Microfluidic systems and methods for combining discrete fluid volumes

• US 20020187560A1
• Filed: 05/16/2002
• Published: 12/12/2002
• Est. Priority Date: 06/07/2001
• Status: Active Grant

• Current Assignee: Agilent Technologies, Inc.
• Original Assignee: Nanostream, Inc.
• Inventors: Dantsker, Eugene, Pezzuto, Marci
• Granted Patent: US 7,318,912 B2
• Time in Patent Office: Days
• US Class Current: 436/180
• CPC Class Codes: B01F 25/314 wherein additional components are introduced at the circumference of the conduit
• CPC Class Codes: B01F 25/432 with means for dividing the material flow into separate sub-flows and for repositioning and recombining these sub-flows; Cross-mixing, e.g. conducting the outer layer of the material nearer to the axis of the tube or vice-versa
• CPC Class Codes: B01F 33/30 Micromixers
• CPC Class Codes: B01F 35/713 comprising breaking packages or parts thereof, e.g. piercing or opening sealing elements between compartments or cartridges containers or packages per se B65D
• CPC Class Codes: B01F 35/7182 with means for feeding the material with a fractal or tree-type distribution in a surface
• CPC Class Codes: B01L 2300/0864 comprising only one inlet and multiple receiving wells, e.g. for separation, splitting
• CPC Class Codes: B01L 2300/0874 Three dimensional network
• CPC Class Codes: B01L 2300/0887 Laminated structure
• CPC Class Codes: B01L 2400/0406 capillary forces
• CPC Class Codes: B01L 2400/0487 fluid pressure, pneumatics
• CPC Class Codes: B01L 2400/06 Valves, specific forms thereof
• CPC Class Codes: B01L 2400/0683 mechanically breaking a wall or membrane within a channel or chamber
• CPC Class Codes: B01L 2400/0688 surface tension valves, capillary stop, capillary break
• CPC Class Codes: B01L 3/502707 characterised by the manufacture of the container or its components by shaping or joining plastic parts B29C59/00, B29C65/00; by laminating B32B37/00; manufacture of microstructural devices in general B81C
• CPC Class Codes: B01L 3/502738 characterised by integrated valves microvalves F16K99/0001
• CPC Class Codes: B81B 2201/058 Microfluidics not provided for in B81B2201/051 - B81B2201/054
• CPC Class Codes: B81C 1/00119 Arrangement of basic structures like cavities or channels, e.g. suitable for microfluidic systems
• CPC Class Codes: B81C 2201/019 Bonding or gluing multiple substrate layers
• CPC Class Codes: Y10T 137/0318 Processes
• CPC Class Codes: Y10T 137/2496 Self-proportioning or correlating systems
• CPC Class Codes: Y10T 137/2501 : Dividing and recombining flow
• CPC Class Codes: Y10T 137/2562 : Dividing and recombining
• CPC Class Codes: Y10T 436/11 : Automated chemical analysis
• CPC Class Codes: Y10T 436/117497 : with a continuously flowing sample or carrier stream
• CPC Class Codes: Y10T 436/118339 : with formation of a segmented stream
• CPC Class Codes: Y10T 436/2575 : Volumetric liquid transfer

Abstract

Microfluidic devices capable of combining discrete fluid volumes generally include channels for supplying different fluids toward a sample chamber and means for establishing fluid communication between the fluids within the chamber. Discrete fluid plugs are defined from larger fluid volumes before being combined. Certain embodiments utilize adjacent chambers or subchambers divided by a rupture region such as a frangible seal. Further embodiments utilize one or more deformable membranes and/or porous regions to direct fluid flow. Certain devices may be pneumatically or magnetically actuated.

Claims

1. A multi-layer microfluidic device comprising:

a first device layer defining a first microfluidic chamber;

a first microfluidic channel for supplying a first fluid to the first microfluidic chamber;

a second device layer defining a second microfluidic chamber disposed below and substantially aligned with the first chamber;

a second microfluidic channel for supplying a second fluid to the second microfluidic chamber; and

a third device layer disposed between the first device layer and the second device layer, the third device layer defining a rupture region separating the first microfluidic chamber from the second microfluidic chamber.

2. The microfluidic device of claim 1, further comprising:

a first fluid inlet and a first fluid outlet in fluid communication with the first microfluidic channel; and

a second fluid inlet and a second fluid outlet in fluid communication with the second microfluidic channel

3. The microfluidic device of claim 1 wherein any of the first device layer and the second device layer is a stencil layer.

4. The microfluidic device of claim 1 wherein the first device layer and the second device layer are stencil layers, the first microfluidic channel is defined through the entire thickness of the first device layer, and the second microfluidic channel is defined through the entire thickness of the second device layer.

