Molybdenum-catalyzed ATRP polymerization electrochemical biosensor for precise detection of esophageal cancer-associated MiRNA-320b

An ultrasensitive electrochemical biosensor has been developed for the detection of miRNA-320b, an exosomal RNA biomarker associated with lymph node metastasis in esophageal squamous cell carcinoma (ESCC). The platform employs a molybdenum-catalyzed atom transfer radical polymerization (Mo-ATRP) signal amplification strategy, eliminating the need for enzymatic or thermal amplification and enabling cost-effective, early-stage cancer diagnostics. A thiolated peptide nucleic acid (PNA) probe is immobilized on a gold electrode to specifically capture miRNA-320b. Upon hybridization, a sodium molybdate (Na 2 MoO 4 )-catalyzed ATRP reaction, initiated by tetrahydrocurcumin (THC), drives the in situ polymerization of 4-methacryloyloxy-2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO) monomers, forming redox-active polymer brushes directly on the electrode surface. The electrochemical response is exclusively derived from the surface-confined poly(TEMPO) layer, which forms only upon successful target recognition, ensuring high signal-to-noise performance. The biosensor achieves a detection limit of 0.417 fM with a linear range spanning 1 × 10 −15 to 1 × 10 −10 M ( R 2 = 0.992) and demonstrates excellent selectivity and robustness in complex biological matrices. Its resistance to common interferents and consistent performance under real-sample conditions underscore its suitability for clinical translation. This Mo-ATRP-based highly sensitive approach provides a promising foundation for non-invasive liquid biopsy and early detection of aggressive cancers such as ESCC.