Integrated multiplex target analysis

• US 9,957,553 B2
• Filed: 10/24/2013
• Issued: 05/01/2018
• Est. Priority Date: 10/24/2012
• Status: Active Grant

• Current Assignee: Roche Molecular Systems (Roche Holding AG)
• Original Assignee: Genmark Diagnostics Incorporated (Roche Holding AG)
• Inventors: Kayyem, Jon Faiz, Srinivasan, Jayashankar, Ford, Sean
• Primary Examiner(s): CROW, ROBERT THOMAS
• Application Number:
  US14/062,865
• Publication Number:
  US 20140194305A1
• Time in Patent Office: 1,650 Days
• Field of Search: None
• CPC Class Codes: B01L 2200/025 Align devices or objects to ensure defined positions relative to each other
• 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 2200/16 Reagents, handling or storing thereof
• CPC Class Codes: B01L 2300/021 Identification, e.g. bar codes
• CPC Class Codes: B01L 2300/0672 Integrated piercing tool
• 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 2300/1822 using Peltier elements
• CPC Class Codes: B01L 2300/1827 using resistive heater
• CPC Class Codes: B01L 2400/0427 Electrowetting
• CPC Class Codes: B01L 2400/0481 squeezing of channels or chambers
• CPC Class Codes: B01L 2400/0683 mechanically breaking a wall or membrane within a channel or chamber
• CPC Class Codes: B01L 3/502715 characterised by interfacing components, e.g. fluidic, electrical, optical or mechanical interfaces
• 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 3/523 with means for closing or opening
• 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: B01L 9/527 for microfluidic devices, e.g. used for lab-on-a-chip
• CPC Class Codes: C12Q 1/6825 Nucleic acid detection involving sensors

Abstract

This invention provides biochip cartridges and instrument devices for the detection and/or analysis of target analytes from patient samples.

Claims

1. A biochip cartridge for detecting a target analyte, the biochip cartridge comprising:

A) a bottom substrate

B) a top plate;

C) a liquid reagent module comprising a plurality of blisters; and

D) an external housing having open areas over at least one of the plurality of blisters.

2. A biochip cartridge according to claim 1, wherein said top plate comprises a conductive surface.

3. A biochip cartridge according to claim 1, wherein said top plate comprises at least one fluid hole spatially corresponding to said bottom substrate.

4. A biochip cartridge according to claim 1, wherein said bottom substrate comprises a dried assay reagent.

5. A biochip cartridge according to claim 1, wherein said liquid reagent module further comprises an aliquot of magnetic capture beads.

6. A biochip cartridge according to claim 3, wherein at least one of said fluid holes is configured to dispense a fluid assay reagent at a location remote from a blister comprising said reagent.

7. A biochip cartridge according to claim 1, wherein said external housing is asymmetrically shaped.

8. A biochip cartridge according to claim 4, wherein said dried assay reagent is selected from the group consisting of:

dNTPs, PCR primers, a nucleic acid polymerase, an exonuclease, labelled signaling probes, and a combination thereof.

9. A biochip cartridge according to claim 1, wherein said external housing further comprises a cartridge identification tag.

10. A biochip cartridge according to claim 1, wherein the plurality of blisters comprise fluid assay reagents selected from the group consisting of:

water, an immiscible fluid, a lysis buffer, a binding buffer, an elution buffer, and a reconstitution buffer.

11. A biochip cartridge according to claim 1, wherein all or part of the top plate is coated with a hydrophilic, oleophobic material.

12. A biochip cartridge according to claim 1, wherein said top plate comprises one or more entry ports configured to allow fluid flow into said reaction chamber.

13. A biochip cartridge according to claim 1, wherein said top plate further comprises one or more vents configured to reduce air bubble formation within the reaction chamber and/or remove any air bubbles that do form within the reaction chamber.

14. A biochip cartridge for detecting a target analyte, the biochip cartridge comprising:

a) a liquid reagent module comprising a blister connected to a sphere blister by a channel;

b) a top plate; and

c) a bottom substrate comprising a printed circuit board.

15. A biochip cartridge according to claim 14, wherein the sphere blister comprises a steel ball bearing.

16. A biochip cartridge according to claim 14, wherein the sphere blister comprises a septum.

17. A biochip cartridge according to claim 14, wherein the blister is connected to the sphere blister by the channel blocked by a breakable seal.

18. A biochip cartridge according to claim 14, wherein the liquid reagent module further comprises magnetic capture beads.

19. A biochip cartridge according to claim 14, wherein the liquid reagent module further comprises a waste chamber.

20. A biochip cartridge according to claim 14, wherein the liquid reagent module further comprises a porous filter.