Development of a new toolbox of sensors for monitoring the status of the gut

Lead Research Organisation: University of Cambridge
Department Name: Chemical Engineering and Biotechnology

Abstract

The gastrointestinal system performs several key regulatory functions within the human body including the movement of food through the body, digestion, and absorption. The enteric nervous system (ENS) controls the gastrointestinal system; the term 'second brain' has been used to discuss the ENS. Gastrointestinal disorders such as irritable bowel syndrome (IBS) and inflammatory bowel disease (IBD) occur when homeostasis of properties of the gut tissue barrier are not maintained. IBS and IBD present symptoms such as abdominal pain and diarrhoea, which can impede the standard of living of those affected. Homeostasis of the gut barrier can be assessed by monitoring certain physiochemical properties such as permeability and contractility.

Despite the importance of our guts in health and disease, very few dedicated devices exist that can measure gut permeability and motility on tissue samples ex vivo or in vivo. Present tools are designed for use in in vitro environments. To translate these devices to in vivo monitoring, an ex vivo device to measure the status of the gut will first be developed as a demonstration of proof-of-concept, this will provide insight into gut barrier function and explore how the ENS is related to maintaining homeostasis. We propose that the dual monitoring of the electrical impedance and the contraction of the gut axis through the development of a quantitative, conformal, dual-modal ex vivo gut barrier sensor will help shed light on the causes, diagnostics, and potential treatment methods of gastrointestinal disorders. The sensor system is heavily related to the sensors and instrumentation, and clinical technologies research areas outlined by the EPSRC.

The three objectives of the project follow chronologically along the three years of the PhD. The objective of the first year is to design, fabricate and test mechanisms for obtaining in vitro readouts of permeability and contractility. Chrysanthi Moysidou, a postdoctoral researcher within the BEST group, has helped characterise a multi-cellular in vitro model of the gut barrier that will be used for testing. In addition, Chrysanthi Moysidou is also working on an organoid model with enteroendocrine cells from sheep that could be utilised. A parylene based peel-off technique for creating PEDOT:PSS devices that can be used for obtaining permeability measurements is employed by the BEST group in other applications. It is expected that the conducting polymers developed by the BEST group will be employed to obtain a quantitative electrical readout of the motility of the gut tissue barrier. This aligns with EPSRC's polymer materials research area. Before this happens, research into how cell contraction affects the mechanical and electrical properties of conducting polymers must be carried out in vitro. The sensing modalities must be integrated into one conformable sensing array and benchmarked against a commercial setup.

The objective of the second year is to extend the sensor technology developed in the first year for use in ex vivo systems. The sensor system will be tested on explanted rat gut tissue. Alexander Boys, a postdoctoral member of the BEST group, has experience in in vivo testing with rats. The device measurements need to be benchmarked with gold standard ex vivo measurements, such as an Ussing chamber. Gareth Sanger, Professor of Neuropharmacology at Barts and the London, has access to Ussing chamber technology.

The objective of the third year is to achieve clinical implementation of device in gut tissue samples of patients with IBD and IBS. Qasim Aziz, Professor of Neurogastroenterology at Barts and the London, is a key contact that will help develop the clinical side of the research. A key milestone would be data from human tissue samples that provides evidence of the sensing system working to monitor gut contraction and permeability. Another milestone is being able to monitor and detect the presence of certain gastrointestinal

Publications

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Studentship Projects

Project Reference Relationship Related To Start End Student Name
EP/S023046/1 30/09/2019 30/03/2028
2408405 Studentship EP/S023046/1 30/09/2020 29/09/2024 Sophie Victoria Oldroyd