A dual-mode self-verification strategy based on the bimetallic ion amplification effect: Enabling highly sensitive detection of the chemotherapy-induced cardiac toxicity biomarkers IL-6 and MPO.

Chemotherapy-induced cardiotoxicity (CIC) is closely associated with the expression of interleukin-6 (IL-6) and myeloperoxidase (MPO). Therefore, concurrent monitoring of IL-6 and MPO is crucial for the early detection of CIC. This study developed a dual-mode self-verification strategy based on a bimetallic ion amplification effect. The electrochemical module uses immunoprobes labeled with Cu2+ and Pb2+ for electrochemical signal recognition and amplification. In contrast, the fluorescence module employs carbon dots that specifically respond to Cu2+ and Al3+ as a fluorescence signal source, thereby establishing an "electrochemical-fluorescence" dual-signal output and self-verification workflow. During the simultaneous detection of IL-6 and MPO, the characteristic differences in the electrochemical potentials of the immunoprobes enable the precise identification and effective differentiation of the two analytes. Additionally, incorporating a fluorescent sensor for self-verification not only reduces the risk of false positives and false negatives associated with single-method approaches but also enhances the reliability of this study. Experiments demonstrate that the dual-mode self-verification strategy developed in this study features a wide linear range (MPO: 2.44 × 102 ∼ 5.00 × 105 pg/mL; IL-6: 9.75 ∼ 2.00 × 104 pg/mL) and low limits of detection (MPO: 49.10 pg/mL, IL-6: 1.03 pg/mL). Analysis of blood samples from healthy individuals has demonstrated that the developed dual-mode self-verification strategy exhibits extremely high accuracy and reliability. The proposed method opens a scalable pathway for the design of early, precise monitoring of CIC and provides new opportunities for the development of highly reliable multi-marker simultaneous detection platforms.