Fluid circuit components based upon passive fluid dynamics

• US 6,296,020 B1
• Filed: 10/13/1999
• Issued: 10/02/2001
• Est. Priority Date: 10/13/1998
• Status: Expired due to Fees

• Current Assignee: Myriad Genetics
• Original Assignee: BioMicro Systems, Inc. (Danaher Corporation)
• Inventors: Oliphant, Arnold R, McNeely, Michael R., Spute, Mark K.
• Primary Examiner(s): CHAMBERS, A MICHAEL
• Application Number:
  US09/417,691
• Time in Patent Office: 720 Days
• Field of Search: 137/806, 137/833, 137/841, 204/601, 422/451
• US Class Current: 137/806
• CPC Class Codes: B01F 2101/23 Mixing of laboratory samples e.g. in preparation of analysing or testing properties of materials
• CPC Class Codes: B01F 25/31 in conduits or tubes through which the main component flows
• 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 25/43211 using a simple by-pass for separating and recombining the flow, e.g. by using branches of different length
• CPC Class Codes: B01F 33/30 Micromixers
• CPC Class Codes: B01F 35/715 Feeding the components in several steps, e.g. successive steps
• CPC Class Codes: B01F 35/7172 using capillary forces
• 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: B01L 2200/025 Align devices or objects to ensure defined positions relative to each other
• CPC Class Codes: B01L 2200/0621 Control of the sequence of chambers filled or emptied
• CPC Class Codes: B01L 2200/0684 Venting, avoiding backpressure, avoid gas bubbles
• 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 2200/12 Specific details about manufacturing devices
• CPC Class Codes: B01L 2300/0864 comprising only one inlet and multiple receiving wells, e.g. for separation, splitting
• CPC Class Codes: B01L 2300/0867 Multiple inlets and one sample wells, e.g. mixing, dilution
• CPC Class Codes: B01L 2300/087 Multiple sequential chambers
• CPC Class Codes: B01L 2300/0874 Three dimensional network
• CPC Class Codes: B01L 2300/0887 Laminated structure
• CPC Class Codes: B01L 2300/165 Specific details about hydrophobic, oleophobic surfaces
• CPC Class Codes: B01L 2300/18 Means for temperature control
• CPC Class Codes: B01L 2400/0406 : capillary forces
• CPC Class Codes: B01L 2400/0487 : fluid pressure, pneumatics
• CPC Class Codes: B01L 2400/0688 : surface tension valves, capillary stop, capillary break
• CPC Class Codes: B01L 2400/0694 : vents used to stop and induce flow, backpressure valves
• 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 3/502738 : characterised by integrated valves microvalves F16K99/0001
• CPC Class Codes: B01L 3/502746 : characterised by the means for controlling flow resistance, e.g. flow controllers, baffles B01L3/502738 takes precedence
• CPC Class Codes: F15C 1/14 : Stream-interaction devices; Momentum-exchange devices, e.g. operating by exchange between two orthogonal fluid jets ; Proportional amplifiers
• CPC Class Codes: F15C 1/146 : multiple arrangements thereof, forming counting circuits, sliding registers, integration circuits or the like F15C1/12 take precedence
• CPC Class Codes: F28F 2245/04 : hydrophobic
• CPC Class Codes: F28F 2260/02 : having microchannels
• CPC Class Codes: G01N 2035/00237 : Handling microquantities of analyte, e.g. microvalves, capillary networks
• CPC Class Codes: G01N 2035/00366 : Several different temperatures used
• CPC Class Codes: G01N 2035/00544 : using fluid flow
• CPC Class Codes: Y10S 366/03 : Micromixers: variable geometry from the pathway influences mixing/agitation of non-laminar fluid flow
• CPC Class Codes: Y10T 137/2076 : Utilizing diverse fluids
• CPC Class Codes: Y10T 137/2224 : Structure of body of device
• CPC Class Codes: Y10T 137/2267 : Device including passages having V over gamma configuration

Abstract

Methods of controlling fluid flow through microchannels by use of passive valves or stopping means in the microchannels is presented. The passive valves act as pressure barriers impeding flow of solution past the stopping means until enough force is built up to overcome the force of the pressure barrier. Well planned use of such stopping means acting as passive valves allows the flow of fluids through microchannels to be regulated so as to allow fluids to be mixed or diluted after being introduced via a single channel, or to be split into multiple channels without the need for individual pipetting. Flow through the multiple channels can be regulated to allow a series of sister wells or chambers to all fill prior to the fluid flowing beyond any one of the sister wells or chambers. The filling of sister wells or chambers in this manner allows all wells or chambers to undergo reactions in unison. The use of air ducts to prevent trapping of air in the microchannels is also presented.

