Microfluidic devices incorporating improved channel geometries

• US 5,976,336 A
• Filed: 04/25/1997
• Issued: 11/02/1999
• Est. Priority Date: 04/25/1997
• Status: Expired due to Term

• Current Assignee: Caliper Holdings Incorporated
• Original Assignee: Caliper Holdings Incorporated
• Inventors: Kennedy, Colin B., Dubrow, Robert S., Bousse, Luc J.
• Primary Examiner(s): Beisner, William H.
• Application Number:
  US08/845,754
• Time in Patent Office: 921 Days
• Field of Search: 204/451, 204/453, 204/455, 204/601, 204/604, 204/605, 435/297.2, 435/288.5, 435/297.3, 435/6, 210/198.2, 210/198.3, 210/656, 210/658, 422/68.1, 422/70, 422/100, 422/102, 436/89, 436/90, 436/94
• US Class Current: 204/453
• CPC Class Codes: B01L 2200/0605 Metering of fluids
• CPC Class Codes: B01L 2300/0816 Cards, e.g. flat sample carriers usually with flow in two horizontal directions
• CPC Class Codes: B01L 2300/0829 Multi-well plates; Microtitration plates
• CPC Class Codes: B01L 2300/0861 Configuration of multiple channels and/or chambers in a single devices
• 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 3/50273 characterised by the means or forces applied to move the fluids micropumps F04B19/006, of the membrane type F04B43/043
• CPC Class Codes: B01L 3/502753 characterised by bulk separation arrangements on lab-on-a-chip devices, e.g. for filtration or centrifugation separation in general B01D; microapparatus for analysis using electrophoresis G01N27/44791; sample preparation G01N1/28
• CPC Class Codes: B01L 3/502784 specially adapted for droplet or plug flow, e.g. digital microfluidics automatic analysis using a stream of discrete samples in a tube system G01N35/08
• CPC Class Codes: G01N 27/44791 Microapparatus sample containers with integrated microfluidic structures B01L3/5027
• CPC Class Codes: Y10T 436/143333 Saccharide [e.g., DNA, etc.]

Abstract

The present invention generally provides microfluidic devices which incorporate improved channel and reservoir geometries, as well as methods of using these devices in the analysis, preparation, or other manipulation of fluid borne materials, to achieve higher throughputs of such materials through these devices, with lower cost, material and/or space requirements.

Claims

1. A microfluidic system, comprising:

a planar substrate having a first surface;

an analysis channel disposed in said substrate;

a sample loading channel disposed in said substrate and in fluid communication and crossing said analysis channel at a first intersection;

a plurality of separate sample sources in fluid communication with said sample loading channel, whereby there is at least one of said plurality of separate sample sources in fluid communication with said sample loading channel on each side of said first intersection; and

first and second load/waste channels disposed in said substrate, each of said first and second load/waste channels intersecting said sample loading channel at second and third intersections, respectively, said second and third intersections being on different sides of said first intersection.

2. The microfluidic system of claim 1, wherein said second and third intersections are each within 5 mm of said first intersection.

3. The microfluidic system of claim 1, wherein said second and third intersections are each within 2 mm of said first intersection.

4. The microfluidic system of claim 1, wherein said second and third intersections are each within 1 mm of said first intersection.

5. The microfluidic system of claim 1, wherein there are at least two sample sources in fluid communication with said sample loading channel on the same side of said first intersection, and said first load/waste channel intersects said sample loading channel at a point between said first intersection and a point at which either of said at least two sample sources are in fluid communication with said sample loading channel.

6. The microfluidic system of claim 1, wherein said plurality of sample sources comprises at least four separate sample sources.

7. The microfluidic system of claim 6, wherein at least two separate sample sources are in fluid communication with said sample loading channel on each side of said first intersection.

8. The microfluidic system of claim 1, wherein said analysis channel comprises a buffer reservoir in fluid communication with a first terminus of said analysis channel, first and second waste reservoirs disposed at termini of the first and second load/waste channels, respectively, and a third waste reservoir in fluid communication with a second terminus of said analysis channel.

9. The microfluidic system of claim 1, wherein said substrate comprises silica.

10. The microfluidic system of claim 1, wherein said substrate comprises:

a first planar member having a first surface, wherein each of said analysis channel, sample loading channel and first and second load waste channels comprise grooves disposed in said first surface; and

a second planar member overlaying and sealably covering said first surface.

11. The microfluidic system of claim 10, wherein each of said plurality of sample sources comprises a separate hole disposed through said second planar member, and in fluid communication with a separate sample channel when said second planar member is overlaying said first planar member, said separate sample channel being in fluid communication with said sample loading channel.

12. The microfluidic system of claim 1, wherein each of said separate sample sources comprises a sample fluid reservoir disposed in said substrate and in fluid communication with said sample loading channel.

