Integrating Bifunctional Peptide on a Cu-MOF/Cu2O Photocathode: Toward an Anti-Interference and Sensitive Photoelectrochemical Protein Biosensor

Developing advanced, practical biosensors capable of reliable detection of complex biological fluids holds significant promise. However, achieving accurate detection remains a major challenge due to the frequent coexistence of typical interfering substances, such as proteins and reducing agents, with target analytes. Herein, we present a robust photoelectrochemical (PEC) biosensor that exhibits both strong anti-interference capabilities and high sensitivity in serum matrices. The biosensor was constructed by integrating a bifunctional peptide (BFP) onto a Cu-MOF/Cu2O photocathode. The BFP adopted a Y-shaped structure with two distinct branches: one for target recognition and the other for interference mitigation. The Cu-MOF/Cu2O photocathode was fabricated by modifying a copper metal–organic framework (Cu-MOF) onto a Cu2O nanorod electrode, which acted as the signal transducer, producing a strong photocurrent response for efficient BFP anchoring. When targeting the protein biomarker annexin A1 (ANXA1), the biosensor exhibited an impressive signal response with a low limit of detection (LOD) of 0.36 pg/mL. The synergistic combination of the BFP’s excellent anti-interference properties and the high-photocurrent response of the Cu-MOF/Cu2O photocathode enabled highly sensitive and precise detection of the target protein in complex biological media. This elegant peptide-integrated photocathode approach provides a promising strategy for advancing the next generation of high-performance, practical PEC biosensors.