Abstract
Diabetes mellitus represents a substantial and growing global health burden, creating an urgent need for convenient, user-friendly, and cost-effective non invasive glucose monitoring systems. Conventional invasive approaches rely on repetitive finger-prick blood sampling, which causes discomfort and reduces long-term adherence. Although numerous non-invasive technologies have been explored, many remain limited by complex instrumentation, suboptimal stability, and restricted practicality. In this context, colourimetric sensing has emerged as a promising strategy for point-of-care and home-based applications due to its low cost, operational simplicity, minimal instrumental dependence, and intuitive visual readout. However, existing colourimetric platforms for non-invasive glucose monitoring are constrained by slow response, poor signal uniformity, and limited detection capability for multiple metabolic markers. This thesis addresses these limitations through a two-stage progression: first, a cascade amplification strategy is developed to enhance the speed and sensitivity of single-analyte glucose sensing in sweat; second, a paper-based microfluidic platform is designed to extend colourimetric detection to simultaneous glucose and ketone body monitoring in urine.To overcome enzymatic instability in sweat analysis, a wearable skin-interfaced epifluidic micropatch was engineered featuring a hierarchical dual-lock mechanism. Specifically, tetrahedral DNA nanostructures co-localize enzymes at defined spacing to promote substrate channeling and accelerate reaction kinetics, while a gelatin hydrogel stabilizes the enzymatic microenvironment during hydration cycles to ensure uniform reaction conditions. As a result, this cascade single-analyte design produced a visible glucose-responsive signal within 30 seconds, with a linear range of 50–400 μM and a detection limit of 9.98 μM. Integrated with passive microfluidics and smartphone imaging, the patch enabled sequential sampling and reliable time-resolved sweat glucose feedback during exercise.
Building on this foundation, a paper-based microfluidic platform was developed for simultaneous detection of glucose and ketone bodies from a single urine sample. Multiple enzymatic colourimetric reactions are integrated into a unified paper-based architecture, with distinct and spatially resolved reaction zones enabling concurrent visual readout without complex instrumentation. Using this design, the platform achieved DKA (diabetic ketoacidosis)-oriented analytical proof-of-concept screening, particularly in euglycemic presentations where glucose-centric diagnostics are inadequate.
Both platforms were comprehensively characterized in terms of structural morphology, fluid transport behaviour, analytical performance (including linear range, limit of detection, response time, and reproducibility), anti-interference capability, and operational stability. Performance was evaluated using standard solutions and human biofluids under controlled conditions. Preliminary validation studies were conducted with collected sweat and urine samples, and the obtained results were benchmarked against high-performance liquid chromatography (HPLC) measurements to verify analytical accuracy and practical feasibility.
Overall, this work advances the rational design and application-oriented development of colourimetric sensing technologies for non-invasive glucose monitoring. The proposed strategies establish a coherent colourimetric glucose sensing framework for non-invasive monitoring, providing a proof-of-concept framework for low-cost non-invasive metabolic assessment.
| Date of Award | 15 Aug 2026 |
|---|---|
| Original language | English |
| Awarding Institution |
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| Supervisor | David Chieng (Supervisor), C.F. Kwong (Supervisor) & Zedong Nie (Supervisor) |
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