Progress and prospects of surface-enhanced Raman spectroscopy in molecular sensing: A critical perspective.

Surface-enhanced Raman spectroscopy (SERS) combines the molecular specificity of Raman spectroscopy with signal amplification from nanostructured surfaces, making it an important technique for molecular sensing. Since its discovery on roughened noble-metal electrodes, SERS has advanced through platforms based on colloidal nanoparticles, patterned substrates, hybrid materials, flexible devices, and tip-enhanced configurations. This review discusses recent progress in SERS, with emphasis on enhancement mechanisms, substrate engineering, instrumentation, data collection, data analysis, quantitative reliability, and sensing applications. Although much of SERS research has focused on achieving high enhancement factors and ultralow detection limits, practical analytical reliability remains underdeveloped because of hotspot heterogeneity, substrate variability, matrix interference, calibration uncertainty, and insufficient standardization. Therefore, this review highlights the gap between laboratory-scale sensitivity and real-world analytical performance and discusses future directions involving reproducible substrates, reliable quantitative methods, integrated sample preparation, sustainable materials, and validated data-analysis strategies. With these advances, SERS can become a more dependable platform for real-world molecular sensing in biomedical, environmental, food-safety, forensic, and materials applications.