Ultra-Sensitive MicroRNA Biosensor Based on Strong Aggregation-Induced Electrochemiluminescence from Bidentate Ligand-Stabilized Copper Nanoclusters in Polymer Hydrogel

Herein, dihydrolipoic acid (DHLA)-stabilized copper nanoclusters (Cu NCs) with high aggregation-induced electrochemiluminescence (AIECL) in polymer hydrogel were prepared to construct an ECL biosensor for detection of microRNA-21. DHLA, a small molecule ligand with two sulfhydryl groups, was used as a protective agent to synthesize Cu NCs, which improved the ECL stability and intensity of Cu NCs. Furthermore, the Cu NCs were loaded into the (PVP-PVA)hydrogel to form the DHLA-Cu NCs@(PVP-PVA)hydrogel composite, which showed effective AIECL performance. The confinement of Cu NCs into the hydrogel increased the local concentration of Cu NCs, which could not only prevent oxides from entering the copper core, but also limit the vibration to reduce non-radiative transitions of Cu NCs, leading to a distinct AIECL emission. Then, combined with the self-priming clip trigger isothermal amplification (SCTIA) technology, an ECL biosensor was constructed to realize the sensitive detection of miRNA-21. Interestingly, SCTIA technology was a simple and efficient strategy that realized multiple-cycle amplified processes to acquire a mass of output DNA, achieving remarkable signal amplification. Therefore, this strategy provided an efficient approach in the preparation of Cu NCs with high AIECL emission and target amplification technology, which might have promising potential in clinical application.