Fluid circuit components based upon passive fluid dynamics

• US 6,591,852 B1
• Filed: 01/30/2002
• Issued: 07/15/2003
• Est. Priority Date: 10/13/1998
• Status: Expired due to Fees

• Current Assignee: Myriad Genetics, Inc.
• 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:
  US10/060,442
• Time in Patent Office: 531 Days
• Field of Search: 137/806, 137/833, 137/841, 137/14, 204/601
• US Class Current: 137/14
• 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 2200/10 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 3/502738 : characterised by integrated valves microvalves F16K99/0001
• 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: G01N 35/08 : using a stream of discrete samples flowing along a tube system, e.g. flow injection analysis
• CPC Class Codes: Y10T 137/0396 : Involving pressure control
• 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 and apparatus for controlling fluid flow through microchannels by use of passive valves or stopping means comprised of abrupt microchannel widenings in the microchannels are presented. Such passive fluid flow barriers create pressure barriers impeding flow of solution past the passive fluid flow barriers until enough force is built up to overcome the force of the pressure barrier. Use of such stopping means acting as passive barriers or 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 in microchannels to prevent trapping of air in the microchannels is also presented.

Claims

1. A method for consolidating fluids from multiple microfluidic channels into a common consolidation well, chamber or channel, comprising the steps of:

c. injecting fluids into multiple microchannels of a microfluidic circuit;

then

d. applying pressure to fluid in each of said multiple microchannels sufficient to force said fluid through said microchannels until it stops at a passive fluid flow barrier formed at the junction of each of said microchannels with the common consolidation well, chamber or channel whereby fluid reaches but does not pass each passive fluid flow barrier; and

then

e. applying further pressure to fluid in each of said multiple microchannels sufficient to overcome said passive fluid flow barriers and permit said fluid to enter said common consolidation well, chamber or channel from each of said multiple microchannels;

wherein said passive fluid flow barrier formed at the junction of each said microchannel with the common consolidation well, chamber or channel is sufficient to at least temporarily block the flow of fluid in said microchannel.

2. The method of claim 1, wherein at least one said passive fluid flow barrier is an abrupt channel widening having an inlet radius equal to the channel radius and an outlet radius equal to the radius of the consolidation chamber.

3. A non-wetted fluid circuit comprising a plurality of connected microchannels, wherein an abrupt microchannel widening is present within one or more of said microchannels, said widening having an inlet radius and an outlet radius, wherein said outlet radius is sufficiently larger than said inlet radius to create a passive fluid flow barrier sufficient to cause fluid which is advancing through said fluid circuit to flow preferentially in an adjoining microchannel connected upstream of said widening rather than to flow past said widening.

4. The fluid circuit of claim 3, wherein said microchannels form a tree-like or fractal branching.

5. The fluid circuit of claim 4, wherein said microchannels connect to one or more chambers or wells.

6. A non-wetted fluid circuit comprising a plurality of connected microchannels, wherein a passive fluid flow barrier exists within at least one of said microchannels, wherein said passive fluid flow barrier comprises an inlet having a radius r₁ and an outlet having a radius r₂, wherein r₁ is sufficiently smaller than r₂ to create a passive pressure barrier causing fluid that is advancing through said fluid circuit to flow into an adjoining microchannel connected upstream of said passive fluid flow barrier rather than to flow past the passive fluid flow barrier, and wherein said passive pressure barrier is sufficient to at least temporarily block the flow of fluid in said at least one microchannel.

7. The non-wetted fluid circuit of claim 6, wherein at least one said microchannel comprises a chamber.

8. The non-wetted fluid circuit of claim 6, wherein radius r₁ is from about 0.1 to about 5000 μ

m in size.

9. The non-wetted fluid circuit of claim 6, wherein radius r₁ is from about 0.1 to about 1000 μ

m in size.

10. The non-wetted fluid circuit of claim 6, wherein radius r₂ is greater than about 1.5 times radius r₁.

11. The non-wetted fluid circuit of claim 6, wherein radius r₂ is greater than about two times radius r₁.

12. The non-wetted fluid circuit of claim 6, wherein radius r₂ is greater than about three times radius r₁.

13. The non-wetted fluid circuit of claim 6, wherein radius r₂ is greater than about five times radius r₁.

14. The non-wetted fluid circuit of claim 6, wherein radius r₂ is greater than about ten times radius r₁.

15. The non-wetted fluid circuit of claim 6 wherein said non-wetted fluid circuit comprises secondary microchannels that include passive fluid flow barriers that create passive pressure barriers to fluid advancing through the fluid circuit.

