MICROFLUIDIC DEVICE WITH A PCR SECTION WITH SINGLE ACTIVATION, OUTLET VALVE

• US 20110312599A1
• Filed: 06/01/2011
• Published: 12/22/2011
• Est. Priority Date: 06/17/2010
• Status: Abandoned Application

• Current Assignee: Geneasys Pty Ltd
• Original Assignee: Geneasys Pty Ltd
• Inventors: Azimi, Mehdi, Silverbrook, Kia, Worsman, Matthew Taylor, Facer, Geoffrey Richard
• Application Number:
  US13/150,167
• Publication Number:
  US 20110312599A1
• Time in Patent Office: Days
• US Class Current: 506/16
• 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 2300/023 Sending and receiving of information, e.g. using bluetooth
• CPC Class Codes: B01L 2300/024 Storing results with means integrated into the container
• CPC Class Codes: B01L 2300/0636 Integrated biosensor, microarrays
• CPC Class Codes: B01L 2300/0654 Lenses; Optical fibres
• CPC Class Codes: B01L 2300/0883 Serpentine channels
• CPC Class Codes: B01L 2300/10 Means to control humidity and/or other gases
• CPC Class Codes: B01L 2300/1827 using resistive heater
• CPC Class Codes: B01L 2400/0406 capillary forces
• CPC Class Codes: B01L 2400/0633 with moving parts
• CPC Class Codes: B01L 2400/0677 phase change valves; Meltable, freezing, dissolvable plugs; Destructible barriers
• CPC Class Codes: B01L 2400/0688 surface tension valves, capillary stop, capillary break
• 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 3/502707 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: 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 1/68 involving nucleic acids
• CPC Class Codes: F16K 99/003 Valves for single use only
• CPC Class Codes: F16K 99/0036 operated by temperature variations
• CPC Class Codes: Y02A 90/10 Information and communication technologies [ICT] supporting adaptation to climate change, e.g. for weather forecasting or climate simulation
• CPC Class Codes: Y10T 137/0352 : Controlled by pressure
• CPC Class Codes: Y10T 137/0391 : Affecting flow by the addition of material or energy
• CPC Class Codes: Y10T 137/1044 : With other condition responsive valve control
• CPC Class Codes: Y10T 137/206 : Flow affected by fluid contact, energy field or coanda effect [e.g., pure fluid device or system]
• CPC Class Codes: Y10T 137/2076 : Utilizing diverse fluids
• CPC Class Codes: Y10T 137/2202 : By movable element
• CPC Class Codes: Y10T 436/107497 : Preparation composition [e.g., lysing or precipitation, etc.]
• CPC Class Codes: Y10T 436/11 : Automated chemical analysis
• CPC Class Codes: Y10T 436/143333 : Saccharide [e.g., DNA, etc.]
• CPC Class Codes: Y10T 436/145555 : Hetero-N
• CPC Class Codes: Y10T 436/173845 : Amine and quaternary ammonium
• CPC Class Codes: Y10T 436/203332 : Hydroxyl containing
• 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.]

Abstract

A microfluidic device for amplifying nucleic acid sequences, the microfluidic device having a polymerase chain reaction (PCR) section for thermally cycling the nucleic acid sequences and a PCR mix of reagents through a denaturation temperature, an annealing temperature and a primer extension temperature, and, a PCR outlet valve to retain the nucleic acid sequences and a PCR mix of reagents in the PCR section during the thermal cycling, wherein, the PCR outlet valve is configured to open in response to an activation signal such that amplicon can flow from the PCR section and once open, the PCR outlet valve is unable to close.

Claims

1. A microfluidic device for amplifying nucleic acid sequences, the microfluidic device comprising:

a polymerase chain reaction (PCR) section for thermally cycling the nucleic acid sequences and a PCR mix of reagents through a denaturation temperature, an annealing temperature and a primer extension temperature; and

,

a PCR outlet valve to retain the nucleic acid sequences and a PCR mix of reagents in the PCR section during the thermal cycling;

wherein,

the PCR outlet valve is configured to open in response to an activation signal such that amplicon can flow from the PCR section and once open, the PCR outlet valve is unable to close.

