Particle Technology is an important discipline that underpins many industrial sectors, including biomedical applications, latex paints and coatings, engine oil additives, viscosity modifiers (thickeners) and emulsion stabilisation. The Principal Investigator, Prof. Steve Armes, is one of the UK's experts in particle science and technology, with more than thirty years of research experience in this field. In particular, he designs a wide range of microscopic polymer particles on the nano-scale (polymers are long-chain molecules that can be programmed to undergo in situ self-assembly during chain growth). He seeks a four-year EPSRC Particle Technology Established Career Fellowship to devote more time to such research activities, which will be conducted in close collaboration with four UK-based companies (GEO Specialty Chemicals, Scott Bader, Lubrizol & Syngenta), four UK academics and three overseas academics. This will enable him to integrate substantial academic and industrial expertise in order to tackle a range of important scientific problems that could not be addressed by a single researcher. Some of these problems are fundamental in nature, such as investigating the precise mechanism of particle formation during heterogeneous polymerisation or developing very fine particle-stabilised oil droplets that exhibit long-term stability towards droplet coalescence. Other aspects of the outlined research programme have obvious potential applications. These include: (i) the development of next-generation hydrogels for the long-term storage of human stem cells, which have the potential to transform regenerative medicine; (ii) the design of highly anisotropic worm-like particles to act as thickeners for a range of oils in cosmetics formulations; (iii) the elucidation of new high-temperature oil-thickening mechanisms for engine oils, which has the potential to improve fuel economy and hence improve air quality. Prof. Armes is well-known for his synthetic expertise in particle design, but in the past five years he has gained substantial experience of particle characterisation studies. In particular, his research group now use a range of advanced instrumentation such as small-angle X-ray scattering for particle size analysis, assessing gel properties via oscillatory rheology and emulsion processing using a high-pressure microfluidiser. In this Fellowship, the focus will be on particle characterisation and evaluation, with underpinning particle syntheses being performed by the ten PhD students in the Armes group. To oversee this ambitious research programme, Prof. Armes seeks 50% of his salary for four years. The four work packages will be undertaken by the four named highly-experienced post-doctoral scientists, who are all current members of the Armes group. A total of 13 post-doc (wo)man-years is requested, plus sufficient funds to access all the state-of-the-art equipment that will be required to rigorously characterise the size distributions and solution behaviour of these new polymer particles. In addition, funds are requested for travel, an outreach programme targeting local and regional primary schoolchildren, and to organise a two-day workshop. Prof. Armes has worked closely with a wide range of companies and his research has already inspired the development of commercial products by BASF, Cabot and DSM. More recently, a UK SME (Diamond Dispersions) tripled its annual sales and doubled its workforce by implementing informal technical advice provided by Prof. Armes. In 2016 Lubrizol scaled-up his nanoparticle formulations from five grams to twenty kilos per batch and conducted an extensive in-house evaluation of their performance as additives for next-generation engine oils, with pilot plant trials now approved for 2017. Thus Prof. Armes has an excellent track record of commercially-relevant technical innovation that is of tangible value to UK plc. This augurs well for maximising the economic impact of this Fellowship.

Human embryonic stem (hES) cells are pluripotent cells that can either self-renew, thereby maintaining their pluripotency, or differentiate depending on the culture conditions. Induced pluripotent stem (iPS) cells, which offer similar clinical potential to hES cells, can be generated by infecting adult cells. In principle, the application of hES and iPS cells in cell therapy and regenerative medicine offers tremendous potential because of their innate ability to differentiate into multiple, clinically-useful cell types. However, well-defined culture conditions are essential for realising the biomedical potential of hES and iPS cells. Matrigel is a gelatinous protein mixture secreted by mouse sarcoma cells and is marketed by BD Biosciences. This complex mixture contains laminin, entactin, collagen and various growth factors; it resembles the complex extracellular environment found in many tissues and is used by cell biologists as a model active substrate for cell culture studies. Matrigel is a liquid at 4oC, but on warming to 37oC it forms a fibrillar gel network. In its diluted form, Matrigel is used as an attachment substrate for culturing embryonic stem cells to maintain their pluripotent, undifferentiated state in the absence of any feeder cells. Despite its high cost, animal origin and poor/variable batch-to-batch reproducibility, Matrigel is nevertheless widely used by cell biologists. However, an alternative wholly synthetic gelling composition that can be reliably employed as a baseline material is urgently required for a wide range of in vitro stem cell experiments aimed at eventual clinical applications. Moreover, it is widely accepted that the effective translation of human pluripotent stem cells into cell therapies will require the development of standardised tests for product consistency, stability, toxicity and immunogenicity. With the aid of this grant, we will develop a range of novel, wholly synthetic hydrogels based on the self-assembly of