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Surface Enhanced Raman Spectroscopy utilizes the unique optical properties of nanostructured metallic substrates to enhance the intensity of the native Raman signal of an adsorbed analyte by several orders of magnitude. Nanostructured substrates composed of noble metals (primarily silver and gold) are capable of supporting localized surface plasmon resonance (LSPR). Localized surface plasmon resonance is a condition induced by the resonant excitation of surface-bound substrate electrons which generates a highly enhanced localized electromagnetic field. Raman scattering intensity is governed by the polarizability of the analyte being interrogated as well as the localized electromagnetic field experienced by the analyte as a result of laser excitation. LSPR results in a significant increase in magnitude of the local electromagnetic field near the surface of a nanostructured substrate. Adsorption of an analyte onto a LSPR-supporting nanostructured substrate followed by excitation with a laser of appropriate wavelength leads to an increase in Raman signal intensity by several orders of magnitude and a significant increase in sensitivity compared to traditional Raman spectroscopy.

The success of a SERS measurement is critically dependent on the ability of the nanostructured substrate to support LSPR. The development of robust, reproducible, and highly-active SERS substrates is an active research topic in the academic and commercial communities. There are several commercially available SERS substrates, mostly utilizing a chip-based array of metallic nanofeatures fabricated using lithographic techniques common to the semi-conductor processing industry. There are several other SERS substrate configurations in use including metallic nanoparticles in solution and thin, nanostructured metallic films supported on dielectric substrates. Substrate suitability is dependent upon several application-specific criteria including wavelength of the Raman excitation source used and adsorption affinity of the analyte for the substrate. Customized substrates can be fabricated to induce analyte-specificity by including a molecular recognition moiety such as an antibody/antigen or an analyte-specific aptamer.