Surface‐Enhanced Raman Spectroscopy‐Based Optical Biosensor for Liquid Biopsy: Toward Precision Medicine

Abstract Liquid biopsy is regarded as a promising strategy for assisting precision medicine because of its convenience, noninvasiveness, and ability to overcome tumor heterogeneity and achieve early detection. Recently, impressive advancements in plasmonic biosensors, artificial intelligence, and portable Raman equipment have yielded unprecedented progress in surface‐enhanced Raman spectroscopy (SERS)–based point‐of‐care testing (POCT) systems for liquid biopsy. The development of these systems presents a paradigm shift in on‐site liquid biopsy applications by leveraging the unique benefits of efficiency, fast analysis, portability, affordability, and user‐friendliness. Herein, these advances are introduced over the last 3 years in the field of SERS‐based POCT systems for labeled and label‐free biomarker analysis in body fluids, including tumor circulating proteins and cells, exosomes, micro‐RNA, and circulating tumor DNA. Additionally, powerful machine learning algorithms (including deep learning algorithms) are integrated with SERS to effectively extract potential data features and generate precise diagnostic models. The review highlights the use of handheld and portable Raman devices in significantly promoting the application of SERS‐based POCT in clinical scenarios. Finally, the review outlines the challenges and future perspectives of this technology.