Ce-doped BiF₃@Pt nanocatalyst enhanced CHA-based electrochemical biosensor for sub-femtomolar detection of miRNA-21

The sensitive detection of disease-related microRNAs in clinical samples remains a challenge requiring robust signal amplification strategies. Herein, we report an electrochemical biosensor for ultrasensitive miRNA-21 detection by integrating a catalytic hairpin assembly (CHA) circuit with a rationally designed cerium-doped bismuth fluoride-supported platinum nanoparticle composite (BiF₃(Ce)@Pt). Cerium doping strategically reconstructs BiF₃ into a porous architecture, enabling high-density, anti-aggregation loading of Pt nanoparticles and significantly enhancing heterogeneous electron transfer at the electrode interface. The BiF₃(Ce)@Pt modified electrode exhibits exceptional electrocatalytic activity toward H₂O₂ reduction, as evidenced by enhanced cathodic current density and accelerated electron transfer kinetics. Serving as a powerful signal tag, BiF₃(Ce)@Pt is anchored onto the electrode surface via target-initiated CHA, where each miRNA-21 recognition event triggers the assembly of multiple nanocatalysts, converting a single binding event into a substantially amplified current response. This dual-amplification strategy achieves a wide linear range from 10 fM to 5 nM and an ultra-low detection limit of 0.38 fM. The biosensor also demonstrates high specificity, excellent reproducibility, and reliable performance in human serum (recovery 101.0-101.3%). Synergizing nucleic acid amplification with advanced nanocatalysis, this work enables sensitive miRNA-21 detection and a generalizable electroanalytical paradigm for biomarker diagnostics.