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.

Fluid dynamics underpins large areas of engineering, environmental and scientific research, and is becoming increasingly important in medical science. At Leeds, we possess research expertise across each of these domains and we have an established record of working across disciplinary boundaries. This proposal builds upon this record through the establishment of a multidisciplinary CDT in Fluid Dynamics. Research techniques that will be applied, and developed, will encompass: mathematical modelling & theory; numerical methods, CFD & high performance computing (HPC); and measurement & experimentation. Engineering application areas to be addressed include: reacting flows; carbon capture, transport & storage; flow of polymer melts; mixing problems; particulate flows; coating & deposition; lubrication; medical devices; pathogen control; heat transport; wind turbines; fluid-structure interaction; and nuclear safety. Environmental application areas will consist of: groundwater flow; river/estuary flows; tidal flows; oceanography; atmospheric pollution; weather forecasting; climate modelling; dynamics of the Earth's interior; and solar & planetary flow problems. Facilities available to undertake this research include: the University's HPC system which, combined with the N8 regional facility that is hosted at Leeds, provides ~10000 computational cores, an extensive suite of licensed software and dedicated support staff; flow measurement techniques (including Particle Imaging Velocimetry (PIV), 2-component Laser Doppler Anemometry (LDA), Phase Doppler Anemometry (PDA) and Ultrasonic Doppler Velocity Profiling (UDVP)); techniques for measuring fluid concentration (Ultrasonic High Concentration Meter (UHCM) and Optical Backscatter Probes (OBS)) and a range of optical metrology systems (e.g. pulsed and continuous wave lasers). The UK has a substantial requirement for doctoral scientists and engineers who have a deep understanding of all aspects of fluid dynamics from theory through to experimental methods and numerical simulation. In manufacturing and process engineering, for example, many processes depend critically on fluid flows (e.g. extrusion of polymer melts, deposition of coatings, spray drying, etc.) and it is essential to understand and control these processes in order to optimize production efficiency and reliability (see letter of support from P&G for example). In large-scale mechanical engineering there is a demand for expertise in reacting turbulent flows in order to optimize fuel efficiency and engine performance, and in wetting and surface flows for the design and manufacture of pumps and filters. There is also a need for a wide variety of skilled experts in environmental fluid flows to support the growing need to understand and predict local pollution and threats to safety (atmospheric, surface water, ocean and sub-surface flows), and to predict weather, climate and space weather for satellite technology. We will train a new generation of researchers who will have a broad range of skills to transfer into industry and environmental agencies, hence our approach will be multi-disciplinary throughout. All students will undertake both modelling and experimental training before embarking on their PhD project - which will be co-supervised by academics from different Schools. The MSc component of the programmee will be specifically tailored to develop expertise in the mathematical background of fluid dynamics, in CFD/HPC, and in experimental techniques. Team-based projects will be used to develop the teamwork and communication skills we believe are essential. Finally, engagement with industry will be a key feature of this CDT: all students will undertake an industrial placement, a large number of projects will be industrially sponsored, and our non-academic partners will contribute actively to our management, implementation and strategic development.

The proposal seeks funds to renew and refresh the Centre for Doctoral Training in Formulation Engineering based in Chemical Engineering at Birmingham. The Centre was first funded by EPSRC in 2001, and was renewed in 2008. In 2011, on its 10th anniversary, the Centre received one of the Diamond Jubilee Queen's Anniversary Prizes, for 'new technologies and leadership in formulation engineering in support of UK manufacturing'. The scheme is an Engineeering Doctoral Centre; students are embedded in their sponsoring company and carry out industry-focused research. Formulation Engineering is the study of the manufacture of products that are structured at the micro-scale, and whose properties depend on this structure. In this it differs from conventional chemical engineering. Examples include foods, home and personal care products, catalysts, ceramics and agrichemicals. In all of these material formulation and microstructure control the physical and chemical properties that are essential to its function. The structure determines how molecules are delivered or perceived - for example, in foods delivery is of flavour molecules to the mouth and nose, and of nutritional benefit to the GI tract, whilst in home and personal care delivery is to skin or to clothes to be cleaned, and in catalysis it is delivery of molecules to and from the active site. Different industry sectors are thus underpinned by the same engineering science. We have built partnerships with a series of companies each of whom is world-class in its own field, such as P&G, Kraft/Mondelez, Unilever, Johnson Matthey, Imerys, Pepsico and Rolls Royce, each of which has written letters of support that confirm the value of the programme and that they will continue to support the EngD. Research Engineers work within their sponsoring companies and return to the University for training courses that develop the concepts of formulation engineering as well as teaching personal and management skills; a three day conference is held every year at which staff from the different companies interact and hear presentations on all of the projects. Outputs from the Centre have been published in high-impact journals and conferences, IP agreements are in place with each sponsoring company to ensure both commercial confidentiality and that key aspects of the work are published. Currently there are 50 ongoing projects, and of the Centre's graduates, all are employed and more than 85% have found employment in formulation companies. EPSRC funds are requested to support 8 projects/year for 5 years, together with the salary of the Deputy Director who works to link the University, the sponsors and the researchers and is critical to ensure that the projects run efficiently and the cohorts interact well. Two projects/year will be funded by the University (which will also support a lecturer, total >£1 million over the life of the programme) and through other sources such as the 1851 Exhibition fund, which is currently funding 3 projects. EPSRC funding will leverage at least £3 million of direct industry contributions and £8 million of in-kind support, as noted in the supporting letters. EPSRC funding of £4,155,480 will enable a programme with total costs of more than £17 million to operate, an EPSRC contribution of 24% to the whole programme.

