Microneedle-based biosensor for rapid interstitial fluid extraction and on-site glucose detection

Microneedle-based biosensor for rapid interstitial fluid extraction and on-site glucose detection

For many years, blood tests have been at the forefront of disease diagnostics and biomarker detection. However, as the world progresses towards point-of-care healthcare diagnostics and rapid services, various body fluids have become alternative sources for diagnostic exploration. Among these, interstitial fluid (ISF) has emerged as one of the most promising sources for biomarker detection. ISF closely mimics blood due to the presence of both common and unique biomarkers. Compared to other biofluids such as urine, saliva, and sweat, ISF is recognised as the most reliable and effective medium, offering significant commercial opportunities and extensive research potential. Micron-sized needles, known as microneedles, provide a novel approach to extracting ISF. These microneedles can be tuned to absorb ISF to detect biomarkers of interest. Despite their potential, the uptake of ISF using microneedles is severely limited by low extraction volumes (< 5 µL) and prolonged extraction times, often exceeding 10 minutes. Additionally, on-site biomarker detection from the extracted ISF remains challenging and time-consuming. To address these limitations, it is essential to explore new microneedle materials, optimise insertion techniques, and develop practical biosensing systems for effective and rapid biomarker detection. The present thesis first reviews the existing methods and highlights the key challenges in interstitial fluid extraction and biosensing. It then introduces spiral-shaped swellable microneedles with interlocking capabilities, composed of novel hydrogel materials, which extract more than 5 µL (7.06 ± 0.44 μL for in-vitro, 12.49 ± 1.26 μL for ex-vivo) of ISF in 5 minutes with stable mechanical strength to penetrate the skin barrier effectively. The study further introduces a new approach by combining applicator-assisted insertion to enhance ISF uptake, penetration depth, and overall insertion efficiency. Additionally, this study also develops an electrochemical biosensing mechanism based on screen-printed electrodes to detect glucose directly from the extracted ISF with high sensitivity (9.68 μA mM −1 cm −2) and a low detection limit (0.08 mM) under optimised conditions. The results demonstrate that the combination of swellable and mechanically robust microneedles, coupled with a custom applicator-assisted insertion technique, enable rapid ISF extraction, while the highly sensitive and selective modified biosensing electrodes facilitate on-site glucose detection, eliminating the need for a finger prick. This complete and optimised system for rapidly extracting clinically relevant volume, and accurately sensing glucose, from the extracted ISF is a significant outcome of this study and highlights the promising future potential of microneedle-based electrochemical biosensing.

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