Development Of Bioelectronic Sensors For Real Time Monitoring Of Gastrointestinal Health

Abstract

The work outlined in this thesis focuses on the gastrointestinal (GI) system, which plays an essential role in maintaining homeostasis within the body, by facilitating digestion, nutrient absorption, and waste excretion. Beyond its fundamental functions, the GI system is intricately connected to various aspects of health, including mental health, neurodegenerative conditions, immune responses, and cardiac function. Disorders like irritable bowel syndrome and inflammatory bowel disease are highly prevalent and have a huge impact on the quality of life for those afflicted by them. There is a need for improved understanding of the biomarkers associated with GI function, such as barrier integrity, motility and enteric nervous system activity. The rising prevalence of GI diseases, driven by factors such as dietary changes, aging populations, and environmental influences, further highlights the importance of advancing GI research to uncover disease mechanisms, identify new therapeutic targets, and improve patient outcomes. This research must start in in vitro and ex vivo environments, where high through-put testing can occur. However, current in vitro and ex vivo methods for measuring biomarkers associated with GI diseases rely on large, cumbersome equipment, time-consuming procedures, and end-point assays. Moreover, existing technologies are designed primarily for in vitro or ex vivo use, making them impractical for translating to in vivo applications. This creates a gap in technology that hinders efficient translation between different research models. Bioelectronic devices hold potential for the study and treatment of GI diseases by providing new avenues for interfacing with in vitro and ex vivo models. Organic thin-film bioelectronics, in particular, offer distinct advantages due to their soft, flexible, and biocompatible nature, which allows them to conform to the dynamic and soft tissue of the GI tract. Their ability to be fabricated on thin, and stretchable substrates makes them ideal for high-resolution monitoring in both in vitro and ex vivo systems, while also potentially enabling minimally invasive in vivo applications. The devices provide high sensitivity and precise interaction with biological tissues, enabling real-time, precise measurements of biomarkers without the drawbacks of traditional rigid electrodes. Despite the rapid progress in bioelectronics, applications specifically targeting the GI system remain relatively underexplored, highlighting the need for further research in this 3 area. The integration of organic thin-film bioelectronics in GI research could change the way biomarkers are measured, enabling more efficient and effective translation from lab-based studies to clinical applications, improving outcomes for patients with GI diseases. The overall aim of this thesis was to design, fabricate, validate, and apply to a clinical environment different bioelectronic devices capable of monitoring aspects of GI health in in vito and ex vivo models. This thesis focused on three critical biomarkers: barrier integrity, motility and enteric nervous system activity. The first and second goals of this thesis focused on the design, fabrication, and characterisation of two conformal bioelectronic devices tailored for these measurements. The first goal involved the development of a conformable, all-planar device for measuring epithelial barrier integrity, featuring a flexible Parylene-C substrate with gold tracks and PEDOT:PSS electrodes. The device's small 400 μm sensing radius, air-liquid interface compatibility, and flexibility make it versatile for use with various in vitro cell types and realtime measurements, with improved sensitivity compared to traditional methods. The second goal focused on the development of a stretchable, flexible device for bimodal monitoring of mechanical and electrical activity in ex vivo GI tissue, using PEDOT:PSS tracks on a PDMS substrate for both strain and electrophysiology measurements. The device's high durability under cyclic strain, sensitivity to strain and electrical activity, and ability to provide electrical stimulation show its potential as a diagnostic and therapeutic tool for GI disorders. The third goal focused on miniaturising the all-planar device for measuring epithelial barrier integrity developed in the first goal. The device was applied to diverse in vitro and ex vivo models, highlighting its versatility for experimental setups and potential for in vivo applications. The device was used within a clinical study using faecal matter samples from irritable bowel syndrome patients, emphasising its potential for improved diagnosis and treatment of IBS by identifying subtypes based on intestinal permeability. Overall, this thesis explores the development of organic bioelectronic devices for GI monitoring, focusing three biomarkers, with applications in both in vitro and ex vivo models. The work highlights the potential for these devices to improve diagnostics and treatments for GI disorders, such as irritable bowel syndrome, by enabling real-time, high-sensitivity measurements and offering new avenues for clinical applications.