| Recent reports have demonstrated that single metal nanoparticles are excellent substrates for surface-enhanced Raman scattering (SERS), and can even allow detection of single molecules. This dissertation describes the use of single-nanoparticle SERS for the exploration of chemical enhancement mechanisms and as potential analogs to fluorescent probes.SERS spectra provide unique spectroscopic signatures for each species, so nanoparticles can be encoded by "Raman reporter" molecules, and used as optical tags, much like fluorescent dyes. It is demonstrated that SERS-active nanoparticles can also be coated with a layer of silica. This core-shell architecture stabilizes the gold colloid from precipitation and provides a surface that is readily modified. After conjugating antibodies to particles, individual cells can be immunologically labeled and imaged. Multiplexed experiments demonstrate the unique advantages of SERS over fluorescence. Similarly, antibodies can be adsorbed directly over the reporter (no silica shell) without contributing to the spectroscopic signature. A tissue microarray with both cancerous and normal tissues is labeled with a high degree of specificity by such particles. An improved synthetic method for colloidal gold is also outlined, with implications toward even more sensitive SERS signals. Not only are the resulting particles more monodisperse than those synthesized by other methods, but evidence indicates that particle shape might also be controllable.Although the sensitivity of SERS is well documented, the enhancement mechanisms are poorly understood. Chemical and electromagnetic mechanisms play a role, but traditional experiments have not adequately separated the two effects. A custom flow cell device allowed investigation of individual silver nanoparticles under controlled chemical treatments without changing their electromagnetic properties. Results indicate that active sites are directly related to the presence of silver cations, which are activated by formation of silver halide species.Single-nanoparticle SERS is expected to become a very important tool. It eliminates ensemble-averaging, thus allowing more detailed fundamental studies. More importantly, continued development should lead to the first practical applications for such a sensitive spectroscopic tool. |
