Microfluidic reaction apparatus for high throughput screening

• US 7,815,868 B1
• Filed: 02/28/2007
• Issued: 10/19/2010
• Est. Priority Date: 02/28/2006
• Status: Expired due to Fees

• Current Assignee: Fluidigm Corporation
• Original Assignee: Fluidigm Corporation
• Inventors: Daridon, Antoine, Wyatt, Paul, May, Andrew, Wang, Jing, Cohen, David, Jones, Robert C.
• Primary Examiner(s): Griffin; Walter D
• Assistant Examiner(s): Young; Natasha
• Application Number:
  US11/680,541
• Time in Patent Office: 1,329 Days
• Field of Search: 422/129, 422/130, 204/451, 204/601
• US Class Current: 422/129
• CPC Class Codes: B01F 25/14 Mixing drops, droplets or bodies of liquid which flow together or contact each other micromixers using where the materials to be mixed are in the form of droplets B01F33/302
• CPC Class Codes: B01F 25/42 in which the mixing is affected by moving the components jointly in changing directions, e.g. in tubes provided with baffles or obstructions
• CPC Class Codes: B01F 33/302 the materials to be mixed flowing in the form of droplets
• CPC Class Codes: B01J 19/00 Chemical, physical or physico-chemical processes in general; Their relevant apparatus
• CPC Class Codes: B01J 2219/00283 Reactor vessels with top opening
• CPC Class Codes: B01J 2219/00286 Reactor vessels with top and bottom openings
• CPC Class Codes: B01J 2219/00315 Microtiter plates
• CPC Class Codes: B01J 2219/00317 Microwell devices, i.e. having large numbers of wells
• CPC Class Codes: B01J 2219/00351 Means for dispensing and evacuation of reagents
• CPC Class Codes: B01J 2219/00355 peristaltic
• CPC Class Codes: B01J 2219/00389 Feeding through valves
• CPC Class Codes: B01J 2219/00418 using pressure
• CPC Class Codes: B01L 2200/16 Reagents, handling or storing thereof
• CPC Class Codes: B01L 2300/0654 Lenses; Optical fibres
• CPC Class Codes: B01L 2300/0829 Multi-well plates; Microtitration plates
• 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 2400/0605 check valves
• CPC Class Codes: B01L 2400/0655 pinch valves
• CPC Class Codes: B01L 3/502715 : characterised by interfacing components, e.g. fluidic, electrical, optical or mechanical interfaces
• CPC Class Codes: B01L 3/502738 : characterised by integrated valves microvalves F16K99/0001
• CPC Class Codes: B01L 3/5085 : for multiple samples, e.g. microtitration plates
• 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

Abstract

An SBS-formatted microfluidic device where the geometry of the plate defines an array of interrogation areas, and where each interrogation area encompasses at least one reaction site.

Claims

1. A SBS-formatted microfluidic device comprising:

a plate having an upper surface and a lower surface, wherein the geometry of the plate defines an array of interrogation areas, wherein each interrogation area encompasses at least one reaction site; and

an elastomeric microfluidic device comprising a network of microfluidic flow channels formed therein in fluid communication with an array of reaction sites configured to mix a plurality of fluids wherein the efficiency of mixing of the fluids is greater than 35%, the network of microfluidic flow channels comprising a set of reagent input channels and a set of sample input channels, the network of microfluidic flow channels further comprising, for each reaction site

a reaction chamber;

a slug channel in communication with the reaction chamber, one of the reagent input channels, and one of the sample input channels;

a first control valve positioned to open and close the slug channel at both its interface with the reaction chamber and its interface with the sample input channel; and

a second control valve positioned to open and close the slug channel at its interface with the reagent input channel.

2. The microfluidic device of claim 1, wherein the reagent channels are in fluid communication with an array of reagent reservoirs, and the sample channels are in fluid communication with an array of sample reservoirs.

3. The microfluidic device of claim 2, wherein the array of reagent reservoirs and the array of sample reservoirs are configured in an SBS format.

4. The microfluidic device of claim 1, further comprising a network of control channels comprising a set of first control channels configured to control the flow of reagents through the reagent channels to the reaction sites, and a set of second control channels configured to control the flow of samples through the sample channels to the reaction sites.

5. The device of claim 1 adapted to perform at least four reactions sequentially.

6. The device of claim 1 adapted to perform at least four reactions simultaneously.

7. The device of claim 1, wherein the geometry of the plate defines an array of 96 interrogation areas.

8. The device of claim 1, wherein the geometry of the plate defines an array of 384 interrogation areas.

9. The device of claim 1, wherein each interrogation areas has an area of about 9 mm² to 63 mm².

10. The device of claim 1, wherein the plate comprises at least 96, at least 192, at least 384, at least 768, at least 1536, at least 3072, at least 6144, or at least 21288 reaction sites.

11. The device of claim 1, wherein each reaction site has an area of about 0.25 mm² and 16 mm².

12. The device of claim 1, wherein each reaction site is defined by a well having a volume of about 1 nL to about 1000 nL.

13. The device of claim 1, wherein the device is compatible with a SBS formatted high throughput screening apparatus.

14. A system for carrying out a reaction, the system comprising the SBS-formatted microfluidic device of claim 1, and at least one flowable reagent wherein the reagent comprises a dye.

15. The system of claim 14 comprising at least two reagents, each of which comprises a different dye.

16. A system comprising the SBS-formatted microfluidic device of claim 1 and a machine for reading such a device, wherein the machine is adapted to accept a SBS-formatted plate.

17. The system of claim 16, wherein the machine comprises a detection apparatus adapted to detect a plurality of signals at a plurality of target locations on an SBS-formatted plate, wherein the target locations are defined by the geometry of the SBS-formatted plate.