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Ubiquitous non- and minimally-invasive biosensing technologies for personalized and precision medicine


Recent advances in miniaturized electronics, microfluidics, and electrochemical sensing platforms have paved the path for the realization of wearable and mobile biosensing systems that can be deployed to longitudinally access the circulating molecular information. Leveraging their non-/minimally-invasive nature and a high sampling rate, these systems provides people with a unprecedented accessibility to their health-related information, opening up new possibilities such as personalized medicine, precision nutrition, and performance enhancement. Towards realizing the envisioned biomonitoring ecosystem, various technical challenges remain unresolved, centering on the sampling and sensing of circulating molecular information. For example, sweat is widely targeted for non-invasive biomonitoring. However, current sweat sampling approaches are mainly stimulation-based (e.g., heat, exercise, iontophoresis), which is associated with user intervention and/or discomfort. Moreover, human subject studies are lacking to establish the physiological significance of the sweat biomarker levels. From the sensing side, electrochemical sensors are widely leveraged to quantify the analyte concentration levels due to their capability to provide sample-to-answer readouts. To accurately analyze untreated biofluids, novel sensor design and multi-dimension optimization are required to simultaneously achieve the required figure of merits, including sensitivity, selectivity, biofouling resistance, and generalizability. In my Ph.D. training, I devised sensor- and system-level solutions to address these challenges. As an immediate group of targets, my research mainly focusses on monitoring circulating drug levels as it can be leveraged to personalize dosing, evaluate adherence, and prevent abuse. In summary of my research work, the thesis is structured as follows: chapter 1 introduces the background of non-/minimally-invasive biomonitoring, including the existing bio-interfaces and electrochemical sensing mechanisms; chapter 2 describes the use of a thin hydrogel patch to simultaneously sample and analyze analyte concentrations in natural perspiration; chapter 3 further expands the innovation from chapter 2 and demonstrates a multi-modal human machine interface; chapter 4 describes an organohydrogel-based one-touch sensing interface for lithium therapy monitoring; chapter 5 focuses on resolving the challenges associated with voltammetry-based sensor—a simple recognition element-free sensing approach to target electroactive analyte—and demonstrates a wearable drug sensing smartwatch; chapter 6 presents my efforts to achieve a generalizable solution, where I demonstrated a microneedle-based aptamer sensor to target interstitial fluid analytes.

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