13. The microfluidic system of claim 1, wherein said analysis channel comprises a separation medium disposed therein.

14. A microfluidic system, comprising:

a planar substrate having a first surface;

an analysis channel disposed in said substrate;

a sample loading channel disposed in said substrate and in fluid communication and crossing said analysis channel at a first intersection;

at least six separate sample sources in fluid communication with said sample loading channel, whereby there is at least one of said at least six sample sources in fluid communication with said sample loading channel on each side of said first intersection; and

first and second load/waste channels disposed in said substrate, each of said first and second load/waste channels intersecting said sample loading channel at second and third intersections, respectively, said second and third intersections being on different sides of said first intersection.

15. The microfluidic system of claim 14, wherein at least three separate sample sources are in fluid communication with said sample loading channel on each side of said first intersection.

16. The microfluidic system of claim 14, comprising at least eight separate sample sources.

17. The microfluidic system of claim 16, wherein at least four separate sample sources are in fluid communication with said sample loading channel on each side of said first intersection.

18. A microfluidic system, comprising:

a planar substrate having a first surface;

an analysis channel disposed in said substrate;

a sample loading channel disposed in said substrate and in fluid communication and crossing said analysis channel at a first intersection;

a plurality of separate sample fluid reservoirs disposed in said substrate and in fluid communication with said sample loading channel, whereby there is at least one of said plurality of sample sources in fluid communication with said sample loading channel on each side of said first intersection, and wherein a distance from each of said sample fluid reservoirs to said first intersection via said loading channel is less than two centimeters; and

first and second load/waste channels disposed in said substrate, each of said first and second load/waste channels intersecting said sample loading channel at second and third intersections, respectively, said second and third intersections being on different sides of said first intersection.

19. The microfluidic system of claim 18, wherein a distance from each of said plurality of sample fluid reservoirs to said first intersection via said loading channel is less than one centimeter.

20. A microfluidic system, comprising:

a planar substrate having a first surface;

an analysis channel disposed in said substrate;

a sample loading channel disposed in said substrate and in fluid communication and crossing said analysis channel at a first intersection;

a plurality of separate sample sources in fluid communication with said sample loading channel, whereby there is at least one of said plurality of sample sources in fluid communication with said sample loading channel on each side of said first intersection; and

first and second load/waste channels disposed in said substrate, each of said first and second load/waste channels intersecting said sample loading channel at second and third intersections, respectively, said second and third intersections being on different sides of said first intersection;

wherein said analysis channel comprises a buffer reservoir in fluid communication with a first terminus of said analysis channel, first and second waste reservoirs disposed at termini of the first and second load/waste channels, respectively, and a third waste reservoir in fluid communication with a second terminus of said analysis channel; and

a material direction system for transporting a sample material from each of said plurality of sample through said sample loading channel and into one of said first and second waste reservoirs.

21. The microfluidic system of claim 20, wherein said material direction system comprises:

a different electrode placed in electrical contact with each of said plurality of different sample sources, said first, second and third waste reservoirs and said buffer reservoir; and

a voltage source for applying a voltage at each of said different electrodes.

22. A microfluidic system, comprising:

a planar substrate;

an analysis channel disposed in said substrate;

a sample loading channel disposed in said substrate and in fluid communication and crossing said analysis channel at a first intersection;

a plurality of separate sample sources in fluid communication with said sample loading channel, whereby there is at least one of said plurality of sample sources in fluid communication with said sample loading channel on each side of said first intersection; and

first and second load/waste channels disposed in said substrate, each of said first and second load/waste channels intersecting said sample loading channel at second and third intersections, respectively, said second and third intersections being on different sides of said first intersection; and

a material direction system for transporting sample material from each of said plurality of sample sources and injecting at least a portion of said sample material into said analysis channel.

23. The microfluidic system of claim 22, wherein the substrate comprises silica.

24. The microfluidic system of claim 22, wherein the substrate comprises a polymer.

25. The microfluidic system of claim 24, wherein the substrate comprises a polymer selected from polydimethylsiloxane, polymethylmethacrylate, polyurethane, polyvinylchloride, polystyrene, polysulfone, and polycarbonate.

26. The microfluidic system of claim 25, wherein the substrate comprises polymethylmethacrylate.

27. The microfluidic system of claim 22, wherein the analysis channel comprises a sieving matrix disposed therein.

28. The microfluidic system of claim 27, wherein the sieving matrix comprises a linear polyacrylamide polymer.

29. The microfluidic system of claim 28, wherein the linear polyacrylamide polymer comprises a charged polymer.

30. The microfluidic system of claim 22, wherein the plurality of sample sources comprises a plurality of separate sample fluid reservoirs disposed in the substrate.

31. The microfluidic system of claim 22, wherein each of the analysis channel, sample loading channel and load/waste channels comprises at least one cross-sectional dimension between about 1 and 100 μ

m.

