Single Photon Emission Computed Tomography (SPECT) is a widely used imaging modality in medicine which uses radio-pharmaceuticals labelled with gamma emitting radioisotopes. Existing SPECT systems have a limiting position resolution of about 10 mm for body imaging and 7 mm for the head. The proposed system will offer an image resolution of 2-3 mm with a sensitivity a factor of ~100 larger than existing systems, while simultaneously enabling SPECT/MRI multimodality imaging. The ProSPECTus imager will open existing markets worth in excess of £300M pa to UK companies, covering medical, pharmaceutical, homeland security, science and defence. The consortium brings an internationally leading reputation and many years experience with semiconductor radiation detectors, electronics and software design. Key clinical input and trials are provided through Clinicians at the Clatterbridge Centre for Oncology , the University of Liverpool Magnetic Resonance Imaging Analysis Research Centre [MARIARC] and the Interventional Radiology and Medical Imaging Group at the Royal Liverpool University NHS Trust.

The IPS Fellow will coordinate the knowledge exchange strategy for Nuclear Physics, Particle Physics and Accelerator Science within the Department of Physics. Healthcare: The University of Liverpool, Department of Physics is one of only three national training providers for the new Modernising Scientific Careers (MSC) Medical Physics MSc, funded by the NHS. This was a highly successful bid, with Liverpool being ranked first against stiff competition. This MSc is delivered in collaboration with the Royal Liverpool University Hospital NHS Trust, the Clatterbridge Centre for Oncology (CCO) and Clinical Engineering with the University of Liverpool. The trainees come from throughout the UK. This provides a unique opportunity to build collaborative research and Continuing Professional Development (CPD) partnerships within the Healthcare sector. The fellow will coordinate these efforts and will help establish a new Medical Physics research institute within the University of Liverpool, which is a strategic goal of the University in its current planning. Security: The Fellow will help coordinate the exploitation of the sensor technology and associated instrumentation and techniques that exists within the research groups. The fellow will help consolidate existing relationships with partner organisations by showcasing the full breadth of STFC science activity. New opportunities for funding R+D will be identified together with establishing relationships with new companies. Energy: Liverpool scientists and engineers are working together as part of a new University Institute focused on research into energy. The Stephenson Institute is developing clean and sustainable energy technologies including hydrogen generation and storage, solar harvesting, wind and marine energy and fusion technology. The institute is in the process of developing expert networks, including policy-makers and management, to highlight global energy and sustainability issues. Making links with far eastern energy providers and attempting to attract a large investment from the University of Liverpool Energy campus we believe will be an important role of the fellow. The IPS Fellow will be fully engaged in this process, ensuring the opportunities for STFC science are fully exploited. The University of Liverpool Engineering, Electrical Engineering and Physics Departments are in the process of forming a Nuclear Engineering alliance which will maximise the exploitation of institutional expertise in autonomous systems, sensors and virtual engineering. The IPS Fellow will help coordinate the relationship between the alliance and external stakeholder organisations such as the National Nuclear Laboratory (NNL) and Sellafield Ltd. IT Developments: The Department was an early developer of large scale computing building the first large scale COTS cluster in n Europe in 2000 (MAP) and innovated specialized middleware . Subsequently the group invested in Grid computing and, at the same time founded the AiMeS Institute for commercial applications with NWDA and EW funding. This led to commercial spin-offs (AiMeS Grid Services) totally independent of the University currently delivering these Grid Services to the wider community. The Departments IT cluster activities, through also led to the introduction /choice of Force10 (now DELL) switches as the core switch technology at CERN; an example of beneficial relationship between industry and research. The group is now (separately from this request) bidding (with computer science partners) to develop a new generation of computers, based on a next generation of GPU chip and switch technology that aims to deliver a factor 1000:1 improvement in performance price of useable CPU cycles within the next decade. The IPS fellow will play a pivotal role in attracting commercial partners and carefully managing the IP issues that will arise.

