Surface enhanced spectroscopy-active composite nanoparticles

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.

What is claimed is: 
     
         1 . A method, comprising:
 (a) contacting a tissue sample with at least one biomolecule-conjugated Surface Enhanced Spectroscopy-Active Composite Nanoparticle (SACN) particle capable of specifically binding to the tissue sample; and   (b) acquiring a Raman image of the tissue/biomolecule-conjugated SACN particles mixture.   
     
     
         2 . The method of  claim 1 , where the tissue is contacted with one or more additional non-SACN reagents. 
     
     
         3 . The method of  claim 2 , where the additional reagent is selected from the group consisting of eosin, hemotoxylin, and a combination of hemotoxylin and eosin. 
     
     
         4 . The method of  claim 1 , further comprising:
 i) acquiring a background Raman image of a tissue sample prior to step (a) of  claim 1 ; and   ii) subtracting the background spectrum from the Raman image of the tissue/biomolecule-conjugated SACN particles mixture acquired in step (b) of  claim 1 .   
     
     
         5 . The method of  claim 4 , where the tissue is contacted with one or more additional non-SACN reagents. 
     
     
         6 . The method of  claim 5 , where said additional reagent is selected from the group consisting of eosin, hemotoxylin, and a combination of hemotoxylin and eosin. 
     
     
         7 . The method of  claim 1 , 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. 
     
     
         8 . A Surface Enhanced Spectroscopy-Active Composite Nanoparticle (SACN), comprising
 a nanoparticle core,   at least two different species of Raman-active reporter molecules, and   a SiO 2  encapsulant.   
     
     
         9 . The SACN of  claim 8 , wherein the SACN produces different Raman scattering spectra at different excitation wavelengths. 
     
     
         10 . The SACN of  claim 1 , wherein the SACN produces different Raman scattering spectra at different relative ratios of the at least two different species of Raman-active reported molecules. 
     
     
         11 . The SACN of  claim 1 , wherein one of the at least two different species of Raman-active reporter molecules is 4-mercaptopyridine (4-MP). 
     
     
         12 . The SACN of  claim 1 , wherein one of the at least two different species of Raman-active reported molecules is trans-4,4′bis(pyridyl)ethylene (BPE).