16. The non-wetted fluid circuit of claim 15 wherein said passive flow barriers are of different strengths, wherein a weaker passive flow barrier will be overcome before a stronger passive flow barrier, and wherein a microchannel downstream of a weaker passive flow barrier will fill before a microchannel downstream of a stronger passive flow barrier.

17. The non-wetted fluid circuit of claim 16 wherein the strengths of said passive flow barriers are selected to determine the order in which said secondary microchannels will fill.

18. The non-wetted fluid circuit of claim 15 wherein one or more of said secondary microchannels comprises a vent.

19. The non-wetted fluid circuit of claim 6 wherein said microchannels form a treelike or a fractal branching.

20. The non-wetted fluid circuit of claim 6 wherein said passive fluid flow barrier comprises a hydrophilic surface.

21. The non-wetted fluid circuit of claim 6 wherein said passive fluid flow barrier comprises a hydrophobic surface.

22. The non-wetted fluid circuit of claim 6 wherein said passive fluid flow barrier comprises a hydrophilic surface.

28. A method of moving a first fluid through the fluid circuit of claim 22, comprising the steps of:

a. injecting a first fluid under pressure into said fluid circuit via said one or more ports; and

b. 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.

23. A non-wetted fluid circuit comprising a plurality of connected microchannels, wherein a first passive fluid flow barrier exists within at least one of said microchannels, and wherein said first passive fluid flow barrier comprises an inlet having a radius r₁ and an outlet having a radius r₂, wherein r₁ is sufficiently smaller than r₂ to create a passive pressure barrier causing fluid that is advancing through said fluid circuit to flow in an adjoining microchannel connected upstream of said first passive fluid flow barrier rather than to flow past said first passive fluid flow barrier, 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 fluid flow barrier immediately upstream of said second point, wherein said first passive pressure barrier is sufficient to at least temporarily block the flow of fluid in said at least one microchannel, and wherein said second passive fluid flow barriers is sufficient to at least temporarily block the flow of fluid in said adjoining microchannel.

24. The non-wetted fluid circuit of claim 23, wherein said microchannels form a treelike or a fractal branching.

25. The non-wetted fluid circuit of claim 23, further comprising one or more ports allowing a gas to enter into said fluid circuit.

26. The non-wetted fluid circuit of claim 25 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.

27. The non-wetted fluid circuit of claim 23 further comprising one or more ports through which a fluid under pressure may enter into said fluid circuit.

29. The non-wetted fluid circuit of claim 23 wherein the fluid circuit comprises one or more wells or chambers joined to a common consolidation well or chamber by one or more microchannels.

30. 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 has a first passive fluid flow barrier comprising a first abrupt microchannel widening at said first intersection and a second passive fluid flow barrier comprising a second abrupt microchannel widening at said second intersection, wherein said second passive fluid flow barrier creates a greater pressure barrier than said first passive fluid flow barrier, wherein said first passive fluid flow barrier is sufficient to at least temporarily block the flow of fluid in said second microchannel, wherein said second passive fluid flow barrier is sufficient to at least temporarily block the flow of fluid in said second microchannel, and wherein said fluid circuit further comprises a vent between said first passive fluid flow barrier and said second passive fluid flow barrier.

31. The fluid circuit of claim 30 wherein said first abrupt microchannel widening comprises a chamber or well between said first intersection and said second intersection.

32. The fluid circuit of claim 30 wherein said second abrupt microchannel widening comprises a chamber or well at said second intersection.

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

advancing fluid in a first microchannel until it is stopped by the fluid engaging a first passive fluid flow barrier;

advancing fluid in a connected neighboring second microchannel until it reaches a second passive fluid flow barrier; and

overcoming the pressure barrier of one of said first and second passive fluid flow barriers by the fluid engaging the other of said first and second passive fluid flow barriers and with the application of sufficient pressure to the fluid;

wherein said first passive fluid flow barrier is sufficient to at least temporarily block the flow of fluid in said first microchannel, wherein said second passive fluid flow barrier is sufficient to at least temporarily block the flow of fluid in said second microchannel, wherein one of said first and second passive fluid flow barriers creates a weaker pressure barrier than the other said passive fluid flow barrier, wherein said weaker barrier is overcome first, and wherein at least one of said passive fluid flow barriers is an abrupt microchannel widening.

34. The method of claim 33, wherein fluid is directed into a connected neighboring second microchannel as a consequence of said fluid engaging said first passive fluid flow barrier in said first microchannel.

35. The method of claim 33, wherein said abrupt microchannel widening is selected from the group consisting of chambers, wells, long channel widenings, and short channel widenings.

36. The method of claim 33 wherein each of said first passive fluid flow barrier and said second passive fluid flow barrier is a capillary barrier having an inlet and an outlet, and wherein the outlet is sufficiently larger than the inlet to create the fluid pressure barrier of the passive fluid flow barrier.