2. The microfluidic device according to claim 1 wherein the PCR outlet valve has a meniscus anchor configured to form a meniscus that retains the nucleic acid sequences and a PCR mix of reagents in the PCR section, and an actuator for receiving the activation signal and actuating in response to the activation signal such that the meniscus unpins from the meniscus anchor and the amplicon flows out of the PCR section.

3. The microfluidic device according to claim 2 wherein the PCR outlet valve has a movable member for contacting the amplicon, and the actuator is a thermal expansion actuator for displacing the movable member to generate a pulse in the amplicon to dislodge the meniscus from the meniscus anchor.

4. The microfluidic device of claim 3 wherein the movable member is configured for movement between a quiescent position and an actuated position displaced from the quiescent position and the meniscus anchor is an aperture configured to arrest any liquid flow out of the PCR section by pinning the meniscus at the aperture.

5. The microfluidic device of claim 4 wherein the movable member at least partially defines the aperture.

6. The microfluidic device of claim 5 wherein the thermal actuator has a resistive element for causing differential thermal expansion to move the movable member.

7. The microfluidic device according to claim 6 wherein during use, the activation signal is a series of electrical pulses and in response the actuator reciprocates the movable member between the quiescent and displaced positions.

8. The microfluidic device according to claim 2 wherein the PCR outlet valve has a movable member for contacting the amplicon, and the movable member is configured to displace from a quiescent position to an actuated position such that displacement of the movable member to the actuated position extends the meniscus into contact with a surface downstream of the PCR outlet valve such that capillary action drives the amplicon flow out of the PCR section.

9. The microfluidic device according to claim 8 wherein the surface downstream of the PCR outlet valve is a capillary initiation feature for reconfiguring the meniscus and moving the meniscus away from the PCR outlet valve.

10. The microfluidic device of claim 9 wherein the thermal expansion actuator is configured to cause differential thermal expansion to move the movable member.

11. The microfluidic device of claim 2 wherein the actuator has a valve heater for heating the meniscus such that the meniscus unpins from the meniscus anchor.

12. The microfluidic device according to claim 11 wherein the meniscus anchor is an aperture configured to arrest liquid flow out of the PCR section by pinning the meniscus at the aperture and the valve heater extends about the periphery of the aperture.

13. The microfluidic device according to claim 12 wherein the valve heater is configured to boil liquid at the meniscus anchor to unpin the meniscus from the meniscus anchor.

14. The microfluidic device according to claim 1 further comprising a supporting substrate and CMOS circuitry on the supporting substrate for operatively controlling the PCR outlet valve.

15. The microfluidic device of claim 14 wherein the PCR section has a sample inlet for receiving a sample of biological material containing the nucleic acid sequences and is configured to produce sufficient amplicon for hybridization with more than 1000 probes in less than 10 minutes after the sample enters the sample inlet.

16. The microfluidic device according to claim 15 wherein the PCR section has a thermal cycle time between 0.45 seconds and 1.5 seconds.

17. The microfluidic device according to claim 14 further comprising a temperature sensor and wherein the PCR section has at least one heater for thermally cycling the nucleic acid sequences and the PCR mix, the temperature sensor and the at least one heater being connected to the CMOS circuitry for feedback control of the at least one heater.

18. The microfluidic device according to claim 14 wherein the CMOS circuitry activates the PCR outlet valve after a predetermined number of thermal cycles.

19. The microfluidic device according to claim 1 further comprising a hybridization section that has an array of probes for hybridization with target nucleic acid sequences in the amplicon.

20. The microfluidic device according to claim 19 wherein the PCR section is configured to generate enough amplicon for hybridization with the probes in less than 220 seconds.