Developing novel signal amplification and transduction technologies is the key to overcoming the bottlenecks of high-sensitivity and on-site detection in nucleic acid analysis. In this study, a dual-mode sensing platform based on organic electrochemical transistors (OPECT) and colorimetry was established to achieve ultrasensitive detection of miRNA-21. 1D/3D CoS/MnCdS Schottky heterojunction was synthesized as the photoactive material, which significantly enhanced the photoelectric conversion efficiency. The sensing and detection system cleverly integrated a quadruple signal amplification mechanism. The target triggered the catalytic hairpin assembly (CHA) reaction, generating H1 and H2 long chains. These chains activated the CRISPR/Cas12a system, which carried out nondiscriminatory cleavage to block the tandem strand displacement reaction (TSDR). This triggered the hybrid chain reaction (HCR) and formation of G-quadruplex/hemin DNAzyme (GQH DNAzyme), realizing cascade signal amplification. Under the catalysis of GQH DNAzyme, the detection had dual-signal outputs. It catalyzed the oxidation of 4-CN to form a deposition layer, inhibiting electron transport and achieving cascade signal amplification for OPECT. It catalyzed the HO-mediated TMB colorimetric reaction to complete the visual colorimetric analysis. Through triple-modal synergistic signal amplification of biological, chemical, and electronic modalities, this biosensing platform reduced the detection limits to as low as 36.5 aM and 3.8 fM, respectively. It provided a new solution for the accurate analysis of miRNA markers in the early diagnosis of cancer. 9 8 0.3 0.7 2 2
