Beyond single-mode detection: Advances in plasmonic dual-mode SERS-based optical sensing platforms for biomedical diagnostics

The development of reliable, highly sensitive analytical tools is essential for accurately detecting disease-related biomarkers and improving clinical decision-making. Dual-mode optical sensors that integrate two optical transduction mechanisms into a single platform are a major focus in nanobiotechnology. They serve as reliable tools in biomedicine for rapid, efficient diagnosis and monitoring and are compatible with point-of-care (POC) applications. Compared with single-mode detection approaches, dual-mode sensing assays reduce analytical uncertainty, expand the linear detection range, improve accuracy, and increase operational flexibility. Among the various combinations, surface-enhanced Raman spectroscopy (SERS) coupled with optical techniques such as colorimetry, fluorescence, electrochemiluminescence, or surface plasmon resonance stands out for its ultrasensitivity and compatibility with POC diagnostics and real-time monitoring. Noble-metal nanoparticles, also called plasmonic nanoparticles (PNPs), are attractive options for such applications because they can serve as sensitive SERS platforms while simultaneously modulating a complementary optical signal. This review summarizes recent progress in the development of plasmon-assisted dual-mode SERS-based biosensing platforms for biomedical diagnosis. Particular emphasis is placed on systems that integrate SERS with colorimetric, fluorescence, electrochemiluminescence, and surface plasmon resonance detection methods. The role of PNPs in enhancing signal transduction and enabling complementary detection mechanisms is discussed, along with strategies to improve the analytical performance of the designed assays. Furthermore, the applicability of these platforms for detecting a wide range of biological targets, from clinically relevant protein biomarkers and nucleic acids to metabolites and pathogens, is highlighted.