Non-Invasive Metabolite Profiling Using Sweat Sensing Wearable Platforms Leveraging Continuous Enzymatic Reactions

Author: Lasalde-Ramirez, José A.

Year: 2027

Degree: Dissertation (Ph.D.)

Advisor: Gao, Wei

Committee Members: Zhang, Anqi; Lester, Henry A.; Gharib, Morteza; Gao, Wei

Option: Medical Engineering

DOI: 10.7907/ega4-ee49

Abstract

Continuous lipid profiling offers a powerful approach to reveal dynamic lipid fluctuations underlying cardiometabolic health. While enzymatic reactions offer great promise for continuous metabolic tracking, existing technologies cannot sustain the multi-enzyme reactions required for continuous lipid detection, particularly those dependent on non-regenerable cofactors. Here, we introduce a wearable epidermal lipid profiler that enables noninvasive, continuous monitoring of cholesterol and triglycerides through a combination of dual-step and cascading enzymatic reactions supported by continuous refreshment of adenosine triphosphate (ATP). The system integrates a polymeric cofactor-releasing (Poly-CORE) module composed of polypyrrole–ATP nanostructures that provide controlled, sweat-triggered ATP replenishment for long-term, continuous biosensing. Complementary glucose, pH, and sweat rate sensors were integrated to offer individualized calibration and contextual metabolic information. We demonstrate real-time lipid tracking during dietary challenges and habitual activities, capturing distinct postprandial responses to macronutrient composition. 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 biosensing framework extends continuous monitoring to complex enzymatic systems and couples dynamic lipidomics with causal inference, establishing a foundation for noninvasive, longitudinal cardiometabolic health assessment.

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