Microfluidic library analysis

• US 20020187564A1
• Filed: 05/31/2002
• Published: 12/12/2002
• Est. Priority Date: 06/08/2001
• Status: Abandoned Application

• Current Assignee: Caliper Life Sciences Incorporated (Revvity, Inc.)
• Original Assignee: Caliper Technologies Corp (Revvity, Inc.)
• Inventors: Parce, J. Wallace, Chow, Calvin Y.H.
• Application Number:
  US10/159,606
• Publication Number:
  US 20020187564A1
• Time in Patent Office: Days
• US Class Current: 436/518
• CPC Class Codes: B01J 2219/00596 Solid-phase processes
• CPC Class Codes: B01J 2219/00605 the compounds being directly bound or immobilised to solid supports
• CPC Class Codes: B01J 2219/00659 Two-dimensional arrays
• CPC Class Codes: B01J 2219/0072 Organic compounds
• 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 2200/16 Reagents, handling or storing thereof
• CPC Class Codes: B01L 2300/0816 Cards, e.g. flat sample carriers usually with flow in two horizontal directions
• CPC Class Codes: B01L 2300/0861 Configuration of multiple channels and/or chambers in a single devices
• CPC Class Codes: B01L 2300/1827 using resistive heater
• CPC Class Codes: B01L 2400/0415 electrical forces, e.g. electrokinetic
• 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

Abstract

The present invention provides novel microfluidic devices and methods for storing, reconstituting and accessing one or more library of assay components within library storage elements in a microfluidic device. In particular, the devices and methods of the invention are useful in screening large libraries of molecules.

Claims

1. A microfluidic device comprising:

(i) a body structure;

(ii) a plurality of dried or immobilized library storage elements located on or within the body structure; and

,

(ii) a plurality of microscale channels located within the body structure, at least one of the plurality of microscale channels being fluidly coupled to the plurality of library storage elements.

2. The microfluidic device of claim 1, wherein the library storage elements are contained within one or more microscale reservoirs.

3. The microfluidic device of claim 2, wherein the one or more microscale reservoirs comprise a largest dimension, which largest dimension is less than about 5 mm.

4. The microfluidic device of claim 3, wherein the largest dimension is less than about 1 mm.

5. The microfluidic device of claim 4, wherein the largest dimension is less than about 500 μ

m.

6. The microfluidic device of claim 5, wherein the largest dimension is about 300 μ

m or less.

7. The microfluidic device of claim 2, wherein the one or more microscale reservoirs is disposed within a surface of the body structure of the microfluidic device.

8. The microfluidic device of claim 7, wherein the one or more microscale reservoirs is disposed within an upper surface of body structure of the microfluidic device.

9. The microfluidic device of claim 1, wherein the plurality of library storage elements comprises at least about 10 to about 1,000,000 or more library storage elements.

10. The microfluidic device of claim 9, wherein the plurality of library storage elements comprises at least about 100 to about 100,000 or more library storage elements.

11. The microfluidic device of claim 10, wherein the plurality of library storage elements comprises at least about 1,000 to about 10,000 or more library storage elements.

12. The microfluidic device of claim 1, wherein the plurality of library storage elements comprises at least about 60,000 to about 600,000 or more library storage elements.

13. The microfluidic device of claim 1, wherein the plurality of library storage elements comprises a density of at least about 5 to about 10,000 or more library storage elements per square centimeter of the body structure.

14. The microfluidic device of claim 13, wherein the plurality of library storage elements comprises a density of at least about 100 to about 5,000 or more library storage elements per square centimeter.

15. The microfluidic device of claim 14, wherein the plurality of library storage elements comprises a density of at least about 1,000 to about 2,500 or more library storage elements per square centimeter.

16. The microfluidic device of claim 13, wherein the plurality of library storage elements comprises a density of at least about 100 to about 500 or more library storage elements per square centimeter.

17. The microfluidic device of claim 13, wherein the plurality of library storage elements comprises a density of at least about 400 to about 4,000 or more library storage elements per square centimeter.

18. The microfluidic device of claim 1, wherein at least one member of the plurality of library storage elements comprises a dried or immobilized test compound.

19. The microfluidic device of claim 1, wherein substantially all members of the plurality of library storage elements comprise a different dried or immobilized test compound.

20. The microfluidic device of claim 1, wherein the plurality of library storage elements comprises a library of test compounds.

21. The microfluidic device of claim 1, wherein at least one member of the plurality of microscale channels includes a fluidic material contained within the microscale channel.

