IP Library Granted Patent US 10,564,144
Granted Patent B2
US 10,564,144 · App. 13/419,383 · Granted Feb 18, 2020

Nanometric material having a nanopore enabling high-sensitivity molecular detection and analysis

Inventors: Slaven Garaj (Cambridge, MA); Jene A. Golovchenko (Lexington, MA); Daniel Branton (Lexington, MA)
Assignee: PRESIDENT AND FELLOWS OF HARVARD COLLEGE
G01N33/48721
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Quick Facts
Patent No.
US 10,564,144
App. No.
13/419,383
Granted
Feb 18, 2020
Kind
B2
Abstract

There is provided a substantially bare, self-supported single-layer graphene membrane including a nanopore extending through a thickness of the graphene membrane from a first to a second membrane surface opposite the first graphene membrane surface. A connection from the first graphene membrane surface to a first reservoir provides, at the first graphene membrane surface, a species in an ionic solution to the nanopore, and a connection from the second graphene membrane surface to a second reservoir is provided to collect the species and ionic solution after translocation of the species and ionic solution through the nanopore from the first graphene membrane surface to the second graphene membrane surface. An electrical circuit is connected on opposite sides of the nanopore to measure flow of ionic current through the nanopore in the graphene membrane.

Claims (37)

1. A graphene nanopore sensor comprising:

a substantially bare, self-supported, single-layer graphene membrane having an ionic conductance between about 27 pS to 70 pS, the graphene membrane including a nanopore with a diameter of between about 1 nm and about 2 nm extending through a thickness of the graphene membrane from a first graphene membrane surface to a second graphene membrane surface opposite the first graphene membrane surface;

a first reservoir including at least one species selected from the group consisting of DNA and RNA in an ionic solution having a pH between about 8.5 and 11 and a salt concentration greater than about 2 M, the first reservoir disposed in fluidic connection with the membrane whereby the first graphene membrane surface and the nanopore are exposed to the ionic solution and species in the ionic solution in the first reservoir;

a second reservoir including an ionic solution having a pH between about 8.5 and 11 and a salt concentration greater than about 2 M, the second reservoir disposed in fluidic connection with the membrane whereby the second graphene membrane surface and the nanopore are exposed to the ionic solution in the second reservoir, and the second reservoir arranged to collect the species and ionic solution after translocation of the species and ionic solution through the nanopore from the first graphene membrane surface to the second graphene membrane surface; and

an electrical circuit connected with the nanopore through said thickness of the graphene membrane from the first reservoir to the second reservoir to measure flow of ionic current through the nanopore in the graphene membrane.

2. The graphene nanopore sensor of claim 1 wherein the electrical circuit is connected between the ionic solution in the first reservoir and the ionic solution in the second reservoir to measure flow of ionic current through the nanopore in the graphene membrane.

3. The graphene nanopore sensor of claim 1 wherein the electrical circuit includes an electrical current monitor connected for measuring time-dependent ionic current flow through the nanopore.

4. The graphene nanopore sensor of claim 3 wherein the electrical current monitor is connected for measuring time-dependent ionic current flow blockages indicative of species translocation through the nanopore.

5. The graphene nanopore sensor of claim 1 further comprising an electrode disposed in the ionic solution in each of the first and second reservoirs for applying a voltage between the first and second reservoirs to electrophoretically cause species translocation through the nanopore.

6. The graphene nanopore sensor of claim 1 wherein the ionic solution is KCl.

7. The graphene nanopore sensor of claim 1 wherein the graphene membrane is characterized by a thickness that is less than about 1 nm.

8. The graphene nanopore sensor of claim 1 wherein the graphene membrane is characterized by a thickness that is less than about 0.7 nm.

9. The graphene nanopore sensor of claim 1 wherein the nanopore is characterized by a diameter that is no more than about 5% larger than a diameter of the species in the ionic solution.

10. The graphene nanopore sensor of claim 1 wherein the graphene membrane is mechanically supported at edges of the membrane by a membrane frame structure.

