Fluid control structures in microfluidic devices

• US 7,445,926 B2
• Filed: 12/29/2003
• Issued: 11/04/2008
• 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: Skelley, Alison, Mathies, Richard A., Liu, Chung N., Grover, William H., Lagally, Eric
• Primary Examiner(s): Beisner; William H
• Application Number:
  US10/750,533
• Publication Number:
  US 20040209354A1
• Time in Patent Office: 1,772 Days
• Field of Search: 435/288.5, 251/331, 137/832, 137/833, 137/863, 417/437
• US Class Current: 435/288.5
• 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 each of a plurality of fluidic channels, said fluidic channels each comprising a discontinuity and wherein the microfluidic structure comprises an elastomer membrane sandwiched between a pneumatic layer and a fluidic layer, wherein;

the pneumatic layer comprises a first surface including at least one pneumatic channel facing the membrane and valve areas aligned with said fluidic channel discontinuities;

the fluidic layer comprises a second surface including the plurality of fluidic channels facing the membrane;

the elastomeric membrane normally prevents fluid flow across the fluidic channel discontinuities; and

a vacuum to the at least one pneumatic channel causes the membrane to deflect to allow a flow of a fluid across the fluidic channel discontinuities, thereby forming the plurality of diaphragm valves.

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

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 in fluidic communication with the microfluidic structure through a plurality of vias.

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 fluidic layer includes a plurality of vias operable to provide paths for fluid flow through the fluidic layer.

7. The microfluidic structure of claim 1 configured as part of one or more pumps, wherein each pump comprises three diaphragm valves in series and comprising an input valve, a displacement valve, and an outlet valve, wherein each diaphragm valve is actuated by a different pneumatic channel and the three diaphragm valves are independently activated in a sequence designed to move fluid through the pump.

8. The microfluidic structure of claim 7, wherein one or more of the pumps is used to form a multi-directional fluidic router, said router comprising one central displacement valve in fluid communication with one or more input valves and one or more outlet valves.

9. The microfluidic structure of claim 7 configured as a mixer, wherein the input valves and output valves of the pump are each connected to admission channels to form a mixer wherein mixing is accomplished by actuating the three diaphragms in a sequence to pump the fluid in a loop or back and forth.

10. The microfluidic structure of claim 1 wherein the pneumatic layer comprises a pneumatic channel comprising a displacement chamber wherein deflection of the membrane forms a fluid reservoir in the fluidic channel.

11. The microfluidic structure of claim 10, wherein mixing is accomplished by moving a fluid between two reservoirs.

12. The microfluidic structure of claim 10, wherein reservoirs in each of a plurality of the fluidic channels are connected by a fluidic bus.

13. The microfluidic structure of claim 10, wherein the reservoir has one or more inputs and is operable as a reactor.

14. The microfluidic structure of claim 1 wherein one pneumatic channel actuates a plurality of diaphragm valves that control fluid flow in a plurality of different fluidic channels.

15. The microfluidic structure of claim 1 wherein different pneumatic channels each actuate a diaphragm valve that controls fluid flow in different fluidic channels.

16. The microfluidic structure of claim 1, wherein the first and second layers are plastic.

17. The microfluidic structure of claim 1 wherein the membrane is PDMS.

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