Systems and methods for characterizing a molecule

• US 9,377,437 B2
• Filed: 10/14/2014
• Issued: 06/28/2016
• Est. Priority Date: 02/08/2010
• Status: Active Grant

• Current Assignee: Roche Sequencing Solutions, Inc. (Roche Holding AG)
• Original Assignee: Genia Technologies, Inc. (Roche Holding AG)
• Inventors: Chen, Roger J. A., Davis, Randy
• Primary Examiner(s): Nguyen, Vincent Q
• Application Number:
  US14/513,642
• Publication Number:
  US 20150094214A1
• Time in Patent Office: 623 Days
• Field of Search: 324/692, 324/693, 324/717, 324/71.1, 435/6.17
• US Class Current: 1/1
• CPC Class Codes: B82Y 30/00 Nanotechnology for materials or surface science, e.g. nanocomposites
• CPC Class Codes: C12Q 1/6816 characterised by the detection means C12Q1/6804 takes precedence
• CPC Class Codes: C12Q 1/6869 Methods for sequencing
• CPC Class Codes: C12Q 2563/116 electrical properties of nucleic acids, e.g. impedance, conductivity or resistance
• CPC Class Codes: C12Q 2565/631 being a biochannel or pore
• CPC Class Codes: G01N 2015/0038 Investigating nanoparticles
• 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 27/447 using electrophoresis
• 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
• CPC Class Codes: Y10T 29/49002 Electrical device making
• CPC Class Codes: Y10T 29/49117 Conductor or circuit manufacturing

Abstract

Techniques for characterizing a molecule are described herein. In one example, a portion of the molecule is trapped in a nanopore, a variable voltage is applied across the nanopore until the trapped portion of molecule is moved within the nanopore, and the molecule is characterized based on the electrical stimulus required to affect movement of at least a portion of the trapped portion of the molecule within the nanopore.

Claims

1. A method analyzing a plurality of molecules, comprising:

(a) forming a plurality of individually addressable nanopore devices on a chip, each individually addressable nanopore device of said plurality of individually addressable nanopore devices containing at least one nanopore formed in a membrane disposed adjacent to an electrode, each individually addressable nanopore device being addressable using row and column addressing;

(b) directing a plurality of molecules to said individually addressable nanopore devices; and

(c) analyzing, with the aid of a processor coupled to said chip, at least a portion of each of said molecules based on electrical signals received from said plurality of individually addressable nanopore devices.

2. The method of claim 1, each individually addressable nanopore device of said plurality of individually addressable nanopore devices including an electrical circuit including a plurality of components, wherein said plurality of components are controllable by using said row and column addressing.

3. The method of claim 1, wherein said plurality of molecules comprises a plurality of nucleic acid molecules.

4. The method of claim 1, wherein said electrode is adapted to supply an electrical stimulus across said membrane, wherein said electrical stimulus enables generation of said electrical signals upon molecular flow of said molecules or portion thereof.

5. The method of claim 1, wherein each individually addressable nanopore device is adapted to regulate molecular flow with the aid of an electrical stimulus applied to said individually addressable nanopore device.

6. A system for analyzing a plurality of molecules, comprising:

(a) a chip comprising a plurality of individually addressable nanopore devices, each individually addressable nanopore device of said plurality of individually addressable nanopore devices containing at least one nanopore formed in a membrane disposed adjacent to an electrode, each individually addressable nanopore device being addressable using row and column addressing; and

(b) a processor coupled to said chip, wherein said processor is programmed to aid in analyzing at least a portion of each of said molecules based on electrical signals received from said plurality of individually addressable nanopore devices.

7. The system of claim 6, each individually addressable nanopore device of said plurality of individually addressable nanopore devices including an electrical circuit including a plurality of components, wherein said plurality of components are controllable by using said row and column addressing.

8. The system of claim 6, wherein said plurality of molecules comprises a plurality of nucleic acid molecules.

9. The system of claim 6, wherein said electrode is adapted to supply an electrical stimulus across said membrane, wherein said electrical stimulus enables generation of said electrical signals upon molecular flow of said molecules or portion thereof.

10. The system of claim 6, wherein each individually addressable nanopore device is adapted to regulate molecular flow with the aid of an electrical stimulus applied to said individually addressable nanopore device.