Ag Nanocubes Coupled with Heating-Enhanced DSN-Assisted Cycling Amplification for Surface-Enhanced Raman Spectroscopy Detection of MicroRNA-21

Surface-enhanced Raman scattering (SERS)-based biosensing has strong potential owing to its high sensitivity and good selectivity. In this study, a SERS biosensing platform for microRNA-21 detection was proposed by combining heating-enhanced duplex-specific nuclease (DSN)-assisted target recycling amplification and silver nanocube (AgNC)-based SERS enhancement. The activity of DSN was greatly enhanced by increasing the surface temperature of a heated Au electrode (HAuE) during the DSN-assisted target recycling process, resulting in dramatic miRNA-21 amplification detection. 4-Mercaptobenzoic acid (4-MBA) acting as a Raman reporter was immobilized onto the surface of AgNC to form a AgNC/4-MBA SERS tag with AgNC providing significantly larger electric field enhancement and thus excellent SERS applications compared with conventional silver or gold nanospheres. This enhancement was attributed to the well-known “lighting rod” effect derived from the sharp geometrical feature of the edges and corners of AgNCs. These factors lead to the high sensitivity of the proposed SERS biosensor for the miRNA-21 measurement. A limit of detection of 2.88 fM (S/N = 3) was achieved at an electrode temperature of 55 °C, which was decreased by more than three magnitudes compared with that at 25 °C.