Advances in fit for use manufacturing of biopharmaceutical drug delivery and pharmaceutical systems are now required to fit Quality by Design (QbD) models. These current regulations require excellence to be built into the preparation of emerging products (both material and process) thereby leading to product robustness and quality. In addition, industrial needs (economical and reproducible quality enhancement) are driving manufacturing towards continuous processes over batch type processes which also rely on QbD (for integrity and quality). EHDA technology is a robust process that has been utilised in various formats (e.g. electrospinning, electrospraying, bubbling and even 3D printing) and is favourable due to applicability with the development of stable nanomedicines and biopharmaceuticals, the emergence of this technology is clearly evident in the UK and on the global scale. Attempts in scaling up (for suitable pharmaceutical scale) and in tandem with continuous processes (including controlled manufacturing) have been very limited. There also, now, remains a huge void in the adaptation of sensible QbD (multi-variate) for the current methods developed and also those required by industry. While lab scale research continues with the ongoing development of such processes (e.g. nanomedicines, smart and controlled delivery), the transition to industry or the clinic will have to meet these regulations (and scales) for there to be a real impact, which is now, also, an important aspect of grass root research in the UK. The EHDA network brings together specialists from academia and industry to advance this technology through several means. Firstly, initiating developments towards a real-viable scale for Pharmaceutical production. Secondly, to incorporate developments in lean manufacturing and legislation (e.g. continuous manufacturing, online diagnostics, QbD and adaptable scale). Thirdly, to marry optimised lean technologies with novel and emerging macromolecular therapies and actives. The network has a wide range of activities and initiatives which will lead to significant developments (and collaborations) in an area of increasing global interest (EHDA processes) - but currently only on a viable lab scale to date. This network will be the first of its kind and will serve as the central and pioneering hub in this remit.

Doctoral Training Partnerships: a range of postgraduate training is funded by the Research Councils. For information on current funding routes, see the common terminology at https://www.ukri.org/apply-for-funding/how-we-fund-studentships/. Training grants may be to one organisation or to a consortia of research organisations. This portal will show the lead organisation only.

MRI scanners are used widely to diagnose disease and to understand the workings of the healthy body. However, while useful for some diagnoses, they do not capture tissue properties at microscopic length scales (thousandths of a millimetre) where important processes occur, e.g. in the 'axons' connecting different brain areas, or in cells in vital organs, e.g. liver. Such detailed examination usually requires an invasive 'biopsy' which is studied under a microscope. However, biopsies only provide information about small regions of an organ, are destructive and so cannot be performed repeatedly for monitoring, and can be risky to collect, e.g. in the brain. This project assembles engineers, physicists, mathematicians and computer scientists to develop new MRI methods for quantifying tissue structure at the microscopic scale. The principal approach looks at how fine tissue structure impedes the movement of water. Current MRI hardware restricts measurement to relatively large molecular displacements and from tissue components with a relatively strong and long-lived signal. This blurs our picture and prohibits us from quantifying important characteristics, such as individual cell dimensions, or packing of nerve fibres. The sensitivity of MRI to smaller molecular movements and weaker signals is mainly limited by the available magnetic field gradients (controlled alterations in the field strength within the scanner). We have persuaded MRI manufacturers to build a bespoke MRI system with ultra-strong gradients (7 times stronger than available on standard MRI scanners) to be situated in the new Cardiff University Brain Research Imaging Centre. One similar system currently exists (in Boston, USA) but is used predominantly to make qualitative pictures of the brain's wiring pattern. Our team has the unique combination of expertise to develop and exploit this hardware in completely new directions. By designing new physics methods to 'tune' the scanner to important (otherwise invisible) signals, developing new biophysical models to explain these signals, and suppressing unwanted signals, we will be able to quantify important tissue properties for the first time. Making such a system usable poses several key engineering challenges, such as modelling of electromagnetic fields, to deal with confounds that become significant with stronger gradients, and modelling of the effects on nerves/cardiac tissue, to impose safety constraints. However, the current work of the consortium of applicants provides strong starting points for overcoming these challenges. Established methods for accelerating MR data acquisition will be compromised with stronger gradients, requiring development of new physics methods for fast data collection. Once achieved, faster acquisition and access to newly-visible signal components will enable us to develop new mathematical models of microstructure incorporating finer length-scales to increase understanding of tissue structure in health and disease, and to make testable predictions on important biophysical parameters such as nerve conduction velocities in the brain. This will result in earlier and more accurate diagnoses, more specific and better-targeted therapy, improved treatment monitoring, and overall improved patient outcome. The ultimate goal is to develop the imaging software that brings this hardware to mass availability, in turn enabling a new generation of mainstream microstructure imaging and macrostructural connectivity mapping techniques to translate to frontline practice.

We are all familiar with the concept of travel, and visiting York from Glasgow is conceptually a trial matter. When we reflect on this process, however, there are lots of potential questions we might ask about the mode of transport, the route and the potential to get lost. A similar range of questions could be asked about chemical reactions. We select starting materials and seek to transform them into products. The route we choose is equally complex. Now, however, the participants are much smaller and very special methods are needed to view them. Furthermore, with an optimal solution we get the most product from the least starting material using the least amount of energy and other resources as possible. If think of a reaction that is undertaken on the 1,000,000 tonne scale it is also clearly vital to minimise waste. In Chemistry, there is a very special and often expensive method called nuclear magnetic resonance spectroscopy (NMR) that allows us to take pictures of the participants as they travel from starting materials to products. This methods is normally very insensitive and hence very expensive large magnets are required. If we want to use this technology to deliver clean and efficient chemistry on an industrial scale we need to find a way to work with smaller lower cost magnets, ideally using the Earth's magnetic field. In this project we aim to develop a new method using such low-magnetic field NMR devices to follow the route taken by molecules during their conversion into high value products in both laboratory and industrial settings. We will use a special form of hydrogen gas, known as parahydrogen to increase the sensitivity of the NMR measurement to a level that will allow to achieve this goal. Parahydrogen was actually the fuel of the space shuttle and one might view it here as acting like a molecular microscope whilst at the same time removing (filtering) any unwanted signals from spectators to the reaction of interest. We will build-up our understanding of the reactions route by taking our NMR pictures which contains precise information about the identity of the participants (molecules) at different times after the start of the reaction. This means that we will monitor the same process several times in order to produce the necessary molecular level picture that will ultimately allow us to optimise our chosen reaction. The enhanced level of information that will be provided by our new device will enable scientists and industrialists to develop and optimise reactions in a way that was previously impossible and hence contribute more positively to society.

This proposal bids for £4.5M to both evolve and renew the Loughborough, Nottingham and Keele EPSRC CDT in Regenerative Medicine. The proposal falls within the 'Healthcare Technologies' theme and 'Regenerative Medicine' priority of the EPSRC call. This unique CDT is fully integrated across three leading UK Universities with complementary research profiles and a long track record of successful collaboration delivering fundamental and translational research. Cohorts of students will be trained in the core scientific, transferable, and translational skills needed to work in this emerging healthcare industry. Students will be engaged in strategic and high quality research programmes designed to address the major clinical and industrial challenges in the field. The CDT will deliver the necessary people and enabling technologies for the UK to continue to lead in this emerging worldwide industry.The multidisciplinary nature of Regenerative Medicine is fully captured in our proposal combining engineering, biology and healthcare thereby spanning the remits of the BBSRC and MRC, in addition to meeting EPSRC's priority area.