Molecular characterization with carbon nanotube control

• US 7,468,271 B2
• Filed: 04/06/2006
• Issued: 12/23/2008
• Est. Priority Date: 04/06/2005
• Status: Active Grant

• Current Assignee: President and Fellows of Harvard College (Harvard Corporation)
• Original Assignee: President and Fellows of Harvard College (Harvard Corporation)
• Inventors: Branton, Daniel, Golovchenko, Jene A.
• Primary Examiner(s): Lam; Ann Y.
• Application Number:
  US11/399,663
• Publication Number:
  US 20080171316A1
• Time in Patent Office: 992 Days
• Field of Search: 436/514, 436/518, 4352871-2873, 4352884-2887, 435/285.2, 435/4, 435/7.1, 435/6
• US Class Current: 435/287.2
• 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: C12Q 1/6869 Methods for sequencing
• CPC Class Codes: C12Q 2565/631 being a biochannel or pore
• CPC Class Codes: G01N 27/44743 Introducing samples
• CPC Class Codes: G01N 27/44791 Microapparatus sample containers with integrated microfluidic structures B01L3/5027
• 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 977/762 Nanowire or quantum wire, i.e. axially elongated structure having two dimensions of 100 nm or less

Abstract

There is provided a first reservoir containing a liquid solution including a molecule to be characterized and a second reservoir for containing a liquid solution including a molecule that has been characterized. A solid state support structure is provided including an aperture having a molecular entrance providing a fluidic connection to the first reservoir and a molecular exit providing a fluidic connection to the second reservoir. First and second electron transport probes are each disposed on the support structure with a surface abutting a perimeter of the aperture. At least one of the probes comprises a fullerene structure, e.g., a carbon nanotube. A voltage source is connected between the probes to apply a voltage bias across the aperture. An electrical current monitor is connected between the probes for monitoring changes in electron transport between the probes corresponding to translocation of a molecule through the aperture.

Claims

1. A molecular characterization device comprising:

a first reservoir containing a liquid solution including a molecule to be characterized;

a second reservoir for containing a liquid solution including a molecule that has been characterized;

a solid state support structure including an aperture having a molecular entrance providing a fluidic connection to the first reservoir and a molecular exit providing a fluidic connection to the second reservoir;

first and second electron transport probes, at least one of the probes comprising a fullerene structure, each of the probes being disposed on the support structure and having a surface abutting a perimeter of the aperture;

a voltage source connected between the probes to apply a voltage bias across the aperture; and

an electrical current monitor connected between the probes for monitoring changes in electron transport between the probes corresponding to translocation of a molecule through the aperture.

2. The molecular characterization device of claim 1 wherein the molecule to be characterized comprises a biomolecule.

3. The molecular characterization device of claim 1 wherein the molecule comprises a polymer molecule.

4. The molecular characterization device of claim 1 wherein the molecule comprises a biopolymer molecule.

5. The molecular characterization device of claim 4 wherein the molecule is selected from the group consisting of proteins, polynucleic acids, DNA, and RNA.

6. The molecular characterization device of claim 1 wherein the molecule to be characterized comprises a molecule coupled to a carbon nanotube.

7. The molecular characterization device of claim 6 wherein the molecule coupled to a carbon nanotube comprises at least one strand of DNA coupled to a carbon nanotube.

8. The molecular characterization device of claim 6 wherein the molecule coupled to a carbon nanotube comprises at least one strand of RNA coupled to a carbon nanotube.

9. The molecular characterization device of claim 6 wherein the carbon nanotube to which the molecule is coupled is connected to a cantilevered actuation tip for translocation of the nanotube through the aperture.

10. The molecular characterization device of claim 1 wherein each of the first and second electron transport probes comprises a fullerene structure.

11. The molecular characterization device of claim 10 wherein the fullerene structure comprises a carbon nanotube.

12. The molecular characterization device of claim 11 wherein the carbon nanotube comprises a semiconducting nanotube.

13. The molecular characterization device of claim 11 wherein the carbon nanotube comprises a metallic nanotube.

14. The molecular characterization device of claim 11 wherein the carbon nanotube comprises a single-walled nanotube.

15. The molecular characterization device of claim 11 wherein at least one of the carbon nanotube electron transport probes is oriented with a nanotube end abutting on the aperture perimeter.

16. The molecular characterization device of claim 15 wherein each of the carbon nanotube electron transport probes is oriented with a nanotube end abutting on the aperture perimeter.

