Gold-Based SERS Platform for Biomedicine: Material Design, Enhancement Mechanisms, and Diagnostic Applications

Surface-enhanced Raman scattering (SERS) has emerged as a powerful analytical technique for biomedical detection owing to its ultrahigh sensitivity, molecular fingerprinting capability, excellent photostability, and potential for multiplex analysis. Among various SERS-active materials, gold-based systems have attracted particular attention due to their superior chemical stability, biocompatibility, and versatile surface functionalization. In this review, we systematically summarize the design strategies and enhancement mechanisms of gold-based SERS substrates. Specifically, we discuss electromagnetically dominated systems, as well as emerging platforms involving chemical enhancement and electromagnetic-chemical (EM-CM) synergistic effects, highlighting the evolution from classical plasmonic enhancement toward interface-mediated mechanisms. Furthermore, we provide a comprehensive overview of the biomedical applications of gold-based SERS platforms, with a focus on the detection of major diseases, including cancer, cardiovascular diseases, and neurological disorders. Finally, we critically analyze the key challenges hindering their practical implementation, such as reproducibility, stability in complex biological environments, and clinical translatability, and outline future perspectives for the development of gold-based SERS toward reliable and task-oriented biomedical applications.