We will launch a new CDT, focused on composite materials and manufacturing, to deliver the next generation of composites research and technology leaders equipped with the skills to make an impact on society. In recent times, composites have been replacing traditional materials, e.g. metals, at an unprecedented rate. Global growth in their use is expected to be rapid (5-10% annually). This growth is being driven by the need to lightweight structures for which 'lighter is better', e.g. aircraft, automotive car bodywork and wind blades; and by the benefits that composites offer to functionalise both materials and structures. The drivers for lightweighting are mainly material cost, fuel efficiency, reducing emissions contributing to climate change, but also for more purely engineering reasons such as improved operational performance and functionality. For example, the UK composites sector has contributed significantly to the Airbus A400M and A350 airframes, which exhibit markedly better performance over their metallic counterparts. Similarly, in the wind energy field, typically, over 90% of a wind turbine blade comprises composites. However, given the trend towards larger rotors, weight and stiffness have become limiting factors, necessitating a greater use of carbon fibre. Advanced composites, and the possibility that they offer to add extra functionality such as shape adaptation, are enablers for lighter, smarter blades, and cheaper more abundant energy. In the automotive sector, given the push for greener cars, the need for high speed, production line-scale, manufacturing approaches will necessitate more understanding of how different materials perform. Given these developments, the UK has invested heavily in supporting the science and technology of composite materials, for instance, through the establishment of the National Composites Centre at the University of Bristol. Further investments are now required to support the skills element of the UK provision towards the composites industry and the challenges it presents. Currently, there is a recognised skills shortage in the UK's technical workforce for composites; the shortage being particularly acute for doctoral skills (30-150/year are needed). New developments within industry, such as robotic manufacture, additive manufacture, sustainability and recycling, and digital manufacturing require training that encompasses engineering as well as the physical sciences. Our CDT will supply a highly skilled workforce and technical leadership to support the industry; specifically, the leadership to bring forth new radical thinking and the innovative mind-set required to future-proof the UK's global competitiveness. The development of future composites, competing with the present resins, fibres and functional properties, as well as alternative materials, will require doctoral students to acquire underpinning knowledge of advanced materials science and engineering, and practical experience of the ensuing composites and structures. These highly skilled doctoral students will not only need to understand technical subjects but should also be able to place acquired knowledge within the context of the modern world. Our CDT will deliver this training, providing core engineering competencies, including the experimental and theoretical elements of composites engineering and science. Core engineering modules will seek to develop the students' understanding of the performance of composite materials, and how that performance might be improved. Alongside core materials, manufacturing and computational analysis training, the CDT will deliver a transferable skills training programme, e.g. communication, leadership, and translational research skills. Collaborating with industrial partners (e.g. Rolls Royce) and world-leading international expertise (e.g. University of Limerick), we will produce an exciting integrated programme enabling our students to become future leaders.

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.

Solid dose forms are the backbone of many manufacturing industries. In pharmaceutical therapeutics, tablets, capsules, dry powder inhalers and powders for re-suspension cover the vast majority of the £5.6Bn sales by this industry in the UK. Food (sales £67Bn) is the single largest industry of the UK manufacturing sector which totalled £365Bn sales in 2014 (Office of National Statistics). In all these manufacturing processes and in final use, the physical behaviour of the powder is at least as important as the chemistry. Stability, weight and content uniformity, manufacturing difficulties and variable performance are determined by decisions made during the formulation process Manufacturing problems are ubiquitous; the Rand report (by E.W. Merrow, 1981) examined powder processes and found on average 2 year over-runs to get to full productivity, and development costs 210% of estimates, due to incompatibility between powder behaviour and process design. In the intervening years, plant engineering techniques have developed, but the rationalisation of formulation decisions has never received more than cursory, empirical study. This project proposes to develop a Virtual Formulation Laboratory (VFL), a software tool for prediction and optimisation of manufacturability and stability of advanced solids-based formulations. The team has established expertise in powder flow, mixing and compaction which will be brought together for the first time to link formulation variables with manufacturability predictions. The OVERALL AIMS of the project are (a) to develop the science base for understanding of surfaces, particulate structures and bulk behaviour to address physical, chemical and mechanical stability during processing and storage and (b) to incorporate these into a software tool (VFL) which accounts for a wide range of material types, particle structures and blend systems to enable the formulator to test the effects of formulation changes in virtual space and check for potential problems covering the majority of manufacturing difficulties experienced in production plants. The VISION for VFL is to be employed widely in the development process of every new formulated powder product in food, pharmaceuticals and fine chemicals within five years of the completion of this project. VFL will consider four processes: powder flow, mixing, compaction and storage; and will predict four manufacturability problems: poor flow/flooding, segregation/heterogeneity, powder caking and strength/breakage of compacts These account for the majority of practical problems in the processing of solid particulate materials The OVERALL OBJECTIVES of the project are: (a) to fill the gaps in formulation science to link molecule to manufacturability, which will be achieved through experimental characterisation and numerical modelling, and (b) establish methodologies to deal with new materials, so that the virtual lab could make predictions for formulations with new materials without extensive experimental characterisation or numerical modelling. This will be achieved through developing functional relationships based on the scientific outcomes of the above investigations, while identifying the limits and uncertainties of these relationships.

