Multilevel microfluidic systems and methods

• US 8,475,743 B2
• Filed: 04/13/2009
• Issued: 07/02/2013
• Est. Priority Date: 04/11/2008
• Status: Active Grant

• Current Assignee: Standard Biotools Incorporated
• Original Assignee: Fluidigm Corporation
• Inventors: Facer, Geoffrey, Fowler, Brian, Quan, Emerson Cheung, Unger, Marc
• Primary Examiner(s): Ramdhanie, Bobby
• Assistant Examiner(s): Wecker, Jennifer
• Application Number:
  US12/422,612
• Publication Number:
  US 20090257920A1
• Time in Patent Office: 1,541 Days
• Field of Search: 422/502, 422/100, 422/537, 422/102, 422/504, 422/507
• US Class Current: 422/537
• CPC Class Codes: B01F 25/20 Jet mixers, i.e. mixers using high-speed fluid streams using jets to create vortex flow B01F25/10
• CPC Class Codes: B01F 33/30 Micromixers
• 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 2200/12 Specific details about manufacturing devices
• CPC Class Codes: B01L 2200/16 Reagents, handling or storing thereof
• CPC Class Codes: B01L 2300/0627 Sensor or part of a sensor is integrated
• CPC Class Codes: B01L 2300/0816 Cards, e.g. flat sample carriers usually with flow in two horizontal directions
• CPC Class Codes: B01L 2300/0874 Three dimensional network
• CPC Class Codes: B01L 2300/0887 Laminated structure
• CPC Class Codes: B01L 2300/123 Flexible; Elastomeric
• CPC Class Codes: B01L 2400/0481 squeezing of channels or chambers
• CPC Class Codes: B01L 2400/0638 membrane valves, flap valves
• 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 3/502738 characterised by integrated valves microvalves F16K99/0001
• CPC Class Codes: B33Y 80/00 Products made by additive manufacturing
• CPC Class Codes: C12Q 1/686 Polymerase chain reaction [PCR]
• CPC Class Codes: F16K 2099/008 Multi-layer fabrications
• CPC Class Codes: F16K 2099/0084 Chemistry or biology, e.g. "lab-on-a-chip" technology
• CPC Class Codes: F16K 99/0015 Diaphragm or membrane valves
• CPC Class Codes: F16K 99/0026 Valves using channel deformation
• CPC Class Codes: F16K 99/0059 : actuated by a pilot fluid
• CPC Class Codes: G01N 2021/0346 : Capillary cells; Microcells
• CPC Class Codes: Y10T 137/0329 : Mixing of plural fluids of diverse characteristics or conditions
• CPC Class Codes: Y10T 137/2164 : Plural power inputs to single device
• CPC Class Codes: Y10T 137/2169 : Intersecting at interaction region [e.g., comparator]
• CPC Class Codes: Y10T 137/2559 : Self-controlled branched flow systems
• CPC Class Codes: Y10T 137/2655 : Biased open isolation valve
• CPC Class Codes: Y10T 137/2688 : Flow rate responsive
• CPC Class Codes: Y10T 137/87249 : Multiple inlet with multiple outlet

Abstract

Multilevel microfluidic devices include a control line that can simultaneously actuate valves for both sample and reagent lines. Microfluidic devices are configured to contain a first reagent in a first chamber and a second reagent in a second chamber, where either or both of the first and second reagents are contained at a desired or selected pressure. Operation of a microfluidic device includes transmitting second reagent from the second chamber to the first chamber, for mixing or contact with the first reagent. Microfluidic device features such as channels, valves, chambers, can be at least partially contained, embedded, or formed by or within one or more layers or levels of an elastomeric block.

Claims

1. A microfluidic device, comprising:

a first flow channel formed in a first layer of a substrate, the first flow channel is in fluid communication with a first chamber;

a first control channel formed in a second layer of a substrate, wherein the second layer is adjacent to the first layer; and

a second flow channel formed in a third layer of a substrate, wherein the third layer is adjacent to the second layer;

a reaction channel formed in the third layer, wherein the reaction channel is in fluid communication with the second flow channel, wherein a first portion of the reaction channel is in fluid communication with the first chamber, wherein a second portion of the reaction channel is in fluid communication with a second chamber, wherein an interface valve is disposed along the reaction channel to isolate the first portion from the second portion; and

a first isolation valve and a second isolation valve, each disposed along the first control channel, wherein a change in pressure within the first control channel actuates the first isolation valve to isolate the first chamber from a portion of the first flow channel and simultaneously actuates the second isolation valve to isolate the second portion of the reaction channel from the second flow channel.

2. The microfluidic device of claim 1, wherein the first isolation valve comprises a deflectable membrane.

3. The microfluidic device of claim 1, wherein the second isolation valve comprises a deflectable membrane.

4. The microfluidic device of claim 1, Wherein the first chamber disposed at least partially within the first layer.

5. The microfluidic device of claim 1, wherein the second chamber disposed at least partially within the first layer.

6. The microfluidic device of claim 1, wherein the substrate comprises an elastomeric material.

19. The microfluidic device of claim 1, wherein the first control channel modulates fluid flow within the first flow channel by deflecting a first membrane in a first direction into the first flow channel and modulates fluid flow within the second flow channel by deflecting a second membrane in a second direction into the second flow channel, wherein the first direction is opposite the second direction.