Claims

1. A non-wetted fluid circuit comprising a first microchannel and a second microchannel wherein said second microchannel branches from said first microchannel at a first intersection and rejoins said first microchannel at a second intersection, wherein said second microchannel comprises a first passive stopping means at said first intersection and a second passive stopping means at said second intersection wherein said second passive stopping means creates a greater pressure barrier than said first passive stopping means, said fluid circuit further comprising a vent between said first passive stopping means and said second passive stopping means.

2. The fluid circuit of claim 1 wherein said first microchannel comprises a chamber or well between said first intersection and said second intersection.

3. The fluid circuit of claim 1 wherein said first microchannel comprises a chamber or well at said second intersection.

4. A method of temporarily bypassing a microchannel within a fluid circuit by applying a first fluid to the fluid circuit of claim 1 until said first fluid reaches a third passive stopping means wherein said third passive stopping means creates a pressure barrier that is stronger than said second passive stopping means whereupon application of additional first fluid, a second fluid or a force causes said first fluid or said second fluid to enter said microchannel.

5. A method of moving a fluid through the fluid circuit of claim 1 by forcing a gas through said one or more ports, said gas thereby forcing fluid to move through said fluid circuit.

36. The fluid circuit of claim 1 wherein said narrowing can be overcome by wetting of both sides of said narrowing.

37. The fluid circuit of claim 1 wherein said short microchannel narrowing comprises a hydrophilic surface.

38. The fluid circuit of claim 1 wherein said short microchannel narrowing comprises a hydrophobic surface.

39. The fluid circuit of claim 1 wherein surface tension between said fluid and a surface of said narrowing is greater than surface tension between a gas in said microchannels and said surface of said narrowing.

40. The fluid circuit of claim 1 wherein said narrowing is in the range of 1-1000 μ

m in length.

41. The fluid circuit of claim 1 wherein said narrowing is in the range of 5-500 μ

m in length.

42. The fluid circuit of claim 1 wherein said narrowing is in the range of 10-300 μ

m in length.

43. The fluid circuit of claim 1 further comprising a plurality of short microchannel narrowings, wherein said narrowings create pressure barriers having different strengths.

44. The fluid circuit of claim 1 wherein said microchannels form a treelike or a fractal branching.

45. The fluid circuit of claim 1 wherein said circuit comprises one or more wells or chambers.

46. The fluid circuit of claim 45 wherein at least a portion of said wells or chambers is flexible.

47. A method of physically displacing a fluid within the fluid circuit of claim 46 by applying a force to said flexible portion of said wells or chambers.

48. The fluid circuit of claim 45 wherein said wells comprise a first section and a second section, wherein said first section is smaller than said second section and wherein said microchannels exit into said first section of each of said wells, further wherein said first section exits into said second section wherein said first section and said second section join at a boundary wherein said boundary forms a narrowing between said first section and said second section.

49. The fluid circuit of claim 1 wherein said circuit comprises one or more wells or chambers joined to a common consolidation well or chamber by one or more microchannels.

50. The fluid circuit of claim 49 further comprising one or more air vents.

51. The fluid circuit of claim 1 further comprising an air vent.

52. The fluid circuit of claim 51 wherein said air vent is a narrow channel or duct.

53. The fluid circuit of claim 51 wherein said air vent comprises a hydrophobic short channel narrowing, a hydrophobic patch, or a surface tension patch, or a hydrophilic short channel narrowing.

54. The fluid circuit of claim 1 further comprising one or more ports allowing a gas to enter into said fluid circuit.

55. The fluid circuit of claim 54 wherein said ports are large enough to allow gas to pass through said ports but small enough to prevent fluids from passing through said ports at a specific operating pressure.

