Fluid control structures in microfluidic devices

• US 9,651,039 B2
• Filed: 09/03/2008
• Issued: 05/16/2017
• 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: Grover, William H., Skelley, Alison, Lagally, Eric, Liu, Chung N., Mathies, Richard A.
• Primary Examiner(s): Beisner, William H.
• Application Number:
  US12/203,800
• Publication Number:
  US 20090060797A1
• Time in Patent Office: 3,177 Days
• Field of Search: 4352885
• 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 plurality of diaphragm valves that control fluid flow along a plurality of non-intersecting portions of microfluidic channels, wherein the plurality of diaphragm valves are configured to be actuated by a pneumatic control channel that connects the plurality of diaphragm valves together and wherein the microfluidic structure comprises a pneumatic layer comprising the pneumatic control channel and a fluidic layer comprising the plurality of non-intersecting portions of the microfluidic channels and a plurality of via holes at each of the plurality of diaphragm valves, wherein the plurality of non-intersecting portions of the microfluidic channels are in fluidic communication with an elastomer membrane sandwiched between the pneumatic layer and the fluidic layer through the plurality of via holes, and wherein applying pneumatic pressure through the pneumatic control channel actuates the plurality of diaphragm valves in parallel.

2. The microfluidic structure of claim 1 wherein the elastomer membrane is a monolithic membrane.

3. The microfluidic structure of claim 1 wherein the elastomer membrane comprises polydimethysiloxane (PDMS).

4. The microfluidic structure of claim 1 wherein the elastomer membrane is thermally bonded to the fluidic layer.

5. The microfluidic structure of claim 1 wherein the elastomer membrane is chemically bonded to the fluidic layer by UV ozone treatment.

6. The microfluidic structure of claim 1 comprising more than four layers.

7. The microfluidic structure of claim 1 wherein the pneumatic pressure is a vacuum that opens the plurality of diaphragm valves.

8. The microfluidic structure of claim 1 wherein the pneumatic pressure is a pressure that closes the plurality of diaphragm valves.

9. The microfluidic structure of claim 1 wherein the fluidic layer comprises glass.

10. The microfluidic structure of claim 1 wherein the fluidic layer comprises plastic.

11. The microfluidic structure of claim 1 wherein the pneumatic layer comprises glass.

12. The microfluidic structure of claim 1 wherein the pneumatic layer comprises plastic.

13. The microfluidic structure of claim 1 wherein fluid flow in each of the plurality of non-intersecting portions of the microfluidic channels is controlled by a plurality of diaphragm valves and the pneumatic layer comprises a plurality of pneumatic control channels each actuating a diaphragm valve in each of a plurality of different non-intersecting portions of the microfluidic channels.

14. The microfluidic structure of claim 1 further comprising a series of three diaphragm valves configured to function as a diaphragm pump for each microfluidic channel.

15. The microfluidic structure of claim 14 wherein the three diaphragm valves are independently actuatable.

16. The microfluidic structure of claim 1 comprising a router, wherein the router comprises at least three microfluidic channels meeting at a central diaphragm valve, wherein fluid flow in each of the at least three microfluidic channels is controlled by a diaphragm valve different from the central diaphragm valve.

17. The microfluidic structure of claim 16 wherein the router comprises four microfluidic channels meeting at the central diaphragm valve, wherein fluid flow in each of the four microfluidic channels is controlled by a diaphragm valve different from the central diaphragm valve.

18. The microfluidic structure of claim 1 comprising a mixing loop, wherein the mixing loop comprises three diaphragm valves connected in a loop and microfluidic fluidic channels providing fluidic access to and from the mixing loop.

19. The microfluidic structure of claim 18 wherein the pneumatic layer comprises a pneumatic channel comprising a displacement chamber wherein deflection of the elastomer membrane forms a fluid reservoir in a microfluidic channel.

20. The microfluidic structure of claim 19 wherein mixing is accomplished by moving a fluid between two fluid reservoirs.

21. The microfluidic structure of claim 19 wherein fluid reservoirs in each of a plurality of microfluidic channels are connected by a fluidic bus.

22. The microfluidic structure of claim 19 wherein the fluid reservoir has one or more inputs and is operable as a reactor.

23. The microfluidic structure of claim 1 wherein the pneumatic layer further comprises one or more pneumatic ports to supply vacuum to the pneumatic control channel.

24. The microfluidic structure of claim 1 wherein the elastomer membrane is a monolithic membrane comprising PDMS, the fluidic layer and the pneumatic layer comprise glass, and the valves are normally closed.

25. The microfluidic structure of claim 1, wherein the plurality of diaphragm valves are normally closed.

26. The microfluidic structure of claim 1, wherein the plurality of diaphragm valves are normally open.

27. The microfluidic structure of claim 1, wherein the pneumatic layer is a single layer.

28. The microfluidic structure of claim 1, wherein the plurality of via holes at each diaphragm valve are in fluidic communication with each other when each valve is normally open.

29. The microfluidic structure of claim 1, wherein the plurality of via holes is a pair of via holes.

30. A microfluidic structure comprising a plurality of diaphragm valves that control fluid flow along a plurality of non-intersecting portions of microfluidic channels, wherein the plurality of diaphragm valves are configured to be actuated by a pneumatic control channel that connects the plurality of diaphragm valves together and wherein the microfluidic structure comprises a pneumatic layer comprising the pneumatic control channel and a single layer fluidic layer comprising the non-intersecting portions of the microfluidic channels and a plurality of via holes at each of the plurality of diaphragm valves, wherein the non-intersecting portions of the microfluidic channels are in fluidic communication with an elastomer membrane sandwiched between the pneumatic layer and the single fluidic layer through the plurality of via holes, and wherein applying pneumatic pressure through the pneumatic control channel actuates the valves in parallel.

31. The microfluidic structure of claim 30, wherein the plurality of diaphragm valves are normally closed.

32. The microfluidic structure of claim 30, wherein the plurality of diaphragm valves are normally open.

33. The microfluidic structure of claim 30, wherein the pneumatic layer is a single layer.

34. The microfluidic structure of claim 30, further comprising a series of three diaphragm valves configured to function as a diaphragm pump for a microfluidic channel.

35. A microfluidic structure comprising a plurality of diaphragm valves that control fluid flow along a plurality of non-intersecting portions of microfluidic channels, wherein the plurality of diaphragm valves are configured to be actuated by a pneumatic control channel that connects the plurality of diaphragm valves together and wherein the microfluidic structure comprises a pneumatic layer comprising the pneumatic control channel and a gas-impermeable fluidic layer comprising the non-intersecting portions of the microfluidic channels and a plurality of via holes at each of the plurality of diaphragm valves, wherein the non-intersecting portions of the microfluidic channels are in fluidic communication with an elastomer membrane sandwiched between the pneumatic layer and the fluidic layer through the plurality of via holes, and wherein applying pneumatic pressure through the pneumatic control channel actuates the valves in parallel.

36. The microfluidic structure of claim 35, wherein the plurality of diaphragm valves are normally closed.

37. The microfluidic structure of claim 35, wherein the plurality of diaphragm valves are normally open.

38. The microfluidic structure of claim 35, wherein the pneumatic layer is a single layer.

39. The microfluidic structure of claim 35, further comprising a series of three diaphragm valves configured to function as a diaphragm pump for each microfluidic channel.