22. The microfluidic device of claim 21, wherein substantially all members of the plurality of microscale channels comprise a fluidic material contained within the microscale channels.

23. The microfluidic device of claim 21, wherein the fluidic material comprises a buffer.

24. The device of claim 1, wherein at least one member of the plurality of library storage elements comprises a dried or immobilized test compound and at least one member of the plurality of microscale channels comprises a fluidic material, which fluidic material contacts the dried or immobilized test compound.

25. The device of claim 1, wherein at least one member of the plurality of library storage elements comprises a dried or immobilized test compound and at least one member of the plurality of microscale channels comprises a fluidic material, which fluidic material contacts the dried or immobilized test compound, which compound has been reconstituted by at least a second fluidic material.

27. The microfluidic system of claim 26, wherein the library storage elements are contained within one or more microscale reservoirs.

28. The microfluidic system of claim 27, wherein the microscale reservoirs comprise a largest dimension, which largest dimension is less than about 5 mm.

29. The microfluidic system of claim 28, wherein the largest dimension is less than about 1 mm.

30. The microfluidic system of claim 29, wherein the largest dimension is less than about 500 μ

m.

31. The microfluidic system of claim 30, wherein the largest dimension is about 300 μ

m or less.

32. The microfluidic system of claim 27, wherein the plurality of microscale reservoirs is disposed within a surface of the body structure.

33. The microfluidic system of claim 32, wherein the plurality of microscale reservoirs is disposed within an upper surface of the body structure.

34. The microfluidic system of claim 26, wherein the plurality of library storage elements comprises at least about 10 to about 1,000,000 or more library storage elements.

35. The microfluidic system of claim 34, wherein the plurality of library storage elements comprises at least about 100 to about 100,000 or more library storage elements.

36. The microfluidic system of claim 35, wherein the plurality of library storage elements comprises at least about 1,000 to about 10,000 or more library storage elements.

37. The microfluidic system of claim 34, wherein the plurality of library storage elements comprises at least about 60,000 to about 600,000 or more library storage elements.

38. The microfluidic system of claim 26, wherein the plurality of library storage elements comprises a density of about 5 to about 10,000 or more library storage elements per square centimeter of the body structure

39. The microfluidic system of claim 38, wherein the plurality of library storage elements comprises a density of at least about 100 to about 5,000 or more library storage elements per square centimeter.

40. The microfluidic system of claim 39, wherein the plurality of library storage elements comprises a density of at least about 1,000 to about 2,500 or more library storage elements per square centimeter.

41. The micro fluidic system of claim 39, wherein the plurality of library storage elements comprises a density of at least about 100 to about 500 or more library storage elements per square centimeter.

42. The microfluidic system of claim 38, wherein the plurality of library storage elements comprises a density of at least about 400 to about 4,000 or more library storage elements per square centimeter.

43. The microfluidic system of claim 26, wherein at l east one member of the plurality of library storage elements comprises a dried or immobilized test compound.

44. The microfluidic system of claim 26, wherein substantially all members of the plurality of library storage elements comprise a different dried or immobilized test compound.

45. The microfluidic system of claim 26, wherein the plurality of library storage elements comprises a library of test compounds.

46. The microfluidic system of claim 26, wherein at least one member of the plurality of microscale channels contains a fluidic material disposed therein.

47. The microfluidic system of claim 46, wherein substantially all members of the plurality of microscale channels contains a fluidic material disposed therein.

48. The microfluidic system of claim 46, wherein the fluidic material comprises a buffer material.

49. The microfluidic system of claim 26, wherein the fluid delivery system includes a pipettor device.

50. The microfluidic system of claim 26, wherein the fluid comprises a buffer material.

51. The microfluidic system of claim 26, wherein the fluid comprises less than about 20 microliters.

52. The microfluidic system of claim 51, wherein the fluid comprises less than about 5 microliters.

53. The microfluidic system of claim 52, wherein the fluid comprises less than about 1 microliter.

54. The microfluidic system of claim 53, wherein the fluid comprises less than about 200 nanoliters.

55. The microfluidic system of claim 54, wherein the fluid comprises less than about 50 nanoliters.

56. The microfluidic system of claim 55, wherein the fluid comprises less than about 10 nanoliters.

57. The microfluidic system of claim 56, wherein the fluid comprises less than about 2 nanoliters.

58. The microfluidic system of claim 57, wherein the fluid comprises about 1 nanoliter or less.

59. The microfluidic system of claim 26, wherein the fluid delivery system simultaneously delivers the fluid to at least about 2 to about 1,000,000 or more library storage elements.

