Systems and methods for controlling position of charged polymer inside nanopore

• US 8,003,319 B2
• Filed: 02/02/2007
• Issued: 08/23/2011
• Est. Priority Date: 02/02/2007
• Status: Active Grant

• Current Assignee: Globalfoundries US Incorporated (GlobalFoundries, Inc.)
• Original Assignee: International Business Machines Corporation
• Inventors: Stolovitzky, Gustavo A., Rossnagel, Stephen M., Polonsky, Stanislav
• Primary Examiner(s): Kapushoc; Stephen
• Assistant Examiner(s): BHAT, NARAYAN KAMESHWAR
• Application Number:
  US11/670,621
• Publication Number:
  US 20080187915A1
• Time in Patent Office: 1,663 Days
• Field of Search: 435/6, 435/7.1, 435/283.1, 435/287.2, 977/924
• US Class Current: 435/6.1
• CPC Class Codes: B82Y 15/00 Nanotechnology for interacting, sensing or actuating, e.g. quantum dots as markers in protein assays or molecular motors
• CPC Class Codes: B82Y 30/00 Nanotechnology for materials or surface science, e.g. nanocomposites
• CPC Class Codes: C12Q 1/6825 Nucleic acid detection involving sensors
• CPC Class Codes: C12Q 1/6869 Methods for sequencing
• CPC Class Codes: C12Q 2563/155 Particles of a defined size, e.g. nanoparticles
• CPC Class Codes: C12Q 2565/607 being a sensor, e.g. electrode
• CPC Class Codes: C12Q 2565/631 being a biochannel or pore
• CPC Class Codes: G01N 2015/0038 Investigating nanoparticles
• 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: Y10S 977/924 using nanostructure as support of dna analysis

Abstract

Techniques for controlling the position of a charged polymer inside a nanopore are provided. For example, one technique includes using electrostatic control to position a linear charged polymer inside a nanopore, and creating an electrostatic potential well inside the nanopore, wherein the electrostatic potential well controls a position of the linear charged polymer inside the nanopore.

Claims

1. A method for controlling a position of a linear charged polymer inside a nanopore, comprising the steps of:

using electrostatic control to position a linear charged polymer inside a nanopore; and

applying an independent voltage to each of three locking electrodes, wherein the three locking electrodes each have a cylindrical geometry and are separated by one or more insulators, creating an electrostatic potential well inside the nanopore that varies along nanopore via setting an electrical potential of each of the three locking electrodes independently, wherein the electrical potential of a second locking electrode differs from the electrical potential of a first and third locking electrode, and

wherein the electrostatic potential well controls a position of the linear charged polymer inside the nanopore, wherein controlling a position of the linear charged polymer inside the nanopore comprises using the electrostatic potential well to lock the position of one monomer of the linear charged polymer inside the nanopore.

2. The method of claim 1, wherein the step of using electrostatic control to position a linear charged polymer inside a nanopore comprises detecting entry of the linear charged polymer inside the nanopore.

3. The method of claim 2, wherein the step of detecting entry of the linear charged polymer comprises measuring a variation of ion current between two or more electrodes used in controlling a position of a linear charged polymer inside a nanopore.

4. The method of claim 1, wherein the linear charged polymer comprises one of deoxyribonucleic acid (DNA), ribonucleic acid (RNA) and a protein molecule.

5. A method for characterizing a linear charged polymer, comprising the steps of:

applying a time-dependent voltage to each of two or more drag electrodes to attract a linear charged polymer from a first part of a reservoir to a second part of a reservoir;

detecting entry of the linear charged polymer inside a nanopore;

reducing the time-dependent voltage from each drag electrode;

applying an independent time-dependent voltage to each of three locking electrodes, wherein the three locking electrodes each have a cylindrical geometry and are separated by one or more insulators, creating an electrostatic potential well inside the nanopore that varies along the nanopore via setting an electrical potential of each of the three locking electrodes independently, wherein the electrical potential of a second locking electrode differs from the electrical potential of a first and third locking electrode, and

wherein the electrostatic potential well controls a position of the linear charged polymer, and wherein controlling a position of the linear charged polymer inside the nanopore comprises using the electrostatic potential well to lock the position of one monomer of the linear charged polymer inside the nanopore; and

performing one or more characterization activities on a monomer of the linear charged polymer.

