NANOSTRUCTURED SUBSTRATES FOR SURFACE ENHANCED RAMAN SPECTROSCOPY (SERS) AND DETECTION OF BIOLOGICAL AND CHEMICAL ANALYTES BY ELECTRICAL DOUBLE LAYER (EDL) CAPACITANCE

• US 20110053794A1
• Filed: 08/26/2010
• Published: 03/03/2011
• Est. Priority Date: 08/26/2009
• Status: Active Grant

• Current Assignee: Clemson University
• Original Assignee: Clemson University
• Inventors: Zhang, Guigen
• Granted Patent: US 8,865,402 B2
• Time in Patent Office: Days
• US Class Current: 506/9
• CPC Class Codes: B01J 19/0046 Sequential or parallel reactions, e.g. for the synthesis of polypeptides or polynucleotides; Apparatus and devices for combinatorial chemistry or for making molecular arrays synthesis methods per se C40B50/00
• CPC Class Codes: B01J 2219/00509 Microcolumns
• CPC Class Codes: B01J 2219/00533 essentially rectangular
• CPC Class Codes: B01J 2219/00585 Parallel processes
• CPC Class Codes: B01J 2219/00596 Solid-phase processes
• CPC Class Codes: B01J 2219/00605 the compounds being directly bound or immobilised to solid supports
• CPC Class Codes: B01J 2219/00653 the compounds being bound to electrodes embedded in or on the solid supports
• CPC Class Codes: B01J 2219/00659 Two-dimensional arrays
• CPC Class Codes: B01J 2219/00704 integrated with the reactor apparatus
• CPC Class Codes: B82Y 30/00 Nanotechnology for materials or surface science, e.g. nanocomposites
• CPC Class Codes: B82Y 40/00 Manufacture or treatment of nanostructures
• CPC Class Codes: C25D 11/045 for forming AAO templates
• CPC Class Codes: G01N 21/658 enhancement Raman, e.g. surface plasmons
• CPC Class Codes: G01N 33/5438 Electrodes
• CPC Class Codes: G01N 33/553 Metal or metal coated

Abstract

Provided according to embodiments of the invention are nanostructured surfaces that include a substrate; and an array of metallic nanopillar islands on the substrate, wherein each metallic nanopillar island includes a metal base layer on the substrate and a plurality of metallic nanopillars on the metal base layer, and wherein portions of the substrate between adjacent metallic nanopillar islands are free of the metal base layer. Also provided according to some embodiments of the invention are nanostructured surfaces that include a non-conductive substrate; and at least one nanoelectrode defined within the non-conductive substrate, wherein the at least one nanoelectrode is sized and/or shaped to immobilize an analyte or a probe molecule. Also provided are apparatuses and methods for SERS and detection of analytes or biological binding by EDL capacitance.

Claims

1. A nanostructured surface comprising:

a substrate; and

an array of metallic nanopillar islands on the substrate, wherein each metallic nanopillar island comprises a metal base layer on the substrate and a plurality of metallic nanopillars on the metal base layer, and wherein portions of the substrate between adjacent metallic nanopillar islands are free of the metal base layer.

2. The nanostructured surface of claim 1, wherein the metallic nanopillar islands are circular.

3. The nanostructured surface of claim 1, wherein the array of nanopillar islands has an inter-island distance in a range of about 100 nm to about 1 mm;

and

wherein each metallic nanopillar island comprises a hexagonal array of metallic nanopillars with an inter-pillar distance in a range of about 1 nm to about 500 nm, wherein the metallic nanopillars have an aspect ratio in a range of about 1;

1 to about 500;

1.

4. The nanostructured surface of claim 3, wherein a width of the metallic nanopillars is in a range of about 10 nm to about 500 nm.

5. The nanostructured surface of claim 1, wherein the metal base layer of each metallic nanopillar island comprises a layer of titanium and/or a layer of gold, and wherein the plurality of metallic nanopillars comprises silver and/or gold.