37. The method of claim 36, wherein the outlet of each of the first and the second passive fluid flow barriers is defined by a radius r₂ which is at least about two times the size of a radius r₁ which defines the inlet of each of the first and the second passive fluid flow barriers.

38. The method of claim 36, wherein the outlet of each of the first and the second passive fluid flow barriers is defined by a radius r₂ that is at least about five times the size of a radius r₁ that defines the inlet of each of the first and the second passive fluid flow barriers.

39. The method of claim 33 wherein the second microchannel branches from the first microchannel at a point immediately upstream of the first passive fluid flow barrier.

40. The method of claim 33 wherein the first and second passive fluid flow barriers each comprise an opening into a well or chamber.

41. The method of claim 33 wherein the fluid circuit comprises one or more wells or chambers joined to a common consolidation well or chamber by one or more microchannels.

42. The method of claim 33 wherein the fluid circuit comprises one or more air vents.

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

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 said circuit of a known volume by a first abrupt microchannel widening within said main microchannel, and wherein said first microchannel comprises a second abrupt microchannel widening that creates a pressure barrier stronger than said first abrupt microchannel widening, wherein said first fluid is of all amount substantially equal to the volume of said first microchannel, and

inserting said second fluid into said main microchannel of said fluid circuit, wherein said second fluid is forced past said first abrupt microchannel widening into a second microchannel, and said first microchannel and said second microchannel converge at said second abrupt microchannel widening 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;

wherein said first abrupt microchannel widening is sufficient to at least temporarily block the flow of fluid in said main microchannel, and wherein said second abrupt microchannel widening is sufficient to at least temporarily block the flow of fluid in said first microchannel.

44. The method of claim 43, wherein said fluid circuit comprises a vent.

45. The method of claim 43, wherein said first abrupt microchannel widening and said second abrupt microchannel widening are capillary barriers selected from the group consisting of chambers, wells, long channel widenings, and short channel widenings.

46. 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 the 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 comprises a first passive fluid flow barrier within each well, chamber or channel that creates a fluid pressure barrier causing fluid to fill said branching channels upstream of said first passive fluid flow barrier prior to moving to a second set of wells, chambers or channels, wherein said second set of wells, chambers or channels comprise a second passive fluid flow barrier within each well, chamber or channel that creates a fluid pressure barrier that is stronger than the fluid pressure barrier created by said first passive fluid flow barriers, wherein the first passive fluid flow barriers comprise said channel opening into said first set of wells, chambers, or channels; and

causing fluid to push past the first passive fluid flow barriers within the first set of wells, chambers or channels and to stop at the second passive fluid flow barriers within the second set of wells, chambers or channels;

wherein each said first passive fluid flow barrier is sufficient to at least temporarily block the flow of fluid in the corresponding upstream branching channel, and wherein each said second passive fluid flow barrier is sufficient to at least temporarily block the flow of fluid in the corresponding upstream well, chamber or channel.

47. A microfluidic circuit comprising:

a. a plurality of microchannels; and

b. a common consolidation clamber;

wherein each of said plurality of microchannels joins to said consolidation chamber at a junction;

wherein said consolidation chamber has a cross sectional area substantially greater than the cross sectional area of each said microchannel; and

wherein a passive fluid flow barrier is formed at the junction of each said microchannel with said consolidation chamber;

wherein said passive fluid flow barrier formed at the junction of each said microchannel with the consolidation chamber is sufficient to at least temporarily block the flow of fluid in said microchannel.

48. The microfluidic circuit of claim 47, wherein at least one of said microchannels comprises a chamber.

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

stopping advancing fluid in a first microchannel with a first passive fluid flow barrier, thereby directing fluid into a connected neighboring second microchannel, wherein said first passive fluid flow barrier comprises an inlet having a radius r₁ and an outlet having a radius r₂, wherein than r₂ is sufficiently larger than r₁ to create a passive pressure barrier causing fluid that is advancing through said fluid circuit to stop at said first passive fluid flow barrier; and

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

wherein said first passive fluid flow barrier is sufficient to at least temporarily block the flow of fluid in said first microchannel, and wherein said second passive fluid flow barrier is sufficient to at least temporarily block the flow of fluid in said second microchannel.

50. The method of claim 49 wherein the second passive fluid flow barrier comprises an inlet having a radius r₁ and an outlet having a radius r₂, wherein r₂ is sufficiently larger than r₁ to create a passive pressure barrier greater than the first passive fluid flow barrier.

51. The method of claim 49 wherein the second microchannel branches from the first microchannel at a point immediately upstream of the first passive fluid flow barrier.

52. The method of claim 49 wherein the fluid circuit comprises one or more wells and chambers.