Fluid circuit components based upon passive fluid dynamics

• US 6,601,613 B2
• Filed: 09/27/2001
• Issued: 08/05/2003
• 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:
  US09/967,402
• Publication Number:
  US 20020036018A1
• Time in Patent Office: 677 Days
• Field of Search: 137/806, 137/833, 137/841, 204/601, 251/368
• US Class Current: 137/833
• 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: B01J 2219/00783 Laminate assemblies, i.e. the reactor comprising a stack of plates
• CPC Class Codes: B01J 2219/00853 Employing electrode arrangements
• CPC Class Codes: B01J 2219/00873 Heat exchange
• CPC Class Codes: B01J 2219/00889 Mixing
• CPC Class Codes: B01J 2219/00891 Feeding or evacuation
• CPC Class Codes: B01J 2219/00952 Sensing operations
• 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 3/5027 : 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: 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: B81B 2201/058 : Microfluidics not provided for in B81B2201/051 - B81B2201/054
• CPC Class Codes: B81C 3/001 : Bonding of two components
• 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 137/2076 : 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 useful for consolidating or mixing fluids, said fluid circuit comprising a first microchannel and a second microchannel joining at an intersection to form a common downstream microchannel, wherein said first microchannel comprises a passive stopping means immediately upstream from said intersection;

wherein said passive stopping means creates resistance to an advancing first fluid to temporarily block the flow of said first fluid in said first microchannel prior to wetting of the downstream side of said passive stopping means, and permits flow of said first fluid through said passive stopping means upon wetting of the downstream side of said passive stopping means by a second fluid entering said intersection from said second microchannel, wherein said passive stopping means comprises a local modification to the dimensions or surface properties of said first microchannel selected from the group consisting of a hydrophobic patch, a surface tension patch, a hydrophobic short channel narrowing, a hydrophilic short channel narrowing, and a hydrophilic channel widening, and wherein said passive stopping means is sufficient to at least temporarily block the flow of fluid in said first microchannel.

2. The fluid circuit of claim 1, wherein said first fluid and said second fluid have substantially the same surface energies.

3. The fluid circuit of claim 1, wherein said passive stopping means is created by an abrupt change in the capillary force experienced by fluid flowing in said first microchannel.

4. The fluid circuit of claim 1, wherein said passive stopping means is created by a change in at least one of the contact angle between said first fluid and said first microchannel and the diameter of said first microchannel.

5. The fluid circuit of claim 1, wherein said passive stopping means is selected from the group consisting of a hydrophobic short channel narrowing, a hydrophilic short channel narrowing, a hydrophilic channel widening, a hydrophobic patch, and a surface tension patch.

6. The fluid circuit of claim 1, wherein at least a portion of the interior of said fluid circuit comprises a hydrophobic material.

7. The fluid circuit of claim 6, wherein said hydrophobic material is selected from the group consisting of polytetrafluoroethylene, fluorinated ethylenepropylene, perfluoralkoxy alkane, and polyvinylidene fluoride.

8. The fluid circuit of claim 1, wherein at least a portion of the interior of said fluid circuit comprises a hydrophilic material.

9. The fluid circuit of claim 8, wherein said hydrophilic material is elastophilic™

.

10. The fluid circuit of claim 1 wherein at least one of said first microchannel and said second microchannel comprises a vent upstream of said intersection.

11. The fluid circuit of claim 10 wherein said vent allows the passage of gaseous materials but not fluids.

12. A fluid circuit comprising:

a parent microchannel having an upstream end and a downstream end;

at least two daughter microchannels branching from said downstream end of said parent microchannel, each said daughter microchannel having an upstream end and a downstream end;

a first passive pressure barrier sufficient to at least temporarily block fluid advancing from said parent microchannel to one said daughter microchannel; and

a second passive pressure barrier sufficient to at least temporarily block fluid advancing out of one said daughter microchannel in a downstream direction;

wherein said second passive pressure barrier provides a greater resistance to advancing fluid than does said first passive pressure barrier.

13. The fluid circuit of claim 12, wherein said first pressure barrier is created by an abrupt change in the capillary force experienced by fluid at said first pressure barrier, and said second pressure barrier is created by an abrupt change in the capillary force experienced by fluid at said second pressure barrier.

14. The fluid circuit of claim 12, wherein said first pressure barrier is created by an abrupt change microchannel diameter at the junction said parent microchannel and said one daughter microchannel.

15. The fluid circuit of claim 12, wherein at least one of said first pressure barrier and said second pressure barrier is selected from the group consisting of a hydrophobic short channel narrowing, a hydrophilic short channel narrowing, a hydrophilic channel widening, a hydrophobic patch, and a surface tension patch.

16. A fluid circuit comprising:

a parent microchannel having an upstream end mid a downstream end;

at least two first generation daughter microchannels branching from said downstream end of said parent microchannel, each said first generation daughter microchannel having an upstream end and a downstream end;

at least two second generation daughter microchannels branching from the downstream end of at least one said first generation daughter microchannel;

at least a first passive pressure barrier sufficient to at least temporarily block fluid advancing out of one said first generation daughter microchannels in a downstream direction prior to wetting of a downstream side of said first pressure baffler; and

at least a second passive pressure barrier sufficient to at least temporarily block fluid advancing out of one said second generation daughter microchannels in a downstream direction prior to wetting of a downstream side of said second pressure barrier;

wherein said second passive pressure barrier provides a greater resistance to advancing fluid than does said first passive pressure barrier.

17. The fluid circuit of claim 16, further comprising at least one well or chamber connected downstream of at least one said second generation daughter microchannel.

18. The fluid circuit of claim 16, wherein said first pressure barrier is created by an abrupt change in the capillary force experienced by fluid at said first pressure barrier, and said second pressure barrier is created by an abrupt change in the capillary force experienced by fluid at said second pressure barrier.

