System and methods for mixing within a microfluidic device

• US 20030064507A1
• Filed: 07/26/2002
• Published: 04/03/2003
• Est. Priority Date: 07/26/2001
• Status: Abandoned Application

• Current Assignee: Amersham Biosciences (GE Healthcare Technologies, Inc.)
• Original Assignee: Amersham Biosciences (GE Healthcare Technologies, Inc.)
• Inventors: Dues, Lawrence, Dorris, David, Franciskovich, Phillip, Anderson, Clifford Lynde Hunt, Chan, Yuk-Tong, Simonson, Norb, De La Cerda, Alan Paul, Kahn, Peter Albert, Gallagher, Sean, Druyor-Sanchez, Roberta
• Application Number:
  US10/206,841
• Publication Number:
  US 20030064507A1
• Time in Patent Office: Days
• US Class Current: 435/287.2
• CPC Class Codes: B01F 29/80 rotating about a substantially vertical axis
• CPC Class Codes: B01F 31/24 the containers being submitted to a rectilinear movement
• CPC Class Codes: B01F 31/31 using receptacles with deformable parts, e.g. membranes, to which a motion is imparted
• CPC Class Codes: B01F 33/30 Micromixers
• CPC Class Codes: B01F 33/452 using independent floating stirring elements
• 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 2219/00385 Printing
• CPC Class Codes: B01J 2219/00479 Means for mixing reactants or products in the reaction vessels
• CPC Class Codes: B01J 2219/00527 Sheets
• CPC Class Codes: B01J 2219/00576 fluorophore
• CPC Class Codes: B01J 2219/00585 Parallel processes
• 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 2219/0061 The surface being organic
• CPC Class Codes: B01J 2219/00612 the surface being inorganic
• CPC Class Codes: B01J 2219/00619 using hydrophilic or hydrophobic regions
• CPC Class Codes: B01J 2219/00626 Covalent
• CPC Class Codes: B01J 2219/0063 Other, e.g. van der Waals forces, hydrogen bonding
• CPC Class Codes: B01J 2219/00637 by coating it with another layer
• CPC Class Codes: B01J 2219/00644 the porous medium being present in discrete locations, e.g. gel pads
• CPC Class Codes: B01J 2219/00653 : the compounds being bound to electrodes embedded in or on the solid supports
• CPC Class Codes: B01J 2219/00659 : Two-dimensional arrays
• CPC Class Codes: B01J 2219/00664 : Three-dimensional arrays
• CPC Class Codes: B01J 2219/00677 : Ex-situ synthesis followed by deposition on the substrate
• CPC Class Codes: B01J 2219/00711 : Light-directed synthesis
• CPC Class Codes: B01J 2219/00722 : Nucleotides
• CPC Class Codes: B01J 2219/00783 : Laminate assemblies, i.e. the reactor comprising a stack of plates
• CPC Class Codes: B01J 2219/00889 : Mixing
• CPC Class Codes: B01J 2219/00907 : using membranes
• 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 2300/0636 : Integrated biosensor, microarrays
• CPC Class Codes: B01L 2300/0819 : Microarrays; Biochips
• CPC Class Codes: B01L 2300/0877 : Flow chambers
• CPC Class Codes: B01L 2300/123 : Flexible; Elastomeric
• CPC Class Codes: B01L 2400/0415 : electrical forces, e.g. electrokinetic
• CPC Class Codes: B01L 2400/043 : magnetic forces
• CPC Class Codes: B01L 2400/0481 : squeezing of channels or chambers
• 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: B82Y 30/00 : Nanotechnology for materials or surface science, e.g. nanocomposites

Abstract

The present invention provides microfluidic systems comprising microfluidic chambers and mixers, and methods of use. The microfluidic chambers of the present invention comprise a flexible membrane which provides efficient mixing of the solution therein. The present invention also provides a microfluidic chamber in fluidic communication with a micro-disk and a microfluidic chamber comprising a shim such that and a contiguous gap is present between a sample fluid and the chamber membrane. The microfluidic systems find use in the decrease in time for reactions occurring therein.

