Polymer composite membranes containing nanostructured fillers have many potential applications in industrial sectors. For example, in emergent technologies ranging from carbon dioxide capture and sequestration to hydrogen purification, and for use in water desalination and vapor recovery systems, as well as in medical devices and smart sensors. Next-generation mixed-matrix membranes (MMMs) which incorporate porous metal-organic frameworks (MOFs), offer the unique opportunity for combining high selectivity and chemical tuneability of MOFs with the ease of processing and robustness intrinsic to conventional polymers. While the development of such MOF-polymer mixed-matrix membranes is in its infancy, there are already archetypal composite systems recently discovered that demonstrate substantial improvement in its functional performance (particularly gas/liquid permeability and selectivity properties). Much progress has been accomplished in this rapidly growing area. However, many important questions remain to be answered about its core mechanical-thermal properties and long-term chemical stability; its structure-function mechanical correlation information is scarce and, hitherto membrane structural integrity (under static or dynamic loading) is not well understood. This project will address the aforementioned problems, establishing an accurate knowledge of the underpinning physical properties, and pinpointing microscopic mechanisms that control the structural and functional performance of novel membranes. This research will yield systematic structure-function relationships, formulate innovative methodologies and detailed material model descriptions, which will enable prediction, rational design and engineering of new membranes. Resilient composite membranes featuring an improved damage tolerance coupled with optimal functionalities will enable many energy, environmental and multifunctional technologies benefitting the wider public.

Within Europe, chronic diseases are currently the leading cause of mortality and morbidity. In England alone, there are 15m people with long-term conditions who are estimated to account for 70% of the total health and social care spend. A significant factor in the management of chronic disease is the long-term nature of the treatment. Although often very efficient, therapies are only effective when combined with long-term medication adherence from the patient. Unfortunately, patient adherence is typically poor within long-term disease patient populations; only about 50% of patients adhere to their treatment regimes. Poor adherence can be addressed by the simplification of therapeutic regimes through reducing the dosing frequency. For example, when self-administered treatment regimens such as oral dosing are replaced with long acting formulations adherence can be greatly improved. Additionally, reducing the frequently of dosing is known to be appealing to patients with long-term therapy requirements. This proposal seeks to develop a new drug delivery system that could be easily injected into the body and would provide long-acting drug release. This technology would address issues caused by poor medication adherence. The drug delivery system would be composed of responsive polymer nanoparticles and drug nanoparticles that form a nanocomposite, entrapping a reservoir of drug upon injection into the body. After the drug has been released the materials would degrade into non-toxic components and leave the body. In order to accelerate the development of this novel technology toward clinical use, this project will consist of closely-integrated materials synthesis and biological assessment. The materials involved will be simultaneously prepared and evaluated in the presence of cells to check that they are biologically compatible. The responsive polymer nanoparticles will be synthesised to combine responsive behaviour with tuneable degradation, while the design of the drug nanoparticles will allow the drug release rate to be altered. A small number of optimised materials will undergo detailed biological evaluation. The resulting novel, biodegradable, nanocomposite material would have appropriate physical and biological properties for injection into the body. This technology will provide tuneable, long-acting release of drugs for the treatment of chronic disease.

The ability to reprogram a cell to direct the packaging of specific molecules into discrete membrane envelopes is a major objective for synthetic biology. This controlled packaging into membrane vesicles will allow biologists to create a plethora of new technologies, which could be applied in both biotechnology and medical industries. These include the generation of novel metabolic factories within a cell for energy production; for rapidly packaging toxic proteins into contained environments before they have a chance to harm any normal metabolic activities, so they can be purified for use in subsequent pharmaceutical applications; the creation of protective packages filled with difficult to isolate biomolecules, which can be kept in stable environment to allow their storage and purification; and also generate simple vehicles for delivery of drugs and vaccines to the patient. Here, we provide a simple and cost effective solution to the problem. We have discovered a method to program a simple cell to create membrane packages which can be filled with different molecules of interest. We have not only discovered a way to fine-tune the shape of the membrane package (e.g. into long tubular matrices or spherical vesicles), but we have also devised controllable mechanisms that either keep the package within, or secrete the package out of the cell. Thus we have therefore made a landmark breakthrough in synthetic biology research. A major aim of this BBSRC key strategic area is to design from new and improve on natural systems and exploit these for the production of commercially important chemicals and biotherapeutics, which is what we have achieved here. Our overall aim in this project is to make use of these exciting discoveries to modify cells, making them capable of creating membrane bound packages filled with any protein of interest, which can then either be secreted from the cell and isolated from the culture media using a simple one step filtration technique, or stored within the cell where it can be made to act as a metabolic micro-factories, producing useful and/or valuable molecules without intoxicating the cells. In this way we hope to develop new ways to produce fine and platform chemicals as well as biotherapeutics. Through the research described in this application we are certain that we will be able to contribute to the development of new sustainable approaches for generating biotherapeutics, which will be assimilated into production techniques by diverse bio-industries.

