Systems and methods for genetic and biological analysis

• US 9,274,077 B2
• Filed: 03/15/2013
• Issued: 03/01/2016
• 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): Woolwine, Samuel
• Assistant Examiner(s): OYEYEMI, OLAYINKA A
• Application Number:
  US13/838,816
• Publication Number:
  US 20140057339A1
• Time in Patent Office: 1,082 Days
• Field of Search: 435/287.1, 257/253
• US Class Current: 1/1
• 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 detecting a biological molecule or a biological reaction associated with said biological molecule, comprising:

a bead in a solution and having attached thereto a biological molecule;

a pair of electrodes in contact with said solution and positioned within the Debye layer of said bead; and

a bead capture feature that immobilizes said bead, in proximity to said pair of electrodes,

wherein, during use, said pair of electrodes and said bead provide an electrical current flow path for the generation of a signal useful for detecting said biological molecule or said biological reaction in said solution.

2. The system of claim 1, wherein one electrode of said pair of electrodes is adjacent to a substrate, wherein a dielectric layer is adjacent to said one electrode, and wherein the other electrode of said pair of electrodes is adjacent to said dielectric layer.

3. The system of claim 1, wherein said pair of electrodes are part of an array of electrodes.

4. The system of claim 3, wherein said array comprises a 2D array of electrodes.

5. The system of claim 1, wherein said solution is an aqueous solution.

6. The system of claim 5, wherein said aqueous solution has an ionic concentration of less than 10⁻

8 molar.

7. The system of claim 1, wherein said solution is a miscible mixture of an aqueous solution and an organic solution.

8. The system of claim 7, wherein said miscible solution has an ionic concentration less than 10⁻

7 molar.

9. The system of claim 1, wherein at least one of said pair of electrodes is shaped to conform to the shape of said bead.

10. The system of claim 9, wherein at least one of said electrode pair of electrodes is shaped at least in part as an arc.

11. The system of claim 1, wherein one electrode of said pair of electrodes is angularly separated relative to the center of said bead from the other electrode of said pair of electrodes by greater than 30 degrees.

12. The system of claim 1, wherein one electrode of said pair of electrodes is angularly separated relative to the center of said bead from the other electrode of said pair of electrodes by an angle between 10 and 90 degrees.

13. The system of claim 1, wherein one electrode of said pair of electrodes is angularly separated relative to the center of said bead from the other electrode of said pair of electrodes by an angle between 30 and 85 degrees.

14. The system of claim 1, wherein one electrode of said pair of electrodes is angularly separated relative to the center of said bead from the other electrode of said pair of electrodes by an angle between 45 and 80 degrees.

15. The system of claim 1, wherein one electrode of said pair of electrodes is angularly separated relative to the center of said bead from the other electrode of said pair of electrodes by an angle between 60 and 75 degrees.

16. The system of claim 1, further comprising a computing system that (i) receives electrical signals from said pair of electrodes during detection of said biological molecule or said biological reaction, and (ii) using said electrical signals, determines a change in impedance resulting from said biological molecule or said biological reaction.

17. The system of claim 16, wherein said computing system uses said signals to determine a change of impedance of said bead.

18. The system of claim 1, wherein, during use, the electrodes of said pair of electrodes are electrically isolated from one another in the absence of said bead.

19. The system of claim 1, wherein an individual electrode of said pair electrodes has a Debye layer.

20. The system of claim 1, wherein said bead capture feature immobilizes said bead in proximity to said pair of electrodes by an immobilizing force.

21. The system of claim 20, wherein said immobilizing force is selected from the group consisting of a magnetic force and an electrical force.

22. The system of claim 20, wherein said bead capture feature comprises a magnet, and wherein said immobilizing force includes a magnetic force.

23. The system of claim 1, wherein said bead capture feature is selected from the group consisting of a magnetic structure and a depression.

24. The system of claim 1, wherein said bead capture feature is part of a magnetic array.