IP Library Granted Patent US 9,625,404
Granted Patent B2
US 9,625,404 · App. 13/801,834 · Granted Apr 18, 2017

Systems and methods for single-molecule detection using nanotubes

Inventors: Sebastian Sorgenfrei (Portland, OR); Kenneth 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
G01N27/041C12Q1/6816C12Q1/6874G01N27/3278
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Quick Facts
Patent No.
US 9,625,404
App. No.
13/801,834
Granted
Apr 18, 2017
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 (25)

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

providing a carbon nanotube having a point defect formed therein and a probe entity attached to the point defect, the probe entity defining a first state of the carbon nanotube, wherein the probe entity comprises a protein;

introducing the carbon nanotube to a target entity to define a second state of the carbon nanotube, wherein the target entity comprises a target protein to bind to the protein of the probe entity;

comparing the electrical conductance of the carbon nanotube in the first and second states to detect the presence of a biomolecular entity.

2. The method of claim 1 , further comprising carbon-generating the point defect in the carbon nanotube and attaching the probe entity to the carbon nanotube at the point defect.

3. The method of claim 2 , wherein the point defect comprises a single carboxyl defect.

4. The method of claim 2 , further comprising attaching the probe entity to the carbon nanotube via a coupling reaction.

5. The method of claim 1 , wherein the probe entity comprises an enzyme.

6. The method of claim 5 , wherein the enzyme comprises DNA polymerase or RNA polymerase.

7. The method of claim 6 , wherein one or more conformational changes of the DNA polymerase or RNA polymerase defines the second state relative to the first state.

8. The method of claim 1 , wherein the introducing further comprises introducing the carbon nanotube to the target entity in a buffer composition containing the target entity.

9. 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 target entity.

10. The method of claim 9 , wherein the predetermined conductance data comprises a calibration curve.

11. The method of claim 1 , wherein the carbon nanotube comprises a single-walled carbon nanotube.

12. The method of claim 1 , wherein the carbon nanotube comprises a field effect transistor that provides an electronic signal for measuring the conductance in the first and second states of the carbon nanotube.

13. The method of claim 1 , wherein the method is label free.

14. The method of claim 1 , further comprising providing single-molecule protein folding activity of the biomolecular entity upon detecting the presence of the biomolecular entity.

15. The method of claim 14 , wherein detection of biomoleculary entity is label free.

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

a carbon nanotube having a point defect formed therein and a probe entity attached to the point defect, the probe entity defining a first state of the carbon nanotube, wherein the probe entity comprises a protein;

a field effect transistor in electronic communication with the carbon nanotube; and

a supply of a target entity that when introduced to the carbon nanotube defines a second state of the carbon nanotube such that the electrical conductance of the carbon nanotube in the first and second states is compared to detect the presence of a biomolecular entity, wherein the target entity comprises a target protein to bind to the protein of the probe entity.

17. The system for single-molecule detection of claim 16 , further comprising a buffer composition to introduce a target nucleotide sequence to the carbon nanotube.

18. The system for single-molecule detection of claim 16 , wherein the probe entity is attached to the carbon nanotube at a point defect.

19. The system for single-molecule detection of claim 16 , wherein the target entity further comprises a complementary target nucleotide sequence.

Assignments (2)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jul 11, 2017
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 042978/0516 →
CONFIRMATORY LICENSE Recorded Aug 5, 2013
From: COLUMBIA UNIVERSITY NEW YORK MORNINGSIDE
To: NATIONAL SCIENCE FOUNDATION
Reel/Frame 030958/0041 →
Continuity (4)
Continuation In Part PCTUS2012020955 · Jan 11, 2012
Provisional Application 61431795 · Jan 11, 2011
Provisional Application 61453344 · Mar 16, 2011
Related Publication 20130285680A1 · Oct 31, 2013