Thermal reaction device and method for using the same

• US 8,247,178 B2
• Filed: 10/14/2009
• Issued: 08/21/2012
• Est. Priority Date: 04/03/2003
• Status: Active Grant

• Current Assignee: Standard Biotools Incorporated
• Original Assignee: Fluidigm Corporation
• Inventors: McBride, Lincoln, Facer, Geoffrey, Unger, Marc, Lucero, Michael, Nassef, Hany Ramez
• Primary Examiner(s): Kim, Young J
• Application Number:
  US12/579,347
• Publication Number:
  US 20100184202A1
• Time in Patent Office: 1,042 Days
• Field of Search: None
• US Class Current: 435/6.12
• CPC Class Codes: B01L 2200/0642 Filling fluids into wells by specific techniques
• 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 2200/142 Preventing evaporation
• CPC Class Codes: B01L 2200/147 Employing temperature sensors
• CPC Class Codes: B01L 2300/06 Auxiliary integrated devices, integrated components
• CPC Class Codes: B01L 2300/0636 Integrated biosensor, microarrays
• 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 2300/0864 comprising only one inlet and multiple receiving wells, e.g. for separation, splitting
• CPC Class Codes: B01L 2300/0867 Multiple inlets and one sample wells, e.g. mixing, dilution
• CPC Class Codes: B01L 2300/0874 Three dimensional network
• CPC Class Codes: B01L 2300/123 Flexible; Elastomeric
• CPC Class Codes: B01L 2300/1805 Conductive heating, heat from thermostatted solids is conducted to receptacles, e.g. heating plates, blocks
• CPC Class Codes: B01L 2400/0481 squeezing of channels or chambers
• CPC Class Codes: B01L 2400/0487 fluid pressure, pneumatics
• CPC Class Codes: B01L 2400/06 Valves, specific forms thereof
• CPC Class Codes: B01L 2400/0638 membrane valves, flap valves
• CPC Class Codes: B01L 2400/0655 pinch valves
• CPC Class Codes: B01L 3/0248 Prongs, quill pen type dispenser
• CPC Class Codes: B01L 3/5025 : for parallel transport of multiple samples
• CPC Class Codes: B01L 3/5027 : by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip B01L3/5023 takes precedence; micromixers B01F33/30; microreactors for synthesis B01J19/0093; microcapillary devices in general B81B1/00
• 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: C12Q 1/68 : involving nucleic acids
• CPC Class Codes: C12Q 1/686 : Polymerase chain reaction [PCR]
• CPC Class Codes: G01N 27/453 : Cells therefor

Abstract

An M×N matrix microfluidic device for performing a matrix of reactions, the device having a plurality of reaction cells in communication with one of either a sample inlet or a reagent inlet through a via formed within an elastomeric block of the device. Methods provided include a method for forming vias in parallel in an elastomeric layer of an elastomeric block of a microfluidic device, the method comprising using patterned photoresist masks and etching reagents to etch away regions or portions of an elastomeric layer of the elastomeric block.

Claims

1. A microfluidic device for nucleic acid analysis, said device comprising a branched partitioning system comprising

a) a first flow channel in fluidic communication with a fluid inlet, said fluid inlet for introduction of a sample fluid comprising a nucleic acid;

b) a plurality of second flow channels branching from, and in fluidic communication with, said first flow channel; and

c) a plurality of valves spaced along each second flow channel, positioned so that when said valves are closed said second flow channels are each partitioned into a plurality of equally sized adjacent fluidically isolated reaction sites, wherein each said reaction site of said plurality of reaction sites is separated from an adjacent reaction site by a single valve, wherein the isolated reaction chambers are not located at intersections of pairs of flow channels;

wherein a sample fluid introduced into the inlet flows through the first flow channel into the second flow channels, and a sample fluid in a second flow channel can flow to the inlet only by passing through the first flow channel.

2. The device of claim 1 comprising one or more control channels, wherein each valve is formed from a deflectable membrane that separates a control channel from a second flow channel, wherein the membrane is disposed to be deflected into or retracted out from the second flow channel in response to an actuation force to the control channel.

3. The device of claim 2 wherein an actuation force to a single control channel closes at least one valve in each second flow channel in the branched partitioning system.

4. The device of claim 2 wherein said valves are under common control and are closed in response to a single actuation force.

5. The device of claim 2 wherein the deflectable membrane is formed from an elastomeric material having a Young'"'"'s modulus in the range of 20 Pa to 1 GPa.

6. The device of claim 4 wherein the device comprises an array of reaction sites having a density of at least 1000 reaction sites/cm².

7. The device of claim 6 wherein the device comprises at least 1000 reaction sites.

8. The device of claim 6 wherein the fluid capacity of said isolated reaction sites is less than 20 nL.

9. The device of claim 8 wherein at least one reaction site in a second flow channel is delimited by one valve and a terminal wall of the second flow channel.

10. The device of claim 2 wherein the microfluidic device comprises two branched partitioning systems, each fluidically isolated from the other, and wherein applying an actuation force to a control channels closes valves in each second flow channel in each of the two branched partitioning systems.

11. The device of claim 1 wherein the first flow channel is in fluidic communication with only one fluid inlet.