Multiplexed 'Touch and Tell' Optical Molecular Sensing and Imaging

This project is all about multi-disciplinary collaboration - and capitalisation in a clinical setting of the many new vistas and opportunities that will arise. As such this research programme brings together a group of world class scientists (physicists, chemists, engineers and computer experts) and clinicians to design, make and test a cutting-edge bedside technology platform which will help doctors in the intensive care unit (ICU) make rapid and accurate diagnoses that would inform therapy and ensure patients get the right treatment, quickly. While we are developing our technology platform with a focus on ICU, it will also be applicable to a wide range of other healthcare situations.

ICU patients suffer high death and disability rates and are responsible for a disproportionate financial burden on the health service. Potentially fatal lung complications are a common problem in ventilated ICU patients and doctors caring for these patients in the ICU face many challenges, often needing to make snap decisions without the information necessary to properly inform those decisions. The technology platform developed in this programme will provide doctors with important information on the state of ICU patients and whether they have infections, inflammation or scarring in their lungs. Currently there are no methods to do this accurately. This information will aid them in making decisions about treatment. A new approach to rapidly diagnose lung complications in ICU would enable doctors to target the correct drugs to the appropriate patients and to withdraw drugs with confidence, with resultant improvement in patient outcomes and major cost efficiencies - thus revolutionising ICU care.

Using advanced fibre optic technology and micro-electronics and new sensor arrays our ground-breaking solution is to create a novel fibre-based probe that can readily be passed into the gas exchanging areas of the lung and blood vessels of ICU patients. The probe will house a variety of special optical fibres, some of which allow clinicians to "view" inside the lung while others will be modified with sensors that can measure important parameters such as oxygen concentration and acidity in both blood and lung. In addition the fibre will deliver tiny amounts (microdoses) of 'smart reagents' that fluorescently detect specific bacteria and other agents that can damage the lung. When integrated together these signals will provide highly specific information about the degree or type of lung damage and the potential causative 'bug' if an infection is suspected. Because of the large amount of information generated and in order to make it easily interpreted by doctors, computing experts will convert these signals into easy-to-understand disease readouts for our clinicians.

Work on the different elements needed to create this technology platform will be undertaken by groups of chemists, physicists, engineers, computer scientists and biologists working at Bath, Heriot Watt and Edinburgh universities. Crucially, this programme will bring these scientific disciplines together in a "hub" where they will work side-by-side, promoting integration of purpose and to ensure that advances are rapidly translated into the clinical setting. This interdisciplinary hub will also provide a fertile training base for new PhD students who will learn the cross-disciplinary skills that will equip them to meet the challenges of translating the current 'revolution' in physical sciences into benefit for UK healthcare.

In summary this project will generate; 1) a new cohort of scientists trained in physical and biological science that have a full appreciation of clinical translational and commercialisation pathways and who are equipped to meet the challenges of converting advances in basic science into healthcare benefit and; 2) a cutting-edge bedside technology platform which will help doctors in the ICU make rapid and accurate diagnoses.

Our proposed research programme will generate numerous avenues for the realisation of impact:

Patients: FOSIP will provide a unique opportunity for clinicians to rapidly monitor key physiological and pathological events simultaneously in the lungs and blood of critically ill patients in 'real time' at the bedside without the need for cumbersome equipment or ionizing radiation. This will permit rapid 'point-of-care diagnosis and informed decision-making in intensive care units. It will also enable patient stratification for 'personalised' new/expensive drug therapy thereby significantly reducing morbidity and mortality. FOSIP would also be readily applicable to other diseased organs accessible to fibrescopes, particularly the genitourinary tract and the upper and lower gastrointestinal tract.

NHS: Although patient numbers in ICUs are comparatively small, the economic burden is disproportionately huge. Rapid and incisive bedside diagnosis, particularly of specific infections or inflammation/scarring processes would lead to stratification of patient care and tailored prescribing patterns, including the use/non-use of expensive and potentially toxic anti-bacterials. Ultimately this would translate into reduced ventilator dependency and reduced mortality and morbidity with a proportionate economic benefit.

UK PLC: UK Healthcare must reap the dividend of the current 'revolution' in physical sciences. This research programme will deliver new leading-edge multi and cross-disciplinary research in exciting and highly translatable areas of optics, imaging, data analysis and chemistry. Our proposed programme is driven by a clear "healthcare pull" from ICU (with application to diseases in other organs); it fits squarely with EPSRC goals in the Healthcare and Life Sciences sector. Enabling activities through our IRC will create a new generation of scientists, engineers and technologists with a translational agenda and mind-set for the benefit of the UK economy.

Training: A central part of our agenda is to break down traditional 'barriers' between physical and biomedical sciences. The PDRA's will benefit immensely from the interdisciplinary, translational thrust of the programme and the cross-fertilisation that will derive from the 'hub' in work package 6. Moreover, through our PhD students specifically engaged in cross-disciplinary projects we will create a new cadre of scientist who are multi-skilled and equipped to meet the challenges of applying new technologies to healthcare provision in the new era. They will gain a wide variety of both "hard and soft" skills that will be readily applied in a variety of employment sectors.

Industry: All the applicants have major interactions with industry, and most have direct personal experience of spin-off/spin-out companies. As the programme progresses new commercial opportunities will undoubtedly arise in fibre technology, engineering, novel chemical probes, image analysis and computing. When the integrative capacity of the programme is realised and FOSIP is applied to human disease and its models, commercialization prospects in the global healthcare arena will be significant.

General: Our multidisciplinary programme will provide many opportunities for involvement in public engagement and dissemination. Research fellows will participate at the International Science Festivals and become involved in a variety of out-reach activities such as the 'Researchers-in-Residence Programme' which places postgraduate students in local secondary schools allowing the public to benefit, as well as engaging the next generation of scientists.