Non-faradaic, capacitively coupled measurement in a nanopore cell array

• US 10,393,700 B2
• Filed: 10/10/2018
• Issued: 08/27/2019
• Est. Priority Date: 10/17/2013
• Status: Active Grant

• Current Assignee: Roche Sequencing Solutions, Inc. (Roche Holding AG)
• Original Assignee: Roche Sequencing Solutions, Inc. (Roche Holding AG)
• Inventors: Chen, Roger J. A.
• Primary Examiner(s): Noguerola, Alexander S
• Application Number:
  US16/157,019
• Publication Number:
  US 20190079049A1
• Time in Patent Office: Days
• CPC Class Codes: G01N 27/3278 involving nanosized elements, e.g. nanogaps or nanoparticles nanopores G01N33/48721; magnetic beads G01N27/745
• CPC Class Codes: G01N 27/4473 by electric means
• CPC Class Codes: G01N 27/44743 Introducing samples
• CPC Class Codes: G01N 27/44791 Microapparatus sample containers with integrated microfluidic structures B01L3/5027
• CPC Class Codes: G01N 33/48721 Investigating individual macromolecules, e.g. by translocation through nanopores Coulter counters in general G01N15/12; fabrication methods for nanoscale apertures B81B1/00; sequencing of nucleic acids C12Q1/68

Abstract

A method of identifying a molecule is disclosed. A molecule is drawn to a nanopore by applying a first voltage signal to a pair of electrodes during a first period, wherein the first voltage signal causes a first ionic current through the nanopore that is indicative of a property of a portion of the molecule proximate to the nanopore. The molecule is released from the nanopore by applying a second voltage signal to the pair of electrodes during a second period, wherein the second voltage signal causes a second ionic current through the nanopore. The first period and the second period are determined based at least in part on a net ionic current through the nanopore comprising the first ionic current and the second ionic current.

Claims

1. A method of analyzing a molecule, comprising:

applying a first voltage signal to a pair of electrodes, wherein the first voltage signal causes a first ionic current in an electrolyte through a nanopore that is indicative of a property of a portion of the molecule proximate to the nanopore, wherein;

a first one of the electrodes comprises a property that facilitates non-faradaic conduction, and the electrolyte includes a redox pair; and

applying a second voltage signal to the pair of electrodes, wherein the second voltage signal causes a second ionic current in the electrolyte that includes the redox pair.

2. The method of claim 1, wherein the first one of the electrodes comprises a noble metal.

3. The method of claim 1, wherein the first one of the electrodes comprises a transition metal.

4. The method of claim 1, wherein the first one of the electrodes comprises gold.

5. The method of claim 1, wherein the first one of the electrodes comprises platinum.

6. The method of claim 1, wherein the first one of the electrodes comprises a spongy structure.

7. The method of claim 1, wherein the redox pair comprises ferrocyanide.

8. The method of claim 1, wherein the redox pair comprises ferricyanide.

9. The method of claim 1, wherein the first and second ionic currents have different polarities.

10. A system for analyzing a molecule, comprising:

a voltage control unit controlling a voltage source;

a pair of electrodes coupled to the voltage source, wherein a first one of the electrodes comprises a property that facilities non-faradaic conduction; and

a measurement circuitry;

wherein the voltage control unit is configured to;

apply a first voltage signal to the pair of electrodes, wherein the first voltage signal causes a first ionic current in an electrolyte through a nanopore that is indicative of a property of a portion of the molecule proximate to the nanopore, wherein the electrolyte includes a redox pair; and

apply a second voltage signal to the pair of electrodes, wherein the second voltage signal causes a second ionic current in the electrolyte through the nanopore;

and wherein the measurement circuitry is configured to measure the first ionic current.

11. The system of claim 10, wherein the first one of the electrodes comprises a noble metal.

12. The system of claim 10, wherein the first one of the electrodes comprises a transition metal.

13. The system of claim 10, wherein the first one of the electrodes comprises gold.

14. The system of claim 10, wherein the first one of the electrodes comprises platinum.

15. The system of claim 10, wherein the first one of the electrodes comprises a spongy structure.

16. The system of claim 10, wherein the redox pair comprises ferrocyanide.

17. The system of claim 10, wherein the redox pair comprises ferricyanide.

18. The system of claim 10, wherein the first and second ionic currents have different polarities.