Nanotube sensor devices for DNA detection

• US 20070178477A1
• Filed: 08/24/2005
• Published: 08/02/2007
• Est. Priority Date: 01/16/2002
• Status: Abandoned Application

• Current Assignee: Nanomix Incorporated (CJY Holdings Ltd.)
• Original Assignee: Nanomix Incorporated (CJY Holdings Ltd.)
• Inventors: Gruner, George, Star, Alexander, Gabriel, Jean-Christophe, Joiner, Charles
• Application Number:
  US11/212,026
• Publication Number:
  US 20070178477A1
• Time in Patent Office: Days
• US Class Current: 435/6
• CPC Class Codes: C12Q 1/6825 Nucleic acid detection involving sensors
• CPC Class Codes: C12Q 2565/107 Alteration in the property of hybridised versus free label oligonucleotides
• CPC Class Codes: C12Q 2565/631 being a biochannel or pore
• CPC Class Codes: G01N 27/4145 specially adapted for biomolecules, e.g. gate electrode with immobilised receptors
• CPC Class Codes: G01N 27/4146 involving nanosized elements, e.g. nanotubes, nanowires

Abstract

A nanotube device is configured as an electronic sensor for a target DNA sequence. A film of nanotubes is deposited over electrodes on a substrate. A solution of single-strand DNA is prepared so as to be complementary to a target DNA sequence. The DNA solution is deposited over the electrodes, dried, and removed from the substrate except in a region between the electrodes. The resulting structure includes strands of the desired DNA sequence in direct contact with nanotubes between opposing electrodes, to form a sensor that is electrically responsive to the presence of target DNA strands. Alternative assay embodiments are described which employ linker groups to attach ssDNA probes to the nanotube sensor device.

Claims

1. A nanotube sensor for sensing an polynucleotide, comprising:

a substrate;

a first nanotube over the substrate;

at least one conducting element in electrical communication with the first nanotube; and

at least one single-strand DNA molecule operatively associated with the first nanotube, the at least one single-strand DNA molecule configured for interacting with a complimentary target DNA strand to alter an electrical property of the nanotube sensor.

2. The nanotube sensor of claim 1, wherein the at least one single-strand DNA is directed attached to the first nanotube.

3. The nanotube sensor of claim 1, wherein the first nanotube is selected from the group consisting of single-walled nanotubes, double-walled nanotubes, multi-walled nanotubes, and onions.

4. The nanotube sensor of claim 1, wherein the first nanotube comprises at least one element selected from the group consisting of carbon, boron, boron nitride, and carbon boron nitride, silicon, germanium, gallium nitride, zinc oxide, indium phosphide, molybdenum disulphide, and silver.

5. The nanotube sensor of claim 1, wherein the first nanotube comprises a single-wall carbon nanotube.

6. The nanotube sensor of claim 1, wherein the at least one conducting element comprises an electrode including at least one material selected from the group consisting of a metal, carbon and conductive polymer.

7. The nanotube sensor of claim 1, wherein the electrical property of the nanotube sensor is a capacitance of at least the first nanotube, and wherein the sensor further comprises a counter electrode configured to permit measurement of the capacitance.

8. The nanotube sensor of claim 1, wherein the at least one conducting element includes at least two conducting elements, and the conducting elements comprise metal electrodes.

9. The nanotube sensor of claim 8, wherein the conducting elements are in direct physical contact with the first nanotube.

10. The nanotube sensor of claim 8, further comprising a gate electrode in proximity to the nanotube.

11. The nanotube sensor of claim 8, further comprising a layer of inhibiting material covering regions of the sensor adjacent to the connections between the conductive elements.

12. The nanotube sensor of claim 8, wherein the nanotube further comprises a two-dimensional nanotube network disposed over the substrate between the two conducting elements.

13. The nanotube sensor of claim 12, wherein the nanotube network comprises a plurality of randomly-oriented carbon nanotubes.

14. The nanotube sensor of claim 12, wherein the two conducting elements comprise a pair of interdigitated electrodes.

15. The nanotube sensor of claim 12, wherein the at least one single-strand DNA further comprises a plurality of identical DNA receptor strands distributed over the two-dimensional nanotube network.

16. The nanotube sensor of claim 15, wherein the plurality of identical DNA receptor strands are directed attached to nanotubes of the two-dimensional nanotube network

17. A method for making a nanoelectronic sensor, comprising:

disposing a film of nanotubes over electrodes on a substrate;

depositing a solution of single-stranded DNA over the substrate, wherein the single-stranded DNA is configured as a complement to a target DNA sequence; and

drying the solution to leave a deposit of the single-stranded DNA over the substrate.

18. The method of claim 17, further comprising removing the deposit of the single-stranded DNA from the substrate except in a region between the electrodes.

19. The method of claim 17, further comprising depositing the electrodes as a conductive deposit over the substrate.

20. The method of claim 19, wherein the depositing the electrodes step further comprises configuring the electrodes to have a plurality of interdigitated fingers.

21. The method of claim 17, further comprising providing a gate electrode configured to operate on a region between the electrodes.

22. The method of claim 21, further comprising removing the deposit of the single-stranded DNA from the substrate except in the region between the electrodes.

23. The method of claim 17, further comprising coating the electrodes with barrier material prior to the depositing step.

24. The method of claim 17, further comprising preparing the solution of single-stranded DNA comprising an oligonucleotide dissolved in water.

25. A method for sensing a particular target polynucleotide sequence, comprising:

exposing a solution to a nanoelectronic sensor, wherein the nanoelectronic sensor comprises a complementary polynucleotide for the target polynucleotide sequence attached to at least one nanotube in a region between conducting electrodes; and

observing at least one electrical property of the nanoelectronic sensor during the exposing step.

