FLUID CONTROL STRUCTURES IN MICROFLUIDIC DEVICES

• US 20090060797A1
• Filed: 09/03/2008
• Published: 03/05/2009
• Est. Priority Date: 12/30/2002
• Status: Active Grant

• Current Assignee: Regents of the University of California (University of California)
• Original Assignee: Regents of the University of California (University of California)
• Inventors: Paegel, Brian, Skelley, Alison, Blazej, Robert, Mathies, Richard A., Grover, William H., Lagally, Eric, Liu, Chung N.
• Granted Patent: US 9,651,039 B2
• Time in Patent Office: Days
• US Class Current: 422/103
• CPC Class Codes: B01F 25/50 Circulation mixers, e.g. wherein at least part of the mixture is discharged from and reintroduced into a receptacle
• CPC Class Codes: B01F 31/65 the materials to be mixed being directly submitted to a pulsating movement, e.g. by means of an oscillating piston or air column
• CPC Class Codes: B01F 33/30 Micromixers
• 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 2300/0654 Lenses; Optical fibres
• CPC Class Codes: B01L 2300/0803 Disc shape
• CPC Class Codes: B01L 2300/0816 Cards, e.g. flat sample carriers usually with flow in two horizontal directions
• CPC Class Codes: B01L 2300/0819 Microarrays; Biochips
• CPC Class Codes: B01L 2300/0861 Configuration of multiple channels and/or chambers in a single devices
• CPC Class Codes: B01L 2300/087 Multiple sequential chambers
• CPC Class Codes: B01L 2300/088 Channel loops
• CPC Class Codes: B01L 2300/0887 Laminated structure
• CPC Class Codes: B01L 2300/123 Flexible; Elastomeric
• CPC Class Codes: B01L 2300/1827 using resistive heater
• CPC Class Codes: B01L 2400/0409 centrifugal forces
• CPC Class Codes: B01L 2400/0421 electrophoretic flow
• CPC Class Codes: B01L 2400/0487 fluid pressure, pneumatics
• CPC Class Codes: B01L 2400/0638 membrane valves, flap valves
• CPC Class Codes: B01L 2400/0655 pinch valves
• CPC Class Codes: B01L 3/5025 for parallel transport of multiple samples
• 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 3/50273 : 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 7/52 : with provision for submitting samples to a predetermined sequence of different temperatures, e.g. for treating nucleic acid samples amplification or hybridisation processes per se C12Q1/68; controlling sequential reactions for synthesis B01J19/0046
• CPC Class Codes: C12Q 1/6806 : Preparing nucleic acids for analysis, e.g. for polymerase chain reaction [PCR] assay C12Q1/6804 takes precedence
• CPC Class Codes: C12Q 1/689 : for bacteria
• CPC Class Codes: C12Q 2565/629 : being a microfluidic device
• CPC Class Codes: F04B 43/06 : Pumps having fluid drive
• CPC Class Codes: F16K 99/0001 : Microvalves microdevices B81B1/00; manufacture or treatment of devices or systems in or on a substrate B81C1/00; microfluidic structures B01L3/5027; micropumps F04B19/006
• CPC Class Codes: G01N 35/00069 : whereby the sample substrate is of the bio-disk type, i.e. having the format of an optical disk
• CPC Class Codes: Y10T 137/0318 : Processes
• CPC Class Codes: Y10T 137/2224 : Structure of body of device
• CPC Class Codes: Y10T 137/87716 : For valve having a flexible diaphragm valving member

Abstract

Methods and apparatus for implementing microfluidic analysis devices are provided. A monolithic elastomer membrane associated with an integrated pneumatic manifold allows the placement and actuation of a variety of fluid control structures, such as structures for pumping, isolating, mixing, routing, merging, splitting, preparing, and storing volumes of fluid. The fluid control structures can be used to implement a variety of sample introduction, preparation, processing, and storage techniques.

Claims

1. A microfluidic structure comprising:

a first surface including a pneumatic channel;

a second surface including a fluidic channel; and

an elastomer membrane located between the first and second surfaces such that the application of a pressure or a vacuum to the pneumatic channel causes the membrane to deflect to modulate a flow of a fluid in the fluidic channel.

2. The microfluidic structure of claim 1, wherein the first and second surfaces are glass, plastic, polymer.

3. The microfluidic structure of claim 1, wherein the membrane is gas permeable.

4. The microfluidic structure of claim 1, further comprising additional surfaces and membranes.

5. The microfluidic structure of claim 4, wherein the additional surfaces have additional channels to provide paths for fluid flow.

6. The microfluidic structure of claim 1, wherein the second surface includes a plurality of vias operable to provide paths for fluid flow.

7. The microfluidic structure of claim 1 configured as part of a pump, the comprising a plurality of valves implemented using the elastomer membrane.

8. The microfluidic structure of claim 7, wherein the pump is used to form a multi-directional fluidic router.

9. The microfluidic structure of claim 1 placed in a loop and configured as part of a mixer.

10. The microfluidic structure of claim 1 placed in a series and configured as a mixer, wherein mixing is accomplished by moving fluid between two chambers.

