Healthcare relies on medical devices, yet often these have significant risk of infection and failure. The medical device market is estimated to be just under US$500 billion, while US$25 billion is spent annually on treatment of chronic wounds. As our populations becomes older, our healthcare systems are also becoming stressed by multi-antibiotic resistance and viral outbreaks. For example, 50% of initial COVID-19 fatalities were due to secondary bacterial infections [Zhou et al. The Lancet, 2020]. Medical device failure rates of up to 20% burden our health service disproportionately through device centred infection, immune rejection, or both. The biomaterials that devices and external wound care products are made from significantly influence immune and healing responses and affect the outcome of infection. In the EPSRC Programme Grant "Next Generation Biomaterials Discovery", physical surface patterns (topographies) combined with novel polymers were found which both reduce bacterial biofilm formation and increase the immune acceptance of materials in vitro and in vivo in preclinical infection models. This provides a new paradigm for biomaterials used as implants and wound care products, where novel polymers can be topographically patterned to improved healing and acceptance using bio-instruction. To exploit these findings requires targeting to specific medical device environments and elucidation of the mechanism of action for translation by industry. This project will utilise 3D printing to manufacture ChemoTopoChips containing over a thousand polymer chemistry-topography combinations that allow the possible design space to be efficiently explored and mapped using semi-automated in-vitro measurements of host immune cell and infecting pathogen interactions individually and in co-culture. These ChemoTopoChips will allow a very high content of molecular information to be extracted from biomolecules secreted into the culture media (the secretome), those adsorbed to the surface (the biointerface) and their impact on both host cells and bacteria. The same fabrication approaches will be used to make devices for preclinical testing; in vivo information will be maximised using minimally invasive monitoring of infection and healing over time and detailed analysis of explants. These information streams will be merged using artificial intelligence (specifically machine learning) to build effective models of performance and provide mechanistic insight, allowing design of materials ready for translation as medical devices outside this project. After consultation with a wide range of clinicians we have chosen to target the following two devices: -Wound care products for chronic/non-healing wounds: dressings to reduce infection, induce immune-homeostasis and promote healing in chronic wounds that result in 7000 diabetes related amputations in the UK per year and cost the NHS £1bn a year to manage. -Implants requiring tissue integration but prone to fibrosis/adhesion and biofilm-associated infection: surgical meshes used for repair of hernias or pelvic organ prolapse commonly afflicting women after childbirth. The NHS undertakes 100k such operation each year with infection rates of up to 10%, plus foreign body response complications. The team assembled to exploit this opportunity has unique experience in the areas of biomaterials, artificial intelligence, additive manufacturing and in vitro and in vivo measurements of immune and bacterial responses to biomaterials. Facilities including the recently opened £100m Nottingham Biodiscovery Institute, the recently funded EPSRC £1m suite of high resolution/high throughput 3D printers and the unique £2.5m 3DOrbiSIMS Cat2 cryo-facility. These investments in Nottingham make this the only location in the world that is capable of undertaking this project. An Advisory Board of clinicians, industrial partners and leading academics will meet annually to provide input to the project.

