MOVING MICRODROPLETS IN A MICROFLUIDIC DEVICE

• US 20130071851A1
• Filed: 09/14/2012
• Published: 03/21/2013
• Est. Priority Date: 03/28/2001
• Status: Active Grant

• Current Assignee: HandyLab Incorporated (Becton, Dickinson & Co)
• Original Assignee: HandyLab Incorporated (Becton, Dickinson & Co)
• Inventors: Handique, Kalyan, Parunak, Gene
• Granted Patent: US 8,703,069 B2
• Time in Patent Office: Days
• US Class Current: 435/6.12
• CPC Class Codes: B01L 2200/0605 Metering of fluids
• CPC Class Codes: B01L 2200/0647 Handling flowable solids, e.g. microscopic beads, cells, particles
• CPC Class Codes: B01L 2200/0673 Handling of plugs of fluid surrounded by immiscible fluid
• CPC Class Codes: B01L 2200/0684 Venting, avoiding backpressure, avoid gas bubbles
• 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 2200/143 Quality control, feedback systems
• CPC Class Codes: B01L 2300/0645 Electrodes
• CPC Class Codes: B01L 2300/0681 Filter
• CPC Class Codes: B01L 2300/0816 Cards, e.g. flat sample carriers usually with flow in two horizontal directions
• CPC Class Codes: B01L 2300/0867 Multiple inlets and one sample wells, e.g. mixing, dilution
• 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 2300/1827 using resistive heater
• CPC Class Codes: B01L 2400/0406 capillary forces
• CPC Class Codes: B01L 2400/0442 thermal energy, e.g. vaporisation, bubble jet
• CPC Class Codes: B01L 2400/0487 fluid pressure, pneumatics
• CPC Class Codes: B01L 2400/0633 with moving parts
• CPC Class Codes: B01L 2400/0688 surface tension valves, capillary stop, capillary break
• CPC Class Codes: B01L 2400/0694 vents used to stop and induce flow, backpressure valves
• CPC Class Codes: B01L 2400/084 Passive control of flow resistance
• 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 3/502738 : characterised by integrated valves microvalves F16K99/0001
• CPC Class Codes: B01L 3/502784 : specially adapted for droplet or plug flow, e.g. digital microfluidics automatic analysis using a stream of discrete samples in a tube system G01N35/08
• 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: C12Q 1/686 : Polymerase chain reaction [PCR]
• CPC Class Codes: F04B 19/006 : Micropumps F04B43/043 and F04B43/095 take precedence
• CPC Class Codes: F04B 19/24 : Pumping by heat expansion of pumped fluid
• CPC Class Codes: G01N 1/4077 : by other techniques involving separation of suspended solids
• CPC Class Codes: G01N 2035/1044 : Using pneumatic means
• CPC Class Codes: Y10T 436/11 : Automated chemical analysis
• CPC Class Codes: Y10T 436/117497 : with a continuously flowing sample or carrier stream
• CPC Class Codes: Y10T 436/118339 : with formation of a segmented stream
• CPC Class Codes: Y10T 436/25 : including sample preparation
• CPC Class Codes: Y10T 436/25375 : Liberation or purification of sample or separation of material from a sample [e.g., filtering, centrifuging, etc.]
• CPC Class Codes: Y10T 436/2575 : Volumetric liquid transfer

Abstract

The present invention relates to a system and method for moving samples, such as fluid, within a microfluidic system using a plurality of gas actuators for applying pressure at different locations within the microfluidic. The system includes a substrate which forms a fluid network through which fluid flows, and a plurality of gas actuators integral with the substrate. One such gas actuator is coupled to the network at a first location for providing gas pressure to move a microfluidic sample within the network. Another gas actuator is coupled to the network at a second location for providing gas pressure to further move at least a portion of the microfluidic sample within the network. A valve is coupled to the microfluidic network so that, when the valve is closed, it substantially isolates the second gas actuator from the first gas actuator.

Claims

1. A method of amplifying a nucleic acid-containing sample within a microfluidic device, the method comprising:

moving the sample from an upstream channel of the microfluidic device into a DNA manipulation module located downstream of the upstream channel, the DNA manipulation module including a DNA manipulation zone configured to perform amplification of the sample, a first valve disposed upstream of the DNA manipulation zone, and a second valve disposed downstream of the DNA manipulation zone, the only ingress to and egress from the DNA manipulation zone being through the first valve and the second valve;

receiving the sample in the DNA manipulation zone;

closing the first valve and the second valve such that gas and liquid are prevented from flowing into or out of the DNA manipulation zone; and

thermal cycling the sample in the DNA manipulation zone.

2. The method of claim 1, wherein moving the sample from an upstream channel into the DNA manipulation module comprises actuating a gas actuator.

3. The method of claim 2, wherein actuating the gas actuator comprises increasing a gas pressure within the upstream channel relative to a gas pressure within the DNA manipulation zone.

4. The method of claim 2, wherein actuating the gas actuator comprises decreasing a gas pressure within the DNA manipulation zone relative to a gas pressure within the upstream channel.

5. The method of claim 1, wherein closing the first valve and the second valve comprises heating a thermally responsive substance in the first valve and the second valve.

6. The method of claim 1, wherein thermal cycling the sample in the DNA manipulation zone comprises cyclically heating the sample with a computer-controlled heat source in thermal contact with the DNA manipulation zone.

7. The method of claim 1, wherein thermal cycling the sample in the DNA manipulation zone comprises controlling a plurality of resistive heaters in thermal contact with the DNA manipulation zone.

8. The method of claim 1, further comprising identifying the presence of one or more nucleic acids within the DNA manipulation zone.

9. The method of claim 8, wherein identifying the presence of one or more nucleic acids comprises introducing light into the DNA manipulation zone, the light selected to generate fluorescence indicative of the presence of amplified nucleic acids within the DNA manipulation zone.

10. The method of claim 1, further comprising identifying an amount of one or more amplified nucleic acids within the DNA manipulation zone.

11. A method of identifying one or more nucleic acids in a sample in a microfluidic process module of a microfluidic device, the method comprising:

moving the sample from an upstream channel into a zone located in the microfluidic process module of the microfluidic device;

closing a first valve disposed upstream of the zone and a second valve disposed downstream of the zone such that gas and liquid are prevented from exiting the zone;

thermal cycling the sample in the zone; and

identifying the presence of one or more nucleic acids in the sample in the zone.

12. The method of claim 11, wherein moving the sample from the upstream channel into the zone comprises actuating a gas actuator.

13. The method of claim 12, wherein actuating the gas actuator comprises increasing a gas pressure in the upstream channel relative to a gas pressure in the zone.

14. The method of claim 12, wherein actuating the gas actuator comprises decreasing a gas pressure in the zone relative to a gas pressure in the upstream channel.

15. The method of claim 11, wherein closing the first valve and the second valve comprises heating a thermally responsive substance in the first valve and the second valve.

16. The method of claim 11, wherein thermal cycling the sample in the zone comprises cyclically heating the sample with a computer-controlled heat source in thermal contact with the zone.

17. The method of claim 11, wherein thermal cycling the sample in the zone comprises controlling a plurality of resistive heaters in thermal contact with the zone.

18. The method of claim 11, wherein identifying the presence of one or more nucleic acids in the sample in the zone comprises introducing light into the zone, the light selected to generate fluorescence indicative of the presence of one or more amplified nucleic acids in the zone.

19. The method of claim 11, further comprising optically detecting an amount of one or more amplified nucleic acids in the zone.

20. The method of claim 11, further comprising changing at least one of the first valve and the second valve from a closed state to an open state.