32. The microfluidic system of claim 22, wherein the plurality of sample sources comprises at least four separate sample sources.

33. The microfluidic system of claim 22, wherein the plurality of sample sources comprises at least eight separate sample sources.

34. A microfluidic system, comprising:

a planar substrate having a first surface;

an analysis channel disposed in said substrate;

a sample loading channel disposed in said surface on a first side of said analysis channel, and intersecting said analysis channel at a first intersection;

a plurality of sample reservoirs in fluid communication with said sample loading channel on said first side of said analysis channel;

a waste channel disposed in said substrate on a second side of said analysis channel, and intersecting said analysis channel at a second intersection; and

a waste reservoir in fluid communication with said waste channel on said second side of said analysis channel; and

wherein said plurality of sample reservoirs comprises at least four separate sample reservoirs.

35. The microfluidic system of claim 34, wherein said plurality of sample sources comprises at least six separate sample reservoirs.

36. The microfluidic system of claim 34, wherein said plurality of sample sources comprises at least eight separate sample reservoirs.

37. The microfluidic system of claim 34, wherein the substrate comprises silica.

38. The microfluidic system of claim 34, wherein the substrate comprises a polymer.

39. The microfluidic system of claim 38, wherein the substrate comprises a polymer selected from polydimethylsiloxane, polymethylmethacrylate, polyurethane, polyvinylchloride, polystyrene, polysulfone, and polycarbonate.

40. The microfluidic system of claim 39, wherein the substrate comprises polymethylmethacrylate.

41. The microfluidic system of claim 34, wherein the analysis channel comprises a sieving matrix disposed therein.

42. The microfluidic system of claim 41, wherein the sieving matrix comprises a linear polyacrylamide polymer.

43. The microfluidic system of claim 42, wherein the linear polyacrylamide polymer comprises a charged polymer.

44. The microfluidic system of claim 34, wherein each of the analysis channel, sample loading channel and load/waste channels comprises at least one cross-sectional dimension between about 1 and 100 μ

m.

45. The microfluidic system of claim 34, wherein the plurality of sample reservoirs comprises at least eight separate sample reservoirs.

46. A microfluidic system, comprising:

a planar substrate having a first surface;

an analysis channel disposed in said substrate;

first and second transverse channels, said first transverse channel being disposed in said substrate on a first side of said analysis channel, and intersecting said analysis channel at a first intersection, and said second transverse channel being disposed in said substrate on a second side of said analysis channel, and intersecting said analysis channel at a second intersection;

a first sample source in fluid communication with said first transverse channel;

at least a second sample source in fluid communication with said second transverse channel;

a first waste channel intersecting said first transverse channel at a third intersection;

at least a second waste channel intersecting said second transverse channel at a fourth intersection; and

a material direction system for individually transporting a sample from each of said first and second sample sources to said first and second waste channels via said first and second transverse channels, respectively, and selectively injecting said samples into said analysis channel.

47. The microfluidic system of claim 46, wherein said first and second intersections are located at the same point along said analysis channel.

48. The microfluidic system of claim 46, wherein the substrate comprises silica.

49. The microfluidic system of claim 46, wherein the substrate comprises a polymer.

50. The microfluidic system of claim 49, wherein the substrate comprises a polymer selected from polydimethylsiloxane, polymethylmethacrylate, polyurethane, polyvinylchloride, polystyrene, polysulfone, and polycarbonate.

51. The microfluidic system of claim 50, wherein the substrate comprises polymethylmethacrylate.

52. The microfluidic system of claim 46, wherein the analysis channel comprises a sieving matrix disposed therein.

53. The microfluidic system of claim 52, wherein the sieving matrix comprises a linear polyacrylamide polymer.

54. The microfluidic system of claim 53, wherein the linear polyacrylamide polymer comprises a charged polymer.

55. The microfluidic system of claim 46, further comprising at least a third sample source in fluid communication with the first transverse channel.

56. The microfluidic system of claim 55, further comprising at least a fourth sample source in fluid communication with the second transverse channel.

57. The microfluidic system of claim 56, wherein each of the analysis channel, first and second transverse channels comprises at least one cross-sectional dimension between about 1 and 100 μ

m.

58. A microfluidic system, comprising:

a planar substrate having a first surface;

an analysis channel disposed in said substrate;

first and second transverse channels, said first transverse channel being disposed in said substrate on a first side of said analysis channel, and intersecting said analysis channel at a first intersection, and said second transverse channel being disposed in said surface on a second side of said analysis channel, and intersecting said analysis channel at a second intersection;

a plurality of sample sources in fluid communication with said first transverse channel;

a first waste channel intersecting said first transverse channel at a third intersection;

at least a second waste channel intersecting said second transverse channel at a fourth intersection; and

a material direction system for individually transporting a sample from each of said plurality of sample sources to said first and second waste channels via said first and second transverse channels, respectively, and selectively injecting said samples into said analysis channel.

