Increasing age is frequently associated with a build-up of faeces in the large bowel due to difficult, infrequent and incomplete emptying of the bowel (chronic constipation) as well as leaking of bowel contents (feacal incontinence). These are known as age-related bowel disorders. Over one third of the over 65-year olds in the community and more than half of those in care homes will suffer these age-related bowel disorders. To the sufferer the symptoms can cause significant embarrassment, loss of dignity and quality of life. To the health service the cost of treating such conditions reached £1 billion in 2010. This age group is predicted to increase, where the number of people aged 65 and over will increase by more than 40 % within 20 years, making this a major social and economic problem. Therefore, there needs to be an approach that allows for the early detection of predictive markers of age-related bowel disorders so that effective treatment can commence at an early stage, delaying/preventing the onset of the disorder and extending healthspan. The movement of faeces through the large bowel requires the coordinated activity of the nerves and muscles that control this region. The outer most layer of the bowel known as the mucosa, has cells that can detect the contents present within our bowels and they release chemicals to communicate to the nerves to coordinate muscle contractions. We have shown that this communication process is altered with age as there are changes in the release of these chemicals. This in turn impairs the function of the muscles and results in a loss in the movement of faecal matter. Therefore, if we can measure the chemicals and the function of the muscle over time, we will be able to detect these changes very early before the patient gets symptoms and start treatments to delay/prevent the onset of these disorders. To meet these challenges, the first step will make an electrochemical probe that can be inserted into the lower bowel to track the changes in the chemicals released from the mucosa and the muscle activity. This will require optimising the design and the electronics to allow us to conduct the required measurements, Additionally, we would like our probe to be able to release drugs locally into the bowel so the device will be constructed with a tube within the probe to allow for this. To make these probes we will utilise 3D printing, which provides a platform for the efficient manufacturing of the parts of the probe. Additionally, this approach will allow us to scale this device, from the small probe developed as part of this study in rodents to a larger probe for use in future human studies. Once these probes have been made, we will explore how modifications to the materials used to construct the probe and the shape of the probe affect its performance. The best prototype will be used for investigations in animal models. Initially our probe will be inserted into the lower bowel of an anaesthetised mouse. These studies will allow us to map how chemicals are released in the lower bowel and how muscle activity varies in the regions measured. Additionally, we can explore the effects of different drugs in the lower bowel. These important studies will allow us to establish key protocols for our ageing studies. Using a mouse model which has similar age-related bowel dysfunction to that experienced in humans and where the bowel is regulated by many of the same chemicals used by humans provides us with an ideal model to carry out a longitudinal exploration of how mucosal chemicals and muscle activity change during the lifespan of an individual animal whilst simultaneously monitoring its faecal output as a marker of dysfunction. This will allow us to showcase how our probe can be an attractive tool for tracking and predicting the likelihood of age-related bowel disorders. Such findings will allow us to rapidly conduct clinical trials of our device in humans.

The Circular Economy (CE) is gaining mainstream attention, but not in all sectors. The linear model, from cradle to grave, still prevails for small Medical Devices (MDs). The perception of cross contamination dominates management and processing practice after first use, but studies show that only a minority of healthcare waste is infectious. Potential innovations in product design, materials, procedure management and post-use processing offer effective infection control to enable a far higher percentage of material to enter additional cycles of functionality beyond first use. With savings from reprocessing reported at around 50%, NHS costs would reduce by hundreds of millions of pounds if such circular use of resources is fully implemented. Additional cycles may be in closed loops of MD functionality, remaining legally compliant, or open loops, where material is used in other sectors. This project aims to develop these technical and non-technical solutions and bring them together in a coherent 'whole system' to demonstrate operation of the Circular Economy for four representative small MDs. This will require a multidisciplinary approach to utilise the expertise of product designers, manufacturers, clinical staff, waste management companies and waste processors. Wider adoption will need the engagement of professionals in health service procurement and intermediary organisations from the commercial and non-profit sectors, such as trade bodies, consultancies and health NGOs. The project will last 2.5 years. Based on a well-defined understanding of the problem, it will start with stakeholder workshops to conduct a deep dive on the planned innovations in product design (including materials) and reprocessing technologies as well as operational and management systems. Separate but coordinated work tracks and teams will then develop innovations in these fields and produce full specifications. These will then be brought together in proof-of-concept experiments to evaluate the whole circular system. The engineering innovations related to adapted or novel small MDs designs, materials and material selection methods, and reprocessing technologies (re-use, remanufacturing or recycling) will be encapsulated in targeted CE specifications for four reference products as well as more abstracted CE guidelines for application to each product category. The specifications for each part of the circular system and the evaluation results will be published in a variety of media and be available for project partners and others to develop into large scale systems. The project will expand knowledge of the principles of effective Circular Economy systems in a part of the healthcare sector and integrate learning from the few previous waste management projects on specific medical devices into a 'whole system' approach. In this way we hope to significantly influence the development of a UK circular Economy for small medical devices.

