Method and apparatus for gradient generation

• US 6,705,357 B2
• Filed: 09/18/2001
• Issued: 03/16/2004
• Est. Priority Date: 09/18/2000
• Status: Expired due to Term

• Current Assignee: President and Fellows of Harvard College (Harvard Corporation)
• Original Assignee: President and Fellows of Harvard College (Harvard Corporation)
• Inventors: Jeon, Noo Li, Dertinger, Stephan K. W., Whitesides, George M., Choi, Insung S., Chiu, Daniel T.
• Primary Examiner(s): Huson, Gregory
• Assistant Examiner(s): DEVORE, PETER T
• Application Number:
  US09/954,710
• Publication Number:
  US 20020113095A1
• Time in Patent Office: 910 Days
• Field of Search: 141/9, 141/100, 141/105-107, 141/236, 141/237, 141/240, 141/285, 141/286, 222/132, 222/145.1, 222/145.5, 137/266, 137/806, 137/814, 137/822
• US Class Current: 141/9
• CPC Class Codes: B01F 25/41 Mixers of the fractal type
• 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 35/81 Forming mixtures with changing ratios or gradients
• 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 2219/0086 Dimensions of the flow channels
• CPC Class Codes: B01J 2219/00889 Mixing micromixers B01F33/30
• CPC Class Codes: B01J 4/001 Feed or outlet devices as such, e.g. feeding tubes
• 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
• CPC Class Codes: G01N 1/2813 Producing thin layers of samples on a substrate, e.g. smearing, spinning-on G01N1/30 takes precedence
• CPC Class Codes: G01N 1/38 Diluting, dispersing or mixing samples

Abstract

A method and apparatus for treating a fluid. A method for treating a fluid may include combining two or more separate streams into a common stream and then splitting the common stream into a new set of separate streams wherein the separate streams may possess different properties. The separate streams may be combined to produce a gradient, such as a concentration gradient or shear gradient. The apparatus of the invention may provide a network of fluidic channels that may be used to manipulate a fluid to produce, for example, a gradient or a series of solutions containing a substance at varying concentrations.

Claims

1. An apparatus comprising:

a first generation comprising at least two first generation channels;

a common channel providing communication between each of the at least two first generation channels;

a second generation comprising at least three second generation channels, each second generation channel having a first end and a second end, the first end of each being in communication with the common channel; and

a third generation, the third generation comprising at least one channel more than the second generation, each third generation channel having a first end and a second end, the first end of each being in communication with the second end of each of the second generation channels.

2. The apparatus of claim 1 further comprising additional generations wherein each successive generation comprises one more channel than does an immediately preceding generation.

3. The apparatus of claim 2 comprising a composite channel, the composite channel being in fluid communication with the second end of at least one of a final generation channel.

4. The apparatus of claim 3 wherein all of the final generation channels are in fluid communication with the composite channel.

5. The apparatus of claim 1 comprising a composite channel, the composite channel being in fluid communication with the second end of at least one of the third generation channels.

6. The apparatus of claim 1 wherein all channels within each generation can provide approximately equal resistance to fluid flow.

7. The apparatus of claim 1 wherein at least one of the channels is in communication with a valve.

8. The apparatus of claim 1 wherein at least a portion of a first generation channel is less than about 1 mm wide.

9. The apparatus of claim 1 wherein at least a portion of a first generation channel is less than about 100 μ

m wide.

10. The apparatus of claim 1 wherein at least a portion of a first generation channel is less than about 50 μ

m wide.

11. The apparatus of claim 1 wherein all of the channels are less than 1 mm wide.

12. The apparatus of claim 1 wherein the second generation comprises at least one channel more than the first generation.

13. The apparatus of claim 1 wherein the first ends of each of two adjacent second generation channels are about equidistant from one of the first generation channels.

14. The apparatus of claim 1 wherein the second generation channels are convoluted.

15. The apparatus of claim 1 wherein the common channel can provide less resistance to flow than can each of the first and second generation channels.

16. The apparatus of claim 1 wherein the channels are made of hydrophilic material.

17. The apparatus of claim 1 wherein the channels are coated with hydrophilic material.

18. The apparatus of claim 1 wherein the channels are made of lipophylic material.

19. The apparatus of claim 1 wherein the channels are coated with lipophylic material.

20. A network comprising two or more of the apparatus of claim 1.

21. A method of forming a gradient comprising:

passing a first fluid through a first channel;

passing a second fluid through a second channel;

joining the first fluid and the second fluid in a common channel;

passing fluid from the common channel into at least three additional channels; and

recombining the fluid from the three additional channels into a single channel under conditions of substantially laminar flow to produce a composite fluid.

22. The method of claim 21 wherein the fluid is a liquid.

23. The method of claim 21 wherein the fluid is a gas.

24. The method of claim 21 further comprising passing at least the first fluid through additional channels in additional stages.

