Bifunctional CuPt Nanoclusters and DSN-Mediated Target Recycling Enabled Dual-Mode OPECT/Colorimetric Biosensing for Ultrasensitive and Wide-Range Detection of miRNA-21

Abstract MicroRNA-21 (miRNA-21) is an important cancer biomarker that requires highly sensitive and reliable detection across a broad concentration range. Here, we report a dual-mode biosensing platform that integrates organic photoelectrochemical transistor (OPECT) amplification with nanozyme-assisted colorimetric transduction for ultrasensitive miRNA-21 analysis. By integrating a CdIn2S4/SnO2 heterojunction photogate, bifunctional CuPt nanoclusters (NCs), and duplex-specific nuclease (DSN)-driven target recycling, molecular recognition events are efficiently translated into two independent yet complementary analytical outputs. Upon target recognition, DSN-assisted cyclic cleavage triggers the accumulation of CuPt NC probes at the sensing interface, which simultaneously suppresses the photogating response through competitive light harvesting and interfacial charge-transfer regulation, while catalyzing the oxidation of TMB via their intrinsic peroxidase-like activity. Benefiting from the synergistic integration of transistor amplification, enzymatic target recycling, and dual-signal transduction, the dual-mode OPECT/colorimetric sensing platform achieves a detection limit of 0.072 fM with a wide range spanning from 0.1 fM to 100 nM, combined with excellent selectivity toward miRNA-21 detection in human serum samples. This work establishes a versatile dual-mode sensing framework that combines the high gain of bioelectronic transistors with the robustness of nanozyme-based colorimetry, offering new opportunities for nucleic acid analysis, early disease diagnosis, and point-of-care bioanalysis.