Design and Fabrication of Optical Filters for Fluorescence-Based Monitoring of Organ Viability

Abstract

This thesis details the development, optimisation, and clinical evaluation of a comprehensive biomedical optical monitoring device designed for the real-time, non-invasive assessment of metabolic parameters in transplantable organs. Addressing the critical need for localised, cellular-level data during ex vivo normothermic machine perfusion (NMP), the research bridges the gap between foundational optical engineering and real-world clinical application. A core focus of this work was the computational modelling and cleanroom fabrication of selective multi-cavity Fabry-Perot (MCFP) optical interference filters. Constructed from alternating dielectric layers, these thin-film stacks were meticulously tuned to achieve the precise spectral separation of excitation and emission wavelengths required for accurate fluorescence detection. Concurrently, bi-functional luminescent hydrogel sensors were synthesised, encapsulated with optimised protective overcoats, and integrated into the device for the continuous monitoring of tissue pH and oxygen (O 2 ) via dual-wavelength excitation (405 nm and 450 nm). Clinical validation was conducted during the NMP of human donor livers at the Erasmus Medical Center (EMC) across two distinct experimental models. Initial trials on a non-viable, defrosted liver confirmed the sensor’s capability to instantaneously track mechanically driven transient shifts in local oxygenation and pH. Subsequently, the platform was deployed on a viable, freshly declined human liver for over six hours, with localised optical readings continuously cross-referenced against gold-standard clinical perfusate analysis. While local O 2 measurements demonstrated high reliability and reflected active biological recovery, pH monitoring faced analytical challenges from hydrogel swelling, blood diffusion barriers, and photobleaching. Notably, UV excitation (405 nm) induced an exponential signal drift, whereas blue light excitation (450 nm) proved significantly more robust for continuous tracking. Ultimately, these trials successfully validated the device’s fundamental architecture, demonstrating strong proof-of-concept capabilities while identifying targeted modifications to enhance long-term clinical transplant monitoring.