Specific and Magnetic Covalent Organic Framework Confined Os Nanoclusterzyme for Interference‐Free and Ultrasensitive Biosensing

Abstract The peroxidase (POD)‐mimic nanozymes can be a potential tool for point‐of‐care (POC) diseases diagnosis. However, the complex sample matrix and unspecific multiple‐enzyme activities of nanozyme can generate false background signal and decrease the diagnostic accuracy. Here, a magnetic and POD‐specific covalent organic framework (COF) confined osmium (Os) nanoclusterzyme Fe₃O₄@COF@Os is developed for biomarkers biosensing. First, found that the catalytic activity and specificity of Fe₃O₄@COF@Os can be regulated by the deoxidizers and the functional groups of COF ligands. By using ascorbic acid as deoxidizer and F functional COF ligands, Fe₃O₄@COF@Os displayed superior POD‐specific activity and negligible oxidase (OXD) and catalase (CAT) mimic activity. Therefore, Fe₃O₄@COF@Os can separate and analyze of targets in bio‐matrix without background interference. For application, Fe₃O₄@COF@Os based lateral flow assay is established for serum cancer biomarker prostate‐specific antigen, the detection limit is 3.83 pg mL⁻¹. For clinical prostatic cancer samples, the accuracy is 100% with a correlation coefficient of 0.998 with commercial ELISA kit. For chronic disease biomarker sensing, salivary glucose can be quantified as low as 0.1 µm, with negligible background interference and favorable recyclability. This specific magnetic nanozymes can offer a promising pretreatment‐free and POC strategy for rapid and accurate diseases diagnosis.