Unveiling practical considerations for reliable and standardized SERS measurements: lessons from a comprehensive...

Recently, there has been an exponential growth in the number of publications focusing on surface-enhanced Raman scattering (SERS), primarily driven by advancements in nanotechnology and the increasing demand for chemical and biological detection. While many of these publications have focused on the development of new substrates and detection-based applications, there is a noticeable lack of attention given to various practical issues related to SERS measurements and detection. This review aims to fill this gap by utilizing silver nanorod (AgNR) SERS substrates fabricated through the oblique angle deposition method as an illustrative example. The review highlights and addresses a range of practical issues associated with SERS measurements and detection. These include the optimization of SERS substrates in terms of morphology and structural design, considerations for measurement configurations such as polarization and the incident angle of the excitation laser, and exploration of enhancement mechanisms encompassing both intrinsic properties induced by the structure and materials, as well as extrinsic factors arising from wetting/dewetting phenomena and analyte size. The manufacturing and storage aspects of SERS substrates, including scalable fabrication techniques, contamination control, cleaning procedures, and appropriate storage methods, are also discussed. Furthermore, the review delves into device design considerations, such as well arrays, flow cells, and fiber probes, and explores various sample preparation methods such as drop-cast and immersion. Measurement issues, including the effect of excitation laser wavelength and power, as well as the influence of buffer, are thoroughly examined. Additionally, the review discusses spectral analysis techniques, encompassing baseline removal, chemometric analysis, and machine learning approaches. The wide range of AgNR-based applications of SERS, across various fields, is also explored. Throughout the comprehensive review, key lessons learned from collective findings are outlined and analyzed, particularly in the context of detailed SERS measurements and standardization. The review also provides insights into future challenges and perspectives in the field of SERS. It is our hope that this comprehensive review will serve as a valuable reference for researchers seeking to embark on in-depth studies and applications involving their own SERS substrates.