Biomarkers detection by surface-enhanced Raman spectroscopy: Analytical strategies

Since the outbreak of COVID-19 pandemic, there is a rising demand of sensitive and fast detection of biomarkers. Surface-enhanced Raman spectroscopy (SERS) is a non-destructive and fast detection technology that highly meets the requirement of biomarkers detection either in speediness or sensitivity. However, direct SERS analysis of biomarkers from multifarious samples is hard due to the serious matrix interference, low content, fluorescence background interference, and weak affinity. With the help of proper sample preparation integrated analytical strategies, target biomarkers in complex samples can be separated, purified, and enriched for SERS analysis. Currently, SERS detection of biomarkers is experiencing a rapid development. Thus, a review is presented to better understand the research progress in the field. Firstly, the analytical strategies enable SERS for biomarkers detection are summarized, which provide the possibility of rapid, selective, and sensitive detection, including magnetic separation, chromatography separation, membrane separation, phase extraction, derivatization SERSactivation, and highly integrated microfluidics. Then, the analytical strategies applied for biological SERS application are listed according to different biomarkers, including breath volatile organic compounds, microbial pathogens, biotoxin, extracellular vesicles, etc. Finally, the progresses of biomarkers detection by SERS are concluded, and perspectives on current challenges and shortcomings limited the further application are presented.