Recent advance in nucleic acid amplification-based surface-enhanced Raman scattering for in vitro and in vivo biosensing

Surface-enhanced Raman spectroscopy (SERS) is a highly effective optical analysis technology with distinct advantages of narrow spectral bandwidth, resistance to photobleaching, fast response, and low background signal. The combination of SERS technology with nucleic acid amplification facilitates in vitro and in vivo detection of DNAs, RNAs, ionics, antibiotics, toxins, antigens, enzymes, proteins, extracellular vesicles (EVs), circulating tumor cells (CTCs), and bacteria with excellent sensitivity and good selectivity. In this review, we give a comprehensive overview about the progress in developing nucleic acid amplification-based SERS methods for in vitro and in vivo biosensing. Nucleic acid amplification is divided into enzyme-catalyzed amplification (e.g., polymerases and nucleases), enzyme-free-catalyzed amplification (e.g., hybridization chain reaction (HCR), catalytic hairpin assembly (CHA), entropy-driven catalytic (EDC) and DNAzyme), and their combinations. This review summarizes the sensing mechanism, features and practical applications of nucleic acid amplification-based SERS methods, and discusses the challenges and future prospects in this field.