This proposal seeks funding to create a Centre for Doctoral Training (CDT) in Connected Electronic and Photonic Systems (CEPS). Photonics has moved from a niche industry to being embedded in the majority of deployed systems, ranging from sensing, biophotonics and advanced manufacturing, through communications from the chip-to-chip to transcontinental scale, to display technologies, bringing higher resolution, lower power operation and enabling new ways of human-machine interaction. These advances have set the scene for a major change in commercialisation activity where electronics photonics and wireless converge in a wide range of information, sensing, communications, manufacturing and personal healthcare systems. Currently manufactured systems are realised by combining separately developed photonics, electronic and wireless components. This approach is labour intensive and requires many electrical interconnects as well as optical alignment on the micron scale. Devices are optimised separately and then brought together to meet systems specifications. Such an approach, although it has delivered remarkable results, not least the communications systems upon which the internet depends, limits the benefits that could come from systems-led design and the development of technologies for seamless integration of electronic photonics and wireless systems. To realise such connected systems requires researchers who have not only deep understanding of their specialist area, but also an excellent understanding across the fields of electronic photonics and wireless hardware and software. This proposal seeks to meet this important need, building upon the uniqueness and extent of the UCL and Cambridge research, where research activities are already focussing on higher levels of electronic, photonic and wireless integration; the convergence of wireless and optical communication systems; combined quantum and classical communication systems; the application of THz and optical low-latency connections in data centres; techniques for the low-cost roll-out of optical fibre to replace the copper network; the substitution of many conventional lighting products with photonic light sources and extensive application of photonics in medical diagnostics and personalised medicine. Many of these activities will increasingly rely on more advanced systems integration, and so the proposed CDT includes experts in electronic circuits, wireless systems and software. By drawing these complementary activities together, and building upon initial work towards this goal carried out within our previously funded CDT in Integrated Photonic and Electronic Systems, it is proposed to develop an advanced training programme to equip the next generation of very high calibre doctoral students with the required technical expertise, responsible innovation (RI), commercial and business skills to enable the £90 billion annual turnover UK electronics and photonics industry to create the closely integrated systems of the future. The CEPS CDT will provide a wide range of methods for learning for research students, well beyond that conventionally available, so that they can gain the required skills. In addition to conventional lectures and seminars, for example, there will be bespoke experimental coursework activities, reading clubs, roadmapping activities, responsible innovation (RI) studies, secondments to companies and other research laboratories and business planning courses. Connecting electronic and photonic systems is likely to expand the range of applications into which these technologies are deployed in other key sectors of the economy, such as industrial manufacturing, consumer electronics, data processing, defence, energy, engineering, security and medicine. As a result, a key feature of the CDT will be a developed awareness in its student cohorts of the breadth of opportunity available and the confidence that they can make strong impact thereon.

Multi-phase, trans/supercritical and non-Newtonian fluid flows with heat and mass transfer are critical in enhancing the performance of energy production, propulsion and biomedical systems. Examples include: hydraulic turbomachines, ship propellers, CO2-neutral e-fuels and e-motor cooling systems, particleladen flows in inhalers and focused ultrasounds for drug delivery. What all these cases have in common is the high level of complexity which makes Direct Numerical Simulations impossible. State-of-the-art LES simulations rely on simplified assumptions but do not have yet the desired accuracy, while often require enormously expensive CPU resources. The aim of project (acronym 'SCALE') is to develop simulation methods and reduced-order models using physics-informed and data-driven Machine Learning and optimisation methods for such flow processes. These will be trained against 'ground-truth' databases that will be generated for the first time using both DNS and experimentally validated, industry-relevant LES and multi-fidelity RANS simulations. The new simulation tools will be applied for the first time to industrial problems and their ability to accelerate design times and improve accuracy will be jointly pursued and evaluated with the non-academic partners of SCALE. These are international corporations and market leaders in the aforementioned areas. Holistic training by experts from science and industry includes broad reviews on relevant scientific topics, modern high performance computing architectures suitable for performing such simulations, big data analytics as well as extensive support for mastering scientific tasks and transferring the knowledge acquired to industrial practice. SCALE will also deliver transferable soft skills training from a well-connected cohort of leaders with the ability to communicate across disciplines and within the general public. This coupling of research with industry makes SCALE a truly outstanding network for doctoral candidates to start their careers.