Chemical Biology is a strategically important area of research for the UK that looks at the development and application of novel tools and techniques for the study of molecular interactions in biological systems. Graduate training in Chemical Biology will play a crucial role in driving innovation and transforming the design process in the biotech and medical technology, agri-science and personal care sectors, as well as stimulating the creation of new start-up enterprises in the UK. In order to meet these skills a new generation of PhD graduates in Chemical Biology must be trained who are able to connect the scientific and commercial/industrial sectors whilst still being supremely well equipped to work across the Physical and Life Sciences interface, allowing for multiple forms of translational activity. This crucial skills gap will be addressed by the new CDT in "Physical Sciences Innovation in Chemical Biology for Bioindustry and Healthcare" which will train > 90 PhD students over the next 5 years, supported by the multi-disciplinary environment of the world leading Institute of Chemical Biology (ICB) at Imperial College. The multidisciplinary nature of Chemical Biology and the translational challenges that it poses to students working at the interface between the physical and life sciences and between the academic and commercial worlds makes a CDT structure highly appropriate for supporting student development. Such multi-disciplinary training at this interface is vital to enabling the UK to adapt to the pace of technological change in the life, personal care and agri-sciences sectors. Furthermore, the particular societal, ethical, industrial and entrepreneurial aspects associated with research that will underpin these new technologies requires a bespoke approach that is most effectively delivered in a CDT context. The ICB and its strategic partners have together crafted a 4-year training and research programme (MRes + 3 Year PhD), which will provide first-hand experience of multi-disciplinary translational research, research leadership, science communication, entrepreneurialism and business skills. This includes technology development in Fab lab type environments, science communication training in collaboration with the BBC, industry led innovation workshops, entrepreneurship training and a "Dragons Den"-type competitions for student-led IP. In addition, we will implement the EVOLVE programme, a journey tailored to the individual designed to give experience of entrepreneurial activities, policy making, media/outreach, industrial research, or research within international academic institutions in the context of achieving a particular goal selected by the CDT student. This closely knit cohort of students will be supported by an integrated community of over 120 research groups from all three faculties across Imperial College. These activities will be further enhanced by the new dedicated Laboratory for Translational Molecular Research (LTMR). The tools and technologies that will emerge from the research programme of the CDT will support drug, agrichemical and personal care product discovery through the development of new functional screens, target validation assays, predictive artificial biomimetic models and by providing insights into potential novel targets. They will also assist and advance basic biology, diagnostic technologies, optical finger printing technologies for label free tracking of biomolecules, smart biodelivery systems with tailored release kinetics, small molecule-membrane protein screening assays, in-vitro screens for the non-specific binding of drug molecules, the discovery of biomarkers and offer access to a new suite of quantitative dynamic molecular information.

Soft matter and functional interfaces are ubiquitous! Be it manufactured plastic products (polymers), food (colloids), paint and other decorative coatings (thin films and coatings), contact lenses (hydrogels), shampoo and washing powder (complex mixtures of the above) or biomaterials such as proteins and membranes, soft matter and soft matter surfaces and interfaces touch almost every aspect of human activity and underpin processes and products across all industrial sectors - sectors which account for 17.2% of UK GDP and over 1.1M UK employees (BIS R&D scoreboard 2010 providing statistics for the top 1000 UK R&D spending companies). The importance of the underlying science to UK plc prompted discussions in 2010 with key manufacturing industries in personal care, plastics manufacturing, food manufacturing, functional and performance polymers, coatings and additives sectors which revealed common concerns for the provision of soft matter focussed doctoral training in the UK and drove this community to carry out a detailed "gap analysis" of training provision. The results evidenced a national need for researchers trained with a broad, multidisciplinary experience across all areas of soft matter and functional interfaces (SOFI) science, industry-focussed transferable skills and business awareness alongside a challenging PhD research project. Our 18 industrial partners, who have a combined global work force of 920,000, annual revenues of nearly £200 billion, and span the full SOFI sector, emphasized the importance of a workforce trained to think across the whole range of SOFI science, and not narrowly in, for example, just polymers or colloids. A multidisciplinary knowledge base is vital to address industrial SOFI R&D challenges which invariably address complex, multicomponent formulations. We therefore propose the establishment of a CDT in Soft Matter and Functional Interfaces to fill this gap. The CDT will deliver multidisciplinary core science and enterprise-facing training alongside PhD projects from fundamental blue-skies science to industrially-embedded applied research across the full spectrum of SOFI science. Further evidence of national need comes from a survey of our industrial partners which indicates that these companies have collectively recruited >100 PhD qualified staff over the last 3 years (in a recession) in SOFI-related expertise, and plan to recruit (in the UK) approximately 150 PhD qualified staff members over the next three years. These recruits will enter research, innovation and commercial roles. The annual SOFI CDT cohort of 16 postgraduates could be therefore be recruited 3 times over by our industrial partners alone and this demand is likely to be the tip of a national-need iceberg.