Rational design of antifouling SERS substrates: bridging the gap between complex matrices and trace detection

Surface-enhanced Raman scattering (SERS) spectroscopy has established itself as a powerful analytical tool for diverse sensing applications, driven by its unparalleled sensitivity and unique molecular fingerprinting capabilities. However, sensing interface fouling caused by non-specific adsorption severely compromises signal accuracy, rendering reliable trace detection in complex matrices a critical challenge. For researchers to well address this challenge, this review highlights the importance of rational design of antifouling SERS substrates driven by interface regulation. First, it elucidates the diverse mechanisms of biological, organic, and inorganic fouling, underscoring the multifaceted nature of surface fouling. Subsequently, it delineates physical, chemical, and physicochemical strategies that enable SERS substrates to effectively repel interferents while maximizing their affinity toward target analytes. Furthermore, guided by the structure-function relationships, these designed antifouling SERS substrates exhibit robust detection performance in biomedicine, aquatic environmental monitoring, and food safety. Finally, the review highlights the current strengths and limitations of antifouling SERS, and looks ahead to future opportunities in artificial intelligence, aiming to facilitate the robust application of SERS technology across a broader range of practical scenarios.