The outcomes of many health interventions critically depend on the ability to identify the disease in a timely manner so the most appropriate therapy can be chosen promptly. Consequently, there is an immediate and growing need to develop healthcare technologies for rapid and accurate detection of bio-markers, associated with specific diseases, and/or disease causative agents, such as pathogenic microorganisms. Microfluidics and lab-on-a-chip technology offer a huge potential for the development of next generation fast and ultra-sensitive bio-analytical devices for diagnostic and therapeutic applications. Particle handling operations - including separation, filtration, concentration, trapping and sorting - are ubiquitous in microfluidic diagnostic technologies and can ultimately dictate the speed, accuracy and selectivity of testing devices. An ideal particle handling technique would be fast (high-throughput), selective (i.e. targeting only the particles of interest), easy to integrate into a multifunctional microfluidic device and, most importantly, not reliant on the use of external fields. This proposal aims to introduce an innovative particle manipulation technique to address all these requirements. This research will also demonstrate the proof-of-concept for using this technique to develop fast and sensitive diagnostic testing devices. Rapid filtration, trapping and accumulation of target particles within the cavities of micro-structured surfaces will be achieved in continuous flow settings by harvesting the chemical energy associated with salt contrast generated by parallel multi-component flows. The mechanisms governing the particle dynamics will be investigated through a combination of experimental and numerical techniques. The dependence of trapping and concentration efficiency on particle properties (especially size and surface chemistry) will be elucidated. The output of this study will be an optimally-designed microfluidic platform, through which two in-vitro diagnostic devices will be developed. One device will enable the rapid filtration of cell-like particles (e.g. liposomes) based on their lipid membrane composition which is an important indicator of a cell's state of health. This assay will offer new opportunities for early detection of drug induced cell death and rapid drug pharmacokinetics screening. Another device will enable the fast and ultrasensitive detection of a biomarker indicative of pathological conditions, including atherosclerosis, pancreatitis and some forms of cancers. Synthetic bio-compatible particles will be incubated in a sample solution where the specific interaction with the disease biomarkers will cause i) the fluorescent signal emission from the particle and ii) a change in particle surface chemistry. The latter effect is intended to enable the conversion of the chemical energy - stored in the form of salt contrast - into particle motion. As a result, the biomarker-activated fluorescent particles will be rapidly trapped and accumulated within target regions of the device whereas the non-fluorescent particles will remain unaffected by the presence of the salt. This will enable a massive signal amplification for the diagnostic assay and, consequently, a fast and accurate detection of biomarker concentration in the analysed sample. In summary, this research will lay the foundation for the development of a new family of low-cost, portable bio-analytical devices based on particle filtration and accumulation by solute-driven transport (FAST) for diagnostic and therapeutic applications. These innovative and highly-sensitive diagnostic tools will enable clinicians to perform rapid and accurate diagnosis and, hence, make timely and informed clinical treatment decisions which are more likely to lead to successful health outcomes.

Abstract from the Case for Support document (section 2):This research project is centred upon the parallel construction, development, and use of two complimentary experimental systems to study processes induced by ionisation in irradiated biomolecular systems. The principle objective is to compare the effects of irradiating a specific target molecule within a cluster with the case of the molecule in isolation. In addition to their fundamental interest in molecular and statistical physics, these experiments will help to bridge the complexity gap between the current understanding of radiation effects in the gas phase and in an absorbing biological medium. This represents a major current research challenge for physicists, chemists, and biologists, with important applications in quantifying the effects of exposure to different types of radiation during cancer therapies.The first experimental system is a versatile and mobile source for hydrated DNA base clusters, proposed for construction at the Open University. During the three year programme, this source will be used to carry out 2- and 1-photon electronic excitation experiments to probe the effects of solvated water molecules upon the valence and Rydberg energy states of key biomolecules and the associated dissociation pathways. The second experimental system, located at the Nuclear Physics Institute of Lyon, will enable a detailed study to be carried out on collisions between fast protons and mass-selected cluster ions comprising DNA bases and water molecules. The major technical challenge in this part of the project is the development of a multi-coincidence detection system for the characterisation of ionisation showers, electron emission, and free radical production induced by proton-cluster collisions. These inter-molecular processes are believed to play important roles in radiation damage to living material.