25. The method of claim 21 further comprising the step of dividing the recombined fluid into four additional channels.

26. The method of claim 21 further comprising passing a third fluid through a third channel and joining the third fluid with the first and second fluids in the common channel.

27. The method of claim 21 further comprising the step of adjusting the rate of flow of at least the first fluid.

28. The method of claim 27 further comprising the step of smoothing the gradient profile in the recombined fluid.

29. The method of claim 28 further comprising the step of allowing substantial diffusion to occur between laminarly flowing streams in the recombined fluid.

30. The method of claim 29 further comprising the step of altering the amount of diffusion by altering the velocity of the flow of at least the first fluid.

31. The method of claim 21 wherein the at least three additional channels each are less than 1 mm wide.

32. The method of claim 21 wherein the at least three additional channels each are less than 100 μ

m wide.

33. The method of claim 21 wherein the at least three additional channels each are less than 50 μ

m wide.

34. The method of claim 21 wherein the at least three additional channels are made of hydrophilic material.

35. The method of claim 21 wherein the at least three additional channels are coated with hydrophilic material.

36. The method of claim 21 wherein the at least three additional channels are made of lipophilic material.

37. The method of claim 21 wherein the at least three additional channels are coated with lipophilic material.

38. A method of diluting a fluid comprising:

feeding a high concentration fluid to a first inlet;

feeding a low concentration fluid to a second inlet;

passing the fluid from the first inlet and the fluid from the second inlet into a first generation common channel;

splitting the fluid in the common channel into at least three second generation channels;

recombining the fluids from the at least three second generation channels into a second generation common channel;

splitting the fluid in the second generation common channel into a plurality of third generation channels; and

collecting fluid from at least one of the plurality of third generation channels.

39. The method of claim 38 wherein the fluid is a liquid.

40. The method of claim 38 wherein the fluid is a gas.

41. The method of claim 38 wherein the fluid passes under conditions of laminar flow through each of the first, second and third generation channels.

42. The method of claim 38 wherein the first, second and third generation channels are in a common plane.

43. The method of claim 38 wherein at least one of the plurality of third generation channels contains the low concentration fluid.

44. The method of claim 38 wherein the fluid is diluted on a continuous basis.

45. The method of claim 38 wherein the fluid comprises water.

46. The method of claim 38 wherein the high concentration fluid and the low concentration fluid are of different pH.

47. The method of claim 38 further comprising varying the flux rate of at least one of the high concentration fluid and the low concentration fluid.

48. The method of claim 38 wherein each of the three second generation channels includes at least a portion that is less than about 1 mm wide.

49. The method of claim 38 wherein each of the three second generation channels includes at least a portion that is less than about 100 μ

m wide.

50. The method of claim 38 wherein each of the three second generation channels includes at least a portion that is less than about 50 μ

m wide.

51. The method of claim 38 wherein all of the first, second and third generation channels are less than 1 mm wide.

52. The method of claim 38 wherein the first, second and third generation channels are made of hydrophilic material.

53. The method of claim 38 wherein the first, second and third generation channels are coated with hydrophilic material.

54. The method of claim 38 wherein the first, second and third generation channels are made of lipophilic material.

55. The method of claim 38 wherein the first, second and third generation channels are coated with lipophilic material.

56. A method of producing a fluid exhibiting two different concentration gradient profiles, the method comprising:

combining at least a first starting fluid with a second starting fluid to form a combined stream, the first starting fluid comprising a first substance that is substantially absent from the second fluid;

dividing the combined stream into a series of second stage streams; and

joining at least two of the second stage streams to form a composite stream wherein the composite stream exhibits a different concentration gradient profile for the first substance and a second substance.

57. The method of claim 56 wherein the fluid is a gas.

58. The method of claim 56 wherein the fluid is a liquid.

59. The method of claim 56 wherein the fluid is water.

60. The method of claim 56 wherein the first starting fluid and the second starting fluid are combined under conditions of laminar flow.

61. The method of claim 56 further comprising combining a third starting fluid with the first and second starting fluids.

62. The method of claim 56 wherein at least one of the gradient profiles is a linear profile.

63. The method of claim 56 wherein one of the gradient profiles is a second order profile.

64. The method of claim 56 wherein at least one of the gradients is a parabolic gradient

65. The method of claim 56 wherein the two different concentration gradient profiles are of different orders.

66. The method of claim 56 wherein at least one of the concentration gradients is a pH gradient.

67. The method of claim 56 wherein the second stage streams are each less than about 1 mm wide.

68. The method of claim 56 wherein the second stage streams are each less than about 100 μ

m wide.

69. The method of claim 56 wherein the second stage streams are each less than about 50 μ

m wide.

70. The method of claim 56 wherein the combined stream, the second stage streams and the composite stream are all less than about 1 mm wide.