Inorganic nanomaterials are widely used in diverse applications such as oil refining, food, coatings, cosmetics, textile, transport, healthcare and electronics and communication, with a global market worth 20 billion EURO. A recent inventory has documented >1800 consumer products that contain nanomaterials and many more non-commodity products such as industrial catalysts and separation media. However, there are limitations in terms of the sustainability of and the attainable product quality from current manufacturing. Industry uses wet (chemical precipitation) and dry (flame or plasma) processes for manufacturing nanomaterials. Despite the advances in the latter, it has been shown that the wet processes are lot more efficient than the dry processes. Anastas and co-workers performed a sustainability analysis for wet processes, which revealed that nanomaterials manufacturing is significantly wasteful when compared to the production of bulk chemicals. This creates an enormous burden on the environment and results in unsustainable manufacturing. Further, some of the key properties of nanomaterials cannot be obtained with existing manufacturing methods. Lab-based methods exist for synthesising nanomaterials of desired properties, however, these methods are very wasteful and uneconomical to scale-up. Hence such high value materials remain at small scales and commercially inaccessible. A World Technology Evaluation Center report, commissioned by the USA's National Science Foundation, explicitly recommended that achieving green manufacturing by 2020 is the "holy grail" and that future research should focus on emulating natural designs to develop scalable processes for manufacturing nanomaterials [Ref. Roco et al., Nanotechnology Research Directions for Societal Needs in 2020, NSF and WTEC, 2010]. I have developed fully synthetic novel bioinspired approaches to nanomaterials, with rapid reactions (takes only 1-5 minutes) at room temperature in water, producing almost no waste, yet providing superior control of product properties. This method can reduce the energy usage of the reaction step by ~95% when compared with a traditional precipitation process and the materials would as cheap as the lowest grade commercial counterparts, yet provide significantly better quality and properties. However, the bulk of research on bioinspired synthesis has been performed at small scales. The bioinspired method cannot be scaled-up yet because there is a critical gap in our knowledge on its scale dependence. This fellowship aims to apply bioinspired routes to deliver sustainable ("green"), low cost and scalable technologies for manufacturing high value functional nanomaterials. I will develop scale-up rules by modelling and experimentally measuring mixing mechanisms. I will design process chemistry to produce bespoke nanomaterials and demonstrate pathways for larger-scale manufacturing. This fellowship has a great potential to take the UK to the world leading stage in sustainable manufacturing of bespoke nanomaterials.

Personalised medicine (PM) is gaining significant attention in recent years as it has the potential to transform healthcare across the globe by moving away from the "one-size-fits-all" model to utilise personal circumstances, medical history and needs to deliver individually suitable treatment. Current bulk manufacturing technologies are unable to meet most of these demands as they are slow in responding to changes, capital intensive, use unsustainable methods and are not flexible to meet PM needs. A recent white paper from the EPSRC funded Redistributed Manufacturing in Healthcare has identified that small-scale, localised, high-speed and automated manufacturing platforms are urgently needed to realise PM. They identified that such "factory-in-a-box" should be: - able to manufacture on-demand, - flexible to deliver multiple products with desired properties, - sustainable (energy efficient and using mild conditions) and - able to integrate various unit operations using data science tools. Given the future needs for PM, recent research efforts have been directed towards redefining the manufacturing of active pharmaceutical ingredient (API) and their formulations into e.g. tablets for oral dosages using advanced methods such as microfluidics, Hot Melt Extrusion or 3D printing. However, as a medicine is a carefully designed formulation of an API with non-active components such as excipients or drug delivery systems (DDS), challenges in manufacturing of the non-active components for PM are also equally important, but have not been addressed. The non-active components improve physicochemical properties and bioavailability of APIs. In its many forms silica is one of the most commonly used component of many current and future API formulations, yet their manufacturing to meet the PM requirements do not exist. Specifically, despite tremendous progress made on the use of silica in pharmaceutical formulations, currently, their on-demand, automated and flexible manufacture to produce silica of desired properties for PM is non-existent. A key reason for this is that the vast majority of promising silicas require synthesis conditions that are prohibitive for any meaningful scale-up and for implementation in a 'factory in a box' platform. Hence, this missing piece, despite the recent developments in manufacturing of API and formulations, creates a significant barrier to making PM a reality. We have shown the potential of bioinspired silica (BIS) as an alternate drug delivery system, which is scalable, economical and sustainable - an ideal candidate for on-demand and flexible manufacturing. This research will rely on a close synergy between computational modelling and experimental synthesis. Green synthesis processes and research on intensified reactors by the applicants will be used as a starting point. A range of intensified reactors and Gaussian Process-based modelling will be used to achieve process intensification of particulate manufacturing processes. Comprehensive models will be used to create digital twins of fluidic devices and recipes of green synthesis of silica particles using those devices. Machine learning approaches based on results of simulations of reactors will be developed to relate quality attributes of silica produced with key process and operating parameters. Device geometry and process parameters will be manipulated to achieve the desired Critical Quality Attributes (CQAs). The work will contribute to revolutionising PM and help deliver table top pharmaceutical manufacturing equipment in hospitals and pharmacies. Ultimately, the impact will include significant improvements in treatments and quality of life as well as the formation of new companies to build such units.

