IP Library Granted Patent US 10,684,240
Granted Patent B2
US 10,684,240 · App. 15/857,010 · Granted Jun 16, 2020

Systems and methods for single-molecule detection using nanotubes

Inventors: Sebastian Sorgenfrei (Portland, OR); Kenneth L. Shepard (Ossining, NY); Chien-Yang Chiu (Goleta, CA); Colin Nuckolls (New York, NY); Steven Warren (White Plains, NY)
Assignee: The Trustees Of Columbia University In the City of New York
G01N27/041C12Q1/6816C12Q1/6874G01N27/3278C12Q2563/116C12Q2563/157C12Q2565/607
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Quick Facts
Patent No.
US 10,684,240
App. No.
15/857,010
Granted
Jun 16, 2020
Kind
B2
Abstract

A method for single-molecule detection is provided and uses a carbon nanotube having a probe entity attached thereto to define a first state of the carbon nanotube. The carbon nanotube is introduced to a target entity to define a second state of the carbon nanotube. The electrical conductance of the carbon nanotube in the first and second states is compared to detect the presence of a biomolecular entity. A system for single-molecule detection including a carbon nanotube is also provided.

Claims (32)

1. A method for single-molecule detection, comprising:

providing a carbon nanotube having a cylindrical outer surface and a single-stranded molecule located in a proximity of the cylindrical outer surface that defines a first state of the carbon nanotube;

incorporating a single nucleotide using synthesis of a double-stranded molecule from said single-stranded molecule and a polymerase, to define a second state of the carbon nanotube; and

comparing the electrical conductance of the carbon nanotube in the first and second states to detect the incorporation of the single nucleotide.

2. The method of claim 1 , wherein the polymerase is selected from the group consisting of DNA polymerase and RNA polymerase.

3. The method of claim 1 , wherein the single-stranded molecule is a DNA molecule.

4. The method of claim 1 , wherein the second state of the carbon nanotube is associated with conformational changes in the polymerase during incorporation of the single nucleotide.

5. The method of claim 1 , wherein the comparing further comprises comparing the electrical conductance of the carbon nanotube in the first and second states to predetermined conductance data to ascertain the identity of the incorporated single nucleotide.

6. A method for single-molecule detection, comprising:

providing a carbon nanotube having a cylindrical outer surface and a single-stranded molecule attached to the cylindrical outer surface that defines a first state of the carbon nanotube;

incorporating a single nucleotide using synthesis of a double-stranded molecule from said single-stranded molecule and a polymerase, to define a second state of the carbon nanotube; and

comparing the electrical conductance of the carbon nanotube in the first and second states to detect the incorporation of the single nucleotide.

7. The method of claim 6 , wherein the polymerase is selected from the group consisting of DNA polymerase and RNA polymerase.

8. The method of claim 6 , wherein the single-stranded molecule is a DNA molecule.

9. The method of claim 6 , wherein the second state of the carbon nanotube is associated with conformational changes in the polymerase during incorporation of the single nucleotide.

10. The method of claim 6 , wherein the comparing further comprises comparing the electrical conductance of the carbon nanotube in the first and second states to predetermined conductance data to ascertain the identity of the incorporated single nucleotide.

11. A method for single-molecule detection, comprising:

providing a carbon nanotube having a cylindrical outer surface and a single-stranded molecule located in a proximity of the cylindrical outer surface with a polymerase bound to the single-stranded molecule that defines a first state of the carbon nanotube;

incorporating a single nucleotide using synthesis of a double-stranded molecule from said single-stranded molecule and said polymerase, to define a second state of the carbon nanotube; and

comparing the electrical conductance of the carbon nanotube in the first and second states to detect the incorporation of the single nucleotide.

12. The method of claim 11 , wherein the polymerase is selected from the group consisting of DNA polymerase and RNA polymerase.

13. The method of claim 11 , wherein the single-stranded molecule is a DNA molecule.

14. The method of claim 11 , wherein the second state of the carbon nanotube is associated with conformational changes in the polymerase during incorporation of the single nucleotide.

15. The method of claim 11 , wherein the comparing further comprises comparing the electrical conductance of the carbon nanotube in the first and second states to predetermined conductance data to ascertain the identity of the incorporated single nucleotide.

16. A method for single-molecule detection, comprising:

providing a carbon nanotube having a cylindrical outer surface and a single-stranded molecule attached to the cylindrical outer surface with a polymerase bound to the single-stranded molecule that defines a first state of the carbon nanotube;

incorporating a single nucleotide using synthesis of a double-stranded molecule from said single-stranded molecule and said polymerase, to define a second state of the carbon nanotube; and

comparing the electrical conductance of the carbon nanotube in the first and second states to detect the incorporation of the single nucleotide.

17. The method of claim 16 , wherein the polymerase is selected from the group consisting of DNA polymerase and RNA polymerase.

18. The method of claim 16 , wherein the single-stranded molecule is a DNA molecule.

19. The method of claim 16 , wherein the second state of the carbon nanotube is associated with conformational changes in the polymerase during incorporation of the single nucleotide.

20. The method of claim 16 , wherein the comparing further comprises comparing the electrical conductance of the carbon nanotube in the first and second states to predetermined conductance data to ascertain the identity of the incorporated single nucleotide.

Assignments (3)
CONFIRMATORY LICENSE Recorded Dec 13, 2022
From: COLUMBIA UNIVERSITY NEW YORK MORNINGSIDE
To: NATIONAL SCIENCE FOUNDATION
Reel/Frame 062205/0133 →
CONFIRMATORY LICENSE Recorded Nov 2, 2020
From: COLUMBIA UNIVERSITY
To: NATIONAL SCIENCE FOUNDATION
Reel/Frame 054279/0314 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Mar 20, 2020
From: SORGENFREI, SEBASTIAN; SHEPARD, KENNETH; CHIU, CHIEN-YANG; NUCKOLLS, COLIN; WARREN, STEVEN
To: THE TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK
Reel/Frame 052177/0835 →
Continuity (7)
Continuation 15646880 · Jul 11, 2017
Continuation 15453628 · Mar 8, 2017
Continuation 13801837 · Mar 13, 2013
Continuation In Part PCTUS2012020955 · Jan 11, 2012
Provisional Application 61453344 · Mar 16, 2011
Provisional Application 61431795 · Jan 11, 2011
Related Publication 20180156746A1 · Jun 7, 2018