Microfluidic rotary flow reactor matrix

• US 7,964,139 B2
• Filed: 07/23/2009
• Issued: 06/21/2011
• Est. Priority Date: 08/11/2003
• Status: Expired due to Fees

• Current Assignee: California Institute of Technology
• Original Assignee: California Institute of Technology
• Inventors: Liu, Jian, Hansen, Carl L., Quake, Stephen R.
• Primary Examiner(s): Griffin; Walter D
• Assistant Examiner(s): Mui; Christine T
• Application Number:
  US12/508,251
• Publication Number:
  US 20100104477A1
• Time in Patent Office: 698 Days
• Field of Search: 422/100, 422/99, 422/50, 422/63, 422/500, 137/824, 435/6, 435/7.9, 435/287.2
• US Class Current: 422/63
• 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 2219/00828 Silicon wafers or plates
• CPC Class Codes: B01J 2219/00833 Plastic
• CPC Class Codes: B01J 2219/00891 Feeding or evacuation
• CPC Class Codes: B01J 2219/0095 Control aspects
• 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 2300/0816 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 2300/088 Channel loops
• CPC Class Codes: B01L 2300/123 Flexible; Elastomeric
• CPC Class Codes: B01L 2300/1827 using resistive heater
• CPC Class Codes: B01L 2400/0481 squeezing of channels or chambers
• 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 3/502715 characterised by interfacing components, e.g. fluidic, electrical, optical or mechanical interfaces
• 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: B81B 3/00 : Devices comprising flexible or deformable elements, e.g. comprising elastic tongues or membranes B81B5/00 takes precedence
• CPC Class Codes: C12Q 1/68 : involving nucleic acids
• CPC Class Codes: F04B 43/043 : Micropumps
• CPC Class Codes: F04B 43/14 : having plate-like flexible members
• CPC Class Codes: G01N 2035/00158 : Elements containing microarrays, i.e. "biochip"

Abstract

A microfluidic device comprises a matrix of rotary flow reactors. The microfluidic matrix device offers a solution to the “world-to-chip” interface problem by accomplishing two important goals simultaneously: an economy of scale in reagent consumption is achieved, while simultaneously minimizing pipetting steps. N² independent assays can be performed with only 2N+1 pipetting steps, using a single aliquot of enzyme amortized over all reactors. The chip reduces labor relative to conventional fluid handling techniques by using an order of magnitude less pipetting steps, and reduces cost by consuming two to three orders of magnitude less reagents per reaction. A PCR format has immediate applications in medical diagnosis and gene testing. Beyond PCR, the microfluidic matrix chip provides a universal and flexible platform for biological and chemical assays requiring parsimonious use of precious reagents and highly automated processing.

Claims

1. A microfluidic device comprising:

a plurality of flow channels defined within an elastomer layer to form a matrix of rotary flow reactors;

a first set of control lines proximate to and separated from the flow channels by first elastomer membranes, the first elastomer membranes actuable to introduce fluids into the rotary flow reactors and to isolate the rotary flow reactors; and

a second set of control lines proximate to and separated from the flow channels by second elastomer membranes, the second elastomer membranes actuable to cause peristaltic pumping of the fluids within the isolated rotary flow reactors.

2. The microfluidic device of claim 1, wherein each rotary flow reactor comprises a plurality of column flow channels and a plurality of row flow channels from the plurality of flow channels.

3. The microfluidic device of claim 2, wherein the plurality of column flow channels and the plurality of row flow channels of each rotary flow reactor comprises a first column flow channel, a second column flow channel, a first row flow channel, and a second row flow channel.

4. The microfluidic device of claim 3, wherein the first column flow channel and the second column flow channel of each respective rotary flow reactor are coupled with at least a third row flow channel forming another rotary flow reactor.

5. The microfluidic device of claim 4, further comprising a third set of control lines proximate to and separated from the flow channels by third elastomer membranes, the third elastomer membranes actuable to isolate the first column flow channel from the second column flow channel of each respective rotary flow reactor.

6. The microfluidic device of claim 1, further comprising a common supply flow channel coupled with at least a subset of the plurality of column flow channels.

7. The microfluidic device of claim 1, further comprising a common waste flow channel coupled with at least a subset of the rotary flow reactors.

8. The microfluidic device of claim 1, further comprising a plurality of chamber structures, wherein each rotary flow reactor is coupled with at least one of the chamber structures.

9. The microfluidic device of claim 2, wherein at least a subset of the row flow channels from the plurality of flow channels each comprises a horizontal branch channel.