Methane is an abundant material that presents huge potential as a feedstock for chemicals synthesis. It is widely available as the major constituent of natural gas, but becomes also increasingly more obtainable from sustainable sources, such as biogas and landfill gas, and unconventional sources, such as shale gas, coalbed methane and methane hydrates. Moreover, it has more than 25 times higher 100-year global warming potential to that of CO2, so the need to develop efficient methane utilization methods towards value-added products is more than clear. Among many uses, methane has been identified as a very promising raw material for the production of ethylene. The latter is the most widely produced base chemical, used e.g. for polymers, but its production depends on crude oil, generating the vast majority of CO2 process emissions in the UK chemical industry. In fact, under the Kyoto Protocol and the UK Climate Change Act, UK has specific international and domestic targets for reducing greenhouse gas emissions. 11% of these are represented by methane originating from agriculture, waste management and the energy industry, hence the production of ethylene from methane can be a promising process with multiple benefits for these sectors. The high temperatures needed, though, for the activation of the stable methane molecule via thermal-catalysis, in conjunction with the use of oxidants to facilitate thermodynamically favourable routes, result in significant amounts of undesired carbon oxide by-products in the currently applied upgrading methods. The combination of non-thermal plasma with catalysis has recently emerged as a promising technology to enable catalysts to operate at low temperatures. In non-thermal plasmas, the overall gas temperature is as low as ambient, however electrons are highly energetic resulting in collisions that easily break down molecule bonds, producing various reactive species like free radicals, excited states and ions that participate in subsequent reactions. The strong non-equilibrium character of these plasmas has been shown to even allow thermodynamically unfavourable reactions to occur under ambient conditions. Being able to carry out direct methane coupling towards ethylene at low temperatures at non-oxidative conditions would present significant benefits, ranging from carbon oxides-free products to drastically reduced energy requirements and would enable alternate production routes towards polymers and high octane-number fuels. Combining the high reactivity of plasma with the high selectivity of the catalytic surface has a huge potential to unravel these benefits, which can further be enhanced by the use of sustainable electricity for the generation of the plasma. Nonetheless, the interaction between non-thermal plasma and catalysts is a highly complex phenomenon. There has been a considerable amount of experimental work aimed at understanding the underlying elementary processes, however most mechanistic details are not yet elucidated. The combination of experimental, theoretical and modelling studies is needed to gain a more fundamental insight. Microkinetic modelling is proposed as a novel approach to enhance the understanding and enable the optimisation of plasma-assisted heterogeneous catalytic reaction systems. With support from BASF, UK and a carefully designed experimental program, the novelty of the proposed project lies on the, for the first time, systematic consideration of all elementary reaction processes taking place in the plasma phase and on the catalyst surface and the explicit description of the interactions among them. The project is very timely, addressing topics in EPSRC's portfolio in relation to energy efficiency and alternative fuels and sources of chemicals. Successful implementation will result in the development of predictive computational tools that can be used to accelerate the design of new processes, reducing the needs for experimentation and associated costs.