Our use of metals is so important that it defines periods of human civilisation - from the Bronze Age (c. 3600 BC) to the Iron Age (c. 1100BC). With our present-day mastery of metals and alloys, the mounting emphasis is now on resources and the environment. The metals industry is looking at new ways to produce lighter, stronger materials in a sustainable, economical and pollution-free manner. Ultrasonic cavitation treatment offers a route to meet these goals. Ultrasonic treatment of the second commonest structural metal, aluminium, causes degassing through the evacuation of dissolved gases that lead to porosity, grain refinement to assist formability, dispersion and distribution of solid or immiscible phases to improve mechanical properties during recycling etc. In spite of the benefits, transfer of this promising technology to industry has been plagued by difficulties, especially in treating large volumes of liquid metal typical in processes such as 'Direct Chill' continuous casting for ingot production. Fundamental research is needed to answer the following practical questions: what is the optimum melt flow rate that maximises treatment efficiency whilst minimizing input power, cost, and plant complexity? What is the optimum operating frequency and acoustic power that accelerates the treatment effects? What is the optimum location of an ultrasonic power source in the melt transfer system in relation to the melt pool geometry? Answering these questions will pave the way for widespread industrial use of ultrasonic melt processing with the benefit of improving the properties of lightweight structural alloys, simultaneously alleviating the present use of polluting (Cl, F) for degassing or expensive (Zr, Ti, B, Ar) grain refinement additives. Capitalising on the unique expertise gained by the proposers during the highly successful UltraMelt project (22 publications), this research aims to answer the challenge of efficiently treating large liquid volumes by developing a comprehensive numerical model that couples all the physics involved: fluid flow, heat transfer, solidification, acoustics and bubble dynamics. Greenwich will lead the development of an improved cavitation model, based on the wave equation and conservation laws, and applied to the two-phase problem of bubble breakup and transport in the melt, and its interaction with solid inclusions (e.g. the solidification front of an aluminium alloy or of any intermetallic impurities present). To improve the efficiency of the ultrasonic cavitation treatment in flowing metal, a launder conduit will be used. The sensitivity of the process with respect to different adjustable parameters (source power, frequency, time in the cavitation zone, baffle location ...) will be examined with parallel computations in a 3D model of melt flow in the launder. This computer model will be validated by experiments in both transparent liquids and aluminium. Water and transparent organic alloy experiments will use a PIV technique by Oxford Brookes University to measure the size, number and positions of bubbles and compared these with the numerical predictions. Mechanisms of intermetallic fragmentation and particle cluster breakup will be observed in real time using a high speed camera at Brunel University and X-ray radiography at the Diamond Light Source facility. Mechanical properties of intermetallic impurities at temperatures relevant to melt processing will be measured using unique nano-indentation technique in collaboration with Anton Paar Ltd. Cavitation pressure measurements in launder conduits will be conducted at Brunel University and the empirical observations will be compared with model predictions. The fully-developed model will be used to optimise the ultrasonic melt treatment in melt flow during direct-chill casting and verified using pilot-scale facilities at AMCC (Brunel, with support of Constellium) and industrial-scale facilities at Kaiser Aluminum.

The flow of geomaterials through the natural environment is of great societal and economic importance. Understanding the flow of these materials - such as magma, submarine sediments, drilling muds, and fluids associated with carbon capture and storage (CCS) - is essential if we are to forecast volcanic eruptions, protect undersea telecoms infrastructure, and lower the impacts of fossil fuel production and use. The key to understanding and predicting flow behaviour lies in accurate measurements of 'rheology', which describes how a material deforms when a force acts on it. This project will create a facility for measuring the rheology of geomaterials, train academic and industrial researchers from the UK's Earth and environmental sciences community to use it, and act as a forum for knowledge exchange in the field of rheology and flow of geomaterials. Geomaterials are often complex. For example, magma is made up of three different phases - molten rock, solid crystals, and deformable gas bubbles - and their relative proportions change as the magma rises through the Earth's crust, decompresses, and cools down. It is common for all geomaterials to change their rheology as they experience extreme variations in temperature and pressure as they move through the upper crust, or across the ocean floor. As a result, the rheology of geomaterials is highly complex, requiring specialist equipment to measure it. It is also essential to be able to measure it over a wide range of pressures and temperatures. There is currently no facility available in the UK that can do this. The new facility is unique because: 1. It can operate over temperatures from -100C to +1600C covering the full range of temperatures found on the Earth's surface, from Antarctic ice-sheets to volcanic lava flows. 2. It can operate at pressures up to 1000 times greater than atmospheric pressure, up to 300C. This covers pressures and temperatures in the deepest oceans, and the deepest boreholes in the Earth's crust. 3. It includes a unique instrument, capable of measuring rheology while replicating the complex changes in flow speed and direction that are common in natural environmental flows. The manufacturer will work with us to validate this functionality and extend it from 600C to 1000C so that we can replicate complex flows of magma. 4. The facility will link in with extensive existing equipment at Durham University that can be used to measure other properties of geomaterials at high temperature, such as the growth or melting of different crystals, changes to the internal structure, and physical properties of drilling muds. The facility will be used by researchers from across the UK to solve a wide range of problems, such as: * What controls where lava flows go? This depends on the rheology of lava as it cools and solidifies. * How can we protect aircraft jet engines from airborne particles? This depends on the mechanical properties of the material produced when the particles weld together in the engine. * How do we reduce the environmental impact of drilling for extraction of resources or energy? We can engineer effective water-based drilling muds with much lower environmental impact than current oil-based muds. We can also develop effective strategies for pumping captured CO2 into crustal storage reservoirs to reduce its climate impact. Both applications depend on measuring the rheological behaviour of geomaterials at the high pressures and temperatures found in the crust. The UK has a large, world-leading community of researchers working on environmental flows involving geomaterials. We will promote the facility as a hub for this research by making it available at cost-price to internal and external users, and by running training and knowledge exchange workshops to bring researchers from universities and industry together. We will support users in preparing research projects that use the facility, and keep an open repository of outputs and data.