The need for more sustainable paints and coatings, which do not release harmful chemicals into the environment when drying, has driven major recent advances in waterborne products. However, a new manufacturing approach is now crucial to produce the next generation of waterborne paints and coatings to help tackle pressing economic and societal challenges, such as healthcare associated infections and the need to increase our production of renewable energies. The accumulation of pathogenic bacteria on surfaces is one of the leading causes of healthcare associated infections, which killed over 5,500 NHS patients in 2017 and cost the NHS more than £2.3 billion per year. New and more effective antibacterial coatings are therefore urgently needed to reduce bacterial accumulation on clinical surfaces and minimize the occurrence of healthcare-associated infections. My platform technology will further be transformative for the renewable energy sector. Although we can fabricate devices which convert over 45% of sunlight into electricity, most solar panels are located in arid or semi-arid regions, where their efficiency can be reduced by up to 30% because of dust and pollen accumulated on the panels. Currently, the anti-soiling coatings that keep solar panels clean are based on fluorinated components that have a have a long-lasting persistence in the environment and high tendency to accumulate in animals and humans. My proposed approach to fabricate anti-soiling coatings will reduce our dependency on fluorinated materials, increasing sustainability and reducing costs. This Fellowship aims to overcome these challenges by developing a bioinspired platform technology that will act as a springboard for the next generation of sustainable functional paints and coatings. As the base of the technology, structures found in the skin of insects that survive floods in the rainforest will be mimicked using a self-assembly process where the different building blocks order themselves during drying. These structures will provide self-cleaning properties to the coatings that are not based on the composition or chemistry of their ingredients (avoiding the need for fluorinated components) but on the surface geometry. This platform technology will then be adapted initially to add coating properties that will target the challenges of healthcare associated infections and solar panel efficiency reductions. To tackle healthcare associated infections, nanomaterials that kill bacteria, in the form of copper or zinc oxide nanoparticles, will be added to the coating formulation. The distribution of these nanomaterials will be optimized to locate them at the top surface of the coating, where they will be most effective as they will be in contact with adhering bacteria. These coatings will be tested in a real hospital environment, to quantify the reduction in bacterial growth when compared with a surface that has not been coated. To increase the efficiency of solar panels, nanomaterials that increase the resistance to wear and abrasion in arid climates will be added to the coating formulation. The composition of the coatings will be tuned to control their optical properties and minimize the adverse effects that sunlight reflection has on the efficiency of solar panels. The coatings will be tested in a real solar platform located in a desert, comparing the efficiency of a coated panel versus an uncoated one. My Fellowship will be transformative in its focus on reproducing the conditions that the paint industry uses when developing new products. In particular, the challenge of obtaining the same structures in a high viscosity/thickness paint, which is required to prevent paint sagging/dripping after application, will be addressed. This will be done in collaboration with three industrial paint partners, as well as preparing pilot scale paint formulations, to ensure a route towards innovation and product development.

Radiotherapy kills cancerous cells by repeatedly targeting a tumour with high energy radiation. Although image assisted pre-treatment planning based on CT is performed to minimise the amount of healthy tissues being irradiated, the planned treatment is delivered in a manner that is effectively blind, because there is no monitoring of the patient motion and internal anatomy during radiation treatment delivery and no, dynamically modelled, consideration of possible body change during treatment period. This uncomfortable state of affairs persists worldwide, despite complex new treatments and image guided radiotherapy (IGRT) which members of the consortium helped to develop. Furthermore, there is a concern on the additional imaging radiation dose to the patient from the IGRT. Hence, the MEGURATH project was proposed to introduce metrology guided radiotherapy (MGRT), where the patient is measured, imaged and modelled during treatment delivery via optical sensing to provide non-invasive, radiation-free, real-time 3D patient position monitoring, and dynamic deformation modelling to determine the internal anatomical changes. The project is considered as a significant one with a leap forward approach for a grand challenge, and has attracted interest from Elekta Oncology Systems, Philips Medical Systems, VisionRT and NHS-IP.The MEGRATH programme consists of not only comprehensive research activities with diverse theoretical topics, but also translation of science and technology to the first purpose built IGRT research facility in the UK at the Christie Hospital, and the support of clinical studies selected from breast, lung, bowel, prostate and bladder cancers. The project is expected to make a world class contribution to radiotherapy by increasing our understanding of tumour target and organ at risk behaviour, treatment delivery and control of their impact on cure and complications. The marriage of anatomical modelling and dynamic 3D measurement on demand 'in-treatment', using light rather than ionising radiation like X-rays, will offer the opportunity to gain the pole position in engineering and computational science for oncology. The Collaborating for Success through People call is a valuable opportunity to support, complement, utilise and extend the MEGURATH project, thereby enabling the consortium to maintain, defend and widen its lead.The proposed programme of people-based activities starts with exploratory mutual visits by the PIs and group leaders for exchange of knowledge, creation of ideas and development of active collaboration, followed by two-way investigative short visits and relatively long research visits by researchers for synergistic development, cross application and performance evaluation of promising approaches, and finished by a workshop to provide a venue for the consortium to lead the development of a joint EU project proposal with the participating partners. To provide significant added value to the MEGURATH project in terms of scientific knowledge and new clinical applications, 7 eminent research groups and 1 leading 3D equipment company are selected for participation in the proposed people-based activities:-Two from Poland: Telemedicine Group from AGH University of Science and Technology, and Department of Scientific Information from Jagiellonian University Collegium Medicum;-Three from France: one from the French National Institute for Research in Computer Science and Control (INRIA), and the other two from National Centre for Scientific Research (CRNS), namely, Lyon Research Centre for Images and Intelligent Information Systems (LIRIS) and Signal and Image Processing Research Laboratory (ETIS);-One from Germany: Institute for Electronics Signal Processing and Communications (IESK) at Otto von Guericke Universitt Magdeburg; -One from Italy: Signals and Images Laboratory from the National Research Council (CNR); and-3dMD with the company headquarters in the USA.

The Collaborative Computing Project for NMR (CCPN) was started in 2000 to improve the interoperability of software for biomolecular Nuclear Magnetic Resonance (NMR), and to promote a collaborative community for software users and programmers. Over the past fifteen years, the project has produced the CcpNmr suite of software for interactive NMR data analysis and software integration, which is now used worldwide by >1000 users. Through its conferences and workshops, CCPN also promotes best practices in both computational and experimental aspects of NMR, thus helping to maximise the impact of biological NMR research. CCPN has a leading role in the development of a NMR data-exchange format and coordination of NMR instrumentation proposals for RCUK and BIS. With the current proposal we seek to continue the CCPN project and to further expand its user community. Hence, over the next grant period we aim to: 1. Maintain and expand the CCPN code base. 2. Expand the capabilities and versatility of the CCPN software package. 3. Facilitate NMR-based scientific developments in collaboration with the partners of the project and the NMR community at large. 4. Promote and expand user uptake and user development of the software. 5. Provide support for research data management (RDM). 6. Support the training of researchers, sharing of knowledge and exchange of best-practices by the UK and international NMR community.