Non-invasive continuous lipid profiling via cofactor-refreshing cascading enzymatic reactions and causal machine learning
摘要
Continuous lipid profiling could reveal dynamic lipid fluctuations underlying cardiometabolic health, yet existing enzymatic sensing strategies cannot sustain the multi-enzyme reactions required for continuous lipid detection, particularly when non-regenerable cofactors are consumed. Here we introduce a wearable epidermal lipid profiler for non-invasive, continuous monitoring of cholesterol and triglycerides using dual-step and cascading enzymatic reactions supported by the continuous refreshment of adenosine triphosphate (ATP). The system integrates a polymeric cofactor-releasing module composed of polypyrrole–ATP nanostructures that provide controlled, sweat-triggered ATP replenishment for long-term biosensing. We demonstrate real-time lipid tracking during dietary challenges and habitual activities, capturing distinct postprandial responses to different macronutrient compositions. In a preclinical study, simultaneous sweat and blood analyses coupled with causal machine learning revealed key physiological confounders and established individualized mappings between sweat and blood lipids. This cofactor-refreshing platform extends continuous monitoring to complex enzymatic systems, establishing a foundation for non-invasive, longitudinal cardiometabolic health assessment.