MICROFLUIDIC DEVICE AND METHOD OF USING SAME

• US 20110053151A1
• Filed: 11/07/2008
• Published: 03/03/2011
• Est. Priority Date: 11/07/2007
• Status: Active Grant

• Current Assignee: University of British Columbia
• Original Assignee: University of British Columbia
• Inventors: HANSEN, Carl Lars Genghis, Tropini, Carolina
• Granted Patent: US 9,211,537 B2
• Time in Patent Office: Days
• US Class Current: 435/6
• CPC Class Codes: B01J 2219/00317 Microwell devices, i.e. having large numbers of wells
• CPC Class Codes: B01J 2219/00396 Membrane valves
• CPC Class Codes: B01J 2219/00398 in multiple arrangements
• CPC Class Codes: B01J 2219/00495 Means for heating or cooling the reaction vessels
• CPC Class Codes: B01J 2219/00529 DNA chips
• CPC Class Codes: B01J 2219/00596 Solid-phase processes
• CPC Class Codes: B01J 2219/00608 DNA chips
• CPC Class Codes: B01J 2219/00659 Two-dimensional arrays
• CPC Class Codes: B01J 2219/00722 Nucleotides
• CPC Class Codes: B01L 2200/0605 Metering of fluids
• CPC Class Codes: B01L 2200/0621 Control of the sequence of chambers filled or emptied
• CPC Class Codes: B01L 2200/0642 Filling fluids into wells by specific techniques
• CPC Class Codes: B01L 2200/0689 Sealing
• CPC Class Codes: B01L 2200/16 Reagents, handling or storing thereof
• CPC Class Codes: B01L 2300/0819 Microarrays; Biochips
• CPC Class Codes: B01L 2300/0829 Multi-well plates; Microtitration plates
• CPC Class Codes: B01L 2300/0864 comprising only one inlet and multiple receiving wells, e.g. for separation, splitting
• 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 2400/0487 fluid pressure, pneumatics
• 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 3/502723 : characterised by venting arrangements
• 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 3/50851 : specially adapted for heating or cooling samples laboratory heating apparatus B01L7/00; incubators C12M
• 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: G06F 3/017 : Gesture based interaction, e.g. based on a set of recognized hand gestures interaction based on gestures traced on a digitiser G06F3/04883
• CPC Class Codes: G06F 3/04815 : Interaction with a metaphor-based environment or interaction object displayed as three-dimensional, e.g. changing the user viewpoint with respect to the environment or object
• CPC Class Codes: G06F 3/04842 : Selection of displayed objects or displayed text elements G06F3/0482 takes precedence

Abstract

A microfluidic device comprising a plurality of reaction chambers in fluid communication with a flow channel formed in an elastomeric substrate, a vapor barrier for preventing evaporation from the plurality of reaction chambers, and a continuous phase fluid for isolation of each of the plurality of reaction chambers.

Claims

1. A microfluidic device comprising:

a plurality of blind reaction chambers in coplanar array, the blind reaction chambers in microfluidic-valveless fluid communication with a flow channel formed in a polymeric substrate; and

a vapor barrier applied in a parallel plane to the plurality of reaction chambers and separated from the reaction chambers by a layer of polymer.

2. The device of claim 1, further comprising a plurality of valves disposed along the flow channel, each of the plurality of valves comprising one or more control channels intersecting the flow channel.

3. The device of claim 1 wherein the valves are positioned at first and second ends of the flow channels.

4. The device of claim 1 wherein the reaction chambers are of less than one nanolitre volume.

5. The device of claim 1 wherein the reaction chambers are about 10 pL to about 100 pL volume.

6. The device of claim 1 wherein the reaction chamber has one or more pre-deposited reagents.

7. The device of claim 1 wherein the blind reaction chambers in coplanar array have a pitch of less than about 200 μ

m.

8. The device of claim 1 wherein the layer of polymer has a thickness of about 10 μ

m to about 1000 μ

m.

9. The device of claim 1 wherein the reaction chambers are present at a density of 5000 or greater chambers/cm².

10. A method of compartmentalizing a liquid in a microfluidic device, comprising:

filling under pressure a flow channel and a plurality of blind reaction chambers in coplanar array and in fluid communication with a flow channel with a first liquid, and displacing air in the blind reaction chambers through walls of the reaction chamber that are permeable to gas but not liquid;

flushing the flow channel with a second liquid and displacing the first liquid from the flow channel and not from the reaction chambers, the second liquid being immiscible with the first liquid;

wherein the first liquid in each of the plurality of reaction chambers is isolated from the first liquid in each of the other reaction chambers by the second liquid in the flow channel.

14. The method of claim 10 wherein the first liquid is an aqueous solution.

15. The method of claim 10 wherein the second liquid is a non-aqueous liquid.

16. The method of claim 10 wherein the first liquid comprises a reaction mix for PCR, or a sample, or a reaction mix for PCR and a sample.

18. The method of claim 10 wherein the reaction chambers have one or more pre-deposited reagents.

19. The method of claim 10 wherein the microfluidic device further comprises a vapour barrier in a parallel plane to the plurality of reaction chambers and separated from the reaction chambers by a layer of polymer.

20. The method of claim 10 for digital quantification of a target nucleic acid, wherein the first liquid comprises a target nucleic acid, and

wherein the method further comprises a step of incubating the microfluidic array.

28. The method of claim 20 wherein the target nucleic acid is at a suitable concentration in the first liquid to provide less than about three target nucleic acids per reaction chamber, averaged over the plurality of reaction chambers.

32. The method of claim 20, wherein the step of incubating comprises thermocycling, or an optically multiplexed assay, or thermocycling and an optically multiplexed assay.

11-13. -13. (canceled)

17. (canceled)

21-27. -27. (canceled)

29-31. -31. (canceled)

33-35. -35. (canceled)

36. A microfluidic device comprising:

a plurality of blind reaction chambers in coplanar array, in connection with a flow channel formed in a polymeric substrate; and

each of the plurality of blind reaction chambers bounded by walls and a fluid barrier preventing fluid communication between two or more reaction chambers.

37. The device of claim 36, further comprising a vapor barrier applied in a parallel plane, to the plurality of reaction chambers and separated from the reaction chambers by a layer of polymer.