According to the World Health Organisation age-related macular degeneration (AMD) is the third most prevalent cause of blindness worldwide, and the leading cause of blindness in industrialised countries. There are two types, the neovascular - which contributes to 10% of cases - and atrophic - which contributes to 90% of cases. In AMD, a section of the retina called the Bruch's membrane thickens with age and can interfere with the waste/nutrient exchange between the retinal pigment epithelial (RPE) cells - the layer upon which photoreceptor cells attach and survive - and the choroid - the intricate network of vessels responsible for blood supply. This interference can cause the retinal pigment epithelial cells to die, which in turn can lead to photoreceptor cell death, eventually causing irreversible central vision loss. The sufferer loses their independence as this prevents them from carrying out everyday tasks such as reading and driving. The main risk factor for AMD is age and it, predominantly, affects people over the age of 50. It has already been reported by clinicians that cases of AMD have doubled between the years of 2000-2010, and with the population living longer the prevalence of this disease is anticipated to rise to more than double by the year 2030. Considering there is no current treatment for atrophic AMD and with its prevalence on the rise, this important issue needs to be addressed now. A number of studies report the use of substrates to deliver healthy RPE cells under the photoreceptor cells before they begin to die. They discuss placing the substrate on top of the diseased Bruch's membrane to deliver a monolayer of RPE cells. I believe that simply placing a novel substrate on top of the diseased membrane could exacerbate the issue. The problem in AMD is the thickened Bruch's membrane, so adding a further layer could further increase the nutrient/waste exchange path leading to damage to the transplanted cells. I hypothesise that a cell transplant substrate can be designed that will unblock the diseased Bruch's membrane while providing support for the healthy RPE monolayer thus leading to improved nutrient/waste exchange between the photoreceptors and the choroidal blood vessels. This project will develop a novel bioengineered persistent substrate with a bioactive layer that will deliver active molecules at a controlled rate. It will deliver the required monolayer of RPE cells in order to ensure photoreceptor cell survival while simultaneously removing and replacing the diseased native Bruch's membrane. These prerequisites address the necessity of having a permanent membrane upon which the retinal pigment epithelial cells can attach and survive, the removal of the diseased tissue, and the integration of the permanent substrate to replace the diseased Bruch's membrane in order to ensure that the optimal exchange pathway thickness is maintained. I believe this novel approach will contribute to improving quality of life by reducing the number of people who lose their independence and require assistance/intervention due to AMD. The project aligns to the key Life Sciences Industrial Strategy challenge of developing advanced therapeutics under the theme of healthy ageing in the Health Advanced Research Programme and contributes to the EPSRC Healthy Nation delivery plan ambitions.

This proposal will develop novel silicone oil tamponades providing controlled drug delivery to the back of the eye to prevent proliferative vitreoretinopathy, a blinding condition with no gold standard for treatment. Proliferative vitreoretinopathy (PVR) is a disease that can develop following retinal detachment. It is the primary cause of failure following surgery to re-attach the retina and often results in poor visual outcome. Despite many strategies, there has been no improvement in outcome over the last 20 years and these patients can lose their sight. Complicated retinal detachments require silicone oil to re-attach the retina. Effective pharmacological treatment of PVR requires controlled, sustained release of a drug. A key challenge is that certain drugs that could be used to control PVR cannot dissolve in the oil. If injected into the eye they accumulate around the oil and cause toxicity to the retina. Furthermore, repeat injections increase the risk of complications. Thus, an entirely new approach is required. This proposal uniquely aims to develop a silicone oil tamponade with a dual role, firstly to act as a tamponade agent and secondly to be a novel drug-delivery system. It will use non-steroidal anti-inflammatory drugs (NSAIDS), which have the potential to address the inflammatory as well as the proliferative stages of PVR. The project will use novel chemical techniques to bind drugs to the silicone oil so that they will be released in a sustained, controlled manner. Preliminary data has demonstrated that drugs can be bound to silicone oil, and that the release profile of the drug can be changed by varying the blend of the oil. An in vitro model of the oil-filled eye, incorporating the flow of aqueous out of the eye, has also been developed. This will allow studies of drug clearance from the eye. This programme proposes the combined development and in vitro biological evaluation of a new drug delivery system, focussed on NSAIDS, with additional drug candidates for risk mitigation. Furthermore, it will develop a new approach to biological evaluation that will make future animal trials more efficient. Drugs will be bound to silicone oil using several strategies and release studies undertaken. The conditions required to