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

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 Fe 3 O 4 @COF@Os is developed for biomarkers biosensing. First, found that the catalytic activity and specificity of Fe 3 O 4 @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, Fe 3 O 4 @COF@Os displayed superior POD‐specific activity and negligible oxidase (OXD) and catalase (CAT) mimic activity. Therefore, Fe 3 O 4 @COF@Os can separate and analyze of targets in bio‐matrix without background interference. For application, Fe 3 O 4 @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 µ m , 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.