56. The fluid circuit of claim 1 further comprising one or more ports allowing a fluid under pressure to enter into said fluid circuit.

57. A method of moving a first fluid through the fluid circuit of claim 56 by forcing a second fluid under pressure through said one or more ports, said second fluid thereby forcing said first fluid to move through said fluid circuit.

6. A method of mixing a first fluid and a second fluid within a non-wetted fluid circuit, said method comprising the steps of

a) inserting said first fluid into a main microchannel of said fluid circuit, wherein said first fluid is forced to flow into a first microchannel of a known volume of said circuit as a result of a first passive stopping means within said main microchannel and wherein said first microchannel comprises a second passive stopping means that creates a pressure barrier stronger than said first passive stopping means, wherein said first fluid is of an amount substantially equal to the volume of said first microchannel, and

b) inserting said second fluid into said main microchannel of said fluid circuit, wherein said second fluid is forced past said first passive stopping means into a second microchannel, and said first microchannel and said second microchannel converge at said second passive stopping means at which point said first fluid and said second fluid will mix upon continued insertion of said second fluid or application of a force causing said first and second fluids to move.

7. The method of claim 6 wherein said fluid circuit comprises a vent.

8. The method of claim 6 wherein said first stopping means and said second stopping means are capillary barriers.

9. The method of claim 8 wherein the capillary barriers are selected from the group consisting of a hydrophobic short channel narrowing, a hydrophilic short channel narrowing, a hydrophobic patch, and a surface tension patch.

10. A method of distributing fluid from one channel to multiple wells, chambers or channels of a non-wetted fluid circuit wherein said method comprises the steps of:

passing said fluid from said one channel to branching channels leading to a first set of wells, chambers or channels, wherein said first set of wells, chambers or channels comprise a first passive stopping means within each well, chamber or channel thereby causing all wells, chambers or channels upstream of said first passive stopping means to fill prior to said fluid moving to a second set of wells, chambers or channels comprising a second passive stopping means within each well, chamber or channel, wherein the second passive stopping means create a pressure barrier stronger than the first passive stopping means; and

causing fluid to push past the first passive stopping means within the first set of wells, chambers or channels and to stop at the second passive stopping means within the second set of wells, chambers or channels.

11. The method of claim 10 wherein there are multiple sets of wells, chambers or channels wherein a first set of wells, chambers or channels has first passive stopping means within each well, chamber or channel thereby causing all wells, chambers or channels of said first set to fill prior to said fluid moving to a second set of wells, chambers or channels.

12. The method of claim 11 wherein said second set of wells, chambers or channels comprises second passive stopping means that are stronger than said first passive stopping means of said first set of wells, chambers or channels.

13. The method of claim 10 wherein said fluid circuit comprises a vent.

14. A method for consolidating fluids from multiple wells into a common consolidation well, chamber or channel wherein said method comprises:

a) inserting said fluids into microchannels of a fluid circuit;

then

b) forcing said fluids through said microchannels and into wells of said fluid circuit by addition of a second fluid into said microchannels wherein said second fluid is more viscous than said fluids, and wherein said wells exit into channels which are narrower than said wells, and further wherein said exit channels connect to said common consolidation well, chamber or channel, wherein sufficient second fluid is added to force said fluids into said common consolidation well, chamber or channel.

15. The method of claim 14 wherein said fluid circuit comprises one or more vents.

16. The method of claim 14 wherein each of said wells exits into more than one channel.

17. A method of temporarily bypassing a microchannel within a fluid circuit by applying a first fluid to the fluid circuit of claim 14 until said first fluid reaches a third passive stopping means wherein said third passive stopping means creates a pressure barrier that is stronger than said second passive stopping means whereupon application of additional first fluid, a second fluid or a force causes said first fluid or said second fluid to enter said microchannel.

18. A method of controlling fluid flow through a non-wetted fluid circuit comprising at least two connected microchannels, each said microchannel containing a passive flow barrier that creates a fluid pressure barrier, said method comprising:

stopping advancing fluid in a first microchannel with a first passive flow barrier, thereby directing fluid into a connected neighboring second microchannel; and

overcoming the pressure barrier of the first passive flow barrier by the advancing fluid engaging a second passive flow barrier in the second microchannel, wherein said second passive flow barrier creates a stronger pressure barrier than the first passive flow barrier.

