Thermal reaction device and method for using the same

• US 20050145496A1
• Filed: 06/23/2004
• Published: 07/07/2005
• Est. Priority Date: 04/03/2003
• Status: Abandoned Application

• Current Assignee: Fluidigm Corporation
• Original Assignee: Fluidigm Corporation
• Inventors: Unger, Marc, Quan, Emerson, Huang, Jiang, Goodsaid, Federico
• Application Number:
  US10/876,046
• Publication Number:
  US 20050145496A1
• Time in Patent Office: Days
• US Class Current: 204/600
• CPC Class Codes: B01L 2200/0642 Filling fluids into wells by specific techniques
• CPC Class Codes: B01L 2200/142 Preventing evaporation
• CPC Class Codes: B01L 2200/147 Employing temperature sensors
• 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 2300/123 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 2400/0638 membrane valves, flap valves
• CPC Class Codes: B01L 2400/0655 pinch valves
• CPC Class Codes: B01L 3/00 Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
• 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 1/686 : 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 reacting M number of different samples with N number of different reagents comprising:

a plurality of reaction cells, each reaction cell comprising a sample chamber and a reagent chamber, said sample chamber and said reagent chamber being in fluid communication through an interface channel having an interface valve associated therewith for controlling fluid communication between said sample chamber and said reagent chamber;

a plurality of sample inlets each in fluid communication with said sample chambers;

a plurality of reagent inlets each in fluid communication with said reagent chambers;

wherein at least one of said chambers contains an oligonucleotide or protein polymer and an intercollating dye.

2. The microfluidic device of claim 1 wherein said reaction cells are formed within an elastomeric block formed from a plurality of layers bonded together and said interface value is deflectable membrane.

3. The microfluidic device of claim 1 wherein said sample inlets are in communication with said sample chamber through a sample channel and said reagent inlet is in fluid communication with said reagent chamber through a reagent channel, a portion of said sample channel and a portion of said reagent channel being oriented about parallel to each other and each having a containment valve associated therewith for controlling fluid communication therethrough.

4. The microfluidic device of claim 3 wherein said valve associated with said sample channel and said valve associated with said reagent channel are in operable communication with each other through a common containment control channel.

5. The microfluidic device of claim 4 wherein said containment common control channel located along a line about normal to one of said sample channel or said reagent channel.

6. The device of claim 1 wherein the intercollating dye is SYBR Green (TM).

7. A method for determining the denaturation temperature of protein or oligonucleotide comprising the steps of providing the device of claim 1, altering the temperature of the device, and detecting a change in the dye.

8. A microfluidic device for reacting M number of different samples with N number of different reagents comprising:

a plurality of reaction cells, each reaction cell comprising a sample chamber and a reagent chamber, said sample chamber and said reagent chamber being in fluid communication through an interface channel having an interface valve associated therewith for controlling fluid communication between said sample chamber and said reagent chamber;

a plurality of sample inlets each in fluid communication with said sample chambers;

a plurality of reagent inlets each in fluid communication with said reagent chambers;

wherein one of said sample inlets or reagent inlets is in fluid communication with one of said sample chambers or one of said reagent chambers, respectively, through a via.

9. The microfluidic device of claim 8 wherein said reaction cells are formed within an elastomeric block formed from a plurality of layers bonded together and said interface valve is deflectable membrane.

10. The microfluidic device of claim 8 wherein said sample inlets are in communication with said sample chamber through a sample channel and said reagent inlet is in fluid communication with said reagent chamber through a reagent channel, a portion of said sample channel and a portion of said reagent channel being oriented about parallel to each other and each having a containment valve associated therewith for controlling fluid communication therethrough.

11. The microfluidic device of claim 10 wherein said valve associated with said sample channel and said valve associated with said reagent channel are in operable communication with each other through a common containment control channel.

12. The microfluidic device of claim 11 wherein said containment common control channel located along a line about normal to one of said sample channel or said reagent channel.

13. A method for making a feature in an elastomeric block comprising the steps of:

providing a first elastomeric layer;

applying a photoresist layer upon a surface of said first elastomeric layer;

applying a light pattern to said photoresist layer to form a pattern of reacted photoresist material;

removing unreacted photoresist material leaving said pattern of reacted photoresist upon said surface of said first elastomeric layer;

applying an etching reagent to said first elastomeric surface to etch said surface of said first elastomeric layer not covered by said pattern of reacted photoresist material thereby removing regions of said first elastomeric layer not covered by said pattern of reacted photoresist and leaving a pattern of said elastomeric layer corresponding to said pattern of reacted photoresist material.

14. The method of claim 13 further comprising the step of removing said pattern of reacted photoresist material.

15. The method of claim 14 wherein said removing is caused by applying an adhesive tape to said surface of said elastomeric layer and said pattern of reacted photoresist material, then separating said adhesive tape from said elastomeric layer while some or all of said pattern of reacted photoresist material is removed from said surface of said elastomeric layer.

16. The method of claim 13 wherein said photoresist is SU8.

17. The method of claim 13 wherein said etching reagent comprises tetrabutylammoniumfluoride-trihydrate.

18. The method of claim 13 wherein said feature is a via.

19. The method of claim 18 wherein said elastomeric block comprises a plurality of elastomeric layers bonded together, wherein two or more elastomeric layers have recesses formed therein and one recess of one elastomeric layer is in communication with a recess of another elastomeric layer through said via.