Fluid control structures in microfluidic devices

• US 9,644,623 B2
• Filed: 05/18/2010
• Issued: 05/09/2017
• 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: Mathies, Richard A., Grover, William H., Skelley, Alison, Lagally, Eric, Liu, Chung N.
• Primary Examiner(s): Beisner, William H
• Application Number:
  US12/782,598
• Publication Number:
  US 20100224255A1
• Time in Patent Office: 2,548 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 method for controlling fluid flow on a microfluidic device, the method comprising:

providing a microfluidic device comprising one or more elastomer membranes sandwiched between a pneumatic layer and a fluidic layer, wherein the fluidic layer comprises a plurality of fluidic channels, each of which comprises of a discontinuity, and a plurality of via holes at the discontinuity, wherein the pneumatic layer comprises a first surface including at least one pneumatic channel facing an elastomer membrane and valve areas aligned with said discontinuities, the fluidic layer comprising a second surface including the plurality of via holes facing the one or elastomer membranes;

controlling fluidic flow across a fluidic channel by varying pneumatic pressure in a pneumatic channel thereby causing an elastomer membrane to deflect at a discontinuity of the fluidic channel to modulate a flow of a fluid volume from one side of the discontinuity, through the plurality of via holes, to the other side of the discontinuity; and

varying pneumatic pressure in one pneumatic channel to thereby cause one or more elastomer membranes to deflect at discontinuities of a plurality of fluidic channels to modulate flow of a plurality of fluid volumes in the plurality of fluidic channels.

2. The method of claim 1, wherein the microfluidic device further comprises an input valve, an output valve and a diaphragm valve, the input valve, output valve and diaphragm valves being in series and wherein the method further comprises opening the input valve and closing the output valve by varying pneumatic pressure to the one or more of the elastomer membranes, opening the 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 fluid through the open output valve.

3. The method of claim 1, wherein causing an elastomer membrane to deflect at a discontinuity of the fluidic channel to modulate a flow of a fluid volume from one side of the discontinuity, through the plurality of via holes, to the other side of the discontinuity comprises causing the elastomer membrane to deflect away from the discontinuity to provide a path for the fluid volume across the discontinuity.

4. The method of claim 1, wherein causing an elastomer membrane to deflect at a discontinuity of the fluidic channel to modulate a flow of a fluid volume from one side of the discontinuity, through the plurality of via holes, to the other side of the discontinuity comprises causing the elastomer membrane to deflect toward from the discontinuity to prevent flow of the fluid volume across the discontinuity.

5. The method of claim 1, wherein the fluidic layer is gas impermeable.

6. The method of claim 1, further comprising varying pneumatic pressure in a plurality of pneumatic channels to thereby cause one or more elastomer membranes to deflect modulate flow of a plurality of fluid volumes in the plurality of fluidic channels.

7. The method of claim 1, further comprising deflecting one or more of the elastomer membranes within a displacement chamber in the pneumatic layer to thereby form a fluid reservoir in a fluidic channel.

8. The method of claim 1, wherein varying the pneumatic pressure in the pneumatic channel comprises applying vacuum to the pneumatic channel.

9. The method of claim 1, wherein varying the pneumatic pressure in the pneumatic channel comprises applying pressure to the pneumatic channel.

10. The method of claim 1, wherein varying the pneumatic pressure in the pneumatic channel comprises applying pressure or vacuum to a port in the pneumatic layer.

11. The method of claim 1, wherein the pneumatic layer is plastic.

12. The method claim 1, wherein the fluidic layer is plastic.

13. The method of claim 1, wherein the microfluidic device has only one elastomeric layer.