Refresh-In-Sensing Reusable Biosensor for Ultrasensitive Analysis of MicroRNA Based on Photoresponsive Plasmonic Nanoprobes

Sensitive and accurate detection of microRNAs (miRNAs) is critical for understanding biological processes, molecular diagnosis, and medical treatment. Plasmonic nanomaterials are powerful tools for optical sensing of nanoscale molecules, including DNA, enabling the construction of designed nanostructures and sensing platforms. However, the stable reusability of the sensing platform remains a challenge for practical sensing. Here, we develop a plasmonic nanobiosensor by integrating a single Au@Ag core-shell nanocube (Au@Ag NC) with azobenzene-functionalized tetrahedron-structured DNA (tsDNA), enabling cyclic microRNA-21 (miRNA-21) detection via photoresponsive conformational switching of doped azobenzene through alternating UV and visible light irradiation. We detect miRNA-21 by measuring the local surface plasmon resonance spectra and find that the peak shift has a wide range of response from 1 fM to 100 nM. The precise molecular recognition, ultrasensitive signal response, and stable photoresponsive reusability of this platform demonstrated its clinical potential as a robust miRNA detection method.