Surface enhanced spectrometry-active composite nanoparticles

• US 20060054506A1
• Filed: 04/25/2005
• Published: 03/16/2006
• Est. Priority Date: 10/06/1999
• Status: Active Grant

• Current Assignee: Becton, Dickinson & Co
• Original Assignee: Becton, Dickinson & Co
• Inventors: Walton, Ian D., Natan, Michael J., Doering, William E., Penn, Sharron Gaynor, Freeman, R. Griffith, Chakarova, Gabriela
• Granted Patent: US 8,497,131 B2
• Time in Patent Office: Days
• US Class Current: 205/112
• CPC Class Codes: B22F 1/054 Nanosized particles
• CPC Class Codes: B22F 1/0547 Nanofibres or nanotubes
• CPC Class Codes: B22F 1/0553 Complex form nanoparticles, e.g. prism, pyramid, octahedron
• CPC Class Codes: B22F 1/056 Submicron particles having a size above 100 nm up to 300 nm
• CPC Class Codes: B22F 1/102 Metallic powder coated with organic material
• CPC Class Codes: B22F 1/17 Metallic particles coated with metal
• CPC Class Codes: B22F 2998/00 Supplementary information concerning processes or compositions relating to powder metallurgy
• CPC Class Codes: B22F 9/14 using electric discharge
• CPC Class Codes: B82Y 30/00 Nanotechnology for materials or surface science, e.g. nanocomposites
• CPC Class Codes: C25D 1/006 Nanostructures, e.g. using aluminium anodic oxidation templates [AAO]
• CPC Class Codes: C25D 1/04 Wires; Strips; Foils
• CPC Class Codes: G01N 21/658 enhancement Raman, e.g. surface plasmons
• CPC Class Codes: G01N 2201/06113 Coherent sources; lasers
• CPC Class Codes: G01N 2201/068 Optics, miscellaneous
• CPC Class Codes: G01N 33/54346 Nanoparticles
• CPC Class Codes: Y10T 436/13 Tracers or tags

Abstract

Submicron-sized particles or labels that can be covalently or non-covalently affixed to entities of interest for the purpose of quantification, location, identification, tracking, and diagnosis, are described.

Claims

1. A method, comprising:

a) causing deposition of a metal into a pore of a template, the pore diameter of which is less than 300 nm;

b) causing deposition of a second material into said pore of said template, wherein the deposition of at least one of said first material and said second material involves faradaic electrochemical processes to generate a segmented, pore-bound nanoparticle;

c) repeating step a); and

d) releasing said second material and said template from said segmented, pore-bound nanoparticle to generate at least two free metal nanoparticles.

2. The method of claim 1, wherein said free metal nanoparticle has a length from 10-300 nm and a width from 15-300.

3. The method of claim 1, further comprising repeating step b) and c).

4. The method of claim 1, wherein said template is alumina.

5. The method of claim 1, wherein the second material is a metal.

6. The method of claim 5, wherein the second material Ag.

7. The method of claim 1, wherein said metal is Au.

8. The method of claim 4, wherein said second material is Ag.

9. The method of claim 8, wherein said template is alumina.

10. The method of claim 1, wherein said releasing comprises treating with a strong acid followed by a strong base.

11. The method of claim 10, wherein said strong acid is nitric acid and said strong base is NaOH.

12. The method of claim 1, wherein said electrodeposition is selected from the group consisting of pulse plating, pulse current plating, reverse pulse current plating, and double pulse plating.

13. The method of claim 1, further comprising providing a short SAM-molecule during step c).

14. The method of claim 1, wherein said releasing comprises using a solution providing a SERS-active molecule.

15. A method, comprising:

a) causing deposition of a metal into a pore of a template, the pore diameter of which is less than 300 nm;

b) causing deposition of a second material into said pore of said template, wherein the deposition of at least one of said first material and said second material involves faradaic electrochemical processes to generate a segmented, pore-bound nanoparticle;

c) repeating step a); and

d) releasing said second material and said template from said segmented, pore-bound nanoparticle with acid treatment to generate at least two porous free metal nanoparticles.

16. A SACN, comprising a nanoparticle core, a Raman-active reporter molecule, an SiO₂ encapsulant, and a reactive group selected from the group consisting of an —

SH group, a —

NH₂ group, and a —

COO⁻

group.

17. A method, comprising

a) providing a nanoparticle:

b) associating a Raman-active reporter molecule with said nanoparticle;

c) encapsulating the nanoparticle with SiO₂; and

d) modifying the SiO₂ to bear a reactive group selected from the group consisting of an —

SH group, a —

NH₂ group, and a —

COO⁻

group, whereby an activated SACN is prepared.

18. A method for detecting an analyte comprising:

a) obtaining a biological sample; and

b) contacting the sample with a bioconjugated SACN comprising a biomolecule that binds to the analyte; and

c) detecting the analyte bound to said bioconjugated SACN.

19. The method of claim 18 wherein the biomolecule and the analyte are complementary nucleotide sequences.

20. The method of claim 18, wherein the sample is selected from the group consisting of blood, serum, saliva, sputum, tears, sweat, another secreted fluid;

urine, fecal matter;

cerebrospinal fluid, interstitial fluid, a cellular extract, and a cell.

21. A method, comprising,

a) contacting a sample suspected of containing an analyte with at least one specific binding partner to the analyte on a lateral-flow assay surface to bind to the analyte in the sample;

b) previously, simultaneously or subsequently to step (a), binding at least one analyte binding partner with a SACN; and

c) detecting a SERS signal whereby the presence of the analyte is determined in the sample by the intensity or presence of the signal, whereby the presence of at least one analyte in the sample is determined.

