Apparatus and method for control of biopolymer translocation through a nanopore

• US 7,282,130 B2
• Filed: 01/31/2003
• Issued: 10/16/2007
• Est. Priority Date: 01/31/2003
• Status: Active Grant

• Current Assignee: Agilent Technologies, Inc.
• Original Assignee: Agilent Technologies, Inc.
• Inventors: Flory, Curt A.
• Primary Examiner(s): Nguyen; Nam
• Assistant Examiner(s): BARTON, JEFFREY THOMAS
• Application Number:
  US10/355,347
• Publication Number:
  US 20040149580A1
• Time in Patent Office: 1,719 Days
• Field of Search: 204/450, 204/600, 20440301-40315, 204775-7945, 4352871-2872
• US Class Current: 204/600
• 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: B82Y 5/00 Nanobiotechnology or nanomedicine, e.g. protein engineering or drug delivery
• 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

The present invention provides an apparatus and method for controlling the movement of a biopolymer translocating a nanopore. The invention provides a first electrode, a second electrode adjacent to the first electrode, a third electrode adjacent to the second electrode and a fourth electrode adjacent to the third electrode. The first electrode is in electrical connection with the third electrode to define a first set of electrodes and the second electrode is in electrical connection with the fourth electrode to define a second set of electrodes. A DC voltage and radio frequency voltage is applied to the first set of electrodes while an opposite DC voltage and phase shifted radio frequency voltage is applied to the second set of electrodes to produce an electric field between the first set of electrodes and the second set of electrodes. The electric field is used to control the movement of a biopolymer translocating a nanopore. A method for controlling the movement of a biopolymer is also disclosed.

Claims

1. A biopolymer translocation apparatus for controlling lateral movement of a biopolymer as it translocates through a nanopore, comprising:

(a) a first electrode;

(b) a second electrode adjacent to said first electrode;

(c) a third electrode adjacent to said second electrode, said third electrode being in electrical connection with said first electrode and defining a first set of electrodes;

(d) a fourth electrode adjacent to said third electrode, said fourth electrode being in electrical connection with said second electrode and defining a second set of electrodes, wherein said first-electrode, said second electrode, said third electrode and said fourth electrodes define a nanopore wherein the nanopore is between the first and third electrodes and between the second and fourth electrodes;

(e) a first voltage source for applying voltages to the first, second, third and fourth electrodes for producing an electric field for controlling lateral movement of said biopolymer as it translocates through said nanopore; and

(f) a second voltage source and a current measuring device in electrical connection with said first and third electrodes for monitoring quantum tunneling through said biopolymer and said first and third electrodes.

2. The apparatus as recited in claim 1, wherein said first voltage source applies a direct current (DC) to at least one electrode.

3. The apparatus as recited in claim 1, wherein said first voltage source applies alternating current (AC) to at least one electrode.

4. The apparatus as recited in claim 1, wherein said first voltage source applies direct current (DC) and alternating current (AC) to at least one electrode.

5. The apparatus as recited in claim 1, further comprising a substrate on which said first electrode is disposed.

6. The apparatus as recited in claim 1, further comprising a substrate on which said second electrode is disposed.

7. The apparatus of claim 1, further comprising a substrate on which said third electrode is disposed.

8. The apparatus of claim 1, further comprising a substrate on which said fourth electrode is disposed.

9. The apparatus of claim 1, wherein said biopolymer is a charged polymer.

10. The apparatus of claim 1, wherein said biopolymer is selected from the group consisting of carbohydrates, proteins, nucleic acids, lipids, glycans, biopolymers, proteoglycans and polypeptides.

11. An apparatus as recited in claim 1, further comprising a substrate having a top surface and a bottom surface, said first electrode, second electrode third electrode and fourth electrode being positioned on said top surface of said substrate.

12. A biopolymer translocation apparatus for controlling lateral movement of a biopolymer as it translocates through a nanopore, comprising:

(a) a first electrode;

(b) a second electrode adjacent to said first electrode;

(c) a third electrode adjacent to said second electrode, said third electrode being in electrical connection with said first electrode and defining a first set of electrodes;

(d) a fourth electrode adjacent to said third electrode, said fourth electrode being in electrical connection with said second electrode and defining a second set of electrodes, wherein said first-electrode, said second electrode, said third electrode and said fourth electrodes define a nanopore there between;

(e) a first voltage source for applying voltages to said electrodes for producing an electric field for controlling lateral movement of said biopolymer as it translocates through said nanopore;

a fifth electrode, a sixth electrode adjacent to said fifth electrode, a seventh electrode adjacent to said sixth electrode and an eighth electrode adjacent to said seventh electrode, said fifth electrode being in electrical connection with said first electrode, said sixth electrode being in electrical connection with said second electrode, said third electrode being in electrical connection with said seventh electrode and said fourth electrode being in electrical connection with said eighth electrode, wherein each of said electrodes are positioned adjacent to said nanopore to create a quadrupole field through the length of said nanopore.