17. The molecular characterization device of claim 11 wherein at least one of the carbon nanotube electron transport probes is oriented with a nanotube side abutting on the aperture perimeter.

18. The molecular characterization device of claim 17 wherein one of the carbon nanotube electron transport probes is oriented with a nanotube end abutting on the aperture perimeter and one of the carbon nanotube electron transport probes is oriented with a nanotube side abutting on the aperture perimeter.

19. The molecular characterization device of claim 11 wherein one of the carbon nanotube electron transport probes is oriented with a first nanotube end abutting on the aperture perimeter at the molecular entrance and a second nanotube end abutting on the aperture perimeter at the molecular exit.

20. The molecular characterization device of claim 11 wherein at least one of the carbon nanotube electron transport probes is oriented with a nanotube surface, abutting on the aperture perimeter, to which a molecule can couple while being translocated through the aperture.

21. The molecular characterization device of claim 20 wherein the molecule comprises a nucleoside base that can couple to the nanotube surface while being translocated through the aperture.

22. The molecular characterization device of claim 11 further comprising a molecular translocation speed control nanotube disposed on the support structure and having a surface, abutting on the aperture perimeter at the molecular entrance, to which a molecule can couple.

23. The molecular characterization device of claim 1 wherein the aperture comprises a pore, extending through the thickness of the support structure, and having a diameter sufficiently small to permit only a single molecule at a time to be translocated through the pore.

24. The molecular characterization device of claim 23 wherein the pore comprises a nanopore having a diameter less than about 100 nm.

25. The molecular characterization device of claim 1 wherein the aperture has a diameter less than about 50 nm.

26. The molecular characterization device of claim 1 wherein the aperture has a diameter less than about 20 nm.

27. The molecular characterization device of claim 1 wherein the aperture has a diameter less than about 10 nm.

28. The molecular characterization device of claim 1 wherein the aperture is coated with an electrically insulating material layer.

29. The molecular characterization device of claim 1 wherein the electron transport probes are coated with an electrically insulating material layer except where they abut on the aperture perimeter.

30. The molecular characterization device of claim 1 wherein the support structure comprises an electrically insulating membrane in which the aperture is provided.

31. The molecular characterization device of claim 30 wherein the membrane comprises a silicon nitride membrane.

32. The molecular characterization device of claim 1 wherein the electrical current monitor connected between the probes is configured to detect a modulation in electron tunneling, between the probes, that corresponds to translocation of a molecule through the aperture.

33. A molecular characterization device comprising:

a first reservoir containing a liquid solution including at least one molecule coupled to a carbon nanotube in a molecule-nanotube complex to be characterized;

a second reservoir for containing a liquid solution including a molecule-nanotube complex that has been characterized;

a solid state support structure including an aperture having a molecular entrance providing a fluidic connection to the first reservoir and a molecular exit providing a fluidic connection to the second reservoir;

an electrical connection to the aperture for detecting translocation of a molecule-nanotube complex through the aperture.

34. The molecular characterization device of claim 33 wherein the electrical connection to the aperture is configured to detect a blockage in ionic current through the aperture as a molecule-nanotube complex is translocated through the aperture.

35. The molecular characterization device of claim 33 wherein the aperture comprises as pore having a diameter sufficiently small to permit only a single molecule-nanotube complex at a time to be translocated through the pore.

36. The molecular characterization device of claim 33 wherein the molecule coupled to a carbon nanotube comprises a polymer biomolecule selected from the group consisting of proteins, polynucleic acids, DNA, and RNA.

37. The molecular characterization device of claim 33 wherein the electrical connection to the aperture comprises first and second electron transport probes, each of the probes being disposed on the support structure abutting on a perimeter of the aperture;

and further comprising;

a voltage source connected between the probes to a apply a voltage bias across the aperture; and

an electrical current monitor connected between the probes for monitoring changes in electron transport between the probes corresponding to translocation of a molecule-nanotube complex through the aperture.

38. The molecular characterization device of claim 37 wherein at least one of the electron transport probes comprises a fullerene structure.

39. The molecular characterization device of claim 38 wherein each of the electron transport probes comprises a carbon nanotube.

40. A method for characterization of a molecule comprising:

translocating a molecule through an aperture in a support structure from a first reservoir containing a liquid solution including the molecule to be characterized to a second reservoir for containing a liquid solution including a molecule that has been characterized;

coupling the molecule to a surface of a carbon nanotube; and

monitoring changes in electron transport across the aperture, between two electron transport probes which each abut on a perimeter of the aperture, the changes in electron transport corresponding to translocation of the molecule through the aperture.