60. The microfluidic system of claim 59, wherein the fluid is simultaneously delivered to at least about 5 or more library storage elements.

61. The microfluidic system of claim 26, wherein the fluid delivery system delivers the fluid to one or more member of the plurality of library storage elements about every 1 minute or less.

62. The microfluidic system of claim 61, wherein the fluid is delivered about every 30 seconds or less.

63. The microfluidic system of claim 65, wherein the fluid is delivered about every 10 seconds or less.

64. The microfluidic system of claim 66, wherein the fluid is delivered about every 5 seconds or less.

65. The microfluidic system of claim 67, wherein the fluid is delivered about every 1 second or less.

66. The microfluidic system of claim 27, wherein the fluid direction system directs:

(i) movement of a first fluidic material through at least a first microscale channel of the plurality of microscale channels to at least a first microscale reservoir which is fluidly connected to at least the first microscale channel; and

(ii) delivery of a second fluidic material to the first microscale reservoir.

67. The microfluidic system of claim 66 wherein the first fluidic material is directed to contact at least one dried or immobilized test compound disposed within the first microscale reservoir.

68. The microfluidic system of claim 67 wherein at least one of the first and second fluidic materials reconstitutes the at least one dried or immobilized test compound.

70. The method of claim 69 wherein the first fluidic material contacts the at least first test compound disposed within the first microscale reservoir.

71. The method of claim 70 further comprising delivering a second fluidic material into at least the first microscale reservoir.

72. The method of claim 71 wherein at least one of the first or second fluidic material reconstitutes the at least first test compound to make the test compound flowable.

73. The method of claim 69 further comprising reconstituting the first test compound prior to said (ii) flowing step

79. The method of claims 71 or 76 further comprising delivering the second fluidic material into at least the first microscale reservoir or test channel by hand pipetting or by robotic pipetting.

80. The method of claim 69, wherein the (ii) and (iii) flowing steps comprise flowing the first fluidic material electrokinetically or by pressure-based flow.

82. The method of claims 71 or 76 wherein the second fluidic material dissolves the first test compound.

83. The method of claim 71 wherein the first fluidic material and the second fluidic material comprise the same material.

84. The method of claim 83, wherein the first fluidic material and the second fluidic material each comprise a buffer material.

26. A microfluidic system, the system comprising:

(i) a body structure having a plurality of microscale channels disposed therein and a plurality of dried or immobilized library storage elements disposed on or within the body structure, at least one of the microscale channels being fluidly connected to the plurality of library storage elements; and

,

(ii) a fluid delivery system operable to deliver at least a first fluid to at least one or more member of the plurality of library storage elements.

69. A method of loading at least a first test compound located within at least a first one of a plurality of microscale reservoirs into a microchannel system, which plurality of microscale reservoirs is fluidly coupled to the microchannel system, the method comprising:

(i) providing the at least first test compound in a dried or immobilized format in the at least first one of the plurality of microscale reservoirs;

(ii) flowing at least a first fluidic material into the at least first microscale reservoir; and

(iii) flowing the first fluidic material from at least the first microscale reservoir through at least a first microchannel into the microchannel system, thereby loading at least the first test compound into the microchannel system.

81. The method of claims 69 or 74 wherein the first fluidic material dissolves the first test compound.

85. The method of claims 69 or 74 further comprising repeating steps (i) through (iii) for at least one or more test compounds.

74. A method of loading at least a first test compound from at least a first one of a plurality of microscale test channels into a microchannel system, which plurality of microscale test channels is fluidly coupled to the microchannel system, the method comprising:

(i) providing the at least first test compound in a dried or immobilized format within the at least first one of the plurality of microscale test channels;

(ii) flowing at least a first fluidic material into the at least first microscale test channel; and

(iii) flowing the first fluidic material from at least the first microscale test channel through at least a first microchannel into the microchannel system, thereby loading at least the first test compound into the microchannel system.

75. The method of claim 74 wherein the first fluidic material contacts the at least first test compound disposed within the first microscale test channel.

76. The method of claim 75 further comprising delivering a second fluidic material into at least the first microscale test channel.

77. The method of claim 76 wherein at least one of the first or second fluidic material reconstitutes the at least first test compound to make the test compound flowable.

78. The method of claim 74 further comprising reconstituting the first test compound prior to said (ii) flowing step

86. A microfluidic device comprising:

(i) a body structure;

(ii) a plurality of dried or immobilized test compounds located on or within the body structure; and

,

(ii) a plurality of microscale channels located within the body structure and fluidly coupled to the plurality of test compounds.