The importance of indoor air quality monitoring to safeguard the health of children and vulnerable adults in the UK cannot be overstated. A primary source of indoor air pollution is everyday household products and materials. Many emit harmful non-methane volatile organic compounds (VOCs), such as formaldehyde, toluene and phthalates. Even in minute concentrations, these specific compounds can induce a variety of respiratory, neurological, endocrine disorders over prolonged low-level exposures. However, current environmental sensors, including those commercialised by major semiconductor integrated device manufacturers and by specialised gas sensor manufacturers (e.g . Bosch Sensortech, Sensirion, AMS, and others), cannot specifically detect these different toxic gases at an acceptable concentration level and are unable to provide any helpful preventive guidance. The challenges faced by current-generation low-cost VOC sensors arise from empirically optimised sensing films for common sensor architectures. This approach has strong drawbacks as it does not have an overarching design consideration for the optimum permeation of gases or analytes through the sensing material for a maximised response. Crucially, these sensors are non-specific and can only detect the total concentration of VOCs (TVOCs), i.e. the total concentration of a subset of airborne VOCs present in the air, as an overall measure of indoor air quality. However, different TVOC measurement methods depend on VOCs' mixture and can yield substantially different estimated TVOC concentrations. Notably, the toxicity thresholds of the individual VOCs differ by orders of magnitude; the total concentration, therefore, does not provide any useful measure of total toxicity. We will design material building blocks engineered to offer a maximum and selective response to target gas molecules to address this challenge. Then, in an ambitious step, through solution-phase additive manufacturing techniques, we will create large-scale self-assembly of these building blocks to obtain a nano- and micro-level structure mimicking the hierarchy of length scales found in xylems and leaf veins in plants. With multiple levels of interconnected channels, this universal structure has evolved over many million years to ensure mass transport (i.e. fluid permeation) with minimum energy expenditure through the preservation of volumetric flow rate. Our approach will therefore allow highly optimum through-flow of gases to the engineered building blocks, providing a fast, highly sensitive and selective response to these toxic gases. The highly repeatable nature of our additively manufactured sensing thin-film with self-assembled blocks will enable unprecedented device-to-device uniformity. We will exploit this to create a new generation of training algorithms to significantly reduce the traditional sensor training time and cost. We envisage that our materials design and manufacturing pathway based on natural laws will offer x10 to x100 times the state-of-the-art toxic VOC sensors' performance, making indoor air quality monitoring affordable and reliable.

KEYWORDS: chemistry, computer vision, image processing, manufacturing, productivity, process monitoring. Chemical and biochemical manufacturing are dominated by colour changes, both subtle and stark. Such phenomena are often reported by-eye but not routinely quantified, especially over time. This renewal of a research and leadership programme aims to empower any chemist with any camera to capture any visible trend from any high-value chemical process, all without having to disturb the process under study. Most industrial chemists are accustomed to extracting chemical monitoring information using invasive, probe-based technologies. These technologies are robust and trusted. However, no current technologies are seamlessly applicable to monitoring chemical processes in real-time on BOTH the high throughput lab scale (the 'teacup') AND process/plant scales (the 'swimming pool'). Instead, current process analytical technologies are oftentimes tied to one specific hardware platform, and each example of such probe-based hardware can only monitor one process at a time. Ultimately, this can produce bottlenecks in analysis, slowing chemical product development and deployment. To address this productivity and chemical data throughput challenge, there is a real drive from R&D budget holders to invest in digital-ready analytical technologies. Computer Vision is the science of digitally quantifying real-world colours and objects using cameras. With cameras and computer vision, and further development through this fellowship renewal, the hardware and software needed for more time-, cost-, and safety-effective monitoring of high-value chemical processes can be realised in an accessible and globally adoptable manner. The global investment for digitalisation of process analytical technology (PAT) in the chemical industry is expected to reach $31 billion by 2028, representing an annual growth rate of approximately 6% from the present $23.5 billion market (sources: Made Smarter Review, 2017. Frost & Sullivan, 2017, and 2022). Underpinning this trend, R&D managers across chemical manufacturing are driving the streamlined adoption of new digital-ready chemical technology, to improve productivity, process safety, and ability to exploit the adjacent evolution of artificial intelligence.