26. The method of claim 25, wherein the exposing step further comprises exposing the solution to the nanoelectronic sensor comprising a field-effect transistor.

27. The method of claim 26, wherein the observing step comprises observing the at least one electrical property comprising a gate voltage.

28. The method of claim 25, further comprising comparing an electrical property observed during the observing step to a corresponding property observed prior to the observing step.

29. An electronic sensor system for target polynucleotides, comprising:

(a) at least one sensor platform having at least one electrical property, the platform including;

a substrate,

at least one electrode disposed adjacent the substrate, and

at least one nanostructured element disposed adjacent the substrate, the nanostructured element in electrical communication with the electrode;

(b) at least one detector probe operatively associated with the sensor platform, the probe including;

a linker group disposed in association with the sensor platform, the linker being connected to one or more of the following;

the nanostructured element, the substrate, and the electrode;

a detector biomolecule having a binding affinity to an analyte polynucleotide.

a bonding connection between the linker group and the detector biomolecule; and

(c) electronic measurement circuitry connected to the electrode, and configured to measure the at least one electrical property of the sensor platform.

30. The sensor system of claim 29, wherein detector biomolecule is selected from the group consisting of polynucleotides, transcription factors and transcription promoters.

31. The sensor system of claim 29, wherein the detector biomolecule comprises a detector polynucleotide having at least one nucleotide sequence which is at least partially complementary to a nucleotide target sequence of the analyte polynucleotide.

32. The sensor system of claim 31, wherein the at least one detector probe operatively associated with the sensor platform is configured so as to influence the at least one electrical property upon engagement of the probe with an analyte polynucleotide by at least partial hybridization of the target sequence.

33. The sensor system as in claim 32, wherein

(a) the at least one electrode includes at least two electrodes disposed in a space-apart arrangement adjacent the substrate, the electrodes each in electrical communication with the nanostructured element so that the nanostructured element provides at least one conduction channel between the electrodes, and

(b) the at least two electrodes connected to the electronic measurement circuitry and configured to measure the at least one electrical property of the sensor platform.

34. The sensor system as in claim 32, wherein the nanostructured element includes a network comprising a plurality of interconnecting single-walled carbon nanotubes.

35. The sensor system as in claim 32, further comprising a gate electrode arranged adjacent the nanostructured element and connected to the electronic measurement circuitry, wherein the circuitry is further configured to selectively bias the gate electrode to at least one voltage during measurement of the at least one electrical property of the sensor platform.

36. The sensor system as in claim 32, wherein the bonding connection between the linker group and the detector polynucleotide comprises at least a chemical bond between the linker group and the detector polynucleotide.

37. The sensor system as in claim 36, wherein the bonding connection between the linker group and the detector polynucleotide comprises at least a covalent bond between the linker group and the detector polynucleotide.

38. The sensor system as in claim 37, wherein the linker group includes an aromatic compound configured to interact non-covalently with the nanostructure.

39. The sensor system as in claim 32, wherein the bonding connection between the linker group and the detector polynucleotide molecule comprises:

at least one tether group connected to the linker group;

at least one tether-mating group connected to the detector; and

wherein the tether group and the tether-mating group (collectively tethering species) have a mutual affinity promoting a self-assembled bonding connection between the tether group and the tether-mating group.

40. The sensor system as in claim 39, wherein the at least one of the tethering species comprises a non-biological molecule.

41. The sensor system as in claim 39, wherein the at least one of the tethering species comprises a biopolymer.

42. The sensor system as in claim 39, wherein the at least one of the tethering species comprises a synthetically-produced polymer substantially equivalent to a naturally occurring biopolymer.

43. The sensor system as in claim 39, wherein:

the at least one tether group includes an antibody connected to the linker group;

the at least one tether-mating group includes a corresponding antigen connected to the detector; and

wherein the mutual affinity between the tether group and the tether-mating group includes the affinity of the antibody binding site to an epitope of the antigen.

44. The sensor system as in claim 39, wherein:

the at least one tether group includes an MHC receptor connected to the linker group;

the at least one tether-mating group includes a corresponding binding peptide connected to the detector; and

wherein the mutual affinity between the tether group and the tether-mating group includes the affinity of the MHC receptor for a corresponding peptide.

45. The sensor system as in claim 39, wherein:

the at least one tether group includes a mammalian cell surface receptor connected to the linker group;

the at least one tether-mating group includes a corresponding specific binding ligand of the receptor, the ligand connected to the detector; and

wherein the mutual affinity between the tether group and the tether-mating group includes the affinity of the cell surface receptor for its corresponding ligand.

46. The sensor system as in claim 39, wherein:

the at least one tether group includes a viron host-attachment-promoting surface group and/or a viron endocytosis-promoting surface group connected to the linker group;

the at least one tether-mating group includes a corresponding mammalian cell surface receptor, the receptor connected to the detector; and

wherein the mutual affinity between the tether group and the tether-mating group includes the affinity of the mammalian cell surface receptor for the corresponding viron surface group.

47. The sensor system as in claim 39, wherein the tether group binding species and the tether-mating group mating species are reversed in attachment order in that the at least one tether group ;

is connected to the detector, and the at least one tether-mating group is connected to the linker group.

48. The sensor system as in claim 39, wherein one or more of the tethering species is synthetic.

49. The sensor system as in any of claim 39, wherein the system further comprises an plurality of said sensors, and wherein different ones of the plurality of sensors include pairs of tethering species with distinctly different mutual binding affinities, so as to permit self assembly of a selected multiplex pattern of different target-specific cDNA probes with respect to two or more of the plurality of sensors.

50. The sensor system of claim 29, wherein the electrical property of the sensor platform is a capacitance of at least the nanostructured element, and wherein the sensor system further comprises a counter electrode configured to permit measurement of the capacitance.