Microfluidic devices with thick-film electrochemical detection

• US 6,878,255 B1
• Filed: 11/02/2000
• Issued: 04/12/2005
• Est. Priority Date: 11/05/1999
• Status: Expired due to Fees

• Current Assignee: Arrowhead Center, Inc.
• Original Assignee: Arrowhead Center, Inc.
• Inventors: Sahlin, Eskil, Tian, Baomin, Wang, Joseph
• Primary Examiner(s): Nguyen, Nam
• Assistant Examiner(s): Mutschler, Brian L.
• Application Number:
  US09/705,100
• Time in Patent Office: 1,622 Days
• Field of Search: 204/451, 204/452, 204/455, 204/601, 204/603, 204/605, 435/6
• US Class Current: 204/452
• CPC Class Codes: G01N 27/4473 by electric means
• CPC Class Codes: G01N 27/44791 Microapparatus sample containers with integrated microfluidic structures B01L3/5027

Abstract

An apparatus for conducting a microfluidic process and analysis, including at least one elongated microfluidic channel, fluidic transport means for transport of fluids through the microfluidic channel, and at least one thick-film electrode in fluidic connection with the outlet end of the microfluidic channel. The present invention includes an integrated on-chip combination reaction, separation and thick-film electrochemical detection microsystem, for use in detection of a wide range of analytes, and methods for the use thereof.

Claims

1. An apparatus for conducting a microfluidic process and analysis, said apparatus comprising:

a first substrate having at least one exterior edge;

at least one elongated separation channel in the first substrate, the separation channel having an inlet end and an outlet end transiting the at least one exterior edge;

a fluidic transport means for transport of fluids through the separation channel;

a second substrate; and

at least one thick-film electrode for analyte detection on the second substrate, the thick-film electrode being in fluidic connection with the outlet end of the separation channel.

2. The apparatus of claim 1, wherein the fluidic transport means comprises a conductive system in fluidic connection with each end of the separation channel for application of a separation voltage.

3. The apparatus of claim 2, wherein the conductive system comprises electrodes.

4. The apparatus of claim 2, further comprising a high-voltage power supply for application of voltage to the conductive system.

5. The apparatus of claim 1, wherein the fluidic transport means comprises electrokinetic fluid transport.

6. The apparatus of claim 1, wherein the fluidic transport means comprises at least one means elected from the group consisting of electrical, mechanical, centrifugal, magnetic, pneumatic, pressure-activated, and vacuum-activated fluid transport.

7. The apparatus of claim 1, further comprising at least one reference electrode in fluidic connection with the thick-film electrode.

8. The apparatus of claim 1, wherein the first substrate comprises at least one member selected from the group consisting of fused-silica, silica-based, polymer, plastic and elastomer substrates.

9. The apparatus of claim 1, wherein the second substrate comprises at least one member selected from the group consisting of ceramic, polymeric and plastic substrates.

10. The apparatus of claim 1, further comprising an electrical contact to the thick-film electrode.

11. The apparatus of claim 10, further comprising an analyte analysis system in electrical contact with the electrical contact to the thick-film electrode.

12. The apparatus of claim 1, further comprising an analyte analysis system for analyzing an analyte at the thick-film electrode.

13. The apparatus of claim 12, wherein the analyte analysis system comprises an amperometric detection system.

14. The apparatus of claim 13, wherein the amperometric detection system comprises at least one member selected from the group consisting of fixed potential and potential-step amperometric detection systems.

15. The apparatus of claim 12, wherein the analyte analysis system comprises at least one member selected from the group consisting of a stripping potentiometry system and a voltammetric detection system.

16. The apparatus of claim 1, wherein the thick-film electrode is a screen-printed electrode.

17. The apparatus of claim 1, wherein the separation channel has an average bore diameter of from about 1 μ

m to about 300 μ

m.

18. The apparatus of claim 17, wherein the separation channel has an average bore diameter of from about 20 μ

m to about 120 μ

m.

19. The apparatus of claim 1, wherein the thick-film electrode has a thickness of from about 1 μ

m to about 100 μ

m.

20. The apparatus of claim 19, wherein the thickness of the thick-film electrode is between about 8 μ

m and 30 μ

m.

21. The apparatus of claim 1, wherein the first substrate comprising at least one elongated separation channel is detachable from the second substrate comprising at least one thick-film electrode.

