Ternary In₂O₃/ZnIn₂S₄/CdS heterojunction-based APE1-assisted "AND" logic gate photoelectrochemical biosensor for dual-miRNA detection

Photoelectrochemical biosensing has become a powerful technique for disease monitoring and therapeutic tracking. Most existing photoelectrochemical platforms are only capable of detecting a single biomarker, which limits their effectiveness in comprehensive disease management. To address this challenge, we developed a novel biosensor that integrates DNA-based logic gates with an In₂O₃/ZnIn₂S₄/CdS photoelectrode for dual-miRNA detection. The rationally designed ternary heterojunction exhibited significantly enhanced photoelectric conversion performance compared with binary composites, providing a high-quality photoelectric sensing platform. Based on it, a photoelectrochemical biosensor with DNA logic gates and a cascade reaction was designed, in which APE1 enabled target recovery and DNA walker movement. MiRNA-144 and Let-7a are recognized as promising diagnostic biomarkers for type 2 diabetes mellitus, early clinical application is hindered for their low-abundance. Upon miRNA introduction, APE1 cleaved hairpins to release strands, leading to GOD immobilization on the electrode. The subsequent reaction with glucose enhanced the photocurrent, enabling quantitative miRNA detection. Benefiting from the APE1-assisted cascade signal amplification strategy, the optimized biosensor displays a good linear correlation between photocurrent response and the logarithmic concentration of dual miRNAs within the range of 0.001 nM-10 nM, with a low detection limit of 0.43 pM (S/N = 3). Moreover, the carefully designed DNA tracks enable a well-ordered sensing interface, offering broad possibilities for clinical diagnosis and disease monitoring.