

83. A microfluidic device as in claim 54, wherein the outlet has a cross-sectional dimension of between about 1 micron and about 5 microns.

84. A microfluidic device as in claim 54, wherein the outlet has a cross-sectional dimension of between about 5 microns and about 50 microns.

85. A microfluidic device for providing one or more substances to a mass spectrometer for analysis of the substances, the microfluidic device comprising:

a microfluidic body having first and second major surfaces and at least one edge surface;

at least one microchannel disposed between the first and second major surfaces, the microchannel having a microfabricated surface; and

a layer of film disposed between the first and second major surfaces to form at least one tip the tip in fluid communication with the microchannel and recessed into the microfluidic body relative to an adjacent portion of the edge surface.