22. The apparatus of claim 21, wherein the first substrate is affixed to the second substrate such that the distance between the thick-film electrode and the outlet end of the separation channel is fixed.

23. The apparatus of claim 22, wherein the distance between the thick-film electrode and the outlet end of the separation channel is from about 1 μ

m to about 500 μ

m.

24. The apparatus of claim 23, wherein the distance is between about 50 μ

m and about 100 μ

m.

25. The apparatus of claim 1, wherein the thick-film electrode comprises a carbon ink electrode.

26. The apparatus of claim 1, wherein the thick-film electrode comprises a metal conducting coating.

27. The apparatus of claim 1, wherein the thick-film electrode comprises at least one member selected from the group consisting of metals, inorganic dopants, organic dopants, nucleic acids, catalytic surface modifiers, enzymatic surface modifiers, and permselective film coatings.

28. The apparatus of claim 1, further comprising at least one cavity in fluidic connection with the inlet end of the separation channel.

29. The apparatus of claim 28, further comprising a buffer cavity and sample cavity in fluidic connection with the inlet end of the separation channel.

30. The apparatus of claim 28, further comprising a reaction cavity in fluidic connection with the inlet end of the separation channel.

31. The apparatus of claim 28, further comprising a plurality of separation channels with the inlet ends thereof in fluidic connection with at least one cavity.

32. The apparatus of claim 1, further comprising at least one cavity in fluidic connection with the outlet end of the separation channel.

33. The apparatus of claim 1, comprising a plurality of separation channels and a plurality of thick-film electrodes.

34. The apparatus of claim 1, wherein both the first substrate and the second substrate are substantially planar, and the second substrate is at an angle to the first substrate.

35. The apparatus of claim 34, wherein the second substrate is perpendicular to the first substrate.

36. The apparatus of claim 1, wherein both the first substrate and the second substrate are substantially planar and parallel to each other.

37. The apparatus of claim 36, wherein the second substrate forms a seal for at least a portion of the separation channel of the first substrate.

38. The apparatus of claim 1, wherein the separation channel further comprises separation media.

39. A method for detecting an analyte, comprising the steps of:

providing a substrate with a microfluidic channel disposed thereon, the microfluidic channel having an inlet end and an outlet end transiting an exterior edge of the first substrate;

introducing the analyte in the inlet end of the microfluidic channel;

transporting the analyte in a fluid solution through the microfluidic channel to the outlet end;

contacting the solution containing the analyte with a thick-film electrode disposed on a second substrate and in fluidic connection with the outlet end of the microfluidic channel;

providing electrical contact to the thick-film electrode; and

analyzing the analyte at the thick-film electrode by electrochemical detection.

40. The method of claim 39 further comprising the step of:

providing electrical contact to at least one counter electrode in fluidic contact with the thick-film electrode.

41. The method of claim 39 further comprising the steps of:

providing at least one reactant for the analyte; and

mixing the at least one reactant and the analyte prior to analyzing the analyte at the thick-film electrode by electrochemical detection.

42. The method of claim 39, wherein the microfluidic channel comprises a microfluidic separation channel.

43. The method of claim 39, wherein transporting the analyte in a fluid solution through the microfluidic channel is by electrokinetic fluid transport.

44. The method of claim 43, wherein the electrokinetic fluid transport is capillary electrophoresis.

45. The method of claim 39, wherein transporting the analyte in a fluid solution through the microfluidic channel comprises at least one method selected from the group consisting of electrical, mechanical, centrifugal, magnetic, pneumatic, pressure-activated, and vacuum-activated fluid transport.

46. The method of claim 39, wherein analyzing the analyte at the thick-film electrode by electrochemical detection comprises amperometric detection.

47. The method of claim 46, wherein the amperometric detection comprises at least one member selected from the group consisting of fixed potential and potential-step amperometric detection.

48. The method of claim 39, wherein analyzing the analyte at the thick-film electrode by electrochemical detection comprises at least one member selected from the group consisting of stripping potentiometry and voltammetric detection.

49. The method of claim 39, wherein the thick-film electrode is a screen-printed electrode.

50. The method of claim 39, wherein the microfluidic channel has an average bore diameter of from about 1 μ

m to about 300 μ

m.

51. The method of claim 50, wherein the microfluidic channel has an average bore diameter of from about 20 μ

m to about 120 μ

m.