6. The nanostructured surface of claim 1, wherein the metal base layer of each metallic nanopillar island comprises a layer of titanium and/or a layer of gold, and wherein the plurality of nanopillars comprises at least one metal selected from the group consisting of aluminum, silver, gold, copper, titanium and tantalum.

7. The nanostructured surface of claim 1, further comprising at least one probe molecule immobilized on at least one metallic nanopillar island.

8. The nanostructured surface of claim 1, wherein two or more metallic nanopillar islands are electrically coupled.

9. The nanostructured surface of claim 1, further comprising a driver circuit in electrical contact with at least one metallic nanopillar island, wherein the driver circuit is configured to generate an electrical potential sufficient to cause at least a portion of the metallic nanopillars of the at least one metallic nanopillar island to shift position.

10. An apparatus for detecting an analyte by Surface Enhanced Raman Spectroscopy comprising:

(i) a nanostructured surface comprising

a substrate; and

an array of metallic nanopillar islands on the substrate, wherein each metallic nanopillar island comprises a metal base layer on the substrate and a plurality of metallic nanopillars on the metal base layer, and wherein portions of the substrate between adjacent metallic nanopillar islands are free of the metal base layer;

(ii) a radiation source, the radiation source operable to provide incident radiation to the nanostructured surface; and

(iii) a detector, the detector positioned to receive radiation scattered from at least one analyte bound to the nanostructured surface, the scattered radiation being used to detect the analyte.

11. The apparatus of claim 10, wherein the array of metallic nanopillar islands has an inter-island distance in a range of about 100 nm to about 1 mm, and

wherein each metallic nanopillar island comprises a hexagonal array of metallic nanopillars with an inter-pillar distance in a range of about 10 nm to about 500 nm, wherein the metallic nanopillars have an aspect ratio in a range of about 1:

1 to about 500;

1.

12. The apparatus of claim 10, wherein the at least one analyte is bound to at least one metallic nanopillar island.

13. The apparatus of claim 10, wherein the incident radiation has a wavelength that excites surface plasmons within a metal in the metal base layer and/or the metallic nanopillars.

14. The apparatus of claim 10, further comprising:

a driver circuit in electrical contact with at least one metallic nanopillar island, wherein the driver circuit is configured to generate an electrical potential sufficient to cause at least a portion of the metallic nanopillars of the at least one metallic nanopillar island to shift position.

15. The apparatus of claim 10, further comprising

a stage, wherein the nanostructured surface is on the stage;

and

a controller, wherein the controller is connected to the stage and is configured to translate and/or rotate the stage.

16. A method of detecting an analyte by Surface Enhanced Raman Spectroscopy comprising

(i) binding at least one analyte to a nanostructured surface that comprises

a substrate;

and

an array of metallic nanopillar islands on the substrate, wherein each metallic nanopillar island comprises a metal base layer on the substrate and a plurality of metallic nanopillars on the metal base layer, and wherein portions of the substrate between adjacent metallic nanopillar islands are free of the metal base layer;

(ii) irradiating the analyte bound to the nanostructured surface; and

(iii) detecting radiation scattered by the at least one analyte.

17. The method of claim 16, wherein the array of metallic nanopillar islands has an inter-island distance in a range of about 100 nm to about 1 mm;

and

wherein each metallic nanopillar island comprises a hexagonal array of metallic nanopillars with an inter-pillar distance in a range of about 10 nm to about 500 nm, and wherein the metallic nanopillars have an aspect ratio in a range of about 1;

1 to about 500;

1.

18. The method of claim 16, wherein the at least one analyte is bound to at least one metallic nanopillar island.

19. The method of claim 16, wherein binding of the at least one analyte to at least one metallic nanopillar island comprises

electrically charging the metallic nanopillars;

trapping the analyte within the metallic nanopillars; and

discharging the metallic nanopillars.

20. The method of claim 16, further comprising:

correlating the radiation scattered by the at least one analyte with a chemical structure of the at least one analyte.

21. The method of-Claim 16, wherein the metallic nanopillars enhance the radiation scattered by the at least one analyte by an enhancement factor in a range of about 10⁸ to about 10¹⁵.