release the drug under clinically relevant conditions, at a concentration identified as being non-toxic but effective at controlling cell behaviour, will be identified. Drug-oil products will also be assessed in a variety of laboratory models to assess how effective they are at controlling PVR-like behaviour, using techniques that are well-established in the host laboratories. The testing will be iterative, with results being fed back to inform the development of the prototype oils. The physical and optical properties of the drug-oil products, as well as suitable methods for sterilisation, will also be assessed. Development of new methods for drug delivery could have significant benefits for industry and the healthcare system. Furthermore, the repurposing of existing drugs for treatment of PVR would speed the translation of treatments to the clinic and represent a new stream of revenue for these drugs. The potential to protect any intellectual property from this project will be kept under review, with a view to future commercial exploitation. Results will also be shared with patient groups in St Paul's Eye Hospital, ensuring end-user engagement. Output from this project will stimulate research into novel routes of ocular drug delivery and further development of in vitro modelling of the eye. Both aspects of the research will be of great interest to academic and industrial researchers. This project will deliver a novel, drug-containing oil that can release drugs at therapeutic levels over several weeks and that will be ready to be tested in animals prior to human trials. This is designed to be an effective therapy for a sight-threatening condition that at the moment has no reliable treatment.

This Healthcare Impact Partnership will use drug delivery technologies previously invented by us to develop novel, injectable devices to provide targeted, controlled and sustained drug delivery to the inside of the eye. These devices will address unmet clinical needs in two groups of patients. In addition, we will develop sophisticated benchtop and computer models of drug release in the eye, to allow us to speed up development and reduce the amount of animal testing required to use the devices in humans. Over 5.7 million people in the UK are living with sight-threatening eye conditions. These include conditions that can develop as a result of diabetes, macular degeneration and retinal detachment. The current best practice for treatment of the scarring that can follow retinal detachment is injection of silicone oil into the eye to replace the vitreous. It has been proposed that, in addition to the oil, sustained drug delivery could help reduce the development of scarring. We have previously developed technology to achieve controlled, extended release of drugs from silicone oils, and now wish to apply these technologies to silicone oils that are suitable for use in patients. Treatment for other sight-threatening conditions requires patients to have frequent injections of drugs directly into the eye over many years. This can be uncomfortable and inconvenient for patients, places a burden on the healthcare system and is not feasible in developing countries. A small number of drug delivery devices that reduce the number of injections needed are available, but these must either be removed once the drug release is complete, or, if the device is degradable, do not last much longer than standard injections. We have previously developed technology to make drugs into nanoparticles. We will develop a drug delivery system constructed of nanoparticles inside a material that forms a gel when it is injected into the eye. After the drug has been released, the gel would degrade into non-toxic components. The advantages of this over existing devices are that this technology could be tailored in terms of the drug and dosing, and that higher doses will be possible due to the use of nanoparticles. Both of our delivery devices are injectable, and will improve patient outcomes, particularly in developing countries and patients that present late. Our team is multidisciplinary, including academics specialising in ophthalmic biomaterials and drug delivery. A clinical ophthalmologist specialising in drug delivery will ensure that our technologies are suitable for clinical use. We will also engage with patients groups, who will help inform our development strategy. In order to accelerate the technologies towards the production of devices that are suitable for use in patients, we have partnered with a company who manufacture silicone oil products used to treat retinal detachment. With their expertise, we will be able to ensure that we include certain crucial aspects as we develop our technologies, such as how to scale up manufacture from the laboratory to that suitable for commercial use, and the generation of data that is required for the products to gain a licence for clinical use. Another commercial partner specialising in the production of models to replace animal testing will help us optimise our models, and promote their use to other organisations who are interested in reducing animal use. We will apply our silicone oil-based drug release technology to commercially-available oils, ensuring the resulting product has appropriate physical properties to remain functional in the eye, is not toxic, and has optimal drug release. We will also develop our nanoparticle system, optimising physical, drug-release and toxic properties. At the same time, we will develop existing benchtop and computer models so that they will be able to predict drug release from our devices.