The increasing applications of surface-enhanced Raman scattering (SERS) has led to the development of various SERS-active platforms (SERS substrates) for SERS measurement. This work reviews the current optimization techniques available for improving the performance of some of these SERS substrates. The work particularly identifies self-assembled-monolayer- (SAM-) based substrate modification for optimum SERS activity and wider applications. An overview of SERS, SAM, and studies involving SAM-modified substrates is highlighted. The focus of the paper then shifts to the use of SAMs to improve analytical applications of SERS substrates by addressing issues including long-term stability, selectivity, reproducibility, and functionalization, and so forth. The paper elaborates on the use of SAMs to achieve optimum SERS enhancement. Specific examples are based on novel multilayered SERS substrates developed in the author’s laboratory where SAMs have been demonstrated as excellent dielectric spacers for improving SERS enhancement more than 20-fold relative to conventional single layer SERS substrates. Such substrate optimization can significantly improve the sensitivity of the SERS method for analyte detection.

Surface-enhanced Raman spectroscopy (SERS) sensors offer many advantages for chemical analyses, including the ability to provide chemical specific information and multiplexed detection capability at specific locations. However, to have operative SERS sensors for probing microenvironments, probes with high signal enhancement and reproducibility are necessary. To this end, dynamic enhancement of SERS (i.e., in-situ amplification of signal-to-noise and signal-to-background ratios) from individual probes has been explored. In this paper, we characterize the use of optical tweezers to amplify SERS signals as well as suppress background signals via trapping of individual SERS active probes. This amplification is achieved through a steady presence of a single "hot" particle in the focus of the excitation laser. In addition to increases in signal and concomitant decreases in non-SERS backgrounds, optical trapping results in an eightfold increase in the stability of the signal as well. This enhancement strategy was demonstrated using both single and multilayered SERS sub-micron probes, producing combined signal enhancements of 24-fold (beyond the native 10 SERS enhancement) for a three-layered geometry. The ability to dynamically control the enhancement offers the possibility to develop SERS-based sensors and probes with tailored sensitivities. In addition, since this trapping enhancement can be used to observe individual probes with low laser fluences, it could offer particular interest in probing the composition of microenvironments not amenable to tip-enhanced Raman spectroscopy or other scanning probe methods (e.g., intracellular analyses, etc.).