A Biomimetic Single‐Atom Nanozyme With a Substrate Pocket for Accurate and Continuous Sweat Glucose Monitoring

Wearable non-invasive glucose sensors are revolutionizing diabetic management by enabling real-time monitoring and personalized care. However, their widespread adoption has been limited by the intrinsic instability and high cost of natural glucose oxidase (GOx). Although nanozymes offer a more robust alternative, their lack of substrate specificity is a major challenge. Herein, a manganese-based tannic acid single-atom nanozyme (TA-Mn SA) with a dual biomimetic architecture was developed. It features atomically dispersed Mn catalytic sites embedded within a tannic acid-derived molecular pocket tailored for selective glucose recognition. This engineered enzyme mimic exhibits exceptional catalytic efficiency and substrate selectivity. The origin of this selectivity and the catalytic cycle were elucidated through both experimental data and density functional theory calculations. When integrated into a wearable sweat sensor, the TA-Mn SA nanozyme reliably tracked blood glucose levels in human trials, capturing personalized metabolic dynamics during fasting, feeding, and exercise. This design is inherently compatible with scalable, low-cost manufacturing, paving the way for a new era of accessible continuous glucose monitoring.