BIORIMA stands for Biomaterial Risk Management. BIORIMA aims to develop an integrated risk management (IRM) framework for nano-biomaterials (NBM) used in Advanced Therapeutic Medicinal Products (ATMP) and Medical Devices (MD). The BIORIMA RM framework is a structure upon which the validated tools and methods for materials, exposure, hazard and risk identification/assessment and management are allocated plus a rationale for selecting and using them to manage and reduce the risk for specific NBM used in ATMP and MD. Specifically, the IRM framework will consist of: (i) Risk Management strategies and systems, based on validated methodologies, tools, and guidance, for monitoring and reducing the risks together with methods for evaluating them; (ii) Validated methodologies and tools to identify the potential Exposure and Hazard posed by NBM to humans and the environment; (iii) A strategy for Intelligent Testing (ITS) and Tiered Risk Assessment for NBM used in ATMP and MD. BIORIMA workplan consists of 7 workpackages covering the major themes: Materials, Exposure, Hazard and Risk. BIORIMA will generate methods and tools for these themes for use in risk evaluation and reduction. The BIORIMA toolbox will consist of validated methods/tools for materials synthesis; reference materials bank; methods for human/environment exposure assessment and monitoring; (eco)-toxicology testing protocols; methods for prevention of accidental risks – massive release or explosion – A tiered risk assessment method for humans/environment; An intelligent testing strategy for NBM and risk reduction measures, including the safer-by-design approach. BIORIMA will deliver a web-based Decision Support System to help users, especially SME, evaluate the risk/benefit profile of their NBM products and help to shorten the time to market for NBM products.

Increased demand on blood sampling requirements has arisen from prolong lifespan and ageing populations. The use of circulating cell-free nucleic acids (cfNAs) as biomarkers for cancer, non-invasive prenatal testing, organ transplant monitoring and more, has grown in popularity since it is non-invasive (simple blood draw) and easily repeated, allowing the possibility to rapidly establish a diagnosis, a prognosis and even used for theranostic applications. So called "liquid biopsies" and cfDNA analysis could for example allow the fourteen millions of cancer patients diagnosed globally each year to access earlier diagnosis and optimised treatments. However, despite numerous translational research programs the detection of cfNA is not currently implemented clinically in daily practice. Several reasons have been emerged for this, including (i) the difficulty in controlling the different biological, environmental and logistic parameters from blood sampling to the analysis of biomarkers (ii) the cost of the currently available techniques, which limit accessibility (iii) the turn-around time needed to be useful for patients and clinicians. Current sample preparation solutions are multi-step which can introduce variations and lead to an erroneous diagnosis. Additionally these solutions are time consuming, not amenable to near-patient extraction following blood draw, and require highly trained technicians. The optimisation of the extraction of cell-free circulating markers is key to their translation from the research setting to clinical deployment. The lack of engineering solutions to address the specificities of circulating cell-free nucleic acid extraction, underpins this programme. To meet the requirements of future healthcare industry, the work proposed will integrate novel advanced materials such as electrospun fibres, packaged with on-chip reagents in a microfluidic cartridge to extract cfNAs from blood. Deployed near-patient, this technology will protect the biomarkers from enzymatic degradation and enrich them against the rest of the nucleic acids present in the sample, allowing an unparalleled standardisation and instant preservation of the true disease state until analysis. The solution proposed involves the use of single-use cartridges, and could generate a significant amount of additional medical waste if implemented. Therefore this programme has a unique sustainable manufacturing component, looking into the use of a naturally-derived plastic (poly-lactic acid) to prototype and manufacture low carbon footprint, disposable, microfluidic cartridges, potential applicable to a large range of point-of-care devices. The solutions developed in this programme have the potential to significantly reduce the overall cost of sample preparation in the field of circulating biomarkers, as well as increasing the robustness and reliability of a range of biomarkers with direct application in clinical diagnostic and biomarker and drug discovery, in a sustainable fashion. Hand-in-hand with novel sensing solutions, this work has the potential to increase life quality from earlier, quicker diagnosis through optimised treatment and better care management. With the global liquid biopsy market forecasts to reach $4.5 billion by 2020, front-end sample preparation constitutes an important area for the UK economy.

For many of us, there is hardly any more life-changing disability imaginable than loss of sight. Whether through trauma or disease, the inability to rely on visual cues impacts on all matters of daily life; doing your job or bringing your kids to school are no longer straightforward activities. Blindness or reduced sight is often caused by a damaged conjunctiva, a super-thin layer of cells covering the white of your eye and inside of your eye-lids. Fortunately for many in the western world, repair of this damaged tissue is possible through established surgical procedures, many of them using a tissue graft sourced during birth called the amniotic membrane (AM). Microscopically, the AM closely resembles the damaged ocular tissue and can be used as a patch (Amniotic Membrane Transplantation, AMT) to help the body regenerate the damaged tissue. There is however a caveat, our population is ageing and AMT is expected to rise. As it can only be sourced during birth (usually during C-section), AM supply is not available in (virtually) unlimited supply, increasing its price and healthcare costs. Furthermore, AM is often stored in expensive facilities with a significant administrative burden (donor tissue traceability), further adding to the costs. Last but not least, donor tissue regulation, unlike medical device regulation, is complicated for international deployment. In developing countries such as India and China, loss of sight is closely correlated with occupational hazards (i.e. chemical burns of the eye) and is estimated that over 2M people in India alone would benefit from AMT procedures. However, high costs and non-existent national tissue donation regulation literally leave these people in the dark. The aim of the proposed project is to assess the technical and commercial feasibility of developing a fully resorbable synthetic AM alternative. The use of nano-fibre technology, called electrospinning, to fabricate such a device will closely mimic the native AM and ocular tissue. Successful adoption of such a device would directly address the global shortage in AM, easing the pressure on tissue banking and simplifying regulation for swift market deployment (medical device). Furthermore, the manufacturing process can be scaled to meet global demand, allowing cost-effective production for low-income countries and making a truly impact on a global level, made in Great Britain.

Taken together the imaging Facilities on the Rutherford Campus will be without equal anywhere in the world. The suite of synchrotron X-ray, neutron, laser, electron, lab. X-ray, and NMR imaging available promises an unprecedented opportunity to obtain information about material structure and behaviour. This infrastructure provides an opportunity to undertake science changing experiments. We need to be able to bring together the insights from different instruments to follow structural evolution under realistic environments and timescales to go beyond static 3D images by radically increasing the dimensionality of information available. This project will use many beamlines at Diamond and ISIS, combining them with laser and electron imaging capability on site, but especially exploiting the 3.3M investment by Manchester into a new imaging beamline at Diamond that will complete in Spring 2012.Traditionally a 3D images are reconstructed from hundreds or thousands of 2D images (projections) taken as the object is rotated. This project will:1) Deliver 3D movies of materials behaviour. 2) Move from essentially black and white images to colour images that reveal the elements inside the material and their chemical state which will be really useful for studying fuel cells and batteries.3) Create multidimensional images by combining more than one method (e.g. lasers and x-rays) to create an image. Each method is sensitive to different aspects.4) Establish an In situ Environments Lab and a Tissue Regeneration lab at the Research Complex. The former so that we can study sample behaviour in real time on the beam line; the latter so that we can study the cell growth and regeneration on new biomaterials. A key capability if we are to develop more effective hard (e.g. artificial hip) and soft tissue (artificial cartilage) replacements.These new methods will provide more detail about a very wide range of behaviours, but we will focus our experiments on materials for Energy and Biomaterials. In the area of energy it will enable us to:