Claims

1. A microfluidic system comprising:

(a) a microfluidic chamber comprising a flexible membrane adhered to a first surface of a substrate, and a first port; and

(b) a mixer.

3. The microfluidic system of claim 1, wherein said flexible membrane comprises a dome.

4. The microfluidic system of claim 1, wherein said flexible membrane is supported by a reinforcement structure.

5. The microfluidic system of claim 1, wherein said flexible membrane comprises polypropylene.

6. The microfluidic system of claim 1, wherein said mixer is a micro-disk in fluidic communication with said chamber.

10. The microfluidic system of claim 1, wherein said mixer is positioned to apply a force to said flexible membrane.

11. The microfluidic system of claim 10, wherein said force is selected from the group consisting of centrifugal, lateral, rotational, vertical, and horizontal.

12. The microfluidic system of claim 10, wherein said force is a variable force.

13. The microfluidic system of claim 10, wherein said force is directly applied to said flexible membrane.

14. The microfluidic system of claim 10, wherein said force is indirectly applied to said flexible membrane.

15. The microfluidic system of claim 10, wherein said force distorts said flexible membrane.

16. The microfluidic system of claim 10, wherein said mixer is a shaker.

17. The microfluidic system of claim 10, wherein said mixer is a rotator.

18. The microfluidic system of claim 1 or 2, wherein said substrate comprises a material selected from the group consisting of ceramic, glass, silicon, and plastic.

19. The microfluidic system of claim 1 or 2, wherein said substrate comprises an array of capture probes.

20. The microfluidic system of claim 1 or 2, wherein said chamber further encloses an array of capture probes.

21. The microfluidic system of claim 1 or 2, wherein said chamber further comprises a second port.

2. A microfluidic system comprising:

(a) a microfluidic chamber enclosing an area of a first surface of a substrate; and

(b) a micro-disk in fluidic communication with said chamber.

7. The microfluidic system of claim 2 or 6, wherein said micro-disk is regulated by a magnetic field.

8. The microfluidic system of claim 7, wherein said substrate further comprises a magnetic field generator.

9. the microfluidic system of claim 7, wherein said system further comprises a magnetic field generator.

22. A microfluidic system comprising:

(a) a microfluidic chamber comprising a membrane adhered to a first surface of a substrate, a spacer, and a first port; and

(b) a mixer.

23. The microfluidic system of claim 22, wherein said chamber contains a fluid and a contiguous gap between said fluid and said membrane.

24. The microfluidic system of claim 22, wherein said chamber comprises an inner surface comprising hydrophilic and hydrophobic regions.

25. The microfluidic system of claim 22, wherein said spacer comprises a shim comprising a low surface energy plastic.

26. The microfluidic system of claim 25, wherein said plastic is selected from the group consisting of polyolefin and PTFE.

27. The microfluidic system of claim 22, wherein said membrane and said spacer are contiguous.

28. The microfluidic system of claim 22, wherein said mixer is selected from the group consisting of a shaker and a rotator.

29. The microfluidic system of claim 22, wherein said mixer is a micro-disk in fluidic communication with said chamber.

30. The microfluidic system of claim 22, wherein said mixer applies a force selected from the group consisting of centrifugal, lateral, rotational, vertical, and horizontal.

31. The microfluidic system of claim 30, wherein said force is a variable force.

32. The microfluidic system of claim 22, wherein said substrate comprises a material selected from the group consisting of ceramic, glass, silicon, and plastic.

33. The microfluidic system of claim 22, wherein said substrate comprises an array of capture probes.

34. The microfluidic system of claim 22, wherein said chamber further encloses an array of capture probes.

35. The microfluidic system of claim 22, wherein said chamber further comprises a second port.

36. A microfluidic system comprising:

(a) first and second microfluidic chambers comprising a flexible membrane, and first and second substrates, wherein opposite sides of said membrane are adhered to said first and second substrates and enclose first and second areas of said substrates, wherein said first and second areas are in fluidic communication, and one of said chambers comprises a first port; and

(b) a mixer.

