Development of a cross-reactive fluorescent sensor array for the detection of liver fibrosis Ross Gillespie, Francesco Zamberlan, Liam T Wilson, William J Peveler University of Glasgow, United Kingdom Liver disease ranks as one of the leading causes of death in the modern day, but unlike the other leading causes, mortality rates of liver disease are increasing. [1] The common end stage for almost all liver disease is fibrosis and then cirrhosis, and a key reason for difficulty in tacking liver disease is that the current diagnosis techniques fail to effectively detect the early stages of liver fibrosis. Recent progress has highlighted that cross-reactive sensors, that operate on the principle of the mammalian nose or tongue, can successfully monitor fibrotic disease in patient blood samples, rather than relying on any one specific biomarker. [2,3] This offers a hope of early detection, but in order to improve the early detection possibilities of such a sensing array, a ‘semi-targeted’ or selective approach, that discriminates whole families of particular biomarkers but still retains a degree of cross-reactivity, may be a powerful tool. [4]
We have engineered a modular molecular architecture that can be synthesised with a variety of targeting ‘warheads’ and fluorescent reporters to create our selective sensing arrays. In particular we have focused initially on detecting and discriminating matrix metalloproteases (MMPs) as markers of fibrogenesis and glutathione S-transferases (GSTs) as markers of the initial signalling pathway. The changes in the total amount, as well as the ratios of different members of these protein families is indicative of the different stages of fibrosis. The warheads are sensitive to a wide variety of members of each protein family, giving cross-reactivity, but still targeting each family selectively. The warhead is appended to a responsive fluorophore that indicates a binding event with the proteins of interest. We present the successful synthesis of our sensing array components and promising initial data demonstrating the detection of target proteins in serum and the discrimination of members of those families. References 1. British Liver Trust. The alarming impact of liver disease in the UK. 2019
2. Rotello, V.M. et al. Adv. Mater. 30, 1-6. 2018 3. Rotello, V.M. ACS Sensors 1, 1282–1285, 2016 4. Marguiles, D. et al. Nat. Nanotechnol. 12, 1161–1168, 2017
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