SERS-Based Nano- and Microsystems Toward Biomedical Applications

Surface-enhanced Raman spectroscopy (SERS) has emerged as a transformative analytical technique for biomedical and bioanalytical sensing, offering molecular specificity and single-molecule sensitivity in biological environments. Recent advances in plasmonic nanomaterials, precision fabrication, and compact optical instrumentation have accelerated the development of SERS platforms with expanding potential toward biomedical applications. Despite extensive studies, clinical translation remains limited, underscoring the need for a systematic evaluation of SERS nanomaterials and device architectures under biomedically relevant conditions. This review provides a current overview of nano- and microscale SERS-based devices reported since 2020, encompassing all aspects from material design to practical applications. We highlight controlled SERS-active architectures, including patterned substrates, nanorods, microspheres, micromotors, and microneedles, as well as combinations of these microfluidic systems. We summarize key studies showing fabrication strategies, instrumentation, and analytical performance with an emphasis on platform capabilities. We present the first focused discussion on static and dynamic SERS platforms for direct, on-site molecular detection in model biological environments, and outline key challenges for biomedical translation, including reproducibility, sample handling, standardization, and integration. This review provides a practical guide for designing SERS-based nano- and microsystems toward biomedical sensing applications, while clarifying current limitations and future opportunities for translation.