Advancements in SERS: Revolutionizing Biomedical Analysis and Applications.

Surface-enhanced Raman scattering (SERS) has emerged as a powerful technique for bioanalysis, offering ultrasensitive molecular detection and identification capabilities. The signal intensity and reproducibility of Raman responses from analytes are primarily influenced by the surface roughness and nanogap architecture of plasmonic materials. Numerous designs, plasmonic nanostructures, and fabrication methods have been explored to optimize these factors. The precise nanogap ranging from 0.5 to 1.0 nm between the metallic nanoparticles and analytes offers significantly higher Raman enhancement, enabling single-molecule detection through SERS. With advancements in nano- and microfabrication techniques, the development of highly efficient SERS substrates has significantly enhanced the analytical performance in various biomedical applications. This review comprehensively examines the latest innovations in nano- and microfabricated SERS sensors, emphasizing their design, fabrication techniques, and functionalization strategies for biomolecular detection, bioimaging, and theranostic applications. Furthermore, we explore the growing role of artificial intelligence (AI) in optimizing SERS-based bioanalysis, from enhancing spectral data processing to developing machine learning models for pattern recognition and diagnostic applications. The integration of AI with SERS technologies holds great promise for revolutionizing point-of-care diagnostics, real-time biomarker monitoring, and personalized medicine.