REFLOWED GOLD NANOSTRUCTURES FOR SURFACE ENHANCED RAMAN SPECTROSCOPY

• US 20150223739A1
• Filed: 02/12/2015
• Published: 08/13/2015
• Est. Priority Date: 02/12/2014
• Status: Active Grant

• Current Assignee: California Institute of Technology, Regents of the University of California (University of California), University of Southern California
• Original Assignee: California Institute of Technology, Regents of the University of California (University of California), University of Southern California
• Inventors: WALAVALKAR, Sameer, CHANG, Chieh-feng, SCHERER, Axel, MARIN, Brandon, FRASER, Scott E.
• Granted Patent: US 9,913,603 B2
• Time in Patent Office: Days
• US Class Current: 1/1
• CPC Class Codes: A61B 2562/0233 Special features of optical sensors or probes classified in A61B5/00
• CPC Class Codes: A61B 2562/0285 Nanoscale sensors
• CPC Class Codes: A61B 2562/12 Manufacturing methods specially adapted for producing sensors for in-vivo measurements
• CPC Class Codes: A61B 5/0075 by spectroscopy, i.e. measuring spectra, e.g. Raman spectroscopy, infrared absorption spectroscopy A61B5/0071 takes precedence
• CPC Class Codes: A61B 5/076 Permanent implantations telemetry using implanted circuitry A61B5/0031; implanted stimulators for therapy A61N1/3605, A61N1/362, A61N1/372
• CPC Class Codes: A61B 5/1459 invasive, e.g. introduced into the body by a catheter A61B5/1464 takes precedence
• CPC Class Codes: A61B 5/14735 comprising an immobilised reagent
• CPC Class Codes: A61B 5/6848 Needles
• CPC Class Codes: A61B 5/686 Permanently implanted devices, e.g. pacemakers, other stimulators, biochips A61B5/6861 takes precedence
• 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: G01N 21/658 enhancement Raman, e.g. surface plasmons
• CPC Class Codes: H01L 27/14698 Post-treatment for the devices, e.g. annealing, impurity-gettering, shor-circuit elimination, recrystallisation

Abstract

Methods and systems for nanopillar sensors are described. Nanopillars can be defined on a substrate, and metal deposited on the nanopillars. A thermal treatment can reflow the metal on the nanopillars forming metallic bulbs on the top end of the nanopillars. These structures can have enhanced optical detection when functionalized with biological agents, or can detect gases, particles and liquids through interaction with the metal layer on the nanopillars.

Claims

1. A method comprising:

providing a substrate;

defining at least one recessed region in the substrate;

forming nanopillars in the at least one recessed region;

depositing a metallic layer on a top end of the nanopillars;

by heating the metallic layer, reflowing the metallic layer on the top end of the nanopillars while removing the metallic layer from a middle portion of the nanopillars, thereby forming metallic bulbs on the top end of the nanopillars; and

functionalizing the metallic bulbs on the top end of the nanopillars.

2. The method of claim 1, further comprising:

defining at least one blank region in the substrate, the at least one blank region being at least one recessed region void of nanopillars; and

depositing a metallic layer on the at least one blank region.

3. The method of claim 1, wherein forming nanopillars and reflowing the metallic layer comprise forming a distance between the metallic bulbs between 5 and 50 nanometers.

4. The method of claim 1, further comprising attaching an imaging device to the substrate on a surface opposite to a surface where the nanopillars are formed.

5. The method of claim 4, wherein the imaging device is a wirelessly-powered complementary metal-oxide semiconductor (CMOS) device, configured to transmit images wirelessly to a receiver.

6. The method of claim 1, wherein the substrate comprises mesas having a height higher than the at least one recessed region on the substrate, and a height of the nanopillars is equal or less than the height of the mesas.

7. The method of claim 1, wherein:

defining at least one recessed region comprises defining an array of recessed regions in the substrate, and

forming nanopillars comprises forming nanopillars in each recessed region of the array of recessed regions.

8. The method of claim 7, wherein forming nanopillars in each recessed region of the array of recessed regions comprises forming nanopillars with at least a first nanopillar shape in at least one recessed regions of the array of recessed regions, and forming nanopillars with at least a second nanopillar shape in at least one recessed regions of the array of recessed regions.

9. The method of claim 7, wherein functionalizing the metallic bulbs comprises using a different functionalizing agent for at least two regions of the array of recessed regions.

10. The method of claim 7, wherein the array of recessed regions is a square array and each corner region of the square array of recessed regions is functionalized with thiol groups.

11. The method of claim 1, further comprising implanting the sensor in human tissue.

12. The method of claim 1, wherein a spacing between the metallic bulbs allows electrical insulation between the metallic bulbs.

13. The method of claim 1, wherein the substrate is silicon, the nanopillars are silicon dioxide and the metallic layer is gold.

14. The method of claim 1, further comprising attaching an optical fiber to one end of the at least one recessed region, wherein an opposite wall of the at least one recessed region comprises a metallic layer, thereby acting as a reflector for the optical fiber, the optical fiber being configured to shine a laser light on the metallic bulbs and collect a signal reflected from the metallic bulbs.

