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.

Building upon our existing flagship industry-linked EPSRC & MRC CDT in Systems Approaches to Biomedical Science (SABS), the new EPSRC CDT in Sustainable Approaches to Biomedical Science: Responsible and Reproducible Research - SABS:R^3 - will train a further five cohorts, each of 15 students, in cutting-edge systems approaches to biomedical research and, uniquely within the UK, in advanced practices in software engineering. Our renewed goal is to bring about a transformation of the research culture in computational biomedical science. Computational methods are now at the heart of biomedical research. From the simulation of the behaviour of complex systems, through the design and automation of laboratory experiments, to the analysis of both small and large-scale data, well-engineered software has proved capable of transforming biomedical science. Biomedical science is therefore dependent as never before on research software. Industries reliant on this continued innovation in biomedical science play a critical role in the UK economy. The biopharmaceutical and medical technology industrial sectors alone generate an annual turnover of over £63 billion and employ 233,000 scientists and staff. In his foreword to the 2017 Life Sciences Industrial Strategy, Sir John Bell noted that, "The global life sciences industry is expected to reach >$2 trillion in gross value by 2023... there are few, if any, sectors more important to support as part of the industrial strategy." The report identifies the need to provide training in skills in "informatics, computational, mathematical and statistics areas" as being of major concern for the life sciences industry. Over the last 9 years, the existing SABS CDT has been working with its consortium of now 22 industrial and institutional partners to meet these training needs. Over this same period, continued advances in information technology have accelerated the shift in the biomedical research landscape in an increasingly quantitative and predictive direction. As a result, computational and hence software-driven approaches now underpin all aspects of the research pipeline. In spite of this central importance, the development of research software is typically a by-product of the research process, with the research publication being the primary output. Research software is typically not made available to the research community, or even to peer reviewers, and therefore cannot be verified. Vast amounts of research time is lost (usually by PhD students with no formal training in software development) in re-implementing already-existing solutions from the literature. Even if successful, the re-implemented software is again not released to the community, and the cycle repeats. No consideration is made of the huge benefits of model verification, re-use, extension, and maintainability, nor of the implications for the reproducibility of the published research. Progress in biomedical science is thus impeded, with knock-on effects into clinical translation and knowledge transfer into industry. There is therefore an urgent need for a radically different approach. The SABS:R^3 CDT will build on the existing SABS Programme to equip a new generation of biomedical research scientists with not only the knowledge and methods necessary to take a quantitative and interdisciplinary approach, but also with advanced software engineering skills. By embedding this strong focus on sustainable and open computational methods, together with responsible and reproducible approaches, into all aspects of the new programme, our computationally-literate scientists will be equipped to act as ambassadors to bring about a transformation of biomedical research.

Flexural transducer currently are only designed for operation in ambient atmospheric conditions, at frequencies of up to approximately 50 kHz, with a long wavelengths in fluids and therefore reduced measurement resolution in many cases. If we could find a way to increase the frequency range of operation of these devices, whilst at the same time creating new designs that could withstand high pressures and temperatures, a plethora of new applications will open up, in some cases enabling measurements to be made that could not otherwise be taken - that is what this project will do, establishing a world lead in this field of research of High Frequency Flexural Transducers. Techniques will be created that used the HiFFUTs for the non-destructive testing of low acoustic impedance materials such as aerospace composites, flow measurements and metrology in hostile environments. Flexural ultrasonic transducers (sometimes referred to as uni-morphs) operate through the action of the bending / flexing of a piezoelectric material that is attached to a passive material. This is exactly how an ultrasonic car parking sensor operates, and these devices operating at twice the maximum audible frequency of humans, of around 40kHz, have had a tremendous impact, particularly on the automotive sector. The key to the success of flexural transducers used in parking sensors lies in the fact that they are extremely sensitive and efficient, whilst at the same time they are relatively simple to construct and are extremely robust. Imagine the typical environment that these sensors have to survive in; high vibration, large fluctuations in operating temperature, corrosive, dirty and wet conditions - whilst operating at a low power with a high sensitivity. So what makes these flexural transducers attractive to the automotive sector, where there is high pressure to keep sensor costs low at the same time as the sensors being very reliable? The two key factors are that (1) the piezoelectric element is bonded to the inside of a metal cap and the rear of the cap is hermetically sealed, and (2) the flexing of the metal cap and thin piezoelectric element, either from piezoelectric excitation or the arrival of a pressure wave requires relatively little energy. There is currently a surprising lack of any published, rigorous scientific study on these types of small flexural transducers, even at low frequencies and nothing appears to have been attempted using these types of transducers in liquids or for non-destructive evaluation. The vibration characteristics of a HiFFUT are dependent on the combined response and interaction of all the sensor's components with the medium it operates within or upon. Usually the mechanical response of these transducers is dominated by the vibration behaviour of the passive flexing membrane of the transducer housing to which the piezoelectric is attached, rather than the thickness or diameter of the piezoelectric element bonded to the housing. There are related examples of MEMs based transducers that operate by a flexural membrane at higher frequencies such as Capacitive Micro-machined Ultrasonic Transducers and Piezoelectric Micro-machined Ultrasonic Transducers and whilst these are clearly elegant devices, there are clearly a number of significant advantages to the use of HiFFUTs in many industrial applications. The most useful modes of operation are probably the axisymmetric modes, which will generate axisymmetric wave fields and work will mainly focus on these, but there may be instances where an anisotropic wave field provides an advantage. Flexural transducers or HiFFUTs can also be driven at a number of axisymmetric harmonic modes or frequencies - using one transducer to cover a wide bandwidth, with each mode having a different directivity pattern will dramatically increase the depth and breadth of information that can be obtained. These transducers are going to find applications in a wide range of industrial application

