Single-Probe Dual-Mode Biosensor for Cross-Validated Detection of cTnI in Myocardial Damage Evaluation

Myocardial damage (MD) is a leading cause of death in cardiovascular disease, and cardiac troponin I (cTnI) has emerged as the cornerstone biomarker for diagnosis and monitoring due to its exceptional cardiac specificity and strong correlation with the extent of myocardial necrosis. This study presents a novel dual-mode biosensor built around a rationally designed Fe-MIL-101/QDs/aptamer-G-quadruplex/Hemin (FQGH) probe that integrates dual catalytic functions for dual-mode signal transduction. The FQGH probe possesses both Fenton-like and peroxidase-like activities. These two catalytic functions are mechanistically distinct and independently generate electrochemiluminescence (ECL) and electrochemical (EC) signals, enabling dual-mode detection of cTnI. In the ECL mode, its Fenton-like activity generates hydroxyl radicals (•OH) to amplify the cathodic ECL emission of CdS QDs. In the EC mode, leveraging its peroxidase-like activity, the probe facilitates the conversion of hydroquinone to benzoquinone, which is then electrochemically reduced to produce a measurable current. By leveraging these two parallel catalytic pathways from a single probe, the platform minimizes signal crosstalk and enables inherent cross-validated detection of cTnI, significantly enhancing assay specificity in complex matrices. This biosensor achieves an ultra-low detection limit of 0.12 pg/mL (ECL) and 0.46 pg/mL (EC), excellent selectivity, and demonstrates strong correlation with enzyme-linked immunosorbent assay (ELISA) in both mouse myocardial injury models and human clinical samples. This work establishes a reliable cross-validated detection platform for cTnI and provides a generalizable design paradigm for multifunctional nanozyme-based dual-mode biosensors.