Systems and methods for genetic and biological analysis

• US 10,494,672 B2
• Filed: 02/22/2019
• Issued: 12/03/2019
• 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:
  US16/283,544
• Publication Number:
  US 20190177791A1
• Time in Patent Office: 284 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 system for nucleic acid sequencing, comprising:

a chip comprising a flow cell, an array in fluidic communication with said flow cell, a plurality of optical sensors in optical communication with said array, and circuitry operatively coupled to said plurality of optical sensors, wherein said array is configured to retain a plurality of nucleic acid molecules having sequences that are substantially identical to a nucleic acid sequence of a template nucleic acid molecule in a manner such that said plurality of nucleic acid molecules is in optical communication with an optical sensor of said plurality of optical sensors,

wherein said circuitry is configured to couple to one or more computer processors external to said chip, which one or more computer processors are configured to (i) bring said plurality of nucleic acid molecules in contact with nucleic acid bases in presence of polymerizing enzymes under conditions sufficient to incorporate at least a subset of said nucleic acid bases into growing strands complementary to said plurality of nucleic acid molecules, (ii) use said optical sensor to detect one or more signals indicative of said nucleic acid bases incorporated into said growing strands, and (iii) use said one or more signals detected in (ii) to identify said at least said subset of said nucleic acid bases, to thereby generate a sequence corresponding to said nucleic acid sequence of said template nucleic acid molecule.

2. The system of claim 1, wherein said system further comprises said one or more computer processors.

3. The system of claim 1, wherein said circuitry is electrically coupled to said plurality of optical sensors.

4. The system of claim 1, wherein said array is configured to retain said plurality of nucleic acid molecules within a Debye length of a surface of said array or a surface of a feature immobilized on said array during sequencing.

5. The system of claim 1, wherein said feature is a well.

6. The system of claim 1, wherein said plurality of optical sensors is configured for reduced cross-talk between said plurality of optical sensors.

7. The system of claim 1, wherein said array comprises a surface coating.

8. The system of claim 1, wherein said plurality of optical sensors comprise complementary metal-oxide semiconductor (CMOS) sensors.

9. The system of claim 1, wherein said plurality of optical sensors comprise charge-coupled device (CCD) sensors.

10. The system of claim 1, wherein said flow cell is configured to direct said nucleic acid bases to said array.

11. The system of claim 1, wherein said array includes capture sequences that are configured to immobilize said plurality of nucleic acid molecules.

12. The system of claim 1, further comprising a fluidics interface configured to provide said nucleic acid bases to said flow cell.

13. The system of claim 12, wherein said fluidics interface and said one or more computer processors are integrated within said system.

14. The system of claim 1, wherein said one or more computer processors are programmed to monitor for phase error.

15. The system of claim 1, wherein said one or more computer processors are programmed to correct for phase error.

16. The system of claim 1, wherein said one or more computer processors are programmed to direct more than one type of nucleic acid base to said flow cell in a given nucleic acid sequencing cycle.

17. The system of claim 1, wherein said one or more computer processors are programmed to direct four types of nucleic acid bases to said flow cell in a given nucleic acid sequencing cycle.

18. The system of claim 1, wherein said one or more computer processors are programmed to direct more than one type of nucleic acid base to said flow cell in sequential nucleic acid sequencing cycles.