13. A biopolymer translocation apparatus for controlling lateral movement of a biopolymer as it translocates through a nanopore, comprising:

(a) a first electrode;

(b) a second electrode adjacent to said first electrode;

(c) a third electrode adjacent to said second electrode, said third electrode being in electrical connection with said first electrode and defining a first set of electrodes;

(d) a fourth electrode adjacent to said third electrode, said fourth electrode being in electrical connection with said second electrode and defining a second set of electrodes, wherein said first-electrode, said second electrode, said third electrode and said fourth electrodes define a nanopore there between;

(e) a first voltage source for applying voltages to said electrodes for producing an electric field for controlling lateral movement of said biopolymer as it translocates through said nanopore;

a substrate having a top surface and a bottom surface, said first electrode, second electrode, third electrode and fourth electrode being positioned on said top surface of said substrate;

a fifth electrode, a sixth electrode adjacent to said fifth electrode, a seventh electrode adjacent to said sixth electrode and an eighth electrode adjacent to said seventh electrode, said fifth electrode being in electrical connection with said first electrode, said sixth electrode being in electrical connection with said second electrode, said third electrode being in electrical connection with said seventh electrode and said fourth electrode being in electrical connection with said eighth electrode, wherein each of said electrodes are positioned adjacent to said nanopore to create a quadrupole field through the length of said nanopore, said fifth electrode, sixth electrode, seventh electrode and eighth electrode being positioned on said bottom surface of said substrate.

14. A biopolymer translocation apparatus for controlling lateral movement of a biopolymer as it translocates through a nanopore, comprising:

(a) a first electrode;

(b) a second electrode adjacent to said first electrode;

(c) a third electrode adjacent to said second electrode, said third electrode being in electrical connection with said first electrode and defining a first set of electrodes;

(d) a fourth electrode adjacent to said third electrode, said fourth electrode being in electrical connection with said second electrode and defining a second set of electrodes, wherein said first-electrode, said second electrode, said third electrode and said fourth electrodes define a nanopore there between;

(e) a first voltage source for applying voltages to said electrodes for producing an electric field for controlling lateral movement of said biopolymer as it translocates through said nanopore;

(f) a second voltage source and a current measuring device in electrical connection with said first and third electrodes for monitoring quantum tunneling through said biopolymer and said first and third electrodes; and

(g) a fifth electrode, a sixth electrode adjacent to said fifth electrode, a seventh electrode adjacent to said sixth electrode and an eighth electrode adjacent to said seventh electrode, said fifth electrode being in electrical connection with said first electrode, said sixth electrode being in electrical connection with said second electrode, said third electrode being in electrical connection with said seventh electrode and said fourth electrode being in electrical connection with said eighth electrode, wherein each of said electrodes are positioned adjacent to said nanopore to create a quadrupole field through the length of said nanopore.

15. A biopolymer translocation apparatus for controlling lateral movement of a biopolymer as it translocates through a nanopore, comprising:

(a) a first electrode;

(b) a second electrode adjacent to said first electrode;

(c) a third electrode adjacent to said second electrode, said third electrode being in electrical connection with said first electrode and defining a first set of electrodes;

(d) a fourth electrode adjacent to said third electrode, said fourth electrode being in electrical connection with said second electrode and defining a second set of electrodes, wherein said first-electrode, said second electrode, said third electrode and said fourth electrodes define a nanopore there between;

(e) a first voltage source for applying voltages to said electrodes for producing an electric field for controlling lateral movement of said biopolymer as it translocates through said nanopore;

(f) a second voltage source and a current measuring device in electrical connection with said first and third electrodes for monitoring quantum tunneling through said biopolymer and said first and third electrodes;

(g) a substrate having a top surface and a bottom surface, said first electrode, second electrode, third electrode and fourth electrode being positioned on said top surface, of said substrate; and

(h) a fifth electrode, a sixth electrode adjacent to said fifth electrode, a seventh electrode adjacent to said sixth electrode and an eighth electrode adjacent to said seventh electrode, said fifth electrode being in electrical connection with said first electrode, said sixth electrode being in electrical connection with said second electrode, said third electrode being in electrical connection with said seventh electrode and said fourth electrode being in electrical connection with said eighth electrode, wherein each of said electrodes are positioned adjacent to said nanopore to create a quadrupole field through the length of said nanopore, said fifth electrode, sixth electrode, seventh electrode and eighth electrode being positioned on said bottom surface of said substrate.