Functional Imaging of Barrier Function in 2D and 3D epithelia

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This project aims to create next-generation drug discovery platforms to characterise barrier function in microphysiological models of epithelial barrier tissues non-invasively. The pharmaceutical industry is increasingly shifting away from animal studies towards cell assays based on human or human-derived cells. Reasons are both ethical and practical, since human cells more accurately mimic human cell tissue behaviour and responses. This saves time and money in drug development pipelines and helps to de-risk lead advancement by providing early data on potential human side-effects. Next generation platform technologies are urgently needed to extract real-time data from "microphysiological" systems, which are being developed through "tissue on chip" approaches. However, we presently lack the ability to combine key physiological requirements such as porosity, polarity, fluidic access, and electrode access with the optical transparency and small dimensions required to achieve scalable manufacture at tractable cost. This project will develop novel imaging and sensing methods to compliment techniques developed at Nottingham (electro-impedance imaging, hydrodynamic Raman imaging) to monitor and characterise electrical molecular barrier function in epithelial (skin) barrier tissue models in routine use in the Webb lab (lung: Calu-3, eye: ARPE-19, gut: Caco-2). Physiological parameters of cell systems using industry-standard methods (Transwell) will be compared with novel advanced materials such as nanoporous nitride (NPN) membranes and microporous bioglasses developed herein, on which 2D and 3D epithelial cultures will be established and characterised. Gold-standard methods will provide quantitative data demonstrating the potential of these novel platforms for the monitoring of physiology in a high-throughput context. We will leverage existing links to UoN IP and potential commercialisation pathways for NPN biosensors, microporous glasses, electroimpedance imaging methods, biocompatible surface coatings, and microphysiological devices to generate an advanced platform for the sensitive and non-invasive monitoring of physiology during exposure to pharmacological (drug candidates, permeation enhancing systems) and physiological (ion replacement, osmotic manipulation) challenges.