6. The method of claim 5, wherein the linear charged polymer comprises DNA, and wherein performing one or more characterization activities comprises DNA sequencing.

7. The method of claim 5, further comprising the steps of

reducing the time-dependent voltage from each of the three locking electrodes and the electrostatic potential well;

and

increasing the time-dependent voltage to each the two or more drag electrodes to translocate the linear charged polymer by one or more monomers.

8. The method of claim 7, further comprising the step of repeating the steps of:

reducing the time-dependent voltage from each of the two or more drag electrodes;

increasing the time-dependent voltage to each of the three locking electrodes to create an electrostatic potential well, wherein the electrostatic potential well controls a position of the linear charged polymer;

performing one or more characterization activities on a monomer of the linear charged polymers;

reducing the time-dependent voltage from each of the three locking electrodes and the electrostatic potential well; and

increasing the time-dependent voltage to each of the two or more drag electrodes to translocate the linear charged polymer by one or more monomers.

9. The method of claim 8, wherein the steps are repeated for the entire linear charged polymer.

10. The method of claim 5, wherein the linear charged polymer comprises deoxyribonucleic acid (DNA).

11. The method of claim 5, wherein the linear charged polymer comprises ribonucleic acid (RNA).

12. The method of claim 5, wherein the linear charged polymer comprises a protein molecule.

13. The method of claim 7, wherein one or more characterization activities comprise counting a number of polymers with a given characteristic that are present in a solution, wherein the characterization activity comprising counting a number of polymers with a given characteristic occurs after the step of applying an independent time-dependent voltage to each of the three locking electrodes, creating an electrostatic potential well inside the nanopore, and before the steps of reducing the time-dependent voltage from each of the three locking electrodes and the electrostatic potential well and increasing the time-dependent voltage to each the two or more drag electrodes to translocate the linear charged polymer by one or more monomers.

14. The method of claim 7, wherein one or more characterization activities comprise counting a number of monomers in each polymer, wherein the characterization activity comprising counting a number of monomers in each polymer occurs after the step of applying an independent time-dependent voltage to each of the three locking electrodes, creating an electrostatic potential well inside the nanopore, and before the steps of reducing the time-dependent voltage from each of the three locking electrodes and the electrostatic potential well and increasing the time-dependent voltage to each the two or more drag electrodes to translocate the linear charged polymer by one or more monomers.

15. The method of claim 7, wherein one or more characterization activities comprise chemical modification of the linear charged polymer, wherein the characterization activity comprising chemical modification of the linear charged polymer occurs after the step of applying an independent time-dependent voltage to each of the three locking electrodes, creating an electrostatic potential well inside the nanopore, and before the steps of reducing the time-dependent voltage from each of the three locking electrodes and the electrostatic potential well and increasing the time-dependent voltage to each the two or more drag electrodes to translocate the linear charged polymer by one or more monomers.

16. The method of claim 7, wherein one or more characterization activities comprise separating two or more polymers according to one or more characteristics, wherein the characterization activity comprising separating two or more polymers according to one or more characteristics occurs after the step of applying an independent time-dependent voltage to each of the three locking electrodes, creating an electrostatic potential well inside the nanopore, and before the steps of reducing the time-dependent voltage from each of the three locking electrodes and the electrostatic potential well and increasing the time-dependent voltage to each the two or more drag electrodes to translocate the linear charged polymer by one or more monomers.

17. The method of claim 5, wherein the three locking electrodes comprise a first locking electrode and a second locking electrode, such that the one or more characterization activities comprise measuring tunnel current between the first locking electrode and the second locking electrode.

18. The method of claim 5, wherein the three locking electrodes comprise a first locking electrode and a second locking electrode, such that the one or more characterization activities comprise measuring capacitance change between the first locking electrode and the second locking electrode.

19. The method of claim 7, wherein the step of increasing the time-dependent voltage to each of the two or more drag electrodes comprises increasing the time-dependent voltage to each of the two or more drag electrodes for a time interval, wherein the time interval is sufficient to translocate each polymer by one monomer.

20. The method of claim 7, wherein the step of increasing the time-dependent voltage to each of the two or more drag electrodes to translocate the linear charged polymer by one or more monomers comprises translocating the linear charged polymer in both directions.