59. The microfluidic system of claim 58, wherein said first and second intersections are located at the same point along said analysis channel.

60. The microfluidic system of claim 58, wherein the substrate comprises silica.

61. The microfluidic system of claim 58, wherein the substrate comprises a polymer.

62. The microfluidic system of claim 61, wherein the substrate comprises a polymer selected from polydimethylsiloxane, polymethylmethacrylate, polyurethane, polyvinylchloride, polystyrene, polysulfone, and polycarbonate.

63. The microfluidic system of claim 62, wherein the substrate comprises polymethylmethacrylate.

64. The microfluidic system of claim 58, wherein the analysis channel comprises a sieving matrix disposed therein.

65. The microfluidic system of claim 64, wherein the sieving matrix comprises a linear polyacrylamide polymer.

66. The microfluidic system of claim 65, wherein the linear polyacrylamide polymer comprises a charged polymer.

67. The microfluidic system of claim 58, wherein the plurality of sample sources in fluid communication with the first transverse channel comprises at least four separate sample sources.

68. The microfluidic system of claim 58, wherein the plurality of sample sources in fluid communication with the first transverse channel comprises at least six separate sample sources.

69. The microfluidic system of claim 66, wherein each of the analysis channel, first and second transverse channels comprises at least one cross-sectional dimension between about 1 and 100 μ

m.

70. A method of analyzing a plurality of different sample materials, comprising:

providing a microfluidic device which comprises;

a planar substrate having a first surface;

an analysis channel disposed in said substrate;

a sample loading channel disposed in said substrate and intersecting said analysis channel at a first intersection, wherein said sample loading channel crosses said analysis channel; and

at least first and second sample sources in fluid communication with said sample loading channel;

a waste reservoir in fluid communication on a same side of said first intersection as said second sample source;

transporting a first sample from a first of said plurality of sample sources, through said sample loading channel to said first intersection;

injecting a portion of said first sample into said analysis channel;

analyzing said first sample in said analysis channel;

transporting said second sample through said sample loading channel and into said waste reservoir; and

injecting a portion of said second sample into said analysis channel.

71. The method of claim 70, wherein said step of transporting said second sample through said sample loading channel and into said waste reservoir is carried out substantially concurrently with said step of analyzing said first sample.

72. The method of claim 70, wherein each of said first and second samples comprises a plurality of nucleic acid fragments and said analysis channel comprises a sieving matrix.

73. The method of claim 70, wherein the step of transporting the first sample comprises electrokinetically transporting the first sample from the first sample source, through the sample loading channel to the intersection.

74. The method of claim 70, wherein the step of analyzing the first sample comprises separating the first sample into constituent elements and detecting the constituent elements.

75. The method of claim 74, wherein the first sample comprises proteins.

76. A method of performing analysis on a plurality of different sample materials, comprising:

providing a microfluidic device which comprises;

a planar substrate having a first surface;

an analysis channel disposed in said substrate;

a sample loading channel disposed in said substrate and intersecting said analysis channel at a first intersection; and

a sample preloading module which comprises at least first and second sample reservoirs and a waste reservoir, wherein each of said plurality of sample reservoirs and said waste reservoir are in fluid communication with said sample loading channel;

transporting a first sample from said first sample reservoir to said first intersection;

injecting a portion of said first sample into said analysis channel;

concurrently analyzing said portion of said first sample in said analysis channel and transporting a second sample from said second sample reservoir into said loading channel and then to said waste reservoir;

transporting said second sample from said loading channel to said intersection;

injecting a portion of said second sample into said analysis channel; and

analyzing said portion of said second sample in said analysis channel.

77. The method of claim 76, wherein the step of transporting the first sample comprises electrokinetically transporting the first sample from the first sample source, through the sample loading channel to the intersection.

78. The method of claim 76, wherein the step of analyzing the first sample comprises separating the first sample into constituent elements and detecting the constituent elements.

79. The method of claim 78, wherein the first sample comprises proteins.

80. The method of claim 76, wherein the sample preloading module further comprises at least a third sample reservoir in fluid communication with the sample loading channel, and further comprising the step of transporting a third sample from said third sample reservoir into said loading channel and then to said waste reservoir, concurrently with the step of analyzing said portion of said second sample in said analysis channel.

81. The method of claim 80, wherein the sample preloading module further comprises at least a fourth sample reservoir in fluid communication with the sample loading channel, and further comprising:

injecting a portion of the third sample into said analysis channel;

analyzing the portion of the third sample in the analysis channel; and

transporting a fourth sample from said fourth sample reservoir into said loading channel and then to said waste reservoir, concurrently with the step of analyzing said portion of said third sample in said analysis channel.