22. An apparatus for detecting an analyte and/or a biological or chemical binding event by electrical double layer capacitance comprising:

(i) a nanostructured surface comprising

a substrate; and

an array of metallic nanopillar islands on the substrate, wherein each metallic nanopillar island comprises a metal base layer on the substrate and a plurality of metallic nanopillars on the metal base layer, and wherein portions of the substrate between adjacent metallic nanopillar islands are free of the metal base layer;

(ii) an electrolyte in contact with at least one metallic nanopillar island;

(iii) a reference electrode in electrical contact with the electrolyte; and

(iv) a meter electrically coupled between the at least one metallic nanopillar island and the reference electrode,

wherein the meter is configured to measure capacitances between the at least one metallic nanopillar island and the reference electrode.

23. The apparatus of claim 22, wherein the meter if further configured to correlate measured capacitances with the presence of the analyte.

24. The apparatus of claim 22, further comprising at least one probe molecule immobilized on the at least one metallic nanopillar island, wherein the meter is further configured to correlate measured capacitances with the binding of the at least one analyte to the at least one probe molecule.

25. The apparatus of claim 22, wherein the array of metallic nanopillar islands has an inter-island distance in a range of about 100 nm to about 1 mm, and

wherein each metallic nanopillar island comprises a hexagonal array of metallic nanopillars with an inter-pillar distance in a range of about 10 nm to about 500 nm.

26. The apparatus of claim 22, further comprising a driver circuit in electrical contact with the at least one metallic nanopillar island, wherein the driver circuit is configured to generate an electrical potential sufficient to cause at least a portion of the metallic nanopillars of the at least one metallic nanopillar island to shift position.

27. The apparatus of claim 24, wherein the at least one probe molecule is immobilized on the at least one metallic nanopillar island by:

electrically charging the metallic nanopillars;

trapping the at least one probe molecule within the metallic nanopillars; and

discharging the metallic nanopillars.

28. A method of detecting at least one analyte and/or a biological or chemical binding event by EDL capacitance comprising

(i) providing at least one analyte to an apparatus comprising

(a) a nanostructured surface comprising

a substrate, and

an array of metallic nanopillar islands on the substrate, wherein each metallic nanopillar island comprises a metal base layer on the substrate and a plurality of metallic nanopillars on the metal base layer, and wherein portions of the substrate between adjacent metallic nanopillar islands are free of the metal base layers;

(b) an electrolyte in contact with at least one metallic nanopillar island;

and

(c) a reference electrode in electrical contact with the electrolyte;

(ii) measuring capacitances between at least one metallic nanopillar island and the reference electrode; and

(iii) correlating the measured capacitances to detect whether the at least one analyte binds to the at least one of metallic nanopillar island.

29. The method of claim 28, wherein the array of metallic nanopillar islands has an inter-island distance in a range of about 100 nm to about 1 mm, and wherein each metallic nanopillar island comprises a hexagonal array of metallic nanopillars with an inter-pillar distance in a range of about 10 nm to about 500 nm.

30. The method of claim 28, further comprising at least one probe molecule immobilized on the at least one metallic nanopillar island and wherein the measured capacitances are correlated to detect whether the at least one analyte binds to the at least one probe molecule.

31. The method of claim 30, wherein the at least one probe molecule and the at least one analyte are nucleic acids that bind by hybridization.

32. The method of claim 30, wherein the at least one analyte and/or the at least one probe molecule is a peptide, protein, virus, nucleotide, cell, bacterium, conjugated nanoparticles and/or lipid bilayer.

33. A nanostructured surface comprising:

a non-conductive substrate; and

at least one nanoelectrode defined within the non-conductive substrate, wherein the at least one nanoelectrode is sized and/or shaped to immobilize an analyte and/or a probe molecule.

34. The nanostructured surface of claim 33, wherein the at least one nanoelectrode comprises a conductive cavity that is sized and shaped to immobilize a biological analyte.

35. The nanostructured surface of claim 34, wherein the conductive cavity has a width in a range of about 10 nm to about 500 nm.