38. The microfluidic system of claim 36, wherein said flexible membrane comprises a dome.

39. The microfluidic system of claim 36, wherein said flexible membrane is supported by a reinforcement structure.

40. The microfluidic system of claim 36, wherein said flexible membrane comprises polypropylene.

41. The microfluidic system of claim 36, wherein said mixer is a micro-disk in fluidic communication with said chamber.

45. The microfluidic system of claim 36, wherein said mixer is positioned to apply a force to said flexible membrane.

46. The microfluidic system of claim 45, wherein said force is selected from the group consisting of centrifugal, lateral, rotational, vertical, and horizontal.

47. The microfluidic system of claim 45, wherein said force is a variable force.

48. The microfluidic system of claim 45, wherein said force is directly applied to said flexible membrane.

49. The microfluidic system of claim 45, wherein said force is indirectly applied to said flexible membrane.

50. The microfluidic system of claim 45, wherein said force distorts said flexible membrane.

51. The microfluidic system of claim 45, wherein said mixer is a shaker.

52. The microfluidic system of claim 45, wherein said mixer is a rotator.

53. The microfluidic system of claim 36 or 37, wherein said substrate comprises a material selected from the group consisting of ceramic, glass, silicon, and plastic.

54. The microfluidic system of claim 36 or 37, wherein said substrate comprises an array of capture probes.

55. The microfluidic system of claim 36 or 37, wherein said chamber further encloses an array of capture probes.

56. The microfluidic system of claim 36 or 37, wherein said chamber further comprises a second port.

37. A microfluidic system comprising:

(a) first and second microfluidic chambers comprising a membrane, and first and second substrates, wherein opposite sides of said membrane are adhered to said first and second substrates and enclose first and second areas of said substrates, wherein said first and second areas are in fluidic communication, and one of said chambers comprises a first port; and

(b) a micro-disk in fluidic communication with at least one chamber.

42. The microfluidic system of claim 37 or 41, wherein said micro-disk is regulated by a magnetic field.

43. The microfluidic system of claim 42, wherein said substrate further comprises a magnetic field generator.

44. The microfluidic system of claim 42, wherein said system further comprises a magnetic field generator.

57. A microfluidic system comprising:

(a) first and second microfluidic chambers comprising a flexible membrane, and a substrate, wherein said membrane is adhered to said substrate and encloses first and second areas of said substrate, wherein said first and second areas are in fluidic communication, and one of said chambers comprises a first port; and

(b) a mixer.

59. The microfluidic system of claim 57, wherein said flexible membrane comprises a dome.

60. The microfluidic system of claim 57, wherein said flexible membrane is supported by a reinforcement structure.

61. The microfluidic system of claim 57, wherein said flexible membrane comprises polypropylene.

62. The microfluidic system of claim 57, wherein said mixer is a micro-disk in fluidic communication with said chamber.

66. The microfluidic system of claim 57, wherein said mixer is positioned to apply a force to said flexible membrane.

67. The microfluidic system of claim 66, wherein said force is selected from the group consisting of centrifugal, lateral, rotational, vertical, and horizontal.

68. The microfluidic system of claim 66, wherein said force is a variable force.

69. The microfluidic system of claim 66, wherein said force is directly applied to said flexible membrane.

70. The microfluidic system of claim 66, wherein said force is indirectly applied to said flexible membrane.

71. The microfluidic system of claim 66, wherein said force distorts said flexible membrane.

72. The microfluidic system of claim 66 wherein said mixer is a shaker.

73. The microfluidic system of claim 66, wherein said mixer is a rotator.

74. The microfluidic system of claim 57 or 58, wherein said substrate comprises a material selected from the group consisting of ceramic, glass, silicon, and plastic.

