Multifunctional CoFcMOF Nanozyme Facilitates a Self-Validating Triple-Modal Immunosensor for CRP in Serum and Synovial Fluid

), and a bioconjugation tag that amplifies the electrochemical impedance spectroscopy (EIS) signal upon immunocomplex formation. Critically, all three mechanistically distinct yet intrinsically linked signaling pathways are intrinsically triggered by a single biorecognition event, enabling real-time and built-in cross-validation. This cooperative design affords exceptional sensitivity, with detection limits of 0.075 pg/mL (ECL), 0.095 pg/mL (EIS), and 0.29 pg/mL (colorimetry) for CRP, while demonstrating outstanding anti-interference performance in serum and synovial fluid samples. Beyond providing a precise and reliable method for CRP analysis, this work establishes a new biosensing paradigm that utilizes rationally engineered multifunctional materials for inherently self-validating, multimechanism detection, paving the way for next-generation diagnostic systems capable of high-accuracy analysis in complex real-world samples.