Moving microdroplets in a microfluidic device

• US 8,273,308 B2
• Filed: 10/30/2007
• Issued: 09/25/2012
• Est. Priority Date: 03/28/2001
• Status: Expired due to Term

• Current Assignee: HandyLab Incorporated (Becton, Dickinson & Co)
• Original Assignee: HandyLab Incorporated (Becton, Dickinson & Co)
• Inventors: Handique, Kalyan, Parunak, Gene
• Primary Examiner(s): Sines, Brian J
• Application Number:
  US11/929,971
• Publication Number:
  US 20080050804A1
• Time in Patent Office: 1,792 Days
• Field of Search: 422/68.1, 422/81, 422/82, 422/100, 422/502, 422/503, 422/504, 422/509
• US Class Current: 422/503
• 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

This disclosure provides systems, methods, and devices for processing samples on a microfluidic device. One system includes a microfluidic device having an upstream channel, a DNA manipulation zone located downstream from the upstream channel and configured to perform PCR amplification of a sample, a first valve disposed upstream of the DNA manipulation zone, and a second valve disposed downstream of the DNA manipulation zone. The system also includes a controller programmed to close the first and second valves to prevent gas and liquid from flowing into or out of the DNA manipulation zone, and a computer-controlled heat source in thermal contact with the DNA manipulation zone.

Claims

1. A system, comprising:

a microfluidic device;

a computer-controlled heat source; and

a detector;

wherein the microfluidic device comprises;

an upstream channel;

a DNA manipulation module located downstream from the upstream channel;

a DNA manipulation zone within the DNA manipulation module and configured to perform PCR amplification of a sample;

a first valve disposed within the DNA manipulation module upstream of the DNA manipulation zone;

a second valve disposed within the DNA manipulation module downstream of the DNA manipulation zone; and

a vent disposed within the DNA manipulation module and separated from the upstream channel by the first and second valves;

a controller programmed to close the first and second valves to prevent gas and liquid from flowing into or out of the DNA manipulation zone when amplification of the sample occurs, wherein the only ingress to and egress from the DNA manipulation zone is through the first and second valves, and wherein the computer-controlled heat source is in thermal contact with the DNA manipulation zone; and

wherein the detector is configured to identify one or more polynucleotides within the DNA manipulation zone.

2. The microfluidic device of claim 1, wherein the DNA manipulation zone is configured to receive a microdroplet of lysed cell sample and reagent fluid from the upstream channel.

3. The microfluidic device of claim 2, wherein the microfluidic device is configured to subject the lysed cell sample and reagent fluid to a polymerase chain reaction thereby providing amplified polynucleotides.

4. The microfluidic device of claim 3, wherein the detector comprises a light source configured to introduce light to the DNA manipulation zone, the light selected to generate fluorescence indicative of the amount of amplified polynucleotides present therein.

5. The microfluidic device of claim 1, wherein the detector is an optical detector in optical communication with the DNA manipulation zone.

6. The microfluidic device of claim 1, wherein the vent is configured to prevent pressure from increasing within the DNA manipulation zone.

7. The microfluidic device of claim 1, wherein the computer-controlled heat source is configured to control thermal cycling of the DNA manipulation zone.

8. The microfluidic device of claim 2 further comprising an actuator configured to move a microdroplet of lysed cell sample into the DNA manipulation zone.

9. The microfluidic device of claim 8, wherein the actuator is a gas actuator, and the device is configured to move the lysed cell sample and reagent fluid from the upstream channel to the DNA manipulation zone by opening the first valve and actuating the gas actuator to thereby increase a gas pressure within the upstream channel relative to a gas pressure within the DNA manipulation zone.

10. The microfluidic device of claim 8, wherein the actuator is a gas actuator, and the device is configured to move the lysed cell sample and reagent fluid from the upstream channel to the DNA manipulation zone by opening the first valve and actuating the gas actuator to thereby decrease a gas pressure within the DNA manipulation zone relative to a gas pressure within the upstream channel.

11. The microfluidic device of claim 1, wherein the first and second valves comprise a thermally responsive substance.

12. The microfluidic device of claim 11, wherein the first and second valves are thermally actuated.

13. The microfluidic device of claim 12, wherein the first and second valves are reversible between an open and a closed state.

14. The microfluidic device of claim 13, wherein the first and second valves are configured, when in the closed state, to prevent gas and liquid within the DNA manipulation zone from entering or exiting the DNA manipulation zone.

15. The microfluidic device of claim 1, wherein the device further comprises a lower substrate and an upper substrate, and the DNA manipulation zone, first and second valves, and vent are integral with the upper substrate.

16. The microfluidic device of claim 15, wherein the computer-controlled heat source comprises a plurality of resistive heaters.

17. The microfluidic device of claim 16, wherein the lower substrate has a glass base and an oxide layer, wherein the oxide layer contains the plurality of resistive heaters, and wherein the upper substrate has a bottom surface bonded to the oxide layer on the lower substrate.

18. A device, comprising:

a microfluidic process module;

a computer-controlled heat source; and

a detector;

wherein the microfluidic process module comprises;

a zone configured to receive a sample and perform amplification of the sample;

a first valve upstream of the zone;

a second valve downstream of the zone; and

a vent separated from the first valve by the second valve;

a controller programmed to close the first and second valves to prevent gas and liquid from flowing into or out of the zone when amplification of the sample occurs in the zone, wherein the only ingress to and egress from the zone is through the first and second valves;

wherein the computer-controlled heat source is in thermal contact with the zone; and

wherein the detector is configured to identify one or more polynucleotides within the zone.

20. The system of claim 18, wherein the first and second valves comprise a thermally responsive substance.

21. The system of claim 18, wherein the first and second valves are thermally actuated.

22. The system of claim 18, wherein the first and second valves are reversible between an open and a closed state.

19. A system, comprising:

a microfluidic device;

a computer-controlled heat source; and

a detector;

wherein the microfluidic device comprises;

an upstream channel;

a DNA manipulation zone located downstream from the upstream channel and configured to perform PCR amplification of a sample;

a first valve disposed upstream of the DNA manipulation zone; and

a second valve disposed downstream of the DNA manipulation zone;

a controller programmed to close the first and second valves to prevent gas and liquid from flowing into or out of the DNA manipulation zone and to isolate and confine the sample to a region between the first and second valves accessible to the detector, wherein the only ingress to and egress from the region accessible to the detector is through the first and second valves; and

wherein the computer-controlled heat source is in thermal contact with the DNA manipulation zone and wherein the detector is configured to identify one or more polynucleotides within the DNA manipulation zone.

23. The system of claim 19, wherein the first and second valves comprise a thermally responsive substance.

24. The system of claim 19, wherein the first and second valves are thermally actuated.

25. The system of claim 19, wherein the first and second valves are reversible between an open and a closed state.