Optical imaging is perhaps the single most important sensor modality in use today. Its use is widespread in consumer, medical, commercial and defence technologies. The most striking development of the last 20 years has been the emergence of digital imaging using complementary metal oxide semiconductor (CMOS) technology. Because CMOS is scalable, camera technology has benefited from Moore's law reduction in transistor size so that it is now possible to buy cameras with more than 10 MegaPixels for £50. The same benefits are beginning to emerge in other imaging markets - most notably in infrared imaging where 64x64 pixel thermal cameras can be bought for under £1000. Far infrared (FIR), or terahertz, imaging is now emerging as a vital modality with application to biomedical and security imaging, but early imaging arrays are still only few pixel research ideas and prototypes that we are currently investigating. There has been no attempt to integrate the three different wavelength sensors coaxially on to the same chip. Sensor fusion is already widespread whereby image data from traditional visible and mid infrared (MIR) sensors is overlaid to provide a more revealing and data rich visualisation. Image fusion permits discrepancies to be identified and comparative processing to be performed. Our aim is to create a "superspectral" imaging chip. By superspectral we mean detection in widely different bands, as opposed to the discrimination of many wavelengths inside a band - e.g. red, green and blue in the visible band. We will use "More than Moore" microelectronic technology as a platform. By doing so, we will leverage widely available low-cost CMOS to build new and economically significant technologies that can be developed and exploited in the UK. There are considerable challenges to be overcome to make such technology possible. We will hybridise two semiconductor systems to integrate efficient photodiode sensors for visible and MIR detection. We will integrate bolometric sensing for FIR imaging. We will use design and packaging technologies for thermal isolation and to optimise the performance of each sensor type. We will use hybridised metamaterial and surface plasmon resonance technologies to optimise wavelength discrimination allowing vertical stacking of physically large (i.e. FIR) sensors with visible and MIR sensors. We ultimate want to demonstrate the world's first ever super-spectral camera.

By 2025 targeted biological medicines, personalised and stratified, will transform the precision of healthcare prescription, improve patient care and quality of life. Novel manufacturing solutions have to be created if this is to happen. This is the unique challenge we shall tackle. The current "one-size-fits-all" approach to drug development is being challenged by the growing ability to target therapies to only those patients most likely to respond well (stratified medicines), and to even create therapies for each individual (personalised medicines). Over the last ten years our understanding of the nature of disease has been transformed by revolutionary advances in genetics and molecular biology. Increasingly, treatment with drugs that are targeted to specific biomarkers, will be given only to patient populations identified as having those biomarkers, using companion diagnostic or genetic screening tests; thus enabling stratified medicine. For some indications, engineered cell and gene therapies are offering the promise of truly personalised medicine, where the therapy itself is derived at least partly from the individual patient. In the future the need will be to supply many more drug products, each targeted to relatively small patient populations. Presently there is a lack of existing technology and infrastructure to do this, and current methods will be unsustainable. These and other emerging advanced therapies will have a critical role in a new era of precision targeted-medicines. All will have to be made economically for healthcare systems under extreme financial pressure. The implications for health and UK society well-being are profound There are already a small number of targeted therapies on the market including Herceptin for breast cancer patients with the HER2 receptor and engineered T-cell therapies for acute lymphoblastic leukaemia. A much greater number of targeted therapies will be developed in the next decade, with some addressing diseases for which there is not currently a cure. To cope, the industry will need to create smarter systems for production and supply to increasingly fragmented markets, and to learn from other sectors. Concepts will need to address specific challenges presented by complex products, of processes and facilities capable of manufacture at smaller scales, and supply chains with the agility to cope with fluctuating demands and high levels of uncertainty. Innovative bioprocessing modes, not currently feasible for large-scale manufacturing, could potentially replace traditional manufacturing routes for stratified medicines, while simultaneously reducing process development time. Pressure to reduce development costs and time, to improve manufacturing efficiency, and to control the costs of supply, will be significant and will likely become the differentiating factor for commercialisation. We will create the technologies, skill-sets and trained personnel needed to enable UK manufacturers to deliver the promise of advanced medical precision and patient screening. The Future Targeted Healthcare Manufacturing Hub and its research and translational spokes will network with industrial users to create and apply the necessary novel methods of process development and manufacture. Hub tools will transform supply chain economics for targeted healthcare, and novel manufacturing, formulation and control technologies for stratified and personalised medicines. The Hub will herald a shift in manufacturing practice, provide the engineering infrastructure needed for sustainable healthcare. The UK economy and Society Wellbeing will gain from enhanced international competitiveness.