Our vision is to challenge the mind-set of pancreatic cancer being a prognosis of extremely limited options and to enable revolutionary future treatments that will save lives and allow patients to live without major side-effects. Novel engineering and physical science has an essential contribution to make against what is currently the deadliest form of cancer (mortality 95% <2yrs). This research will centre around the creation of new minimally-invasive technologies based on microscale, magnetically-driven, soft continuum robots. These will newly enable non-destructive access to the intricate sensitive internal anatomy of the pancreas and allow targeted treatments to be delivered. These new technologies will tackle current clinical challenges in pancreatic cancer, while also providing the treatment methods that will be required as possibilities for earlier diagnosis emerge in the future.

There is a pressing need to improve the precision, control and selectivity of surgical procedures addressing several high-incidence cancers. For example in the UK, the incidence of basal cell carcinoma (BCC) has increased by approximately 250% since the 1990s, with 137,000 new cases of BCC each year. Bowel cancer is the 4th most common cancer and is the second most common cause of cancer death. Some 15% of new bowel cancer cases are early stage and amenable to potential endoluminal surgery; this proportion is increasing with national screening programs. Delayed diagnosis and incomplete excision of tumours are key drivers of patient morbidity, and squander limited surgical resources. Streamlining screening and early diagnosis processes is now even more important with more patient backlog caused by Covid-19. The default surgical practice is to remove cancers wherever possible, along with a margin of healthy tissue. Leaving cancer cells behind leads to reoccurrence, but removing too much healthy tissue increases both the risk of complications and the loss of normal function. Trying to optimise this balance is a global challenge. For example, BCCs often spread out beneath the surface of the skin such that their entirety cannot be detected until surgery. Moh's micrographic surgery is the gold standard for treating BCCs: the tumour is removed section by section and examined under the microscope until no further tumour can be seen. This is both time consuming and traumatic for the patient, typically resulting in larger skin grafts than expected. If the extent of the tumour could be accurately determined, using terahertz (THz) imaging prior to surgery, the procedure would be faster, and grafts better planned. Similarly, if a diagnostic THz imaging capability could be added to a flexible endoscope, more colorectal tumours could be identified in situ and resected without waiting for histology results (typically 2 weeks) and a follow-up procedure. In this programme, a highly interdisciplinary team consisting of investigators at Universities of Warwick, Exeter and Leeds in Physics, Engineering and Medicine, and at the University Hospital of Coventry and Warwickshire and the Leeds Teaching Hospitals NHS Trust, join forces to optimise patient diagnosis and treatment. The team is supported by industry partners including TeraView Ltd, Intuitive Surgical, Kuka (world leader of industrial robots), QinetiQ, the National Physical Laboratory and Lubrizol (an international cosmetics company). THz light is non-ionising, uses low power levels such that thermal effects are insignificant and is consequently safe for in vivo imaging of humans. It is very sensitive to intermolecular interactions such as hydrogen bonds, and probes processes that occur on picosecond timescales. Owing to the high sensitivity of THz light to tissue hydration and composition, THz spectroscopic imaging can help locate and diagnose lesions that cannot be seen by other imaging modalities. In Terabotics, we will integrate THz technology into robotic probes to develop improved platforms for cancer detection and surgical removal. We will develop probes that can be used on the skin as well as in the abdominal cavity and, by miniaturising the technology, we will also develop a new flexible probe for robotic colonoscopy. In this way the project will lead to more efficient cancer diagnosis and surgery, saving surgeons' operating time and reducing the number of surgeries needed. This is because accurately determining the extent of cancers prior to surgery will enable better surgical planning and reduce the need for a second surgery. Being able to diagnose cancers in situ will also give a faster diagnosis to treatment time. These factors will reduce trauma, costs, patient backlog and waiting lists, and improve patient outcomes. In short, our breakthrough in developing in situ diagnosis will bring step changes in the detection and treatment of cancer for many years to come.