Antimicrobials, commonly known as antibiotics, are becoming less effective because of resistance. Antibiotic resistance is when bacteria or other microbes change so that antibiotics no longer work to treat infections. Antibiotic resistance is a global problem that is being made worse by antibiotic overuse. We can combat antibiotic resistance by developing better antibiotics as well as improving the way we use existing ones. Patients will continue to need antibiotics, particularly to treat serious infections, like sepsis, so we need to improve how they are used. Right now, 'broad-spectrum' antibiotics, that kill a wide range of bacteria, are often given in high doses to ensure that enough antibiotic reaches the microbes at the site of infection. Much higher doses than would be needed if we could deliver antibiotics just at the site of infection are used. These antibiotics kill many of the beneficial 'resident' bacteria living in our bodies, which drives resistance. It would be much better if we could use a 'personalised medicine' approach where antibiotics are delivered locally, at the site of infection, at doses necessary to treat the problem. By giving lower doses of targeted treatment and avoiding exposure of the normal colonising bacteria to antibiotics, our vision is to improve health outcomes and reduce the selection of resistant microbes. Our project involves using tiny bubbles similar to those already used with ultrasound scanning to study the flow of blood through the heart and are currently being tested to treat cancers. These bubbles are given by injection into a vein. We propose to develop bubbles so that they can deliver antibiotics directly to a site of infection. The bubbles can also be burst using higher powered ultrasound, which is another possible way to kill bacteria. The bubbles are tiny, not much bigger than the bacteria, and will be coated with molecules that will allow the bubbles to stick to the surface of specific bacteria. This is known as 'molecular targeting'. By combining bubbles with ultrasound to trigger the release of antibiotics just at the site of infection, we aim to reduce the amount of antibiotics required to kill bacteria, without killing the helpful bacteria that live elsewhere in the body. Antibiotics often fail because the bacteria create their own local environment, the "biofilm", full of sticky chemicals, which also reduces the killing effects of antibiotics. Our approach will harness the energy released when an ultrasound pulse bursts bubbles to help drive drugs deep into this "biofilm" and hence help kill bacteria more effectively. In addition to getting more antibiotic into a biofilm, these drug-loaded bubbles will allow us to deliver new types of drugs, e.g. antimicrobial peptides (AMPs). AMPs are very effective at killing bacteria, but many cannot be given in the usual way, via a drip, into a vein to treat infections because they tend to be broken down in the blood before getting to the infection site. We can overcome this problem by loading the AMPs into tiny protective capsules attached to the bubbles and release them where/when they are required. Finally, we plan to investigate if bacteria can be released from their local biofilm environment using bubbles plus ultrasound. Here we will harness the mechanical energy released by bursting bubbles to break up the biofilm. The bacteria released from the biofilm are known as 'planktonic' and are more susceptible to conventional antibiotic treatments. In summary, we propose to: 1. Develop new targeting agents to bind bubbles to bacteria and new drug-loaded cargoes to kill bacteria/ destroy biofilms. 2. See if bubbles and ultrasound can be used together to deliver drugs into bacterial biofilms and kill bacteria more effectively. 3. Use our approaches to deliver drugs that cannot currently be used to treat patients because they are broken down in the blood.

Ammonia, a highly hydrogenated molecule, has been identified as an important means to support a transition to hydrogen economy, as it can be used to store and distribute hydrogen easily because of the already existing infrastructure for transport and storage of ammonia. If hydrogen is to be extracted from ammonia at the point of use, the thermo-catalysis of ammonia back to hydrogen requires a high amount of energy. Preferably ammonia is used directly as a carbon-free liquid fuel for combustion engines in power generation, marine vessels and long-haul vehicles where batteries cannot be used due to their low energy density (hence large volume and weight), high cost and long charging times. However, the significantly lower energy density (as measured by calorific value) of ammonia requires much larger fuel storage space and weight to be used. More importantly, the direct application of ammonia in combustion engines suffers from incomplete combustion and poor engine performance due to ammonia's higher ignition energy, higher auto-ignition temperature as well as significantly lower flame speed. In order to address the aforementioned challenges of ammonia and hydrogen for their applications in transport, a new type of liquid ammonia blended with hydrogen will be researched and demonstrated in this project with advanced modelling and experimental techniques. The proposed novel fuel has both ammonia and hydrogen molecules, and will enable (1) immediate and wider use of carbon free ammonia and hydrogen in existing engines, particularly for long haul vehicles, marine vessels and power generators, (2) significantly improved engine performance and lower emissions through increased energy density, faster and complete combustion. Therefore, the developed liquid ammonia blended with hydrogen would enable an immediate, cost-effective and 100% reduction in CO2 emissions to achieve net zero target in long haul transport, shipping, and power generation sectors by and beyond 2050 that will be difficult to achieve with existing technologies in use or in development.