The UK Foundation Industries (Glass, Metals, Cement, Ceramics, Bulk Chemicals and Paper), are worth £52B to the UK economy, produce 28 million tonnes of materials per year and account for 10% of the UK total CO2 emissions. These industries face major challenges in meeting the UK Government's legal commitment for 2050 to reduce net greenhouse gas emissions by 100% relative to 1990, as they are characterised by highly intensive use of both resources and energy. While all sectors are implementing steps to increase recycling and reuse of materials, they are at varying stages of creating road maps to zero carbon. These roadmaps depend on the switching of the national grid to low carbon energy supply based on green electricity and sustainable sources of hydrogen and biofuels along with carbon capture and storage solutions. Achievement of net zero carbon will also require innovations in product and process design and the adoption of circular economy and industrial symbiosis approaches via new business models, enabled as necessary by changes in national and global policies. Additionally, the Governments £4.7B National Productivity Investment Fund recognises the need for raising UK productivity across all industrial sectors to match best international standards. High levels of productivity coupled with low carbon strategies will contribute to creating a transformation of the foundation industry landscape, encouraging strategic retention of the industries in the UK, resilience against global supply chain shocks such as Covid-19 and providing quality jobs and a clean environment. The strategic importance of these industries to UK productivity and environmental targets has been acknowledged by the provision of £66M from the Industrial Strategy Challenge Fund to support a Transforming Foundation Industries cluster. Recognising that the individual sectors will face many common problems and opportunities, the TFI cluster will serve to encourage and facilitate a cross sectoral approach to the major challenges faced. As part of this funding an Academic Network Plus will be formed, to ensure the establishment of a vibrant community of academics and industry that can organise and collaborate to build disciplinary and interdisciplinary solutions to the major challenges. The Network Plus will serve as a basis to ensure that the ongoing £66M TFI programme is rolled out, underpinned by a portfolio of the best available UK interdisciplinary science, and informed by cross sectoral industry participation. Our network, initially drawn from eight UK universities, and over 30 industrial organisations will support the UK foundation industries by engaging with academia, industry, policy makers and non-governmental organisations to identify and address challenges and opportunities to co-develop and adopt transformative technologies, business models and working practices. Our expertise covers all six foundation industries, with relevant knowledge of materials, engineering, bulk chemicals, manufacturing, physical sciences, informatics, economics, circular economy and the arts & humanities. Through our programme of mini-projects, workshops, knowledge transfer, outreach and dissemination, the Network will test concepts and guide the development of innovative outcomes to help transform UK foundation industries. The Network will be inclusive across disciplines, embracing best practice in Knowledge Exchange from the Arts and Humanities, and inclusive of the whole UK academic and industrial communities, enabling access for all to the activity programme and project fund opportunities.

We will install a 300kV aberration corrected STEM that utilises artificial intelligence (AI) to simultaneously improve the temporal resolution and precision/sensitivity of images while minimizing the deleterious effect of electron beam damage. Uniquely, this microscope goes beyond post-acquisition uses of AI, and integrates transformational advances in data analytics directly into its operating procedures - experiments will be designed by and for AI, rather than by and for a human operator's limited visual acuity and response time. This distributed algorithm approach to experimental design, is accomplished through a compressed sensing (CS) framework that allows measurements to be obtained under extremely low dose and/or dose rate conditions with vastly accelerated frame rates. Optimizing dose / speed / resolution permits diffusion to be imaged on the atomic scale, creating wide-ranging new opportunities to characterise metastable and kinetically controlled materials and processes at the forefront of innovations in energy storage and conversion, and the wide range of novel engineering/medical functionalities created by nanostructures, composites and hybrid materials. The microscope incorporates in-situ gas / liquid / heating / cryo and straining / indentation stages to study the dynamics of synthesis, function, degradation / corrosion and regeneration / recycling on their fundamental length and time scales. It will be housed in the Albert Crewe Centre (ACC), which is a University of Liverpool (UoL) shared research facility (SRF) specialising in new experimental strategies for high-resolution/operando electron microscopy in support of a wide range of academic/industrial user projects. UoL supports all operational costs for the SRFs (service contracts, staff, consumables, etc), meaning that access to the microscope will always be "free at the point of use" for all academic users. This open accessibility is managed through a user-friendly online proposal submission and independent peer review mechanism linked to an adaptable training/booking system, which allows the ACC to provide extensive research opportunities and training activities for all users. In particular, for early career scientists, we commit experimental resources supporting UoL's commitment to the Prosper project for flexible career development and the Research Inclusivity in a Sustainable Environment (RISE) initiative that is creating a research culture maximising inclusivity and diversity synergistically with encouraging creativity and innovation. This new microscope aligns to several priority areas of research into materials, energy and personalised medicine at the UoL, priority research areas of EPSRC and national facilities in electron microscopy, imaging and materials science, and UKRI plans for infrastructure growth (https://www.ukri.org/research/infrastructure/). In addition to supporting extensive research programs at UoL linked to investments in the Materials Innovation factory (MIF), the Stephenson Institute for Renewable Energy (SIRE) and the new Digital Innovation Facility (DIF), this unique and complimentary microscope will be affiliated to and leverage from partnership with the national microscopy facilities at Harwell (ePSIC) and Daresbury (UKSuperSTEM) and the Henry Royce Institute, as well as form extensive research links to the Rosalind Franklin Institute and the Faraday Institution. We have established (and will expand through outreach activities) an extensive network of partners/collaborators from the N8 university group, Johnson Matthey and NSG, the Universities of Swansea, Birmingham, Warwick, Oxford, Cambridge, Loughborough, Edinburgh and Glasgow and Northwest UK area SME's as well as from universities in the USA, Ireland, Germany, Japan, France, Italy, Denmark, India, Singapore, China, South Africa and Spain who will create a dynamic, innovative and collaborative community driving the long-term research impact of this facility.

