Gapping into Ultrahigh Surface-Enhanced Raman Scattering Amplification

Since its discovery in 1974 by Martin Fleischmann et al., surface-enhanced Raman scattering (SERS) has become a powerful sensing and imaging technique in biomedicine. SERS is based on the physical phenomenon of plasmon resonance whereby the inelastic scattering of photons can be significantly enhanced during the adsorption of molecules on metallic surfaces. A widely accepted mechanism for this effect is attributed to the excitation of localized surface plasmons on metal surfaces, resulting in concentrated electromagnetic optical fields and a greater increase in the electric field interactions with surrounding analyte molecules. Due to the influence of these localized surface plasmon “hot spots”, the close proximity of an analyte to metallic surfaces at nanometer length scales significantly intensifies the analyte’s Raman scattering. With enhancement factors of up to 10 orders of magnitude, SERSbased techniques are posed to achieve sensitivities significantly higher than conventional fluorescence microscopy. While the SERS technique offers unprecedented possibilities in biomedicine, its translation into the clinics has been largely impeded because of poor reproducibility of SERSactive structures. Dana Dlott and co-workers report that less than 1% of Raman-active dye molecules on a silver-coated nanosphere have enhancement factors on the order of 10, while they are significantly lower for the rest. This poor distribution of SERS enhancement factors is the result of an inability to control particle−dye interactions with precision. Thus, the main challenge for improving SERS techniques lies in amalgamating dye and nanostructures effectively to manufacture reproducible SERS-active “hot spots” to develop bioprobes with a narrow distribution of high enhancement factors, moving the field a step closer to the adoption of SERS-based probes in clinical applications.