41. The method of claim 40 wherein the molecule is coupled to a surface of a carbon nanotube as the molecule is translocated through the aperture.

42. The method of claim 40 wherein the carbon nanotube surface to which the molecule is coupled abuts a perimeter of the aperture.

43. The method of claim 40 wherein the carbon nanotube surface to which the molecule is coupled abuts a perimeter of the aperture at a molecular entrance to the aperture that is in fluidic connection with the first reservoir.

44. The method of claim 40 wherein the carbon nanotube surface to which the molecule is coupled is a nanotube end.

45. The method of claim 40 wherein the carbon nanotube surface to which the molecule is coupled is a nanotube side.

46. The method of claim 40 further comprising transiently controlling a voltage bias of the nanotube relative to the liquid solution to control molecule translocation speed through the aperture.

47. The method of claim 40 wherein each of the electron transport probes comprises a carbon nanotube.

48. The method of claim 40 wherein the molecule comprises a DNA nucleoside base and coupling of the DNA base to the carbon nanotube surface spatially orients the base relative to the nanotube surface.

49. The method of claim 40 wherein the molecule comprises a RNA nucleoside base and coupling of the RNA base to the carbon nanotube surface spatially orients the base relative to the nanotube surface.

50. The method of claim 40 wherein coupling the molecule to a surface of a carbon nanotube comprises first coupling the molecule to the surface of the carbon nanotube in a nanotube configuration abutting on the aperture perimeter at an aperture molecular entrance and then coupling the molecule to a surface of a second carbon nanotube configured as an electron transport probe.

51. A method for characterization of a molecule comprising:

coupling a molecule to a carbon nanotube in a liquid solution to form a molecule-nanotube complex;

translocating the coupled molecule-nanotube complex through an aperture in a support structure from a first reservoir containing a liquid solution including the coupled molecule-nanotube complex to be characterized to a second reservoir for containing a liquid solution including a molecule-nanotube complex that has been characterized; and

detecting translocation of the molecule-nanotube complex through the aperture.

52. The method of claim 51 wherein detecting translocation of the molecule-nanotube complex comprises detection of a blockage in ionic current through the aperture as the molecule-nanotube complex is translocated through the aperture.

53. The method of claim 51 wherein detecting translocation of the molecule-nanotube complex comprises monitoring changes in electron transport between two electron transport probes disposed on the support structure and each having a surface abutting on a perimeter of the aperture, while applying a voltage bias across the aperture.

54. The method of claim 51 wherein the molecule coupled to a carbon nanotube comprises a polymer biomolecule selected from the group consisting of proteins, polynucleic acids, DNA, and RNA.

55. A method for characterization of a molecule comprising:

translocating a molecule through an aperture in a support structure from a first reservoir containing a liquid solution including the molecule to be characterized to a second reservoir for containing a liquid solution including a molecule that has been characterized;

coupling the molecule to a surface of a carbon nanotube; and

monitoring changes in conductance of the nanotube corresponding to translocation of the molecule through the aperture.

56. The method of claim 55 wherein a side of the carbon nanotube is disposed at the aperture as a molecular coupling surface at the aperture.

57. The method of claim 55 wherein monitoring changes in carbon nanotube conductance comprises measuring electrical current through the carbon nanotube as a molecule translocates through the aperture.

58. The method of claim 55 wherein monitoring changes in carbon nanotube conductance comprises configuring the carbon nanotube in an electrical circuit in which an electrical bias voltage is applied between ends of the nanotube.

59. The method of claim 55 wherein monitoring changes in carbon nanotube conductance comprises measuring electrical current through the carbon nanotube arranged in an PET configuration.

60. The method of claim 55 wherein the molecule comprises a polymer biomolecule selected from the group consisting of proteins, polynucleic acids, DNA, and RNA.

61. The method of claim 55 wherein the carbon nanotube comprises a semiconducting nanotube.

62. The method of claim 55 wherein the carbon nanotube comprises a single-walled nanotube.

63. The method of claim 55 wherein the molecule comprises a nucleoside base that can couple to the nanotube surface while being translocated through the aperture.

64. The method of claim 55 wherein the aperture comprises a pore, extending through the thickness of the support structure, and having a diameter sufficiently small to permit only a single molecule at a time to be translocated through the pore.

65. The method of claim 55 wherein the aperture is coated with an electrically insulating material layer.

66. The method of claim 55 wherein the support structure comprises an electrically insulating membrane in which the aperture is provided.