The UK engineering coatings industry is worth over £11bn and affects products worth £140bn. The vision of this project is to create internationally unique multi-purpose PVD/PECVD coatings system which will enable innovation in advanced science of future hybrid coatings. This new facility would be built on the existing Leeds coating platform capability and would create system with no similar functionality available internationally. Using existing Leeds coating platform we can already deposit carbides, nitrides and diamond-like carbide (DLC) coatings, and we are exploiting this mainly for tribological applications with automotive, energy and lubricant companies. With this investment, we will be able to additionally process novel nanocomposite coatings, next generation of DLC coatings (with incorporated nanoparticles), advanced optical coatings and sensor coatings, carry out functionalisation of powders, barrier layers, coatings on polymers and coatings on complex shapes. This proposal aligns with a major new initiative at the University of Leeds to create an integrated gateway to Physical Sciences and Engineering by investing in the collaborative Bragg Centre that will house new state-of-the-art research facilities for the integrated development, characterisation and exploitation of novel advanced functional materials. This proposal also coincides with Leeds University investment in the Nexus Centre - a hub for the local innovation community as well as national and international organisations looking to innovate and engage in world-leading research. The upgraded coating platform would play a strategic role in the UK Surface Engineering landscape and complement existing national facilities. It would form a part of the new Sir Henry Royce Institute for Advanced Materials, of which Leeds is a partner. The configuration of the new instrument is designed to be versatile and serve a wide range of internal and external users with widely different classes of advanced materials. A number of specific activities have been planned to ensure that potential beneficiaries have the opportunity to engage with new coating facility. The economic competitiveness of the UK's manufacturing industry will benefit from new, commercially exploitable IP in novel cutting-edge Surface Engineering technology. Members of an academic community and industry will be able to benefit directly from the proposed research and generated new knowledge. They will gain new skills and know-how related to the latest advancements of PVD technologies. Improved adoption of Surface Engineering will result in wider UK PLC economic and societal impacts associated with development of functional surfaces for automotive, aerospace, biomedical, healthcare, defence, agriculture, oil & gas and packaging industries.

Most advanced materials are actually composite systems where each part is specifically tailored to provide a particular functionality often via doping. In electronic devices this may be p- or n-type behaviour (the preference to conduct positive of negative charges), in optical devices the ability to emit light at a given wavelength (such as in the infrared for optical fibre communications), or in magnetic materials the ability to store information based on the direction of a magnetic field for example. To enable the realisation of new devices it is essential to increase the density of functionality within a given device volume. Simple miniaturisation (i.e. to fit more devices of the same type but of smaller size) is limited in scope as the nanoscale regime is reached, not only by the well-known emergence of quantum effects, but by the simple capability to control the materials engineering on this scale. Self-assembly methods for example enable the creation of 0D (so called 'quantum dots' or 'artificial atoms'), 1D (wire-like) and 2D (sheet-like) materials with unique properties, but the subsequent control and modification of these is non-trivial and has yet to be demonstrated in many cases. This research aims to establish a Platform for Nanoscale Advanced Materials Engineering (P-NAME) facility that incorporates a new tool which will provide the capability required to deliver a fundamental change in our ability to design and engineer materials. The principle of the technique that we will adapt, is that which revolutionised the micro-electronics industry in the 20th century (ion-doping) but applied on the nanoscale for the first time. Furthermore, the P-NAME tool will be compatible with a scalable technology platform and therefore compatible with its use in high-tech device manufacture. Without this capability the production of increasingly complex materials offering enhance functionality at lower-power consumption will be difficult to achieve. The P-NAME facility will be established within a new UK National Laboratory for Advanced Materials (the Henry Royce Institute) at the University of Manchester. Access to the tool will be made available to UK academics and industry undertaking research into advanced functional materials and devices development.