Medical imaging has transformed clinical medicine in the last 40 years. Diagnostic imaging provides the means to probe the structure and function of the human body without having to cut open the body to see disease or injury. Imaging is sensitive to changes associated with the early stages of cancer allowing detection of disease at a sufficient early stage to have a major impact on long-term survival. Combining imaging with therapy delivery and surgery enables 3D imaging to be used for guidance, i.e. minimising harm to surrounding tissue and increasing the likelihood of a successful outcome. The UK has consistently been at the forefront of many of these developments. Despite these advances we still do not know the most basic mechanisms and aetiology of many of the most disabling and dangerous diseases. Cancer survival remains stubbornly low for many of the most common cancers such as lung, head and neck, liver, pancreas. Some of the most distressing neurological disorders such as the dementias, multiple sclerosis, epilepsy and some of the more common brain cancers, still have woefully poor long term cure rates. Imaging is the primary means of diagnosis and for studying disease progression and response to treatment. To fully achieve its potential imaging needs to be coupled with computational modelling of biological function and its relationship to tissue structure at multiple scales. The advent of powerful computing has opened up exciting opportunities to better understand disease initiation and progression and to guide and assess the effectiveness of therapies. Meanwhile novel imaging methods, such as photoacoustics, and combinations of technologies such as simultaneous PET and MRI, have created entirely new ways of looking at healthy function and disturbances to normal function associated with early and late disease progression. It is becoming increasingly clear that a multi-parameter, multi-scale and multi-sensor approach combining advanced sensor design with advanced computational methods in image formation and biological systems modelling is the way forward. The EPSRC Centre for Doctoral Training in Medical Imaging will provide comprehensive and integrative doctoral training in imaging sciences and methods. The programme has a strong focus on new image acquisition technologies, novel data analysis methods and integration with computational modelling. This will be a 4-year PhD programme designed to prepare students for successful careers in academia, industry and the healthcare sector. It comprises an MRes year in which the student will gain core competencies in this rapidly developing field, plus the skills to innovate both with imaging devices and with computational methods. During the PhD (years 2 to 4) the student will undertake an in-depth study of an aspect of medical imaging and its application to healthcare and will seek innovative solutions to challenging problems. Most projects will be strongly multi-disciplinary with a principle supervisor being a computer scientist, physicist, mathematician or engineer, a second supervisor from a clinical or life science background, and an industrial supervisor when required. Each project will lie in the EPSRC's remit. The Centre will comprise 72 students at its peak after 4 years and will be obtaining dedicated space and facilities. The participating departments are strongly supportive of this initiative and will encourage new academic appointees to actively participate in its delivery. The Centre will fill a significant skills gap that has been identified and our graduates will have a major impact in academic research in his area, industrial developments including attracting inward investment and driving forward start-ups, and in advocacy of this important and expanding area of medical engineering.

