Systems and methods for biological analysis

• US 9,809,852 B2
• Filed: 03/14/2014
• Issued: 11/07/2017
• Est. Priority Date: 03/15/2013
• Status: Active Grant

• Current Assignee: Sequencing Health Incorporated
• Original Assignee: GenapSys, Inc.
• Inventors: Esfandyarpour, Hesaam, Rategh, Hamid, Barmi, Meysam R., Parizi, Kosar B., Kaviani, Kambiz
• Primary Examiner(s): Wilder, Cynthia B
• Application Number:
  US14/653,230
• Publication Number:
  US 20150376692A1
• Time in Patent Office: 1,334 Days
• Field of Search: 435 61
• 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: C12Q 1/6874 involving nucleic acid arrays, e.g. sequencing by hybridisation
• CPC Class Codes: C12Q 2563/116 electrical properties of nucleic acids, e.g. impedance, conductivity or resistance
• CPC Class Codes: C12Q 2563/143 Magnetism, e.g. magnetic label
• CPC Class Codes: C12Q 2563/149 Particles, e.g. beads
• 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 27/4062 Electrical connectors associated therewith
• CPC Class Codes: G01N 27/745 for detecting magnetic beads used in biochemical assays concerning the assays G01N33/54326; sensors therefor G01R33/1269; automatic analysers therefor G01N35/0098
• CPC Class Codes: G01N 33/5438 Electrodes

Abstract

Provided herein are devices and methods suitable for sequencing, amplifying, analyzing, and performing sample preparation procedures for nucleic acids and other biomolecules.

Claims

1. A method for nucleic acid sequencing, comprising:

(a) directing a plurality of particles onto an array of sensors, wherein an individual particle among said plurality of particles comprises a template nucleic acid molecule coupled thereto, wherein said array comprises a plurality of sensors, wherein an individual sensor among said plurality of sensors comprises a transmitter electrode and a receiver electrode, which transmitter electrode or receiver electrode is coupled to at least another individual sensor among said plurality of sensors;

(b) positioning said individual particle adjacent to said individual sensor;

(c) performing a primer extension reaction on said template nucleic acid molecule coupled to said individual particle at said individual sensor; and

(d) during or subsequent to performing said primer extension reaction, measuring a signal that is indicative of a change in impedance between said transmitter electrode and receiver electrode.

2. The method of claim 1, wherein said at least another individual sensor is directly adjacent to said individual sensor.

3. The method of claim 1, wherein said at least another individual sensor is separated from said individual sensor by one or more intermediate sensors of said array of sensors.

4. The method of claim 1, wherein said individual particle is positioned at said individual sensor such that said transmitter electrode and receiver electrode are electrically coupled to a Debye layer of said individual particle.

5. The method of claim 1, wherein said transmitter electrode and receiver electrode are electrically isolated in the absence of said individual particle positioned adjacent thereto.

6. The method of claim 5, wherein in (b), said individual particle is positioned adjacent to said transmitter electrode and receiver electrode, thereby bringing said transmitter electrode in electrical communication with said receiver electrode.

7. The method of claim 1, wherein said transmitter electrode or receiver electrode, but not both, is shared with said at least another individual sensor.

8. The method of claim 1, further comprising amplifying said template nucleic acid molecule prior to (c).

9. The method of claim 8, wherein said template nucleic acid molecule is amplified while said individual particle is held at said individual sensor.

10. The method of claim 1, wherein said individual particle is positioned adjacent to said individual sensor using a magnetic field.

11. The method of claim 1, wherein (d) comprises measuring a signal that is indicative of a change in impedance across (i) said individual particle or (ii) a fluid environment comprising said individual particle.

12. The method of claim 1, wherein both of said transmitter electrode and said receiver electrode are shared with another individual sensor among said plurality of sensors.