Multilevel microfluidic systems and methods

• US 8,616,227 B1
• Filed: 06/03/2013
• Issued: 12/31/2013
• 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:
  US13/909,000
• Publication Number:
  US 20130337457A1
• Time in Patent Office: 211 Days
• Field of Search: 422/100, 422/502, 422/504, 422/507, 422/537
• US Class Current: 137/3
• 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 method of mixing materials in a microfluidic device, comprising:

flowing a first material through a first flow channel formed in a first layer of a substrate;

flowing the first material through a first isolation valve, wherein the first isolation valve is disposed along the first flow channel, 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 a first chamber;

flowing the first material from the first flow channel into the first chamber;

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

flowing the second material through a second isolation valve, wherein the second isolation valve is disposed along the second flow channel, 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 a second chamber;

flowing the second material from the second flow channel into the second chamber;

actuating the control channel so as to inhibit flow through the first and second isolation valves;

flowing the first material from the first chamber through an interface valve into the second chamber, so as to mix the first material with the second material, 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 between the first chamber and the second chamber.

2. The method of claim 1, wherein the first isolation valve comprises a first deflectable membrane, the second isolation valve comprises a second deflectable membrane, and actuating the control channel comprises actuating the first and second deflectable membranes.

3. The method of claim 2, further comprising actuating an interface channel to provide fluid communication between the first chamber and the second chamber.

4. The method of claim 3, 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 a reaction channel formed in the third layer.

5. The method of claim 3, wherein the interface valve comprises a deflectable membrane, and actuating the interface channel comprises actuating the deflectable membrane.

6. The method of claim 3, comprising holding the first material in the first chamber at first pressure and holding the second material in the second chamber at a second pressure, prior to flowing the first material into the second chamber.

7. The method of claim 6, wherein the first pressure is greater than the second pressure.

8. The method of claim 6, wherein the first pressure is about 10 psi and the second pressure is about 0 psi.