Surface-enhanced spectroscopy-active sandwich nanoparticles

Abstract

Surface-enhanced Raman spectroscopy (SERS) uses nanoscale metal particles (SERS-active particles) or surface roughness to enhance the Raman signal of Raman-active analytes contacting the surface. SERS sandwich particles contain SERS-active particles sandwiching a Raman-active substance and serve as optical tags. Preferably, the particles are rod-shaped, with each layer (SERS-active and Raman-active) formed as a distinct stripe of the particle. These freestanding particles can be derivatized with surface ligands capable of associating with analytes of interest in, for example, a biological sample. The acquired Raman spectrum of the particle encodes the identity of the ligand. Because of the simplicity and intensity of Raman spectra, highly multiplexed assays are capable using SERS particles with different Raman-active species.

1 . A method of manufacturing a particle comprising: 
 a) associating at least two surface-enhanced spectroscopy (SES)-active outer regions with a spectroscopy-active analyte positioned between said outer regions; and    b) coating said outer regions and said analyte at least partially with an encapsulant;    wherein said spectroscopy-active analyte has a measurable SES spectrum.    
     
     
         2 . The method of  claim 1 , wherein said outer region comprises a metal selected from the group consisting of Au, Ag, Cu, Na, Al, Li and Cr.  
     
     
         3 . The method of  claim 2 , wherein said outer region comprises Au.  
     
     
         4 . The method of  claim 2 , wherein said outer region comprises Ag.  
     
     
         5 . The method of  claim 1 , wherein said outer region has a length less than about 200 nm.  
     
     
         6 . The method of  claim 5 , wherein said outer region has a length less than about 150 nm.  
     
     
         7 . The method of  claim 6 , wherein said outer region has a length less than about 100 nm.  
     
     
         8 . The method of  claim 1 , wherein said encapsulant has a thickness less than about 1 micron.  
     
     
         9 . The method of  claim 8 , wherein said encapsulant has a thickness between about 0.5 nm and about 100 nm.  
     
     
         10 . The method of  claim 1 , wherein said outer region comprises an alloy of metals selected from the group consisting of Au, Ag, Cu, Na, Al, Li and Cr.  
     
     
         11 . The method of  claim 1 , wherein said spectroscopy-active analyte forms a submonolayer coating on said outer region.  
     
     
         12 . The method of  claim 1 , wherein said spectroscopy-active analyte forms a monolayer coating on said outer region.  
     
     
         13 . The method of  claim 1 , wherein said spectroscopy-active analyte forms a multilayer coating on said outer region.  
     
     
         14 . The method of  claim 1 , wherein said encapsulant comprises a material selected from the group consisting of glass, polymers, metals, metal oxides, and metal sulfides.  
     
     
         15 . The method of  claim 1 , wherein said encapsulant comprises a plurality of materials selected from the group consisting of glass, polymers, metals, metal oxides, and metal sulfides.  
     
     
         16 . The method of  claim 1 , wherein said encapsulant comprises glass oxide (SiO x ).  
     
     
         17 . The method of  claim 1 , wherein said encapsulant comprises TiO x .  
     
     
         18 . The method of  claim 1 , wherein said surface-enhanced spectrum is obtained by a method selected from the group consisting of SERS, SERRS, SEHRRS and SEIRA.  
     
     
         19 . The method of  claim 1 , wherein said surface-enhanced analyte is an aromatic analyte.  
     
     
         20 . The method of  claim 1  further comprising the step of functionalizing the surface of the encapsulated particles.