75. The microfluidic system of claim 57 or 58, wherein said substrate comprises an array of capture probes.

76. The microfluidic system of claim 57 or 58, wherein said chamber further encloses an array of capture probes.

77. The microfluidic system of claim 57 or 58, wherein said chamber further comprises a second port.

58. A microfluidic system comprising:

(a) first and second microfluidic chambers comprising a membrane, and a substrate, wherein said membrane is adhered to said substrate and encloses first and second areas of said substrate, wherein said first and second areas are in fluidic communication, and one of said chambers comprises a first port; and

(b) a micro-disk in fluidic communication with at least one chamber.

63. The microfluidic system of claim 58 or 62, wherein said micro-disk is regulated by a magnetic field.

64. The microfluidic system of claim 63, wherein said substrate further comprises a magnetic field generator.

65. the microfluidic system of claim 63, wherein said system further comprises a magnetic field generator.

78. A method of mixing a fluid comprising:

applying a force to a flexible membrane of a microfluidic chamber containing a fluid, whereby said fluid is mixed.

79. The method of claim 78, wherein said flexible membrane is a dome.

80. The method of claim 78, wherein said flexible membrane comprises a reinforcement structure.

81. The method of claim 78, wherein said flexible membrane comprises polypropylene.

82. The method of claim 78, wherein said force is selected from the group consisting of centrifugal, lateral, rotational, vertical, and horizontal.

83. The method of claim 78, wherein said force is a variable force.

84. The method of claim 78, wherein said force is directly applied to said flexible membrane.

85. The method of claim 78, wherein said force is indirectly applied to said flexible membrane.

86. The method of claim 78, wherein said chamber further contains an array of capture probes.

87. The method of claim 78, wherein said force is applied by a mixer.

88. The method of claim 87, wherein said mixer is a shaker.

89. The method of claim 87, wherein said mixer is a rotator.

90. A method of mixing a fluid comprising:

applying a force to a fluid in a microfluidic chamber using a micro-disk in fluidic communication with said chamber, whereby said fluid is mixed.

91. The method of claim 90, wherein said chamber contains an array of capture probes.

92. The method of claim 90, wherein said chamber comprises a flexible membrane.

93. The method of claim 92, wherein said flexible membrane is a dome.

94. The method of claim 92, wherein said flexible membrane comprises a reinforcement structure.

95. The method of claim 92, wherein said flexible membrane comprises polypropylene.

96. The method of claim 90, wherein said force is a variable force.

97. A method of mixing a fluid comprising:

applying a force to a fluid in a microfluidic chamber comprising a membrane adhered to a first surface of a substrate, a spacer, a contiguous gap between said fluid and said membrane, and a first port, whereby said fluid is mixed.

98. The method of claim 97, wherein said chamber comprises an inner surface of hydrophilic and hydrophobic regions.

99. The method of claim 97, wherein said spacer comprises a low surface energy plastic.

100. The method of claim 99, wherein said plastic is selected from the group consisting of polyolefin and PTFE.

101. The method of claim 97, wherein said membrane and said spacer are contiguous.

102. The method of claim 97, wherein said force is a applied by a mixer.

103. The method of claim 102, wherein said mixer is selected from the group consisting of a shaker and rotator.

105. The method of claim 97, wherein said force is a variable force.

106. The microfluidic system of claim 97, wherein said substrate comprises a material selected from the group consisting of ceramic, glass, silicon, and plastic.

107. The microfluidic system of claim 97, wherein said substrate comprises an array of capture probes.

108. The microfluidic system of claim 97, wherein said chamber further encloses an array of capture probes.

109. The microfluidic system of claim 97, wherein said chamber further comprises a second port.

104. The method of 102, wherein said mixer applies a force selected from the group consisting of centrifugal, lateral, rotational, vertical, and horizontal.

110. A microfluidic chamber comprising a flexible membrane adhered to a first surface of a substrate, and a first port.

111. A microfluidic chamber in fluidic communication with a micro-disk.

112. A microfluidic chamber comprising a membrane adhered to a first surface of a substrate, a spacer, and a first port.

113. The microfluidic chamber of claim 112, wherein said chamber contains a fluid and a contiguous gap between said fluid and said membrane.