52. The method of claim 39, wherein the thick-film electrode has a thickness of from about 1 μ

m to about 100 μ

m.

53. The method of claim 52, wherein the thickness of the thick-film electrode is between about 8 μ

m and 30 μ

m.

54. The method of claim 39, wherein the distance between the thick-film electrode in fluidic connection with the outlet end of the microfluidic channel and the microfluidic channel is fixed.

55. The method of claim 54, wherein the distance between the thick-film electrode and the outlet end of the microfluidic channel is from about 1 μ

m to about 500 μ

m.

56. The method of claim 55, wherein the distance is between about 50 μ

m and about 100 μ

m.

57. The method of claim 39, wherein the thick-film electrode comprises a carbon ink electrode.

58. The method of claim 39, wherein the thick-film electrode comprises a metal conducting coating.

59. The method of claim 39, wherein the thick-film electrode comprises at least one member selected from the group consisting of metals, inorganic dopants, organic dopants, nucleic acids, catalytic surface modifiers, enzymatic surface modifiers, and permselective film coatings.

60. The method of claim 39, wherein the fluid solution comprises a buffer solution.

61. The method of claim 39, wherein the analyte comprises at least one member selected from the group consisting of nitroaromatic compounds, catecholamines, hydrazine compounds, phenolic compounds, enzyme-specific compounds, amino acids, nucleic acids, metal ions and anions.

62. The method of claim 61, wherein said nucleic acids are selected from the group consisting of DNA, scDNA, ssDNA, dsDNA, RNA and tRNA.

63. The method of claim 39, wherein the microfluidic channel further comprises separation media.

64. An apparatus for conducting a microfluidic process and analysis, said apparatus comprising:

a first substantially planar substrate having at least one defined edge;

at least one elongated separation channel in the first substrate, the separation channel having an inlet end and an outlet terminating at a defined edge;

a second substrate with at least one thick-film electrode for analyte detection disposed thereon, the second substrate being removably positionable at a non-zero angle with respect to the first substrate and the thick-film electrode being in fluidic connection with the outlet end of the separation channel.

65. The apparatus of claim 64, wherein the second substrate is removably positionable perpendicular to the first substrate.

66. The apparatus of claim 64, further comprising a holder for holding the first substrate in a removably positionable position with respect to the second substrate.

67. The apparatus of claim 66, wherein the first substrate is attached to the holder and the second substrate is removably attached to the holder.

68. The apparatus of claim 66, wherein the first substrate and the second substrate are removably attached to the holder.

69. The apparatus of claim 64, further comprising a conductive system in fluidic connection with each end of the separation channel for application of a separation voltage.

70. The apparatus of claim 64, further comprising an electrokinetic fluid transport system.

71. The apparatus of claim 64, further comprising a fluidic transport means for transport of fluid through the separation channel comprising at least one means elected from the group consisting of electrical, mechanical, centrifugal, magnetic, pneumatic, pressure-activated, and vacuum-activated fluid transport.

72. The apparatus of claim 64, further comprising at least one reference electrode in fluidic connection with the thick-film electrode.

73. The apparatus of claim 64, wherein the thick-film electrode is a screen-printed electrode.

74. The apparatus of claim 64, wherein the thick-film electrode has a thickness of from about 1 μ

m to about 100 μ

m.

75. The apparatus of claim 74, wherein the thickness of the thick-film electrode is between about 8 μ

m and 30 μ

m.

76. The apparatus of claim 64, wherein the second substrate is adjustably positionable relative to the first substrate such that the distance between the thick-film electrode and the outlet of the separation channel is variably and adjustably positionable.

77. The apparatus of claim 76, wherein the distance between the thick-film electrode and the outlet of the separation channel is from about 1 μ

m to about 500 μ

m.

78. The apparatus of claim 77, wherein the distance is between about 50 μ

m and about 100 μ

m.

79. The apparatus of claim 64, wherein the thick-film electrode comprises a carbon ink electrode.

80. The apparatus of claim 64, wherein the thick-film electrode comprises a metal conducting coating.

81. The apparatus of claim 64, wherein the thick-film electrode comprises at least one member selected from the group consisting of metals, inorganic dopants, organic dopants, nucleic acids, catalytic surface modifiers, enzymatic surface modifiers, and permselective film coatings.

82. The apparatus of claim 64, comprising a plurality of separation channels and a plurality of thick-film electrodes.