5. The microfluidic device of claim 1 wherein the various device layers are bound together to form a substantially sealed structure.

6. The microfluidic device of claim 1 wherein any device layer is fabricated with self-adhesive tape.

7. The microfluidic device of claim 1 wherein any of the first device layer, the second device layer, and the third device layer is fabricated with a polymeric material.

8. The microfluidic device of claim 1 wherein the rupture region includes a scored portion of the third device layer.

9. The microfluidic device of claim 1 wherein the third device layer has a thickness, and the rupture region includes a slit defined through the entire thickness of the third device layer.

10. The microfluidic device of claim 1 wherein the rupture region includes a frangible seal.

11. The microfluidic device of claim 10 wherein the frangible seal has a region weakened by a method selected from the group consisting of:

mechanical treatment, chemical treatment, and electromagnetic treatment.

12. The microfluidic device of claim 1 wherein each chamber of the first microfluidic chamber and the second microfluidic chamber has a volume of less than about 1 microliter.

14. The microfluidic device of claim 13, further comprising:

a first fluid inlet and a first fluid outlet in fluid communication the at least one first microfluidic channel; and

a second fluid inlet and a second fluid outlet in fluid communication with the at least one second microfluidic channel.

15. The microfluidic device of claim 13 wherein the first plurality of microfluidic chambers and the second plurality of microfluidic chambers are arranged to form a two-dimensional array.

16. The microfluidic device of claim 13 wherein the device is constructed with at least one stencil layer.

17. The microfluidic device of claim 13 wherein:

the first device layer is a stencil layer;

the least one first microfluidic channel defined through the entire thickness of the first device layer;

the second device layer is a stencil layer; and

the least one second microfluidic channel defined through the entire thickness of the second device layer.

18. The microfluidic device of claim 13 wherein the device includes multiple device layers bound together to form a substantially sealed structure.

19. The microfluidic device of claim 13 wherein any device layer is fabricated with self-adhesive tape.

20. The microfluidic device of claim 13 wherein any of the first device layer, the second device layer, and the third device layer is fabricated with a polymeric material.

21. The microfluidic device of claim 13 wherein the rupture region includes a scored portion of the third device layer.

22. The microfluidic device of claim 13 wherein the third device layer has a thickness, and the rupture region includes a slit defined through the entire thickness of the third device layer.

23. The microfluidic device of claim 13 wherein the rupture region includes a frangible seal.

24. The microfluidic device of claim 23 wherein the frangible seal has a region weakened by a method selected from the group consisting of:

mechanical treatment, chemical treatment, and electromagnetic treatment.

25. The microfluidic device of claim 13 wherein at least one of the first plurality of microfluidic chambers and the second plurality of microfluidic chambers are bounded along a surface by a substantially optically transmissive material.

26. The microfluidic device of claim 13 wherein each chamber of the first plurality of microfluidic chambers and the second plurality of microfluidic chambers has a volume of less than about 1 microliter.

28. The microfluidic device of claim 27 wherein the engagement between the deformable membrane and the first surface is established with a non-permanent adhesive.

29. The microfluidic device of claim 27 wherein the engagement between the deformable membrane and the first surface is established with localized heating.

30. The microfluidic device of claim 27 wherein the localized heating is applied by a process selected from the group consisting of:

laser heating, ultrasonic heating, resistance heating, and contact heating.

31. The microfluidic device of claim 27 wherein the first device layer is formed with a substantially optically transmissive material.

32. The microfluidic device of claim 27, further comprising an actuation chamber in fluid communication with the deformable membrane,

33. The microfluidic device of claim 32 wherein the actuation chamber is adapted to permit manipulation of the deformable membrane.

34. The microfluidic device of claim 27 wherein the deformable membrane includes a ferromagnetic or paramagnetic material.

35. The microfluidic device of claim 27, further comprising:

a first fluid outlet in fluid communication the microfluidic chamber; and

a second fluid outlet in fluid communication the microfluidic chamber.

36. The microfluidic device of claim 27, further comprising a second device layer disposed between the first device layer and the deformable membrane, the second device layer being a stencil layer.

37. The microfluidic device of claim 36 wherein the first fluid inlet includes a first microfluidic channel defined through the entire thickness of the second layer, and the second fluid inlet includes a second microfluidic channel defined through the entire thickness of the second layer.

38. The microfluidic device of claim 36 wherein the various layers are bound together to form a substantially sealed structure.

39. The microfluidic device of claim 36 wherein any device layer is fabricated with self-adhesive tape.

40. The microfluidic device of claim 37 wherein any of the first device layer and the deformable membrane is fabricated with a polymeric material.

