GENETIC ANALYSIS LOC WITH IN-LOC STORAGE OF ALL REQUIRED REAGENTS

• US 20110312763A1
• 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
• Application Number:
  US13/150,119
• Publication Number:
  US 20110312763A1
• Time in Patent Office: Days
• US Class Current: 506/39
• 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 (LOC) device for genetic analysis having a supporting substrate, a microsystems technology (MST) layer supported on the substrate, the MST layer having an inlet for receiving a biological sample containing target nucleic acid sequences, probes for hybridization with the target nucleic acid sequence to form probe-target hybrids, and, a plurality of reagent reservoirs containing all reagents necessary for performing the diagnostic assay.

Claims

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

a supporting substrate;

a microsystems technology (MST) layer supported on the substrate, the MST layer having an inlet for receiving a biological sample containing target nucleic acid sequences;

probes for hybridization with the target nucleic acid sequence to form probe-target hybrids; and

,

a plurality of reagent reservoirs containing all reagents necessary for performing the diagnostic assay.

2. The LOC device according to claim 1 further comprising a flow-path extending from the inlet to the probes wherein the reagent reservoirs are positioned along the flow-path for addition to the sample in the flow-path upstream of the probes.

3. The LOC device according to claim 2 wherein the reagent reservoirs each have an outlet in fluid communication with the flow-path, the outlet having a surface tension valve for retaining the reagent in the reservoir with a reagent meniscus until contact with flow of the sample along the flow-path removes the reagent meniscus.

4. The LOC device according to claim 3 wherein the reagent reservoirs each have a volume less than 1,000,000,000 cubic microns.

5. The LOC device according to claim 4 wherein each of the reagent reservoirs are supported on the MST layer, such that the MST layer is between the reagent reservoirs and the supporting substrate.

6. The LOC device according to claim 5 wherein the reagent reservoirs are defined in a cap, the cap comprising a layer of material with cavities to define the reagent reservoirs.

7. The LOC device according to claim 6 wherein at least one of the reagent reservoirs has a plurality of the outlets to increase the reagent flow rate out of the reservoir.

8. The LOC device according to claim 6 wherein the flow-path extends through the MST layer and the cap.

9. The LOC device according to claim 1 wherein the reagent reservoirs each have a vent to atmosphere sized to prevent leakage of the reagent during storage and handling of the LOC device, and allow airflow into the reagent reservoir as the reagent is added to the sample.

10. The LOC device according to claim 1 further comprising a photosensor wherein the probe-target hybrids each have a fluorophore for emitting a fluorescence signal in response to an excitation light such that the photosensor senses the fluorescence signal to generate an output indicating hybridization of the probes with the target nucleic acid sequence.

11. The LOC device according to claim 10 further comprising a hybridization chamber containing the probes, the hybridization chamber having an optical window for exposing the probes to the excitation light.

12. The LOC device according to claim 10 wherein the MST layer has a polymerase chain reaction (PCR) section for amplifying the oligonucleotides in the sample of biological material.

13. The LOC device according to claim 12 wherein the reagents contained in the reagent reservoirs include:

lysis reagent;

anticoagulant;

polymerase;

dNTP'"'"'s;

primers;

or,

ligase.

14. The LOC device according to claim 12 further comprising CMOS circuitry positioned between the MST layer and the supporting substrate, the CMOS circuitry incorporating the photosensor and bond-pads for communication with an external device.

15. The LOC device according to claim 14 wherein the CMOS circuitry controls activation and deactivation of an external light source configured to generate the excitation light.

16. The LOC device according to claim 14 further comprising an array of hybridization chambers containing different types of the probes, the probes being fluorescence resonance energy transfer (FRET) probes configured for hybridization with different target nucleic acid sequences, and the photo sensor being an array of photodiodes such that each of the hybridization chambers corresponds to a respective one of the photodiodes.

17. The LOC device according to claim 16 wherein the flow-path is configured to draw the sample from the inlet to all the hybridization chambers by capillary action.

18. The LOC device according to claim 14 wherein the CMOS circuitry has memory for identity data for the different FRET probe types.

19. The LOC device according to claim 16 wherein the array of photodiodes is less than 249 microns from the FRET probes.

20. The LOC device according to claim 1 wherein the fluorophore has a fluorescence lifetime greater than 100 nanoseconds.