11. The microfluidic structure of claim 1 configured as part of a reservoir.

12. The microfluidic structure of claim 11, wherein mixing is accomplished by moving a fluid between two reservoirs.

13. The microfluidic structure of claim 11, wherein multiple reservoirs are connected by a fluidic bus.

14. The microfluidic structure of claim 11, wherein the reservoir has one or more inputs and is operable as a reactor.

15. The microfluidic structure of claim 1, wherein the membrane normally prevents the flow of a fluid in the fluidic channel, the application of a vacuum to the pneumatic channel causing the membrane to deflect to allow the flow of a fluid in the fluidic channel.

16. A microfluidic structure comprising:

a first surface including a pneumatic channel;

a second surface including a plurality of vias;

a third surface including a fluidic channel; and

an elastomer membrane located between the first and second surfaces such that the application of a pressure or a vacuum to the pneumatic channel causes the membrane to deflect to modulate a flow of a fluid in the fluidic channel.

17. The microfluidic structure of claim 16, wherein the first, second, and third surfaces are glass, plastic, or polymer.

18. A microfluidic structure comprising:

means for allowing flow of a fluid on a first layer;

means for modulating the flow of the fluid on the first layer using the application of a pneumatic pressure or vacuum to control an area of a membrane coupled to the first layer.

19. A microfluidic device, comprising:

a chemically compatible layer, the chemically compatible layer having a plurality of channels, the channels operable to provide paths for fluid flow; and

a membrane layer coupled to the chemically compatible layer, wherein applying pneumatic pressure to regions of the membrane layer is operable to actuate a plurality of pneumatically switchable valves, wherein the pneumatically switchable valves are operable to control fluid flow on the microfluidic device.

20. The microfluidic device of claim 19, wherein the chemically compatible layer is a glass, plastic, or polymer layer.

21. The microfluidic device of claim 20, further comprising a pneumatic layer, the pneumatic layer having a plurality of etched channels, the etched channels operable to distribute the pneumatic pressure to regions of the membrane layer.

22. The microfluidic device of claim 21, wherein the membrane layer is sandwiched between the glass layer and the pneumatic layer.

23. The microfluidic device of claim 19, wherein three pneumatically switchable valves in series is operable to form a pump.

24. The microfluidic device of claim 23, wherein the three valves include an input valve, a diaphragm valve, and an output valve.

25. The microfluidic device of claim 19, wherein four pneumatically switchable valves are operable to form a router.

26. The microfluidic device of claim 19, wherein pneumatically switchable valves are operable to form a mixer, wherein a fluid analyte is moved back an forth between chambers to allow mixing.

27. The microfluidic device of claim 22, wherein the pneumatic layer is glass.

28. The microfluidic device of claim 20, wherein the valves are closed when no pneumatic pressure is applied.

29. The microfluidic device of claim 20, wherein a single port supplying pneumatic pressure is operable to open multiple valves.

30. The microfluidic device of claim 29, wherein the glass layer includes immunocapture chambers operable to capture a target provided to the immunocapture chambers through etched channels.

31. The microfluidic device of claim 30, wherein the plurality of immunocapture chambers are configured to hold selected antibodies.

32. The microfluidic device of claim 31, wherein the selected antibodies are held with beads, frits, sol-gels, gels, or polymer monoliths.

33. The microfluidic device of claim 32, wherein the immunocapture chambers provide the target to DNA analysis mechanisms.

34. The microfluidic device of claim 33, wherein DNA analysis mechanisms include PCR and CE mechanisms integrated on the microfluidic device.

35. The microfluidic device of claim 19, wherein three valves are placed in a loop to form a mixer.

36. The microfluidic device of claim 19, wherein valves held in the open position are operable to function as reservoirs.

37. The microfluidic device of claim 19, wherein mixing is accomplished by moving a fluid between two reservoirs.

38. The microfluidic device of claim 19, wherein multiple reservoirs are connected by a fluidic bus to form a bus valve.

39. The microfluidic device of claim 36, wherein reservoirs with one or more inputs is operable as a reactor.

40. A method for controlling fluid flow on a microfluidic device, the method comprising:

opening an input valve and closing an output valve by varying pneumatic pressure to one or more regions of a membrane layer coupled to a glass layer, the glass layer having a plurality of etched channels, the etched channels operable to provide paths for fluid flow;

opening a diaphragm valve and closing the input valve by varying pneumatic pressure; and

opening the output valve and closing the diaphragm valve, wherein closing the diaphragm valve pumps analyte fluid through the open output valve.

41. The method of claim 40, wherein varying pneumatic pressure includes applying pressure or applying vacuum pressure.

42. The method of claim 40, wherein the microfluidic device comprises a pneumatic layer, the pneumatic layer having a plurality of etched channels, the etched channels operable to distribute the pneumatic pressure to regions of the membrane layer.

43. A microfluidic device, comprising:

means for opening an input valve and closing an output valve by varying pneumatic pressure to one or more regions of a membrane layer coupled to a glass layer, the glass layer having a plurality of etched channels, the etched channels operable to provide paths for fluid flow;

means for opening a diaphragm valve and closing the input valve by varying pneumatic pressure; and

means for opening the output valve and closing the diaphragm valve, wherein closing the diaphragm valve pumps analyte fluid through the open output valve.

44. The microfluidic device of claim 43, wherein varying pneumatic pressure includes applying pressure or applying vacuum pressure.