Pressurised gyration processes, which are the focus of this grant application is an emerging technique that utilises centrifugal force and the dynamic fluid flow to jet out advanced functional materials consistently. This technique has shown great potential in overcoming the limitations of the existing techniques to manufacture functional materials and structures that can safely, consistently and cost-effectively be up-scaled. Thus in the past 5 years pressurised gyration, and several sister-processes (infusion gyration, melt pressurised gyration, pressure-coupled infusion gyration) have been developed and applied to prepare functional materials for different applications. The overall motivation of this research is to manufacture a wide variety of "core-sheath" structures, that are not fully exploited commercially in functional applications (e.g. healthcare) simply because of lack of innovative manufacturing. The overall aim of the project is to develop pressurised gyration as a novel means of effective manufacturing of multi-material core-sheath structures. Therefore, a very significant aspect of this project is to develop a pressurised gyration technique based on exploratory experimental evidence, to generate core-sheath structures on a large scale. A newly created exploratory device containing two chambers has been used to manufacture a wide range of polymer nanofibres with different polymers in both aqueous and non-aqueous solutions as core and sheath components at various concentrations, pressures and rotating speeds. In addition antibacterial metallic nanoparticles loaded nanofibres were also produced using this device. The manufacturing of core-sheath structure has been demonstrated by using a high speed camera and microscopy. Thus, the proposed research pays attention on developing a new high yield device for manufacturing layered core-sheath structures based on our existing preliminary device. Also a considerable effort will be devoted to analyse the new process to make quantitative assessment in order to understand the theoretical issues. It will focus on investigating the forming of core-sheath fibres and core-shell capsules from micro-nanoscale. Functionalising those core-sheath structures produced with additions of other, organic, inorganic and particulate materials will be an important feature. The processed core-sheath structures will be characterised with advanced tools to explore their unique physical, chemical and biological properties.

The proposed research describes a novel engineering approach to point-of-need delivery of controlled release medications for wound and burn treatment, based on an innovative portable device which allows in situ generation of nano-/micro fibrous meshes. These fibres can contain multiple layers of active pharmaceutical ingredients (APIs) in a core-shell configuration (potentially up to at least four layers), allowing compartmentalisation of agents ranging from proteins to low molecular weight antibiotics and including innovative therapeutic oligosaccharides. Nano- and microfibres with compartmentalised structures are currently attracting a great deal of interest within the drug delivery arena due to the advantages of high surface area, high fluid permeation, ready separation of incompatible drugs into physically distinct environments, the ability to tune drug release rates via incorporation into controlled release polymers and the physical flexibility and versatility of the macroscopic mesh structure. Furthermore, given recent emphasis on combination therapies, the possibility of generating compartmentalised systems using, for example, coaxial and multi-axial electrohydrodynamic (EHD) technology is highly attractive. One example of such an application is the treatment of wounds and burns, whereby the flexibility of shape of the meshes to neatly fill the lesion, the high fluid permeation of the mesh facilitating tissue regrowth, the tunable release of therapeutic agents and the biodegradation of the mesh are all perfectly feasible attributes that would render a drug-loaded nanofibre approach highly advantageous. A further possibility, not yet realised in practice, is the generation of micro/nanofibres in situ at the point of trauma. Were this to be possible, then valuable time to treatment would be saved as agents designed to stop bleeding, prevent infection, reduce pain or promote healing could be administered quickly in a form which could be applied to a wide range of lesion architectures and areas. Indeed, a portable system could also be used in conflict situations, for patients with mobility difficulties being treated at home for conditions such as diabetic ulcer or for otherwise medically inaccessible regions such as refugee camps, while the use of biodegradable polymer bases would allow the mesh to simply be resorbed over a period of time without damage to the lesion associated with dressing removal. Moreover, the capability to generate highly permeable microfibrous meshes at point-of-need enables an alternative nasal route for sustained and controlled drug release when oral/intravenous drug delivery is rendered impractical during emergencies where the patient may be unconscious with poor vein access (e.g. heroin overdose) or may even be having a seizure (e.g. status epilepticus). Overall, therefore, a 'field' system for simple and inexpensive administration of complex drug-loaded fibre meshes would have huge patient benefit for a wide range of conditions and would represent a significant breakthrough in engineering-led therapeutic development. Clearly, however, such a system would present a series of profound engineering challenges. Despite recent advances in fibre production technology, the generation of fibres with compartmentalised systems requires bulky, expensive (>£20k), bench-top high voltage supply and syringe pumps that are confined to a laboratory or factory environment. Developing a portable, hand-held, cheaper (<£2k), miniature EHD device that can generate multilayered therapeutic materials could revolutionise the practical applicability of micro/nanofibres. We believe, based on our work to date, that such an approach is now possible and the project outlined here, which focuses on the engineering issues associated with the development of our prototype device and the challenges of drug incorporation, would lay the foundation for the use of this approach in a wide range of therapeutic applications.