15. The method of claim 1, further comprising, after forming nanopillars and prior to depositing a metallic layer, oxidizing the nanopillars.

16. The method of claim 1, wherein:

defining at least one recessed region comprises etching the substrate; and

forming nanopillars comprises etching the at least one recessed region; and

depositing a metallic layer comprises sputtering the metallic layer.

21. The method of claim 1, further comprising applying a polymer layer on a top surface of the at least one recessed region in between the nanopillars.

22. The method of claim 1, wherein forming nanopillars comprises spacing the nanopillars and the metallic bulbs at a distance based on a desired resonant wavelength.

23. The method of claim 1, wherein heating the metallic layer is at 675°

C.

26. The method of claim 1, further comprising, after defining at least one recessed region and prior to forming nanopillars, forming mesas in the substrate and oxidizing the mesas.

35. The method of claim 1, wherein at least one of the one or more biomolecules is a protein.

17. A method comprising:

providing a substrate;

etching at least one recessed region in the substrate;

etching at least one groove on a surface of the at least one recessed region;

forming nanopillars in the at least one recessed region close to but not within the groove;

depositing a metallic layer on a top end of the nanopillars and on a side surface of the at least one recessed region;

by heating the metallic layer, reflowing the metallic layer on the top end of the nanopillars while removing the metallic layer from a middle portion of the nanopillars, thereby forming metallic bulbs on the top end of the nanopillars;

functionalizing the metallic bulbs on the top end of the nanopillars; and

attaching an optic fiber to the groove, the optic fiber having a surface substantially parallel and opposite to the side surface of the at least one recessed region.

24. The method of claim 17, wherein heating the metallic layer is at 675°

C.

18. A method comprising:

providing a substrate;

forming nanopillars on the substrate;

depositing a metallic layer on a top end of the nanopillars;

by heating the metallic layer, reflowing the metallic layer on the top end of the nanopillars while removing the metallic layer from a middle portion of the nanopillars, thereby forming metallic bulbs on the top end of the nanopillars;

functionalizing the metallic bulbs on the top end of the nanopillars;

etching the substrate on a surface opposite the surface with the nanopillars;

inserting an optic fiber in the etched side of the substrate, on the surface opposite the surface with the nanopillars; and

lifting the nanopillars with the optic fiber.

19. The method of claim 18, further comprising inserting the optic fiber with the nanopillars within the needle.

20. The method of claim 18, further comprising applying a layer of glue to a surface of the optic fiber prior to inserting, thereby gluing the nanopillars to the optic fiber when lifting the nanopillars with the optic fiber.

25. The method of claim 18, wherein heating the metallic layer is at 675°

C.

27. A method to detect one or more biomolecules, the method comprising:

providing a sensor, the sensor comprising

a substrate,

at least one recessed region on the substrate,

nanopillars defined in the at least one recessed region,

metallic bulbs on a top end of the nanopillars;

exposing the sensor to a composition comprising said one or more biomolecules; and

illuminating, by a laser, the metallic bulbs on the top end of the nanopillars, thereby detecting presence or absence of the one or more biomolecules.

28. The method of claim 27, wherein the sensor further comprises one or more functionalizing agents on the metallic bulbs on the top end of the nanopillars.

29. The method of claim 28, wherein the functionalizing agent is a nucleic acid aptamer.

30. The method of claim 28, wherein the functionalizing agent is an antibody.

31. The method of claim 28, wherein the functionalizing agent is cDNA.

32. The method of claim 28, wherein the sensor comprises two or more different functionalizing agents.

33. The method of claim 28, wherein the one or more functionalizing agents specifically bind to the one or more biomolecules.

34. The method of claim 33, wherein said binding is reversible.

36. The method of claim 27, wherein at least one of the one or more biomolecules is an mRNA.

37. The method of claim 27, wherein at least one of the one or more biomolecules is a cytokine.

38. The method of claim 27, wherein the one or more biomolecules is a molecular marker of disease.

39. The method of claim 38, wherein the disease is oral cancer.

40. The method of claim 38, wherein the disease is whooping cough.

41. The method of claim 27, wherein the biomolecule is tracheal cytotoxin.

42. The method of claim 27, wherein the biomolecule is thrombin.

43. The method of claim 27, wherein the sensor further comprises a polymer layer on a top surface of the at least one recessed region in between the nanopillars.

44. The method of claim 27, wherein the sensor further comprises an optical fiber attached to one end of the at least one recessed region, wherein an opposite wall of the at least one recessed region comprises a metallic layer, thereby acting as a reflector for the optical fiber, the optical fiber being configured to shine a laser light on the metallic bulbs and collect a signal reflected from the metallic bulbs.

45. The method of claim 44, wherein the sensor is embedded in a biological medium or tissue.

46. The method of claim 44, wherein the optical fiber comprised in the sensor is inserted within a needle.