41. The microfluidic device of claim 27 wherein the microfluidic chamber has a volume of less than about 1 microliter.

13. A multi-layer microfluidic device comprising:

a first device layer defining a first plurality of microfluidic chambers;

at least one first microfluidic channel for supplying at least one fluid to the first plurality of microfluidic chambers;

a second device layer defining a second plurality of microfluidic chambers, the second plurality of microfluidic chambers being disposed below and substantially aligned with the first plurality of microfluidic chambers;

at least one second microfluidic channel for supplying at least one fluid to the second plurality of microfluidic chambers; and

a third device layer disposed between the first device layer and the second device layer, the third device layer defining a rupture region separating at least one chamber of the first plurality of microfluidic chambers from at least one chamber of the second plurality of microfluidic chambers.

27. A multi-layer microfluidic device comprising:

a first device layer

a deformable membrane;

a microfluidic chamber bounded along a first surface by the first device layer and bounded along a second surface by the deformable membrane, the second surface being disposed substantially opposite the first surface, wherein the deformable membrane is adapted to selectively engage the first device layer to partition the microfluidic chamber into a first discrete subchamber and a second discrete subchamber;

a first fluid inlet in fluid communication with the microfluidic chamber capable of supplying a first fluid to the first discrete subchamber; and

a second fluid inlet in fluid communication with the microfluidic chamber capable of supplying a second fluid to the second discrete subchamber.

42. A multi-layer microfluidic device for combining discrete volumes of at least two fluids, the device comprising:

a microfluidic chamber;

a first microfluidic channel adapted to supply a first fluid to the microfluidic chamber;

a second microfluidic channel adapted to supply a second fluid to the microfluidic chamber;

a deformable membrane bounding a surface of the microfluidic chamber, the deformable membrane being adapted to selectively block the passage of the first fluid from the first microfluidic channel into the microfluidic chamber and selectively block the passage of the second fluid from the second microfluidic channel into the microfluidic chamber.

43. The microfluidic device of claim 42 wherein the first microfluidic channel is a first microfluidic branch channel and the second microfluidic channel is a second microfluidic branch channel, the device further comprising:

a first microfluidic trunk channel in fluid communication with the first microfluidic branch channel, the first microfluidic trunk channel having a first fluid inlet and a first fluid outlet; and

a second microfluidic trunk channel in fluid communication with the second microfluidic branch channel, the second microfluidic trunk channel having a second fluid inlet and a second fluid outlet.

44. The microfluidic device of claim 42 wherein the deformable membrane is adapted to divide the microfluidic chamber into a plurality of discrete subchambers.

45. The microfluidic device of claim 42, further comprising at least one actuation chamber in fluid communication with the deformable membrane, the actuation chamber being adapted to permit manipulation of the deformable membrane.

46. The microfluidic device of claim 42 wherein the deformable membrane includes a ferromagnetic or paramagnetic material.

47. The microfluidic device of claim 42 wherein the microfluidic chamber is bounded along at least one surface by a substantially optically transmissive material.

48. The microfluidic device of claim 42, further comprising a plurality of microfluidic chambers arranged in a two-dimensional array

49. The microfluidic device of claim 42 wherein at least one layer of the multi-layer device is a stencil layer.

50. The microfluidic device of claim 42 wherein at least one layer of the multi-layer device is fabricated with self-adhesive tape.

51. The microfluidic device of claim 42 wherein at least one layer of the multi-layer device is fabricated with a polymeric material.

52. The microfluidic device of claim 42, further comprising a porous region in fluid communication with the microfluidic chamber.

53. The microfluidic device of claim 52 wherein the porous region is vented to atmosphere.

54. The microfluidic device of claim 52 wherein the porous region is in selective fluid communication with a vacuum source.

55. The microfluidic device of claim 42 wherein the microfluidic chamber has a volume of less than about 1 microliter.

57. The microfluidic device of claim 56 wherein the first liquid permeability is substantially greater than the second liquid permeability.

58. The microfluidic device of claim 56 wherein the second chamber is microfluidic.

59. The microfluidic device of claim 56 wherein the second chamber is vented to atmosphere.

60. The microfluidic device of claim 56 wherein the second chamber is fluidically coupled to a vacuum source.

61. The microfluidic device of claim 56, further comprising:

a first trunk channel having a first fluid inlet and a first fluid outlet; and

a second trunk channel having a second fluid inlet and a second fluid outlet;

wherein the first microfluidic channel is a first microfluidic branch channel in fluid communication with the first trunk channel, and the second microfluidic channel is a second microfluidic branch channel in fluid communication with the second trunk channel.