Increasing emission levels of air pollution and greenhouse gases (GHGs) in large urban areas have become a great global concern due to their detrimental impact on human health, climate and the entire ecosystem. In order to cut emission levels, mitigation strategies are in place, however, to evaluate the effectiveness of these mitigation measures, the first step will be to improve the air quality (AQ) monitoring networks by deploying high density and high precision sensor networks to accurately capture spatial variability and emission hotspots in real-time. The traditional and more accurate air quality monitoring instrumentation are large, complex and costly, and hence are only sparsely deployed which provide accurate data but only in few locations, not providing enough information to protect the health of the population or to accurately evaluate the mitigation strategies. The emergence of low-cost sensors (LCS) within the last decade enabled observations at high spatial resolution in real-time, however, due to their poor selectivity, their measurement data is highly dependent on atmospheric composition, and also on meteorological conditions that the data generated by these platforms are of poor quality. In this fellowship, I will develop the first low-cost and high precision air pollution monitor based on photonic integrated circuits (PICs) for the next generation air quality monitoring networks. Photonic integration allows hundreds of photonic components to be fabricated on a single chip, and this step-change in technology will deliver a low-cost, on-chip, versatile instrumentation, stabilised to metrological precision that can be deployed in high density networks to accurately monitor a wide range of pollutants within industrial cities with high spatial and temporal resolution. The captured data can be transferred to the cloud servers over the existing mobile networks from which the users can easily monitor air quality with high accuracy at any time and from anywhere. The proposed instrumentation can also be deployed in balloon and satellite missions for in-situ probing of the constituents of the upper atmosphere, aiding the study of complex atmospheric processes to understand its influence on climate change. EPSRC Open Fellowship will enable me to consolidate my expertise gained over the years in industry and academia and gain my research independence. During these five years, I will have established myself to lead a team of 3 -5 researchers and will have enhanced my research output in novel photonic integrated solutions to combat the challenges faced today. This will aid me to be more competitive in applying for traditional Grants to extend my research portfolio and my research team, and become a leader in this field of research. In 10 years, my vision will be to exploit photonic integration technology for wider applications, including medical imaging, material science and non-destructive testing, and provide outstanding training opportunities to research students and early career researchers who will grow to be future academic and industrial leaders in science and engineering in the UK.

Powered by data, Industrial Digital Technologies (IDTs) such as artificial intelligence and autonomous robots, can be used to improve all aspects of manufacturing and supply of products along supply chains to the customer. Many companies are embracing these technologies but uptake within the pharmaceutical sector has not been as rapid. The Medicines Made Smarter Data Centre (MMSDC) looks to address the key challenges which are slowing digitalisation, and adoption of IDTs that can transform processes to deliver medicines tailored to patient needs. Work will be carried out across five integrated platforms designed by academic and industrial researcher teams. These are: 1) The Data Platform, 2) Autonomous MicroScale Manufacturing Platform, 3) Digital Quality Control Platform, 4) Adaptive Digital Supply Platform, and 5) The MMSDC Network & Skills Platform. Platform 1 addresses one of the sector's core digitalisation challenges - a lack of large data sets and ways to access such data. The MMSDC data platform will store and analyse data from across the MMSDC project, making it accessible, searchable and reusable for the medicines manufacturing community. New approaches for ensuring consistently high-quality data, such as good practice guides and standards, will be developed alongside data science activities which will identify what the most important data are and how best to use them with IDTs in practice. Platform 2 will accelerate development of medicine products and manufacturing processes by creating agile, small-scale production facilities that rapidly generate large data sets and drive research. Robotic technologies will be assembled to create a unique small-scale medicine manufacturing and testing system to select drug formulations and processes to produce stable products with the desired in-vitro performance. Integrating several IDTs will accelerate drug product manufacture, significantly reducing experiments and dramatically reducing development time, raw materials and associated costs. Platform 3 focusses on the digitalisation of Quality Control (QC) aspects of medicines development which is important for ensuring a medicine's compliance with