biocompatible methacrylic block copolymer worm-like particles, which are readily prepared in concentrated aqueous solution. Such gels are highly biocompatible and, unlike many hydrogels, can be readily sterilised simply by cold ultrafiltration: this is possible because the worms transform into free-flowing spherical nanoparticles when cooled to 5oC and reform worm gels on returning to ambient temperature. In a year-long informal collaboration, we have conducted proof-of-concept studies (see A. Blanazs et al., JACS, 2012, 134, 9741) and filed a U. Sheffield patent application, thus we already have a strong background IP position. However, there are many remaining technical challenges and a concerted inter-disciplinary research effort is now required to overcome these problems. Our new worm gels are expected to replace Matrigel (and related animal-derived materials) as the most convenient medium for the long-term storage, manipulation and proliferation of human stem cells while retaining their pluripotent state. Prof. Steve Armes will lead on the synthetic polymer chemistry aspects of this inter-disciplinary study, while Prof. Harry Moore will lead on the stem cell research. We request funding to support two experienced post-doctoral research scientists to work in close collaboration on this project. We have identified two appropriate industrial partners for this EPSRC grant. GEO is a UK-based speciality chemicals company that will provide the monomer building blocks required for the synthesis of the block copolymer worms, assist with the scale-up studies and act as a raw materials supplier in the event of future commercialisation. Plasticell is a UK-based biotech SME specialising in stem cell technologies. This company is ideally placed to help us assess and optimise our worm gels to ensure that they provide an appropriate technical solution for stem cell biologists. These two companies have each pledged £ 5 K cash to provide the £ 10 K contribution required by EPSRC.

This Centre for Doctoral Training (CDT) is in the field of Polymers, Soft Matter and Colloids. This area of science deals with long-chain molecules, gels, particles, pastes and complex fluids. It is of fundamental importance for many commercial sectors, including paints & coatings, home & personal care products, agrochemicals, engine oils & lubrication, enhanced oil recovery, biomedical devices & drug delivery. Thus substantial EPSRC investment in this industrially-relevant field will directly support the UK economy and enhance its competitiveness over the longer term, as well as contributing to our scientific capacity to address important technical challenges and major societal problems such as sustainability and energy security. Sheffield Polymer Centre academics have a wealth of research experience in the areas of polymer chemistry, polymer physics, colloid science, soft matter physics and polymer engineering. This breadth of expertise is unique and is certainly unrivalled anywhere in the UK. Between us, we offer a superb range of research facilities and state-of-the-art instrumentation that provide excellent postgraduate training opportunities. We have also run a popular annual industrial training course and three relevant taught MSc courses for many years. Thus the logistical experience of our current administrative staff and existing teaching infrastructure will provide invaluable support in running this new CDT. Moreover, this prior activity underlines our institution's deep commitment to this important interdisciplinary field. Our vision is to engage closely with a wide range of companies, e.g. AkzoNobel, Lubrizol, P & G, Cytec, Synthomer, Scott Bader, GEO, Wellstream, LBFoster, Philips, Ossila, Syngenta, DSM, Ashland, BP and Unilever, in order to provide the next generation of highly skilled PhD scientists with high-level technical skills, intellectual rigour, excellent communication skills, flexibility and business acumen. This is essential if we are to produce the creative problem-solvers that will be required to tackle the many formidable technical and societal challenges now facing mankind. Our ambition is to secure at least £2.0 million from our industrial partners in order to support fifty CASE PhD projects over five years. Six PhD studentships p.a. (i.e. thirty in total) are requested from EPSRC, which will be supplemented by a substantial institutional contribution of three studentships p.a. (i.e. fifteen in total). This institutional commitment is in recognition of the continuing strategic importance of this research area to the University of Sheffield. An additional studentship p.a. (i.e. five in total) will be funded by top-slicing the enhanced CASE contributions from our industrial partners to make up the annual cohort of ten students. EPSRC investment in this CDT is warranted given our substantial institutional portfolio of many active EPSRC grants (including Programme and Platform grants), plus a £2.0 M ERC grant. Our CDT training programme will include the following highly distinctive features: (i) our unrivalled breadth of academic knowledge and experience; (ii) a choice of research projects for our PhD students prior to their enrolment; (iii) an initial two-week training course on the basic principles of polymer science and engineering; (iv) a monthly seminar programme led by industrial scientists to expose our students to a wide range of commercially-relevant topics; (v) a six-month secondment with the industrial partner in the latter part of the research programme, which will provide our students with invaluable experience of the workplace and hence prepare them for their industrial and/or managerial careers; (vi) a 'business enterprise' course led by an external consultant (Jo Haigh) and one of our industrial partners (Synthomer) to develop and encourage entrepreneurial flair in each PhD cohort; (vii) a visit to an overseas academic laboratory to facilitate international collaboration.