Atomic Fe-Centered Hemin–TiO ₂ Graphdiyne Nanozyme Sensor for Colorimetric Fingerprinting of Bacterial Extracellular Vesicles

Accurate identification of urinary pathogens is essential for the timely diagnosis and effective management of urinary tract infections (UTIs). Bacterial extracellular vesicles (bEVs), which carry pathogen-specific surface antigens, represent an attractive diagnostic target. However, their clinical translation is impeded by the time-consuming and labor-intensive isolation process (typically requiring up to 72 h) from complex biological samples such as urine. To overcome this limitation, we report an intelligent colorimetric sensor array capable of decoding pathogen-specific biochemical signatures for the direct, accurate and rapid identification of bEVs in UTIs. It is realized by inventing a three-dimensional biomimetic nanozyme comprising TiO₂ nanoparticles-bridged Hemin molecules anchored on graphdiyne with a sandwich configuration, thus enabling both selective capture of bEVs and enhanced peroxidase (POD)-like catalytic activity. The specificity arises from the atomic Fe centers in Hemin molecules, which establish stable coordination interactions with the O-antigens of lipopolysaccharides on the bEV surface. Upon bEV recognition, the biomimetic nanozyme exhibits pH-dependent suppression of POD-like activity, generating distinctive colorimetric fingerprints. Coupled with machine learning, the platform accurately classifies bEV subtypes. Clinical validations demonstrate a diagnostic accuracy of 100.0% within 30 min, underscoring the promising point-of-care UTI management.