GENETIC ANALYSIS LOC WITH THERMAL BEND ACTUATED PRESSURE PULSE VALVE

• US 20110312600A1
• 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: Silverbrook, Kia, Azimi, Mehdi, Worsman, Matthew Taylor
• Application Number:
  US13/150,173
• Publication Number:
  US 20110312600A1
• 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 lab-on-a-chip device (LOC) for genetic analysis having a supporting substrate, an array of probes for hybridization with target nucleic acid sequences to form probe-target hybrids, a channel for directing a flow of liquid containing the target nucleic acid sequences, the channel having an inlet, an outlet and a meniscus anchor between the inlet and the outlet such that the flow from the inlet towards the outlet stops at the meniscus anchor where the liquid forms a meniscus, and, an actuator valve with a movable member for contacting the liquid, and a thermal expansion actuator for displacing the movable member to generate a pulse in the liquid to dislodge the meniscus such that the liquid flow towards the outlet resumes.

Claims

1. A lab-on-a-chip device (LOC) for genetic analysis comprising:

a supporting substrate;

an array of probes for hybridization with target nucleic acid sequences to form probe-target hybrids;

a channel for directing a flow of liquid containing the target nucleic acid sequences, the channel having an inlet, an outlet and a meniscus anchor between the inlet and the outlet such that the flow from the inlet towards the outlet stops at the meniscus anchor where the liquid forms a meniscus; and

,

an actuator valve with a movable member for contacting the liquid, and a thermal expansion actuator for displacing the movable member to generate a pulse in the liquid to dislodge the meniscus such that the liquid flow towards the outlet resumes.

2. The LOC device according to claim 1 wherein the channel is configured to draw liquid from the inlet to the outlet by capillary action.

3. The LOC device according to claim 2 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 the liquid flow by pinning the meniscus at the aperture.

4. The LOC device according to claim 3 wherein the movable member at least partially defines the aperture.

5. The LOC device according to claim 4 wherein the thermal actuator has a resistive element for causing differential thermal expansion to move the movable member.

6. The LOC device according to claim 5 wherein the actuator valve reciprocates the movable member between the quiescent and displaced positions until the channel immediately downstream of the aperture is filled enough for capillary action to re-establish the liquid flow in the flow direction.

7. The LOC device according to claim 6 further comprising CMOS circuitry positioned between the channel and the supporting substrate for operatively controlling the actuator valve;

and,

at least one sensor responsive to the liquid flow wherein the at least one sensor provides feedback to the CMOS circuitry for use in the operative control of the actuator valve;

wherein,

the at least one sensor is a liquid sensor for sensing the presence or absence of liquid at a position in the channel.

8. The LOC device according to claim 7 wherein the aperture is a nozzle in the movable member.

9. The LOC device according to claim 8 wherein the movable member is a cantilevered structure with the nozzle at the free end and the resistive element between the nozzle and the fixed end.

10. The LOC device according to claim 9 further comprising a polymerase chain reaction (PCR) section for thermally cycling oligonucleotides and a PCR mix of reagents through a denaturation temperature, an annealing temperature and a primer extension temperature wherein the actuator valve is a PCR section outlet valve for retaining the oligonucleotides and a PCR mix of reagents in the PCR section during the thermal cycling, and the PCR outlet valve being configured to open in response to an activation signal such that amplicon can flow to the array of probes.

11. The LOC device according to claim 10 wherein the PCR section is configured to produce sufficient amplicon for more than 1000 of the probes in less than 10 minutes after the sample enters the sample inlet.

12. The LOC device according to claim 10 wherein the PCR section has a thermal cycle time between 0.45 seconds and 1.5 seconds.

13. The LOC device according to claim 10 further comprising a temperature sensor and wherein the PCR section has at least one heater for thermally cycling the oligonucleotides 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.

14. The LOC device according to claim 10 wherein the CMOS circuitry activates the PCR outlet valve after a predetermined number of thermal cycles.

15. The LOC device according to claim 1 wherein the PCR section has a plurality of elongate PCR chambers having a longitudinal extent much greater than its lateral dimensions, and a plurality of heaters, each of the heaters being elongate and parallel with the longitudinal extent of the PCR chambers.

16. The LOC device according to claim 15 wherein the PCR section has a microchannel with a PCR inlet and a PCR outlet, and the elongate PCR chambers are sections of the microchannel.

17. The LOC device according to claim 16 wherein the microchannel is configured to draw liquid containing the nucleic acid sequences from the PCR inlet to the PCR outlet by capillary action.

18. The LOC device according to claim 17 wherein the microchannel has a serpentine configuration formed by a series of wide meanders, each of the wide meanders being a channel section that forms one of the elongate PCR chambers.

19. The LOC device according to claim 18 wherein the channel section forming each of the wide meanders has a plurality of the elongate heaters.

20. The LOC device according to claim 19 wherein the plurality of elongate heaters are independently operable.