19. The method of claim 18 wherein the first passive flow barrier and the second passive flow barrier are capillary barriers.

20. The method of claim 19 wherein the capillary barriers are selected from the group consisting of a hydrophobic short channel narrowing, a hydrophilic short channel narrowing, a hydrophobic patch, and a surface tension patch.

21. The method of claim 18 wherein the second microchannel branches from the first microchannel at a point immediately upstream of the first passive flow barrier.

22. The method of claim 21 wherein the second microchannel rejoins the first microchannel at a point immediately downstream of the second passive flow barrier.

23. The method of claim 18 wherein the fluid circuit comprises one or more wells and chambers.

24. The method of claim 23 wherein the wells comprise a first section and a second section, wherein said first section is smaller than said second section and wherein a microchannel exits into the first section of each said wells, further wherein said first section exits into said second section wherein said first section and said second section join at a boundary wherein said boundary forms a narrowing between said first section and said second section.

25. The method of claim 18 wherein the fluid circuit comprises one or more wells or chambers joined to a common consolidation well or chamber by one or more microchannels.

26. The method of claim 18 wherein the fluid circuit comprises one or more air vents.

27. A method to overcome a capillary stopping means in a non-wetted microchannel comprising the steps:

stopping advancing fluid flow in a fluid circuit with a capillary stopping means that creates a pressure barrier due to capillary forces dependent upon the presence of a gas-fluid interface, wherein said capillary stopping means has an upstream side and a downstream side in the fluid circuit, and wherein the gas-fluid interface is disposed between the upstream and downstream sides of the capillary stopping means; and

overcoming the pressure barrier by introducing a fluid to the downstream side of the capillary stopping means that wets the downstream side of the capillary stopping means to eliminate the gas-fluid interface at the capillary stopping means.

28. A non-wetted fluid circuit comprising a plurality of connected microchannels, wherein passive stopping means exist within one or more of said microchannels causing fluid that is advancing through said fluid circuit to flow in an adjoining microchannel connected upstream of said passive stopping means rather than to flow past said stopping means, wherein said fluid circuit further comprises a channel with a chamber wherein said chamber comprises secondary channels.

29. The fluid circuit of claim 28 wherein said secondary channels comprise passive stopping means.

30. The fluid circuit of claim 29 wherein each of said passive stopping means can be of different strengths from each other thereby dictating an order in which each secondary channel will fill.

31. The fluid circuit of claim 28 wherein one or more secondary channels comprise a vent.

32. A non-wetted fluid circuit comprising a first microchannel and a second microchannel wherein said second microchannel branches from said first microchannel upstream of a first passive stopping means within said first microchannel and rejoins said first microchannel downstream of a second passive stopping means within said first microchannel, further wherein said second passive stopping means creates a greater pressure barrier than said first passive stopping means, said fluid circuit further comprising a vent between said first passive stopping means and said second passive stopping means.

33. The fluid circuit of claim 32 wherein said first microchannel comprises a chamber or well between said first stopping means and said second stopping means.

34. A non-wetted fluid circuit comprising a plurality of connected microchannels, wherein passive stopping means exist within one or more of said microchannels, causing fluid that is advancing through said fluid circuit to flow in an adjoining microchannel connected upstream of said passive stopping means rather than to flow past said passive stopping means, wherein at least one of said microchannels branches at a first point into an adjoining microchannel which rejoins said one of said microchannels at a second point and wherein said adjoining microchannel comprises a second passive stopping means immediately upstream of said second point.

35. A non-wetted fluid circuit comprising a plurality of connected microchannels, wherein a short microchannel narrowing exists within one or more of said microchannels, said microchannel narrowing having an inlet and an outlet, said narrowing having a cross-sectional configuration relative to the inicrochannel that creates a passive pressure barrier causing fluid which is advancing though said fluid circuit preferably to flow in an adjoining microchannel connected upstream of said narrowing rather than to flow past said narrowing.

58. The fluid circuit of 1 wherein the narrowing is sufficiently short to produce little or no pressure drop across the narrowing in established flow conditions.