Microfluidic system with fluid pickups

Patent metadata

Field	Value
Publication number	US-9687848-B2
Application number	US-201615230757-A
Country	US
Kind code	B2
Filing date	Aug 8, 2016
Priority date	Jun 21, 2013
Publication date	Jun 27, 2017
Grant date	Jun 27, 2017

Abstract

Microfluidic system, including methods and apparatus, for processing fluid, such as by droplet generation. In an exemplary method, a sample-containing fluid may be dispensed into a well through a sample port of a channel component. The channel component may include (a) a body having a bottom surface attached to the well, and a top surface with a microchannel formed therein, and (b) an input tube projecting into the well from the bottom surface of the body. The sample-containing fluid when dispensed may contact a bottom end of the input tube and may be retained, with assistance from gravity, out of contact with the microchannel. A pressure differential may be created that drives at least a portion of the sample-containing fluid from the well via the input tube and through the microchannel.

First claim

We claim:

1. A method of processing fluid, the method comprising:
selecting a microfluidic device including at least one well component, the at least one well component providing an input well and an output well, the microfluidic device also including a channel component attached directly to a top side of the at least one well component, the channel component including
(a) a substantially planar body including a microchannel disposed substantially horizontally in operation,
(b) an input tube projecting from the body and located in the input well, and
(c) a sample port that communicates with the input well separately from the input tube;

introducing, with a fluid-transfer device, a sample-containing fluid into the input well through the sample port and into contact with a bottom end of the input tube;
operatively connecting at least one vacuum/pressure source to the microfluidic device; and
creating a pressure differential with the at least one vacuum/pressure source that drives at least a portion of the sample-containing fluid from the input well to the output well on a path defined by the channel component, wherein the path extends upward through the input tube, through the microchannel, and downward to the output well.

2. The method of claim 1 , wherein a channel network including the microchannel is formed in a top surface of the body, further comprising a step of generating an emulsion of sample-containing droplets in the channel network.

3. The method of claim 2 , further comprising a step of collecting at least a portion of the emulsion in the output well.

4. The method of claim 3 , wherein the step of introducing includes a step of introducing at least one sample-containing fluid into each of a plurality of input wells provided by the at least one well component, and wherein the step of collecting includes a step of collecting a plurality of emulsions in a plurality of output wells provided by the at least one well component.

5. The method of claim 1 , wherein the channel component includes a cover disposed on a top surface of the body and forming a top wall of the microchannel, and wherein the step of creating a pressure differential includes a step of applying a vacuum or positive pressure to the channel component at an opening defined by the cover.

6. The method of claim 4 , wherein each emulsion of the plurality of emulsions is formed in the same channel network, and wherein each emulsion of the plurality of emulsions is formed at a different region of the channel network than each other emulsion of the plurality of emulsions.

7. The method of claim 4 , wherein droplets of each emulsion of the plurality of emulsions are disposed in a carrier fluid that forms a continuous phase of the emulsion, further comprising a step of supplying at least a portion of the carrier fluid to the channel network from a carrier port of the channel component that receives the carrier fluid from a position over the carrier port in response to the pressure differential.

8. The method of claim 1 , wherein the step of creating a pressure differential includes a step of piercing a cover disposed on the top surface of the body to create an opening in the cover, and a step of applying a vacuum or positive pressure to the channel component at the opening.

9. The method of claim 1 , further comprising a step of collecting at least a portion of the sample-containing fluid in the output well, and a step of deforming one or more channels that communicate with the output well to block fluid flow through the one or more channels and fluidically isolate the at least a portion of sample-containing fluid collected in the output well.

10. The method of claim 9 , further comprising a step of thermocycling the at least a portion of sample-containing fluid while such portion of sample-containing fluid is contained by the output well.

11. A method of processing fluid, the method comprising:
selecting a microfluidic device including at least one well component, the at least one well component providing an input well and an output well, the microfluidic device also including a channel component attached directly to a top side of the at least one well component, the channel component including
(a) a body having a top surface, wherein a plurality of microchannels are formed in the top surface, and wherein the plurality of microchannels meet one another at a channel intersection,
(b) a cover bonded to the top surface of the body and forming a top wall of each of the plurality of microchannels,
(c) an input tube projecting from a bottom surface of the body and located in the input well, and
(d) a sample port that communicates with the input well separately from the input tube;

introducing, with a fluid-transfer device, a sample-containing fluid into the input well through the sample port and into contact with a bottom end of the input tube;
operatively connecting at least one vacuum/pressure source to the microfluidic device; and
creating a pressure differential with the at least one vacuum/pressure source that drives at least a portion of the sample-containing fluid from the input well to the output well on a path defined by the channel component, wherein the path extends upward through the input tube, through the channel intersection, and downward to the output well.

12. The method of claim 11 , further comprising a step of forming sample-containing droplets at the channel intersection in response to the step of creating a pressure differential.

13. The method of claim 12 , further comprising a step of collecting an emulsion including the sample-containing droplets in the output well.

14. The method of claim 13 , further comprising a step of connecting the channel component to a source of carrier fluid, wherein the step of creating a pressure differential includes a step of driving carrier fluid from the source to the channel intersection, and wherein the emulsion includes the carrier fluid as a continuous phase.

15. The method of claim 12 , wherein the channel component includes a plurality of channel intersections, and wherein the step of creating a pressure differential includes a step of forming a respective set of sample-containing droplets at each of the channel intersections.

16. The method of claim 15 , the at least one well component providing a plurality of output wells, further comprising a step of collecting each respective set of sample-containing droplets in a different one of the output wells.

17. The method of claim 11 , wherein the step of creating a pressure differential includes a step of applying a vacuum to the output well.

Assignees

• Bio Rad Laboratories Inc

Inventors

• Makarewicz Jr Anthony J
• Bousse Luc
• Schiaffino Stefano

Classifications

• C12N15/1075

  by coupling phenotype to genotype, not provided for in other groups of this subclass · CPC title

• B01L3/502746

  characterised by the means for controlling flow resistance, e.g. flow controllers, baffles or throttle valves · CPC title

• C12Q1/6806

  Preparing nucleic acids for analysis, e.g. for polymerase chain reaction [PCR] assay (C12Q1/6804 takes precedence) · CPC title

• B01L3/502715

  characterised by interfacing components, e.g. fluidic, electrical, optical or mechanical interfaces · CPC title

• B01L3/50273

  characterised by the means or forces applied to move the fluids · CPC title