Systems and methods for genetic and biological analysis

• US 10,612,091 B2
• Filed: 02/22/2019
• Issued: 04/07/2020
• Est. Priority Date: 05/27/2011
• Status: Active Grant

• Current Assignee: Sequencing Health Incorporated
• Original Assignee: GenapSys, Inc.
• Inventors: Esfandyarpour, Hesaam, Parizi, Kosar Baghbani, Oldham, Mark F., Nordman, Eric S., Reel, Richard T., Baumhueter, Susanne, Heiner, Cheryl, Lee, Frank
• Primary Examiner(s): Thomas, David C
• Application Number:
  US16/283,531
• Publication Number:
  US 20190177790A1
• Time in Patent Office: 410 Days
• CPC Class Codes: B01L 2300/06 Auxiliary integrated devices, integrated components
• CPC Class Codes: B01L 2300/0627 Sensor or part of a sensor is integrated
• CPC Class Codes: B01L 3/502715 characterised by interfacing components, e.g. fluidic, electrical, optical or mechanical interfaces
• CPC Class Codes: C12Q 1/6874 involving nucleic acid arrays, e.g. sequencing by hybridisation
• CPC Class Codes: C12Q 2527/119 pH
• CPC Class Codes: C12Q 2549/126 using oligonucleotides as clamps
• CPC Class Codes: C12Q 2563/116 electrical properties of nucleic acids, e.g. impedance, conductivity or resistance
• CPC Class Codes: C12Q 2565/607 being a sensor, e.g. electrode
• CPC Class Codes: G01N 27/327 Biochemical electrodes , e.g. electrical or mechanical details for in vitro measurements
• CPC Class Codes: G01N 33/54313 the carrier being characterised by its particulate form
• CPC Class Codes: G01N 33/5438 Electrodes

Abstract

The invention relate to systems and methods for sequencing polynucleotides, as well as detecting reactions and binding events involving other biological molecules. The systems and methods may employ chamber-free devices and nanosensors to detect or characterize such reactions in high-throughput. Because the system in many embodiments is reusable, the system can be subject to more sophisticated and improved engineering, as compared to single use devices.

Claims

1. A method for nucleic acid sequencing, comprising (a) bringing a template nucleic acid molecule in contact with a nucleotide or nucleotide analog under conditions sufficient to permit said nucleotide or nucleotide analog to be incorporated into a strand complementary to said template nucleic acid molecule, and (b) detecting impedance or conductivity, or change thereof, in a solution comprising said template nucleic acid molecule to identify said nucleotide or nucleotide analog incorporated into said strand.

2. The method of claim 1, wherein (a) comprises bringing said template nucleic acid molecule in contact with said nucleotide analog.

3. The method of claim 2, wherein said nucleotide analog comprises a charge modifying structure.

4. The method of claim 1, wherein (b) comprises detecting said impedance or change thereof.

5. The method of claim 1, wherein (b) comprises detecting said conductivity or change thereof.

6. The method of claim 1, wherein said template nucleic acid molecule is part of a clonal population of template nucleic acid molecules.

7. The method of claim 6, wherein said clonal population of template nucleic acid molecules is coupled to a support.

8. The method of claim 7, wherein said support is a bead.

9. The method of claim 8, further comprising using a magnetic field to immobilize said bead adjacent to a sensor that detects said impedance or conductivity, or change thereof.

10. The method of claim 7, wherein said support is a surface of a sensor that detects said impedance or conductivity, or change thereof.

11. The method of claim 1, wherein said impedance or conductivity, or change thereof, is detected by a sensor having said template nucleic acid molecule disposed adjacent thereto.

12. The method of claim 11, wherein said sensor comprises at least two electrodes, and wherein said at least two electrodes are exposed to said solution.

13. The method of claim 12, wherein said template nucleic acid molecule is disposed adjacent to said at least two electrodes.

14. The method of claim 1, further comprising repeating (a)-(b) with an additional nucleotide or nucleotide analog to generate a sequence of said template nucleic acid molecule.

15. The method of claim 1, wherein said template nucleic acid molecule is contacted with a plurality of nucleotides or nucleotide analogues comprising said nucleotide or nucleotide analog.

16. The method of claim 15, wherein said plurality of nucleotides or nucleotide analogues comprises different types of nucleotides or nucleotide analogues.

17. The method of claim 15, wherein said plurality of nucleotides or nucleotide analogues is of a same type of nucleotides or nucleotide analogues.

18. The method of claim 1, wherein identifying said nucleotide or said nucleotide analog comprises detecting said impedance or conductivity, or change thereof, within an electrical current flow path comprising said template nucleic acid molecule.