A HPRR-based diatomic catalyst electrochemical biosensor for detecting cancer-related extracellular vesicles†

Cancer-associated extracellular vesicles (EVs) are crucial biomarkers for cancer diagnosis as they contain abundant tumor cell information. To efficiently and accurately detect cancer-associated EVs, an electrochemical hydrogen peroxide reduction reaction (HPRR)-based biosensor was developed, utilizing enzyme-linked immunosorbent and diatomic catalyst strategies for catalytic HPRR current amplification for specific identification and highly sensitive detection. The anti-CXCR4 antibody was immobilized on a Au-plated electrode to selectively capture EVs from the sample. Subsequently, Fe/Cu diatomic catalysts, modified with an anti-CD63 antibody, were bound to the CD63 on the EVs. Quantitative detection of EVs was achieved by measuring the electrical signals from the HPRR catalyzed by the labeled Fe/Cu diatomic catalysts. Under optimized conditions, the electrochemical signals exhibited a linear relationship with EV concentration in the range of 500 to 1 × 10⁷ particles mL⁻¹, with a detection limit of 117 particles mL⁻¹, maintaining accuracy even in FBS. With its affordability, high sensitivity, and ease of use, this sensor holds significant potential for medication guidance and postoperative evaluation.