19. The fluid circuit of claim 16 wherein said first pressure barrier is created by an abrupt change in microchannel diameter at the junction said one first generation daughter channel and one said second generation daughter microchannel.

20. The fluid circuit of claim 16, wherein at least one of said first pressure barrier and said second pressure barrier is selected from the group consisting of a hydrophobic short channel narrowing, a hydrophilic short channel narrowing, a hydrophilic channel widening, a hydrophobic patch, and a surface tension patch.

21. A non-wetted fluid circuit having an hydrophobic inner surface and comprising a plurality of connected microchannels, wherein at least one said microchannel comprises a short microchannel narrowing, said microchannel narrowing having an inlet, an outlet, and a cross-sectional configuration relative to the microchannel tat creates a passive pressure barrier sufficient to temporarily block the flow of fluid that is advancing through said fluid circuit prior to wetting of a downstream side of said narrowing and to cause the fluid preferably to flow in an adjoining microchannel connected upstream of said narrowing rather to flow past said narrowing.

22. The fluid circuit of claim 21, wherein said fluid circuit is formed in a hydrophobic material.

23. The fluid circuit of claim 22, wherein said hydrophobic material comprises one or more materials selected from the group consisting of polytetrafluoroethylene, fluorinated ethylenepropylene, perfluoralkoxy alkane, and polyvinylidene fluoride.

24. The fluid circuit of claim 21, wherein the inner surface of said fluid circuit comprises a hydrophobic coating.

25. The fluid circuit of claim 24, wherein said hydrophobic coating comprises one or more materials selected from the group consisting of polytetrafluoroethylene, fluorinated ethylenepropylene, perfluoralkoxy alkane, and polyvinylidene fluoride.

26. A non-wetted fluid circuit having an hydrophilic inner surface and comprising a plurality of connected microchannel, wherein at least one said microchannel comprises a short microchannel narrowing, said microchannel narrowing having an inlet, an outlet, and a cross-sectional configuration relative to the microchannel that creates a passive pressure barrier sufficient to temporarily block the flow of fluid that is advancing through said fluid circuit prior to wetting of a downstream side of said narrowing and to cause the fluid preferably to flow in an adjoining microchannel connected upstream or said narrowing rather than to flow past said narrowing.

27. The fluid circuit of claim 26, wherein said fluid circuit is formed in a hydrophilic material.

29. The fluid circuit of claim 26, wherein the inner surface of said fluid circuit comprises a hydrophilic coating.

30. The fluid circuit of claim 29, wherein said hydrophilic coating is elastophilic™

.

31. A non-wetted fluid circuit comprising a plurality of connected microchannels, wherein at least one said microchannel comprises a passive pressure barrier sufficient to temporarily block the flow fluid that is advancing through said fluid circuit prior to wetting of a downstream side of said passive pressure barrier and to cause the fluid preferably to flow in an adjoining microchannel connected upstream of said passive pressure baffler rather than flowing through said passive pressure barrier, wherein said passive pressure baffler comprises a local modification to the dimensions or surface properties of said at least one microchannel selected from the group consisting of a hydrophobic patch, a surface tension patch, a hydrophobic short channel narrowing, a hydrophilic short channel narrowing, and a hydrophilic channel widening to, and wherein said passive pressure barrier is sufficient to at least temporarily block the flow of fluid in said at least one microchannel.

32. The fluid circuit of claim 31, further comprising a coating on at least a portion of said fluid circuit.

33. The fluid circuit of claim 32, wherein said coating comprises a hydrophobic material.

34. The fluid circuit of claim 33, wherein said hydrophobic material is selected from the group consisting of polytetrafluoroethylene, fluorinated ethylenepropylene, perfluoralkoxy alkane, and polyvinylidene fluoride.

35. The fluid circuit of claim 32, wherein said coating comprises a hydrophilic material.

36. The fluid circuit of claim 35, wherein said hydrophilic material is elastophilic™

.

37. A fluid circuit comprising at least a first microchannel and a second microchannel, said second microchannel joining said first microchannel at an intersection, said first microchannel comprising a passive stopping means downstream of said intersection, said passive stopping means causing fluid which is advancing through said fluid circuit preferably to flow in said second microchannel rather than to flow past said passive stopping means, wherein said passive stopping means is created by an abrupt change in the capillary force experienced by fluid advancing in said first microchannel, wherein said passive stopping means comprises a local modification to the dimensions or surface properties of said first microchannel selected from the group consisting of a hydrophobic patch, a surface tension patch, a hydrophobic short channel narrowing, a hydrophilic short channel narrowing, and a hydrophilic channel widening to, and wherein said passive stopping means is sufficient to at least temporarily block the flow of fluid in said first microchannel.

28. The fluid circuit of claim 37, wherein said hydrophilic material comprises one or more materials selected from the group consisting of metal, glass, PMMA, polycarbonate, nylon 6/12 and PVC.

38. The fluid circuit of claim 37, wherein said passive stopping means is created by a change in at least one of the contact angle between said fluid and said first microchannel and the diameter of said first microchannel.

39. 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 each of said first and second passive fluid flow barriers comprises a local modification to the dimensions or surface properties of the microchannel in which it is located selected from the group consisting of a hydrophobic patch, a surface tension patch, a hydrophobic short channel narrowing, a hydrophilic short channel narrowing, and a hydrophilic channel widening,

wherein said first and second passive fluid flow barriers are sufficient to at least temporarily block the advancing flow of fluid in the microchannel; and

wherein one of said first and second passive fluid flow barriers creates a weaker pressure barrier than the other said passive fluid flow barrier, and wherein said weaker barrier is overcome first.

40. The method of claim 39, 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.