20. The microfluidic device of claim 1, wherein the first and second isolation valves are disposed at different positions horizontally along the first control channel.

21. The microfluidic device of claim 1, wherein height of the first chamber is greater than height the first flow channel.

7. A microfluidic device, comprising:

a substrate having a first layer, a second layer, and a third layer, wherein the second layer is disposed between the first and third layers;

a first chamber formed at least partially within the first layer of the substrate;

a second chamber formed at least partially within the first layer of the substrate; and

a first control channel formed in the second layer of the substrate; and

a flow channel formed in the third layer;

a reaction channel formed in the third layer, wherein the reaction channel is in fluid communication with the flow channel, wherein a first portion of the reaction channel is in fluid communication with the first chamber, wherein a second portion of the reaction channel is in fluid communication with a second chamber, wherein an interface valve is disposed along the reaction channel to isolate the first portion from the second portion; and

a first isolation valve and a second isolation valve, each disposed along the first control channel,

wherein a change in pressure within the first control channel actuates the first isolation valve to modulate a first fluid flow passing through the first layer and into the first chamber, and also simultaneously actuates the second isolation valve to modulate a second fluid flow passing through the third layer and into the second chamber.

8. The microfluidic device of claim 7, wherein the interface valve is disposed along an interface channel that provides fluid communication between the first chamber and the second chamber.

9. The microfluidic device of claim 8, wherein the interface channel is formed in the third layer.

10. The microfluidic device of claim 7, wherein the interface valve comprises a deflectable membrane.

11. A microfluidic device, comprising:

a first flow channel formed in a first layer of a substrate;

a first chamber in fluid communication with the first flow channel;

a first isolation valve disposed along the first flow channel, wherein the first isolation valve comprises a first portion of a control channel formed in a second layer of the substrate adjacent to the first layer, and is configured to control flow through the first flow channel into the first chamber;

a second flow channel formed in a third layer of the substrate adjacent to the second layer;

a second chamber in fluid communication with the second flow channel;

a second isolation valve disposed along the second flow channel, wherein the second isolation valve comprises a second portion of the control channel formed in a second layer of the substrate, and is configured to control flow through the second flow channel into the second chamber;

a reaction channel formed in the third layer of the substrate, in fluid communication with the first chamber and the second chamber;

an interface valve disposed along the reaction channel between the first and second chamber, wherein the interface valve comprises a portion of an interface channel formed in a fourth layer of the substrate adjacent to the third layer, and is configured to control flow through the reaction channel.

12. The microfluidic device of claim 11, wherein the first isolation valve comprises a deflectable membrane.

13. The microfluidic device of claim 11, wherein the second isolation valve comprises a deflectable membrane.

14. The microfluidic device of claim 11, wherein the interface valve comprises a deflectable membrane.

15. The microfluidic device of claim 11, wherein the first chamber defines a first chamber volume, the second chamber defines a second chamber volume, and the first chamber volume is less than the second chamber volume.

16. The microfluidic device of claim 11, wherein the first chamber defines a first chamber volume within a range from about 0.1 nanoliters to about 10 nanoliters.

17. The microfluidic device of claim 11, wherein the reaction channel spans a distance between the first chamber and the second chamber, and the distance comprises a length within a range from about 200 μ

m to about 400 μ

m.

22. The microfluidic device of claim 11, wherein the first and second isolation valves are disposed at different positions horizontally along the first control channel.

23. The microfluidic device of claim 11, wherein height of the first chamber is greater than height the first flow channel.

18. A microfluidic device, comprising:

a plurality of first flow channels formed in a first layer of a substrate;

a plurality of first chambers, wherein each one of the plurality of first chambers is in fluid communication with a corresponding first flow channel of the plurality of first flow channels;

a plurality of control channels formed in a second layer of the substrate adjacent to the first layer;

a plurality of first isolation valves, wherein each one of the plurality of first isolation valves is disposed along a corresponding first flow channel of the plurality of first flow channels, comprises a first portion of a corresponding control channel of the plurality of control channels, and is configured to control flow through the corresponding first flow channel into a corresponding first chamber of the plurality of first chambers;

a plurality of second flow channels formed in a third layer of the substrate adjacent to the second layer;

a plurality of second chambers, wherein each one of the plurality of second chambers is in fluid communication with a corresponding second flow channel of the plurality of second flow channels;

a plurality of second isolation valves, wherein each one of the plurality of second isolation valves is disposed along a corresponding second flow channel of the plurality of second flow channels, comprises a second portion of the corresponding control channel of the pluralityof control channels, and is configured to control flow through the corresponding second flow channel into a corresponding second chamber of the plurality of second chambers;

a plurality of reaction channels formed in the third layer of the substrate, wherein each one of the plurality of reaction channels is in fluid communication with a corresponding first chamber of the plurality of first chambers and a corresponding second chamber of the plurality of second chambers;

a plurality of interface valves, wherein each one of the plurality of interface valves is disposed along a corresponding reaction channel of the plurality of reaction channels between the corresponding first chamber and the corresponding second chamber, comprises a portion of a corresponding interface channel of a plurality of interface channels formed in a fourth layer of the substrate adjacent to the third layer, and is configured to control flow through the corresponding reaction channel.