Development of a microfluidic paper-based device for the detection and quantification of aluminium in urine

: implications for Alzheimer's disease prevention and diagnosis

Abstract

This thesis reports a complete assessment of the development and application of a microfluidic paper-based analytical device (µPAD) for the quantitative detection of aluminium in urine, with considerable implications for Alzheimer's disease (AD) research and diagnostics. The core of the research focuses on the design, fabrication, and optimisation of a novel µPAD. This device utilizes the principles of capillary action and colorimetric detection to reach rapid and sensitive aluminium quantification. The µPAD's performance is rigorously assessed against established analytical methods, with particular emphasis on sensitivity, specificity, and reproducibility in complex urinary matrices. A key innovation of this work is centred on the integration of a carefully selected chromogenic reagent system within the paper substrate, enabling visual and instrumental quantification of aluminium. The study clarifies the chemical mechanisms essential the colorimetric reaction and explores strategies to enhance signal intensity and stability. Statistical analyses are employed to confirm the µPAD's analytical performance, including limit of detection (LOD) of 0.12 mg/L, limit of quantification (LOQ) of 0.40 mg/L, linear range, and inter- and intra-assay variability. The device's robustness is further evaluated through recovery studies and analysis of real urine samples from a cohort of subjects. This research contributes to the field of AD diagnostics by providing a cost-effective, portable, and user-friendly tool for aluminium detection in urine. The developed µPAD shows potential for both clinical and epidemiological applications, potentially facilitating early detection of elevated aluminium levels and monitoring of AD progression. Furthermore, this work lays the groundwork for future investigations into the utility of urinary aluminium as a biomarker for AD risk assessment and therapeutic monitoring.

Date of Award	27 Mar 2025
Original language	English
Awarding Institution	Universidade Católica Portuguesa
Supervisor	Raquel Mesquita (Supervisor) & António O. S. S. Rangel (Co-Supervisor)