62. The microfluidic device of claim 56, further comprising a plurality of first microfluidic chambers arranged in a two-dimensional array

63. The microfluidic device of claim 56 wherein at least one layer of the multi-layer device is a stencil layer.

64. The microfluidic device of claim 56 wherein at least one layer of the multi-layer device is fabricated with self-adhesive tape.

65. The microfluidic device of claim 56 wherein at least one layer of the multi-layer device is fabricated with a polymeric material.

66. The microfluidic device of claim 56 wherein each chamber of the first microfluidic chamber and the second microfluidic chamber has a volume of less than about 1 microliter.

68. The method of claim 67, wherein the engaging step includes locally heating at least a portion of the deformable membrane or at least a portion of the first surface.

69. The method of claim 68, wherein the local heating is applied by a process selected from the group consisting of:

laser heating, ultrasonic heating, electromagnetic heating, resistance heating, and contact heating.

70. The method of claim 67, wherein the disengaging step includes pressurizing at least one of the first discrete subchamber and the second discrete subchamber.

71. The method of claim 67 wherein the microfluidic device includes an actuation chamber in fluid communication with the deformable membrane, and wherein the disengaging step includes reducing the pressure within the actuation chamber.

72. The method of claim 67 wherein the deformable membrane includes a ferromagnetic or paramagnetic material, and wherein the disengaging step includes applying a magnetic field to the deformable membrane.

73. The method of claim 67, further comprising the step of agitating the contents of the microfluidic chamber.

74. The method of claim 67, further comprising the step of analyzing the contents of the microfluidic chamber.

56. A multi-layer microfluidic device for combining discrete volumes of at least two fluids, the device comprising:

a first microfluidic chamber;

a first microfluidic channel adapted to supply a first fluid to the microfluidic chamber;

a second microfluidic channel adapted to supply a second fluid to the microfluidic chamber;

a first porous region having a first liquid permeability, the first porous region being disposed between the first microfluidic channel and the first microfluidic chamber and further disposed between the second microfluidic channel and the first microfluidic chamber;

a second chamber;

a second porous region having a second liquid permeability, the second porous region being disposed between the first microfluidic chamber and the second chamber

wherein the first liquid permeability is substantially different from the second liquid permeability.

67. A method for combining microscale fluid volumes, the method comprising the steps of:

providing a microfluidic device having a microfluidic chamber bounded along a first surface by a first device layer and bounded along a second surface by a deformable membrane;

engaging a portion of the deformable membrane to the first device layer to partition the microfluidic chamber into a first discrete subchamber and a second discrete subchamber;

filling the first discrete subchamber with a first fluid;

filling the second discrete subchamber with a second fluid; and

disengaging the deformable membrane from the first surface.

75. A method for combining microscale fluid volumes, the method comprising the steps of:

providing a microfluidic device having a microfluidic chamber bounded along a surface by a deformable membrane, a first microfluidic channel adapted to supply a first fluid to the microfluidic chamber, and a second microfluidic channel adapted to supply a second fluid to the microfluidic chamber;

manipulating the deformable membrane to disallow fluid communication between the first microfluidic channel and the microfluidic chamber and disallow fluid communication between the second microfluidic channel and the microfluidic chamber;

filling the first microfluidic channel with the first fluid;

filling the second microfluidic channel with the second fluid; and

manipulating the deformable membrane to permit the first fluid and the second fluid to enter the microfluidic chamber.

76. The method of claim 75 wherein the microfluidic device includes an actuation chamber in fluid communication with the deformable membrane, and wherein the manipulating steps include altering the pressure within the actuation chamber.

77. The method of claim 75 wherein the deformable membrane includes a ferromagnetic or paramagnetic material, and wherein at least one of the manipulation steps includes applying a magnetic field to the deformable membrane.

78. The method of claim 75, further comprising the step of agitating the contents of the microfluidic chamber.

79. The method of claim 75, further comprising the step of analyzing the contents of the microfluidic chamber.

80. The method of claim 75 wherein:

the microfluidic device includes a first trunk channel and a second trunk channel;

the first microfluidic channel is a first microfluidic branch channel in fluid communication with the first trunk channel;

the second microfluidic channel is a second microfluidic branch channel in fluid communication with the second trunk channel;

the first filling step includes filling the first microfluidic branch channel with the first fluid from the first trunk channel and thereafter flushing any remaining first fluid from the first trunk channel; and

the second filling step includes filling the second microfluidic branch channel with the second fluid from the second trunk channel and thereafter flushing any remaining second fluid from the second trunk channel.