Apparatus for microarray binding sensors having biological probe materials using carbon nanotube transistors

• US 20080035494A1
• Filed: 03/19/2007
• Published: 02/14/2008
• Est. Priority Date: 03/17/2006
• Status: Active Grant

• Current Assignee: Government Of The United States Of America, Represented By The Secretary, Department Of Health And Human Services, University of Maryland, College Park
• Original Assignee: University of Maryland, College Park
• Inventors: Wei, Jun, Gomez, Romel, Aschenbach, Konrad, Pandana, Herman, Khan, Javed, Fuhrer, Michael
• Granted Patent: US 8,017,938 B2
• Time in Patent Office: Days
• US Class Current: 205/792
• 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: G01N 33/5438 Electrodes
• CPC Class Codes: Y10S 977/702 having biological material component
• CPC Class Codes: Y10S 977/92 Detection of biochemical
• CPC Class Codes: Y10S 977/938 Field effect transistors, FETS, with nanowire- or nanotube-channel region

Abstract

A microarray apparatus is provided which contains at least one chip having source and drain electrodes positioned on an array of carbon nanotube transistors which allows for electronic detection of nucleic acid hybridizations, thereby affording both increased sensitivity and the capability of miniaturization.

Claims

1. An apparatus comprising:

a) at least one chip incorporating a source and drain electrode, each comprised on a carbon nanotube transistor on a silicon substrate and covered by a thin insulating oxide or nitride layer with exposed metallic terminals,

b) a conducting metal to provide electrical conductivity to the transistor terminals,

c) a multiplicity of specific probe materials immobilized on the insulating oxide or nitride later,

d) a microfluidic channel above the oxide to direct the flow of liquid solutions that contain target sequences,

e) an electronic circuitry to detect the change in electrical charge due to hybridization of the probe materials and target materials therefor,

f) means for using the detected change in electrical charge of claim 1(e) to directly quantify the amount of bound target; and

g) an automated sensing system, which determines a relative abundance of specific target sequences using input from e) and f).

2. The apparatus of claim 1, wherein the carbon nanotube transistors are made by electrically contacting each nanotube in two places, and allowing electrical current to flow through each nanotube;

in proximity to a third electrode separated by an insulting barrier where a voltage applied will cause an electric field to affect the conductance of the nanotube.

3. The apparatus of claim 1, wherein there are two or more metallic layers to form the electrical connection to the nanotubes.

4. The apparatus of claim 1, wherein the substrate is glass or non-conducting polymer.

5. The apparatus of claim 1, wherein the thin insulating layer is an oxide.

6. The apparatus of claim 1, wherein the fluidic channel is made from PDMS polymer.

7. The apparatus of claim 1, wherein the probe materials comprise DNA, RNA or PNA.

8. The apparatus of claim 1, wherein the probe materials comprise peptides or proteins.

9. The apparatus of claim 1, wherein one of the terminals is located on the back side of the substrate.

10. The apparatus of claim 1, wherein the electronic circuitry is external to the at least one chip array.

11. The apparatus of claim 1, wherein the automated sensing system is external to the at least one chip array.

12. The apparatus of claim 1, wherein said at least one chip is comprised on an array of about 20 to 50 carbon nanotube transistors.

13. The apparatus of claim 5, wherein the thin insulating oxide layer is a silicon oxide layer.

14. The apparatus of claim 1, wherein the nanotubes bridge a gap between the source and drain electrodes.

15. The apparatus of claim 1, wherein the probe materials comprise aptamers.

16. The apparatus of claim 12, which comprises at least 1,000 chips.

17. The apparatus of claim 1, having one chip.

18. The apparatus of claim 1, wherein the probe materials comprise cell surface receptor sequences.

19. The apparatus of claim 1, wherein the drain electrode is gold.

20. The apparatus of claim 1, wherein a separation distance between the source and drain electrode is about 5 nm.

21. The apparatus of claim 1, wherein further comprising a gate oxide on top of a drain source gap to avoid electrolyte current leakage, the gate oxide not being insulated by the thin insulating oxide or nitride layer.

22. The apparatus of claim 21, wherein the gate oxide is aluminum oxide.

23. The apparatus of claim 22, wherein the aluminum oxide is about 100 nm thick.

24. The apparatus of claim 1, wherein the specific probe materials are immobilized on the insulating oxide or nitride layer by silane functionalization.

25. The apparatus of claim 24, wherein the silane functionalization comprises MPTMS coupled to a hydroxylated surface of the insulating oxide or nitride layer.

26. A method of electronically detecting a target biological material in a mixture containing the target biological material and other biological materials, which comprises:

a) exposing the mixture containing the target biological material and other biological materials to the at least one chip of the apparatus of claim 1;

and

b) determining an absolute amount of the target biological material in the mixture by a change in electrical charge due to binding of the target biological material to a probe material on said at least one chip.

27. The method of claim 26, which further comprises electronically determining a relative abundance of target biological materials in a mixture comprising more than one target biological material.

28. The method of claim 26, wherein the apparatus comprises one chip.

29. The method of claim 26, wherein the target biological material is DNA.

30. The method of claim 26, wherein the target biological material is RNA.

31. The method of claim 30, wherein the RNA is miRNA.

32. The method of claim 26, wherein the probe material is DNA, RNA or PNA.

33. A method of electronically detecting a target biological material, which comprises detecting a change in electrical charge due to binding of the target biological material to a probe biological material on a carbon nanotube transistor.

34. The method of claim 33, wherein the target biological material is DNA.

35. The method of claim 33, wherein the target biological material is RNA.

36. The method of claim 33, wherein the change in electrical charge comprises a channel conductance increase.

37. The method of claim 33, wherein the change in electrical charge comprises a shift in V_GS.

38. A carbon nanotube transistor having probe DNA, RNA or PNA bound thereto, which comprises:

a) drain and source electrodes having a carbon nanotube channel bridging the drain and source electrodes;

b) an oxide or nitride layer insulating the drain and source electrodes and carbon nanotube channel; and

c) a gate electrode contactable with an electrolyte solution containing at least one target biological material for the probe DNA, RNA or PNA.

39. The carbon nanotube transistor of claim 38, wherein the probe is DNA.

40. The carbon nanotube transistor of claim 38, wherein the probe is RNA.

41. A method of detecting binding of a probe biological material and a target biological material, which comprises detecting an electrical signal resulting from a change in electrical charge due to binding of the probe and target biological materials.

43. The method of claim 41, wherein the iron-containing nanoparticles are Fe nanoparticles.

44. The method of claim 41, wherein the iron-containing nanoparticles are FePt nanoparticles.

42. A method of making carbon nanotubes, which comprises growing carbon nanotubes on iron-containing nanoparticles.