Plasmonic and surface-enhanced Raman nanobiosensors for quantitative molecular detection

Plasmonic surface-enhanced Raman scattering (SERS) nanobiosensors employ nanoscale electromagnetic field amplification to achieve ultrasensitive, multiplex molecular detection. This review systematically outlines the fundamental plasmonic principles, nanostructure engineering strategies, and surface chemical functionalization approaches that dictate sensor performance. Quantitative analysis methodologies—including internal standards, ratio-based quantification, and machine learning-driven spectral interpretation—are critically examined. Potential clinical and field applications are highlighted through examples involving nucleic acids, proteins, pathogens, and environmental toxicants. Key technical challenges, such as reproducibility, scalable manufacturing, and methodological standardization, are discussed in detail. Finally, future directions are proposed, emphasizing single-molecule quantification, in vivo SERS applications, and the integration of sustainable materials into sensor design.