SERS-Driven Evolution of Lateral and Vertical Flow Assays in Medical Diagnostics.

Surface-enhanced Raman scattering (SERS) has emerged as a powerful signal amplification strategy to address the inherent limitations of conventional flow-based diagnostic methods such as lateral flow analysis (LFA) and vertical flow analysis (VFA). By incorporating SERS-active nanostructures into these platforms, SERS-integrated LFA and VFA systems have significantly improved sensitivity, specificity, and multiplexing performance while maintaining the simplicity and portability of conventional approaches. In this review, we summarize recent advances in SERS-enhanced flow-based diagnostics with a focus on exogenous and endogenous disease detection. Exogenous targets include viral antigens, bacterial pathogens, and foodborne contaminants such as mycotoxins and antibiotic residues. Endogenous applications include therapeutic drug monitoring, inflammation profiling, cancer biomarker detection, and exosome-based molecular subtyping. We highlight the structural differences between LFA and VFA approaches and their impact on analytical performance, and explore the advantages of SERS-integrated platforms for rapid and multiplexed detection in complex biological matrices. Finally, we provide an overview of key technical challenges, such as signal reproducibility, matrix interference, and device integration, and discuss future directions for clinical implementation of SERS-based flow diagnostics in point-of-care settings.