We will create an artificially intelligent system which will self-optimise chemical manufacturing to flexibly adapt to variation in external factors (e.g. supply chain issues, cost, environment) by utilising chemical molecular property maps to suggest alternative suitable reagents, catalyst, solvents. This rapid, flexible system will be essential for promoting manufacturing by developing a more responsive chemical manufacturing framework. Here the routes will be tailored for agrochemical applications in line with our industrial partners' interests, but the components of the technology will be transferable across differing chemical manufacturing sectors. We will assemble and program a system capable of conducting several discrete chemical processing options including (i) changing catalyst or reagent choice (ii) altering reactor configuration (e.g. batch to CSTR) (iii) differing requirements based on response to external influences (e.g. cost changes due to COVID19). The system will be programmed by computationally intelligent algorithms which enable self-optimisation of the processes without user interaction or their immediate knowledge (i.e. being invisible) and made accessible through a user-friendly interface.

Our society is completely dependent upon polymers (plastics) in every facet of our lives; from clothes to computers to novel composites and cosmetics. But this brings problems. In 2010 every citizen of the USA discarded 140 kg of plastic into land-fill; and those figures are rising across the globe. As more of the World's economies move towards Western levels, we simply will not be able to continue to use polymers in the same way, nor will our oil reserves provide sufficient raw materials with security of supply. There are alternatives, derived from renewable resources, and these can also lead to degradable polymers that could have a significant positive impact and could help solve the issues of landfill. But despite all the hype and expectation, renewables currently account for less than 5% of all polymers. One of the major routes to achieving better market penetration of renewable polymers is to lower the price, and one of the biggest fixed costs is in the energy required to carry out the polymerisation reactions that make these polymers on the commercial scale. Our industry partners have told us clearly that lowering the energy costs and shaving off a just a few pence per kg of the overall cost of the polymer would have a dramatic effect on their ability to sell more renewable polymers into the marketplace. Our project addresses this issue directly and focuses on new energy efficient polymerisations. Our approach is novel, using high pressure carbon dioxide as a processing aid to enhance polymerisations at lower temperatures. If successful we will achieve not only significant energy savings, but also, by using lower temperatures, we will open up a completely new range of polymer properties, such as increased heat resistance and enhanced mechanical properties that have not been easily accessible before, and certainly cannot be achieved through the traditional high temperature commercial processes. This project will tackle both the technical and engineering aspects around the use of high pressure carbon dioxide in polymerisation reactions and will provide new approaches to overcoming the key hurdles that are currently preventing larger scale manufacture of renewable polymers. Our project will also produce valuable life cycle and energy consumption data on our new process. These data will be useful in helping our industry partners to build a credible business case for utilising high pressure carbon dioxide to improve their processes and polymer products.

Our society is completely dependent upon polymers (plastics) in every facet of our lives; from clothes to computers to novel composites, cars and cosmetics. A key question is how can we continue to use and consume polymers in the future? In 2010 every citizen of the USA discarded 140 kg of plastic into land-fill and those figures are similar and rising in many other societies around the globe. As more economies move towards Western levels of consumption, we simply will not be able to continue to use polymers in the same way. There are alternative polymers that are derived from renewable resources, and learning to make and use these will have a significant positive impact and will help to alleviate the issues of landfill, particularly when the renewable polymers are degradable. But despite all the hype and expectation, renewable polymers currently account for less than 5% of all polymers produced commercially. This figure is growing but the problem is that most renewable polymers simply do not perform as well as the traditional commodity polymers that are derived from oil. In this proposal we focus upon utilising terpenes to form a range of valuable new polymers. Terpenes are derived from citrus waste ( eg. d-limonene from orange peel) and from wood waste (eg. the alpha- and beta-pinenes) and are already available on the multi-tonne scale and sold into markets from fragrances to aromas and healthcare. There have been significant efforts in the past to create polymers directly from terpenes because their structures contain alkene moieties that appear to offer the opportunity for polymerisation via free radical routes under simple, readily accessible conditions that could easily be scaled. Unfortunately, extensive studies have yielded only poor quality low molecular weight or cross-linked polymers that have not found commercial utility. Now, we will build on recent proof of concept studies at Nottingham that could overcome this log-jam. We have developed a simple and versatile approach to produce new terpene based monomers that can be easily "dropped-in" to existing commercial polymerisation processes. Our approach offers the possibility to use readily available free radical and controlled polymerisation routes to create new polymers and co-polymers that can be tailored for application across the commodity and specialty plastics landscape. To achieve these goals we have assembled a multidisciplinary academic team that brings together all of the key skills and expertise needed to deliver these new monomers and polymers, and to characterise their properties to determine suitable application areas. In addition, we will utilise strong input, support and advice from industry partners from across the polymer sector to target the new materials towards focussed potential applications and products.

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 manufacture of chemicals makes a major contribution to the UK's economy; £10 bn p.a. in the chemicals and £9bn in the pharmaceuticals sectors alone. The recent report of the Chemistry Growth Strategy Group states that 'By 2030, the UK chemical industry will have further reinforced its position as the country's leading manufacturing exporter and enabled the chemistry-using industries to increase their Gross Value Added contribution to the UK economy by 50%' with "smart manufacturing" as one of three priorities in realising their vision. Our proposal aims to contribute to this smart manufacturing by transforming the way in which continuous photochemistry can be applied to commercial chemical manufacture. There is considerable current academic interest in new photochemical reactions for organic synthesis but how they might be used industrially is usually ignored. Nevertheless the potential of photochemistry in manufacturing is widely recognized if only it could be made scalable and efficient. Traditionally the pharmaceutical and fine chemicals industries have used batch reactors for manufacture, which are difficult to adapt effectively for photochemistry. Therefore, this proposal focuses on continuous reactors which not only permit innovation in design to overcome technical limitations of current photoreactors but also provide a direct route to increased throughput via scale up or scale out. We will tackle some of the technical and engineering issues inherent in conventional photoreactors. These engineering problems include getting light efficiently into the reactors, build-up of opaque material on transparent surfaces key safety issues, particularly in reactions involving oxidation, as well as cost issues related to low efficiency of many light sources and difficulties of scale up. Our project proposes to create new engineering approaches to continuous photochemical manufacture of chemicals, which could transform chemical processes and cost. Our proposal addresses key technical/scientific barriers frustrating current commercial use of photochemistry and promises cheaper products in the pharmaceutical, agrochemical and fine chemicals sectors. Our team consists of three investigators with a proven track record of taking chemical processes from laboratory to commercial plant. Between us, we have the expertise needed for success; namely, in photochemistry, continuous organic reactions, manufacturing, mechanical and chemical engineering and process monitoring.