22. A method, comprising:

a) providing a microscope coupled to a CCD camera;

b) providing a cell;

c) contacting the cell with at least one SACN capable of specifically binding to the cell or a portion of the cell;

d) providing a wavenumber filtering device between the cell and the camera

e) acquiring a plurality of data sets; and

f) assembling the data sets;

whereby a spatial profile of the SACN is acquired.

23. The method of claim 22, wherein the wavenumber filtering device is selected from the group consisting of a monochromator, a notch filter, a filter wheel, acousto-optic tunable filter, Fourier transform interference filter, a liquid crystal tunable filter, and combinations of the foregoing.

24. The method of claim 22, wherein said wavenumber filtering device comprises a liquid crystal tunable filter, and said acquiring comprises:

a) acquiring data at a first frequency; and

b) optionally acquiring data at a second and subsequent frequencies.

25. The method of claim 22, wherein said acquiring comprises:

a) dispersing light from a single point of a location through a monochromator;

b) acquiring the complete Raman spectrum of that point on an array detector; and

c) repeating a) and b) multiple locations.

26. The method of claim 22, wherein said acquiring comprises:

a) exciting the sample with a line of radiation;

b) acquiring the complete spectrum of each spatial pixel in the line; and

c) scanning the line across the sample.

27. A nanoparticle, comprising:

a) a core/shell nanoparticle;

b) at least one Raman-active reporter molecule associated with said core/shell nanoparticle; and

c) an SiO₂encapsulant.

28. The nanoparticle of claim 27, further wherein said core/shell nanoparticle is selected from the group consisting of an Au₂S core/Au shell particle, an Ag core/Au shell particle, silica core/Au shell particles, silica core/Ag shell particles, alumina core/Au shell particles, alumina core/Ag shell particles, TiO₂ core/Au shell particles, and TiO₂ core/Ag shell particles.

29. A nanoparticle comprising:

a) a an isotropic metal nanoparticle;

b) a SERS-active reporter molecule associated with said anisotropic metal nanoparticle;

c) SiO₂ encapsulating the anisotropic metal nanoparticle.

30. The nanoparticle of claim 29, wherein the anisotropic metal nanoparticle has a shape selected from the group consisting of a spheroid, rod, disk, pyramid, cube, cylinder, nanohelix, nanospring, nanoring, rod-shaped nanoparticle, arrow-shaped nanoparticle, teardrop-shaped nanoparticle, tetrapod-shaped nanoparticle, prism-shaped, porous, and non-geometric shaped nanoparticle.

31. The nanoparticle of claim 30, wherein the nanoparticle is non-geometric shaped, and approximates a nanorod.

32. The method of claim 31, wherein the nanoparticle has a diameter of about 250 nm and length of about 250 nm.

33. A method comprising,

a) administering a SACN nanoparticle imaging agent to a patient,

b) scanning the patient using a system that can perform spectral imaging;

and

c) generating a spectrum or image of an internal region of the patient.

34. The method of claim 33, wherein said system is selected from the group consisting of a spot scanning confocal microscope, a line scanning system, an Optical Coherence tomographic system, a system that detects only over a single wavelength band, a fluorescence imaging system comprising an excitation light source and filtered image detection.

35. The method of claim 33, wherein the region of a patient is selected from the group consisting of the whole patient, the vasculature, heart, liver, and spleen, the gastrointestinal region.

36. The method of claim 33, wherein the system that can perform spectral imaging is a portable system.

39. The method of claim 33, wherein said SACN is non-covalently associated with an imaging probe, wherein said administering comprises introducing the imaging probe, and wherein said SACNs disassociate into the tissue or a bodily fluid.

37. A method, comprising:

a) introducing a plurality of SACNs targeted to a molecule involved in an abnormal pathology into a patient with the abnormal pathology, wherein the SACNs become associated to a molecule associated with the abnormal pathology; and

b) obtaining an imaging of the associated SACNs, whereby an abnormal pathology may be diagnosed.

38. The method of claim 37, wherein said the location of the abnormal pathology comprises the gastro-intestinal tract, heart, lung, liver cervix, breast, and colon.

40. A method for labeling an animal with a SACN, comprising introducing a SACN into an animal, wherein said introducing is selected from the group consisting of subcutaneous implantation, intravenous introduction.

41. The method of claim 40, further comprising detecting the SACN or labeled animal.

42. A method, comprising:

(a) contacting a tissue sample with at least one biomolecule-conjugated SACN particle capable of specifically binding to the tissue sample; and

(b) acquiring a Raman image of the tissue/biomolecule-conjugated SACN particles mixture.

43. The method of claim 42, where the tissue is contacted with one or more additional non-SACN reagents.

44. The method of claim 43, where the additional reagent is selected from the group consisting of eosin, hemotoxylin, and a combination of hemotoxylin and eosin.

45. The method of claim 42, further comprising:

(a) acquiring a background Raman image of a tissue sample prior to step (a) of claim 42;

and

(b) subtracting the background spectrum from the Raman image of the tissue/biomolecule-conjugated SACN particles mixture acquired in step (b) of claim 42.

46. The method of claim 45, where the tissue is contacted with one or more additional non-SACN reagents.

47. The method of claim 45, where said additional reagent is selected from the group consisting of eosin, hemotoxylin, and a combination of hemotoxylin and eosin.

48. The method of claim 42, further comprising comparing the Raman image with an image of a tissue sample which has been stained with strongly colored organic dyes to Visualize cell size and shape.