This year, the global demand for nanomaterial, which is already a multi-billion$ industry, will have grown 2.5-fold since 2012. Current nanomaterials production methods are at least 1000 times more wasteful when compared to the production of bulk and fine chemicals. Consequently there is an urgent need to develop green production methods for nanomaterials which can allow greater control over materials properties, yet require less energy, produce less waste (i.e. eco-friendly) and are cost-effective. Nature produces more than 60 distinct inorganic nanomaterials (e.g. CaCO3, Fe3O4, silica) on the largest of scales through self-assembly under ambient conditions (biomineralisation). Although biological methods for nanomaterials synthesis (e.g. using microorganisms or complex enzymes) are effective in reducing environmental burden, they are expensive, inefficient and/or currently not scalable to industrial production. We will adopt a synthetic biology (SynBio) approach, which is one of the EPSRC's core strategic themes, by harnessing the biological principles to design advanced nanomaterials leading to novel manufacturing methods. SynBio is a very powerful tool for the production of high-precision advanced functional nanomaterials and our approach marries two of the "8 great technologies for the future" ("Synthetic Biology" and "Advanced Nanomaterials"). Instead of using cells or microbes, our SynBio strategy uses synthetic molecules (SynBio additives) inspired from biomineralisation. SynBio produces a wide range of well-defined and tunable nanomaterials under mild (ambient) conditions, quickly and with little waste. Our SynBio approach offers the potential for high-yields, like the traditional chemical precipitation method, together with the precision, customisation, efficiency and low waste of biomineralisation. The bulk of research on bioinspired synthesis of nanomaterials has been performed at small scales and, although there are good opportunities for developing nanomaterials manufacturing based on bioinspired approaches, there are no reports on larger-scale investigations. Adopting a bioinspired SynBio approach, this project will enable the controlled synthesis and scalability of silica and magnetic nanoparticles (SNP and MNP) which are worth ~$11 billion globally. These methods are far more amenable to scale-up and can truly be considered 'green'. This SynBio process can reduce the manufacturing carbon footprint (by >90%), thus providing a significant cost benefit to industry.

The Centre for Doctoral Training in "Molecular Modelling and Materials Science" (M3S CDT) at University College London (UCL) will deliver to its students a comprehensive and integrated training programme in computational and experimental materials science to produce skilled researchers with experience and appreciation of industrially important applications. As structural and physico-chemical processes at the molecular level largely determine the macroscopic properties of any material, quantitative research into this nano-scale behaviour is crucially important to the design and engineering of complex functional materials. The M3S CDT offers a highly multi-disciplinary 4-year doctoral programme, which works in partnership with a large base of industrial and external sponsors on a variety of projects. The four main research themes within the Centre are 1) Energy Materials; 2) Catalysis; 3) Healthcare Materials; and 4) 'Smart' Nano-Materials, which will be underpinned by an extensive training and research programme in (i) Software Development together with the Hartree Centre, Daresbury, and (ii) Materials Characterisation techniques, employing Central Facilities in partnership with ISIS and Diamond. Students at the M3S CDT follow a tailor-made taught programme of specialist technical courses, professionally accredited project management courses and generic skills training, which ensures that whatever their first degree, on completion all students will have obtained thorough technical schooling, training in innovation and entrepreneurship and managerial and transferable skills, as well as a challenging doctoral research degree. Spending >50% of their time on site with external sponsors, the students gain first-hand experience of the demanding research environment of a competitive industry or (inter)national lab. The global and national importance of an integrated computational and experimental approach to the Materials Sciences, as promoted by our Centre, has been highlighted in a number of policy documents, including the US Materials Genome Initiative and European Science Foundation's Materials Science and Engineering Expert Committee position paper on Computational Techniques, Methods and Materials Design. Materials Science research in the UK plays a key role within all of the 8 Future Technologies, identified by Science Minister David Willetts to help the UK acquire long-term sustainable economic growth. Materials research in UCL is particularly well developed, with a thriving Centre for Materials Research, a Materials Chemistry Centre and a new Centre for Materials Discovery (2013) with a remit to build close research links with the Catalysis Technology Hub at the Harwell Research Complex and the prestigious Francis Crick Institute for biomedical research (opening in 2015). The M3S will work closely with these centres and its academic and industrial supervisors are already heavily involved with and/or located at the Harwell Research Complex, whereas a number of recent joint appointments with the Francis Crick Institute will boost the M3S's already strong link with biomedicine. Moreover, UCL has perhaps the largest concentration of computational materials scientists in the UK, if not the world, who interact through the London-wide Thomas Young Centre for the Theory and Simulation of Materials. As such, UCL has a large team of well over 100 research-active academic staff available to supervise research projects, ensuring that all external partners can team up with an academic in a relevant research field to form a supervisory team to work with the Centre students. The success of the existing M3S CDT and the obvious potential to widen its research remit and industrial partnerships into topical new materials science areas, which lie at the heart of EPSRC's strategic funding priorities and address national skills gaps, has led to this proposal for the funding of 5 annual student cohorts in the new phase of the Centre.