Functional coatings are highly engineered drug delivery systems whose structure and composition are critical to the controlled release of the active pharmaceutical ingredient in the human body. These products are at the high value end of the market and represent sophisticated solutions to difficult disease management. Manufacturing these products is challenging largely because pharmaceutical processing is complex that has traditionally been dominated by empirical understanding. The increase in manufacturing complexity coincides with the paradigm shift that the pharmaceutical industry is facing today where emphasis is now being placed on fostering a greater product and manufacturing understanding for building quality into the product and enable continuous manufacturing. Building on the recent successful demonstration of combined optical coherence tomography and terahertz real-time sensing for a coating process where an unprecedented level of in-process diagnostic information were obtained, we will now perform systematic coating process investigation to quantify and model the effects of the key process parameters. The developed data-driven models will in turn allow us to identify the optimal process conditions for validation against science-based process modelling, which can then be used to explain process observations. Ultimately, enhanced process understanding will enable the development of model-based predictive control for the full implementation of continuous manufacturing for producing next generation pharmaceutical products. This project will be supported by a world leading supplier of manufacturing equipment (Bosch, Germany), academic technology collaborators (University of Cambridge, UK and University of Liverpool, UK) and coating materials suppliers (BASF, UK and Colorcon, UK).

Nearly 140,000 industrial materials and chemicals are marketed worldwide. Most of them are made from fossil feedstocks with high CO2 emission embedded, and very low resources efficiency. To maintain the UK's global competitiveness, it is vital to identify sustainable alternatives for the manufacturing of these chemicals and materials. Biomanufacturing, that utilises biological systems to produce commercially important biomaterials and biomolecules plays an important role in sustainable development, and has shown successful applications in manufacturing electronic components (e.g., bio-based flexible printed circuits), fine or specialty chemicals (e.g., bio-lubricants), building and construction (e.g., biocementation), consumer products (e.g., bio-based detergents), food (e.g., vitamin and amino acid fortification) and pharmaceuticals (e.g., vaccine production). However, none of the current biomanufacturing routes has achieved zero carbon loss or emission. In fact, many bioprocesses (such as those involving fermentation) will emit large amounts of CO2. In a typical biomanufacturing, only 2/3 of the carbon resources flow ends up in final products, while the rest 1/3 are lost during the manufacturing process, in the form of CO2 emissions and residue wastes. To address this challenge, the project will create the first-of-its-kind Zero Carbon Loss biomanufacturing system that will pave the way for the UK to reach the 2050 Net Zero target. This will be achieved by developing novel sustainable biomanufacturing of aromatics, heterocyclics and other lignocellulosics products with integrated carbon capture and utilization within the manufacturing process. These bio-based products, like building blocks of Lego, then will be used in different combinations to make various product such as pharmaceuticals, plastics, textile, composite materials, etc, with overall net zero carbon loss (emission and waste) throughout the manufacturing life cycle. The technology innovation and resources optimisation of the BMCCU manufacturing route (WP1) will be guided by real-time system wide sustainability assessments (WP3), linked by an interoperable digital twin of the manufacturing process beyond the state of the art (WP2). It creates a new approach in which the lifecycle sustainability assessments will serve as an interactive decision-making tool fully embedded in the early-stage technology developments, rather than traditional retrospective assessment. The project will contribute significantly to the UK's National Industrial Biotechnology Strategy, with a potential scope of £4.5 billion GVA, 63,000 jobs, and 2.5 billion tonnes of CO2 saving per year by 2030. To achieve the vision, this proposal brings together a diverse multidisciplinary team from Loughborough University, Heriot-Watt University and Imperial College London, with world leading expertise in circular economy, intelligent manufacturing, industrial digitalisation and decarbonisation.