Antibiotic residue detection based on SERS technology: enhancement mechanisms, material innovations, and challenges in on-site applications

In the face of the serious threat of antibiotic residues in food to human health, it is urgent to develop efficient and sensitive detection techniques. Traditional methods have limitations in sensitivity, efficiency, and multi-component detection capabilities. Surface-enhanced Raman scattering (SERS) technology has become a cutting-edge analytical tool due to its high sensitivity, photobleaching resistance, and multi-component detection potential close to the single-molecule level. However, the practical deployment of SERS remains hindered by critical challenges. Specifically, the ambiguous mechanisms governing substrate-analyte interactions limit rational substrate design, thereby compromising analytical sensitivity and selectivity. Furthermore, severe interferences from complex sample matrices frequently suppress intrinsic SERS signals, drastically reducing quantitative accuracy. The inter-batch consistency and long-term stability of the substrate need to be improved. In this paper, the synergistic mechanism of electromagnetic (EM) and chemical (CM) enhancement of SERS detection of antibiotics is comprehensively reviewed, and the innovative substrate strategies covering noble metal nanostructure optimization, functional composite material design (such as core-shell structure, MOF complex) and flexible substrate construction are discussed in depth. These strategies significantly improve the substrate performance and applicability by accurately constructing "hot spots" and enhancing interface charge transfer. Aiming at the bottleneck problem of the transformation from laboratory research to practical application, this review focuses on accurate signal analysis under complex matrix interference (such as machine learning deconvolution), on-site portable integration (microfluidic SERS, side-stream chromatography) and stability improvement path (such as packaging technology, regenerated substrate). Through the integration of material science innovation and intelligent analysis methods, SERS technology is expected to develop into a transformative platform with ultra-high sensitivity, multi-component screening and on-site real-time analysis capabilities, providing solid theoretical support and practical guidance for the food safety supervision system.