regulatory standards and patient safety requirements. Currently, QC checks are carried out after a process has been completed possibly spotting problems after they have occurred. This approach is inefficient, fragmented, costly (>20% of total production costs) and time consuming. The digital QC platform will research how to transform QC by utilising rich data from IDTs to confirm in real time product and process compliance. Platform 4 will generate new understanding on future supply chain needs of medicines to support adoption of adaptive digital supply chains for patient-centric supply. IDTs make smaller scale, autonomous factory concepts viable that support more flexible and distributed manufacture and supply. Supply flexibility and agility extends to scale, product variety, and shorter lead-times (from months to days) offering a responsive patient-centric or rapid replenishment operating model. Finally, technology developments closer to the patient, such as diagnostics provide visibility on patient specific needs. Platform 5 will establish the MMSDC Network & Skills Platform. This Network will lead engagement and collaboration across key stakeholder groups involved in medicines manufacturing and investments. The Network brings together the IDT-using community and other relevant academic and industrial groups to share developments across pharmaceuticals and broader digital manufacturing sectors ensuring cross-sector diffusion of MMSDC research. Existing strategic networks will support MMSDC and act as gateways for IDT dissemination and uptake. The lack of appropriate skills in the workforce has been highlighted as a key barrier to IDT adoption. An MMSDC priority is to identify skills needs and with partners develop and deliver training to over 100 users

Formulation engineering is concerned with the manufacture and use of microstructured materials, whose usefulness depends on their microstructure. For example, the taste, texture and shine of chocolate depends on the cocoa butter being in the right crystal form - when chocolate is heated and cooled its microstructure changes to the unsightly and less edible 'bloomed' form. Formulated products are widespread, and include foods, pharmaceuticals, paints, catalysts, structured ceramics, thin films, cosmetics, detergents and agrochemicals, with a total value of £180 bn per year. In all of these, material formulation and microstructure control the physical and chemical properties that are essential to the product function. The research issues that affect different industry sectors are common: the need is to understand the processing that results in optimal nano- to micro structure and thus product effect. Products are mostly complex soft materials; structured solids, soft solids or structured liquids, with highly process-dependent properties. The CDT fits into Priority Theme 2 of the EPSRC call: Design and Manufacture of Complex Soft Material Products. The vision for the CDT is to be a world-leading provider of research and training addressing the manufacture of formulated products. The UK is internationally-leading in formulation, with many research and manufacturing sites of national and multinational companies, but the subject is interdisciplinary and thus is not taught in many first degree courses. A CDT is thus needed to support this industry sector and to develop future leaders in formation engineering. The existing CDT in Formulation Engineering has received to date > £6.5 million in industry cash, has graduated >75 students and has 46 currently registered. The CDT has led the field; the new National Formulation Centre at CPI was created in 2016, and we work closely with them. The strategy of the new Centre has been co-created with industry: the CDT will develop interdisciplinary research projects in the sustainable manufacture of the next generation of formulated products, with focus in two areas (i) Manufacturing and Manufacturability of New Materials for New Markets 'M4', generating understanding to create sustainable routes to formulated products, and (ii) 'Towards 4.0rmulation': using modern data handling and manufacturing methods ('Industry 4.0') in formulation. We have more than 25 letters from companies offering studentships and >£9 million of support. The research of the Centre will be carried out in collaboration with a range of industry partners: our strategy is to work with companies that are are world-leading in a number of areas; foods (PepsiCo, Mondelez, Unilever), HPC (P+G, Unilever), fine chemicals (Johnson Matthey, Innospec), pharma (AstraZeneca, Bristol Myers Squibb) and aerospace (Rolls-Royce). This structure maximises the synergy possible through working with non-competing groups. We will carry out at least 50 collaborative projects with industry, most of which will be EngD projects in which students are embedded within industrial companies, and return to the University for training courses. This gives excellent training to the students in industrial research; in addition to carrying out a research project of industrial value, students gain experience of industry, present their work at internal and external meetings and receive training in responsible research methods and in the interdisciplinary science and engineering that underpin this critical industry sector.