11. A graphene nanopore sensor comprising:

a substantially bare, self-supported, single-layer graphene membrane having an ionic conductance between about 27 pS to 70 pS, the graphene membrane including a nanopore extending through a thickness of the graphene membrane from a first graphene membrane surface to a second graphene membrane surface opposite the first graphene surface and having a diameter that is no greater than about 4 nm and greater than the graphene thickness;

a first reservoir including polymer molecules in an ionic solution having a pH between about 8.5 and 11 and having a salt concentration greater than about 2 M, the polymer molecules having a polymer molecule diameter, with the first graphene membrane surface and the nanopore exposed to the ionic solution and polymer molecules in the ionic solution of the first reservoir and the nanopore having a nanopore diameter that is no more than about 5% larger than the diameter of the polymer molecules in the ionic solution;

a second reservoir, the second reservoir including an ionic solution having a pH between about 8.5 and 11 and having a salt concentration greater than about 2 M, with the second graphene membrane surface and the nanopore exposed to the ionic solution in the second reservoir, the second reservoir arranged to collect the polymer molecules and the ionic solution after translocation of the polymer molecules and the ionic solution through the nanopore from the first graphene membrane surface to the second graphene membrane surface; and

an electrical circuit connected with the nanopore through said thickness of the graphene membrane from the first reservoir of ionic solution to the second reservoir of ionic solution to measure flow of ionic current through the nanopore in the graphene membrane.

12. The graphene nanopore sensor of claim 11 wherein the species in the ionic solution to translocate through the nanopore comprises biomolecules.

13. The graphene nanopore sensor of claim 11 wherein the species in the ionic solution to translocate through the nanopore comprises DNA molecules.

14. The graphene nanopore sensor of claim 11 wherein the species in the ionic solution to translocate through the nanopore comprises RNA molecules.

15. The graphene nanopore sensor of claim 11 wherein the species in the ionic solution to translocate through the nanopore comprises oligonucleotides.

16. The graphene nanopore sensor of claim 11 wherein the species in the ionic solution to translocate through the nanopore comprises a protein.

17. The graphene nanopore sensor of claim 11 wherein the species in the ionic solution to translocate though the nanopore comprises nucleotides.

18. The graphene nanopore sensor of claim 11 wherein the electrical current monitor is connected for measuring time-dependent ionic current flow blockages indicative of polymer molecule translocation through the nanopore.

19. The graphene nanopore sensor of claim 11 further comprising an electrode disposed in the ionic solution in each of the first and second reservoirs for applying a voltage between the first and second reservoirs to electrophoretically cause species translocation through the nanopore.

20. A nanopore sensor comprising:

a substantially bare, self-supported, single-layer graphene membrane having an ionic conductance between about 27 pS to 70 pS, the graphene membrane having a thickness, between a first membrane surface and a second membrane surface opposite the first membrane surface, that is less than about 1 nm;

a nanopore extending through the membrane thickness between the first and second membrane surfaces and having a diameter that is greater than the membrane thickness;

a first reservoir including a species in an ionic solution having a pH between about 8.5 and 11 and a salt concentration of at least about 2 M, the species having a species diameter, with the first membrane surface and the nanopore exposed to the ionic solution and species in the ionic solution in the first reservoir and the nanopore having a nanopore diameter that is no more than about 5% larger than the diameter of the species in the ionic solution;

a second reservoir including an ionic solution having a pH between about 8.5 and 11 and a salt concentration of at least about 2 M, with the second membrane surface and the nanopore exposed to the ionic solution in the second reservoir, the second reservoir arranged to collect the species and ionic solution after translocation of the species and ionic solution through the nanopore from the first membrane surface to the second membrane surface; and

an electrical circuit connected with the nanopore through said thickness of the membrane from the first reservoir to the second reservoir to monitor translocation of the species in the ionic solution through the nanopore in the solid state membrane.

21. The nanopore sensor of claim 20 wherein the nanopore is characterized by a diameter that is between about 1 nm and about 10 nm.

22. The nanopore sensor of claim 20 wherein the nanopore is characterized by a diameter that is between about 1 nm and about 5 nm.

23. The nanopore sensor of claim 20 wherein the nanopore is characterized by a diameter that is no greater than about 4 nm.

24. The nanopore sensor of claim 20 wherein the nanopore is characterized by a diameter that is less than about 2.5 nm.

Assignments (2)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Oct 16, 2013
From: BRANTON, DANIEL; GARAJ, SLAVEN; GOLOVCHENKO, JENE
To: PRESIDENT AND FELLOWS OF HARVARD COLLEGE
Reel/Frame 031412/0949 →
CONFIRMATORY LICENSE Recorded Apr 9, 2012
From: HARVARD UNIVERSITY
To: NATIONAL INSTITUTES OF HEALTH (NIH), U.S. DEPT. OF HEALTH AND HUMAN SERVICES (DHHS), U.S. GOVERNMENT
Reel/Frame 028010/0137 →
Continuity (4)
Continuation In Part PCTUS2010049238 · Sep 17, 2010
Provisional Application 61243607 · Sep 18, 2009
Provisional Application 61355528 · Jun 16, 2010
Related Publication 20120234679A1 · Sep 20, 2012