EPSRC IRC Proteus - Multiplexed 'Touch and Tell' Optical Molecular Sensing and Imaging - Lifetime and Beyond

The EPSRC IRC Proteus is made up of a group of world-leading scientists, engineers and clinicians. Interdisciplinarity is at our heart - we work across traditional boundaries linking together disciplines such as optical physics, chemical biology, biology and engineering to name but a few. The ambition and desire is to translate technologies to help patients - empowering clinicians to "see disease" in front of their eyes at the bedside and help them to make the right decisions and give the right treatments at the right time.

This highly interdisciplinary collaboration driven by clinical need and pull, has led to the design, fabrication and testing in patients of a number of world-leading bedside-based technology platforms. Our technology platform combines advanced fibre optic technology (that can be readily be passed into the lung of patients) and highly sensitive detectors in association with highly sensitive fluorescent chemical reagents to diagnose disease. This allows clinicians to "view" inside the lung to detect bacteria or aberrant disease signatures of disease.

Clinical pull: Intensive care unit (ICU) patients suffer high death and disability rates and are responsible for a disproportionate financial burden on the health service (the equivalent of 1% of USA GDP is spent on patients in intensive care). 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 new technology platforms being developed by Proteus are helping doctors in the intensive care unit to make rapid and accurate diagnoses of patients, allowing them to direct and inform therapy and ensure patients get the right treatment, at the right time and quickly. Although our technology platforms have a focus at this time on being used in the intensive care unit, it is widely applicable to a wide range of lung conditions and other healthcare situations, such as bowel or pancreatic cancer.

The next steps for the IRC are to take our technology into a new area in which different flavours of light can be used to diagnose disease - using the teams' highly advanced light sensors (that are able to count a single photon). In addition the proposal moves the IRC towards sustainability, creating a legacy from the EPSRC investment - accelerating the pathways to take new technology into patients, while developing commercial opportunities.

In summary the EPSRC IRC Proteus has generated a new cohort of young interdisciplinary scientists trained in physical and biological sciences and engineering that have a full appreciation and practical experience of clinical translational and commercialisation pathways. They will be able to meet the challenges of converting advances in science and engineering into healthcare benefits with the development of a number of cutting-edge bedside technology platforms which will help doctors make rapid and accurate diagnoses. The team, in association with the partner Universities, have also begun to make major strides towards full sustainability of the IRC - making major impacts in the areas of clinical and commercial translation, with significant academic outputs and public engagement activities.

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

Research Areas - The research proposed pushes the technologies that we have developed as part of the original IRC into advanced technology readiness. We have for example developed and fabricated three world-leading detectors. They offer enormous power and potential, but took some 3 years to design/test/evaluate with advanced software having to be written to control and utilize their outputs. They are now ready to be exploited to the full.

Clinical Translation: We have developed a regulatory pathway that has allowed us to carry out first in-human studies (both device and probes). Proteus has, to date, delivered into the clinic a device (VersiColour) and three imaging reagents (Bac-One, Bac-Two and Fib-One) - and the team will deliver into the clinic and into patients at least 2 devices, 3 fibres and 2 chemical probes as part of this "next steps funding". As such the stage is now set with multiple new opportunities that can be grasped and exploited and opened up to other groups.

Communication and Outreach - Through public lectures, open meetings and publication in the scientific and lay press we have engaged in public, scientific and commercial disseminations - e.g. The British Science Festival, Family Weekend Event (Swansea) -September 2016 with a Permanent Proteus Exhibit at Glasgow Science Centre now being constructed. Our interdisciplinary programme will continue to provide multiple opportunities for involvement in public engagement and dissemination in which team members will play a variety of active roles.

Patients: Proteus is providing unique opportunities for clinicians to rapidly monitor events deep in the lungs of critically ill patients in 'real time' at the bedside. This will permit rapid point-of-care diagnosis and informed decision-making in intensive care units and patient stratification. We are actively involving patients in our programme to increase impact and involve patients in our research ideas and plans.

NHS: The economic burden of ICU patients is huge. Rapid and incisive bedside diagnosis, particularly of specific infections 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 antibiotic use, reduced ventilator dependency and reduced mortality and morbidity with a proportionate economic benefit.

Interdisciplinarity: A central part of our agenda has been to break down traditional 'barriers' between physical and biomedical sciences. The team have benefitted immensely from the interdisciplinary translational thrust of the programme and the cross-fertilisation derived from the 'Hub'. Moreover, the PhD students provided by the Universities have been specifically engaged in cross-disciplinary projects - thus allowing us to train a cadre of scientists who are multi-skilled and equipped to meet the challenges of applying new technologies to healthcare provision in the new era.

Commercial Translation: The UK must reap the dividend of the current "revolution" in physical sciences. Proteus has generated multiple packages of IP whose commercial opportunities are being explored in areas associated with fibre technology, novel chemical probes, image processing and life-time imaging. Proteus is delivering leading-edge interdisciplinary and translational research in exciting and highly translatable areas of photonics, optics, imaging, data analysis and chemistry - driven by a clear "healthcare pull". The enabling activities through our IRC has created a new generation of scientists, engineers and technologists with a translational agenda and mind-set for the benefit of the UK economy. Building on this, Proteus is also leading the establishment of a UK Healthcare Technology Accelerator Facility.