36. The nanostructured surface of claim 34, wherein the conductive cavity is sized and shaped to immobilize a virion.

37. The nanostructured surface of claim 33, wherein the at least one nanoelectrode comprises a planar conductive surface.

38. The nanostructured surface of claim 33, wherein the at least one nanoelectrode projects from the plane of the non-conductive substrate.

39. The nanostructured surface of claim 38, wherein the at least one nanoelectrode comprises a spherical-shaped projection.

40. The nanostructured surface of claim 38, wherein the at least one nanoelectrode comprises a rod-shaped projection.

41. The nanostructured surface of claim 33, wherein the at least one nanoelectrode is present in an array of nanoelectrodes within the non-conductive substrate.

42. The nanostructured surface of claim 41, wherein at least two nanoelectrodes of the array of nanoelectrodes are electrically coupled.

43. The nanostructured surface of claim 33, wherein the at least one nanoelectrode comprises at least one conductive material selected from the group consisting of platinum, gold, titanium, copper, carbon, indium tin oxide and conductive polymer.

44. The nanostructured surface of claim 33, further comprising at least one analyte and/or probe molecule immobilized by the at least one nanoelectrode.

45. The nanostructured surface of claim 44, wherein the at least one analyte and/or probe molecule comprises a virion, bacterium or cell.

46. An apparatus for detecting at least one analyte and/or a biological or chemical binding event by electrical double layer capacitance comprising:

(i) a nanostructured surface comprising a non-conductive substrate and at least one nanoelectrode defined within the non-conductive substrate, wherein the at least one nanoelectrode is sized and/or shaped to immobilize the at least one analyte and/or at least one probe molecule;

(ii) an electrolyte in contact with the at least one nanoelectrode;

(iii) a reference electrode in electrical contact with the electrolyte; and

(iv) a meter electrically coupled between the at least one nanoelectrode and the reference electrode,

wherein the meter is configured to measure capacitances between the at least one nanoelectrode and the reference electrode.

47. The apparatus of claim 46, further comprising the at least one analyte and/or the at least one probe molecule immobilized by the at least one nanoelectrode.

48. The apparatus of claim 46, wherein the meter is further configured to correlate measured capacitances with immobilization of the at least one analyte and/or the immobilization of the at least one probe molecule by the at least one nanoelectrode.

49. The apparatus of claim 46, wherein the at least one nanoelectrode comprises a conductive cavity that is sized and/or shaped to immobilize a biological analyte.

50. The apparatus of claim 49, wherein the conductive cavity has a width in a range of about 10 nm to about 500 nm.

51. The apparatus of claim 49, wherein the conductive cavity is sized and shaped to immobilize a virion.

52. The apparatus of claim 46, wherein the meter is further configured to correlate measured capacitances with the binding of the at least one analyte to the least one probe molecule.

53. A method of detecting at least one analyte and/or a biological or chemical binding event by EDL capacitance comprising

(i) providing at least one analyte to an apparatus comprising

(a) a nanostructured surface comprising a non-conductive substrate and at least one nanoelectrode defined within the non-conductive substrate, wherein each nanoelectrode is sized and/or shaped to immobilize the at least one analyte and/or at least one probe molecule;

(b) an electrolyte in contact with the at least one nanoelectrode; and

(c) a reference electrode in electrical contact with the electrolyte;

(ii) measuring capacitances between the at least one nanoelectrode and the reference electrode; and

(iii) correlating the measured capacitances to detect whether the at least one analyte and/or the at least one probe molecule is immobilized by the at least one nanoelectrode.

54. The method of claim 53, further comprising correlating the measured capacitances to detect whether the at least one analyte is bound to the at least one probe molecule.

55. The method of claim 53, wherein the at least one nanoelectrode comprises a conductive cavity that is sized and shaped to immobilize a biological analyte.

56. The method of claim 53, wherein the conductive cavity is sized and shaped to immobilize a virion.

57. The method of claim 53, wherein the at least one analyte and/or the at least one probe molecule comprises a virion, a bacteria and/or a cell.