Abstract
Traditional tissue biopsy is limited in understanding heterogeneity and dynamic evolution of tumors. Instead, analyzing circulating cancer markers in various body fluids, commonly referred to as "liquid biopsy", has recently attracted remarkable interest for their great potential to be applied in non-invasive early cancer screening, tumor progression monitoring and therapy response assessment. Among the various approaches developed for liquid biopsy analysis, surface-enhanced Raman spectroscopy (SERS) has emerged as one of the most powerful techniques based on its high sensitivity, specificity, tremendous spectral multiplexing capacity for simultaneous target detection, as well as its unique capability for obtaining intrinsic fingerprint spectra of biomolecules. In this review, we will first briefly explain the mechanism of SERS, and then introduce recently reported SERS-based techniques for detection of circulating cancer markers including circulating tumor cells, exosomes, circulating tumor DNAs, microRNAs and cancer-related proteins. Cancer diagnosis based on SERS analysis of bulk body fluids will also be included. In the end, we will summarize the "state of the art" technologies of SERS-based platforms and discuss the challenges of translating them into clinical settings.