Over 120,000 people in the USA and over 6000 people in the UK are waiting for organ transplants, and many more are suffering from organ failure. Many donor organs are not transplanted (approximately 60% of donor hearts and 20% of kidneys are not used), often because they can only be kept for a short time. Long term preservation would mean better matching with recipients over larger geographical areas, reducing the chances of rejection and increasing the number of organs that could be used. One potentially transformative method of preserving organs for a longer time is cryopreservation. This involves freezing the organs at very low temperatures and then defrosting them when needed. However, this is currently limited to small volumes (<3 ml), largely due to the difficulty in rewarming the tissues without damage after freezing. To avoid damage on rewarming, tissues must be heated quickly and uniformly. This is not possible with existing water bath methods so the development of new methods for volumetric rewarming of large tissue volumes is critical. The aim of this fellowship is to develop a novel method of tissue rewarming using ultrasound. As ultrasound passes through frozen tissue, it loses energy which is deposited as heat. By controlling the pattern of the ultrasound waves entering the tissue, heat can be deposited as needed to raise the temperature of the tissue quickly and uniformly. First, the ultrasound parameters will be optimised for maximum cell viability and optimal heating rate using small volumes of cells. An ultrasound array based on these parameters will then be developed with methods of steering and shaping the acoustic field to uniformly and rapidly heat larger volumes of cells. This will be extended to warming tissues with inhomogeneous acoustic and thermal properties and larger volumes, using real time feedback to control the heating distribution, with the ultimate vision of creating a fully flexible tool that can be used to rewarm whole organs. Ultrasonic volumetric warming has the potential to enable long-term storage of tissues and organs which would transform the availability of organs for transplant. It would also have many other applications such as increasing access to therapies involving implanting cells and tissues in the body for diseases such as type 1 diabetes or for restoration of fertility after cancer therapy.

Colorectal Cancer (CRC) is the third most common cancer in the UK, with approximately 32,300 new cases diagnosed and 14,000 deaths in England and Wales each year. Occurrence of colorectal cancer is strongly related to age, with 83% of cases arising in people older than 60 years. It is anticipated that as our elderly population increases, CRC will increase in prevalence (National Institute for Clinical Excellence, www.nice.org.uk). This raises important questions relating to treatment in elderly patients balanced with quality-of-life and health economics considerations. The challenge to nanotechnology and engineering is to deliver cost-effective, less invasive treatments with fewer side-effects and potential benefits for quality of life in patients. This is particularly important in CRC at the present time as the NHS bowel-screening programme is rolled out for all individuals aged 60 to 69. This raises important issues for rapid, accurate, and acceptable, safe and cost-effective investigation and treatment of older symptomatic patients. Ultrasound has a clear and growing role in modern medicine and there is increasing demand for the introduction of ultrasound contrast agents such as microbubbles (MBs). These MBs are typically less than one hundredth of a millimetre in size, so that they can pass through the vasculature, and lead to imaging enhancements by scattering of the ultrasound signal. So-called third generation MBs will not only perform functional imaging with greatly enhanced sensitivity and specificity but will also carry therapeutic payloads for treatment or gene therapy. These will most likely be released by destroying the bubbles at the targeted site and their effect enhanced further by sonoporation (sound induced rupture of the cell walls to allow drugs in). Although the focus of our proposal is therapeutic delivery for cancer treatment, the basic technologies for MB development and ultrasound technology are equally applicable to other conditions e.g. cardiovascular and musculoskeletal disease where there is an unmet clinical need, particularly in ageing populations. As such this is a generic technology development relevant to different diseases.Our programme of research addresses several key issues central for the successful development of these 3rd Generation MBs. Firstly, we propose to develop a machine, based on microfluidics, for the creation of MBs of uniform size (necessary for human application). This instrument will also allow us to put suitable coatings on the MBs to target them specifically at cancerous cells. Secondly, we will develop novel coatings to allow control over the way bubbles respond to ultrasound signals. We will then add payloads of the required drug to be delivered onto the micro-bubble surface. At the same time we will develop novel methods of generating ultrasound signals which can be used to selectively destroy the MBs and simultaneously create holes in the cells to which the drugs should be delivered. A necessary part of such a programme of research is the full testing and evaluation of the MBs developed for targeted therapy of CRC using a combination models. Firstly, against cancer cells grown in test tubes and secondly, against mice infected with the relevant cancer. At the conclusion of our research project we will have enhanced our understanding of how MB and ultrasound technologies can be combined to yield new routes for therapeutic delivery/gene therapy. This will provide a platform to launch the next stage of research, required before such an approach could be used clinically.