SERS probes for cancer detection: Innovations and applications

Liquid biopsy has revolutionized cancer detection, offering a non-invasive alternative to traditional tissue biopsies and enabling early diagnosis. Recent advancements in surface-enhanced Raman scattering (SERS) technology have significantly enhanced its applicability in liquid biopsy, particularly through the development of novel nanomaterial-based substrates, enabling multiplexed detection, real-time analysis, and higher diagnostic accuracy. This review explores and compares the methodologies involved in critical stages of the SERS-based liquid biopsy workflow, including biomarker enrichment, SERS measurement, and subsequent data analysis. Emphasis is placed on the development of SERS probe, detailing advanced techniques for the design and fabrication of SERS substrates, the various types of substrates available, and the application of diverse biorecognition elements, Raman reporters, and molecular linkers. We also present and compare the applications of extracellular vesicles (EVs), circulating tumor cells (CTCs), DNA, and RNA in cancer detection, providing insights into their transformative potential for advancing precision medicine.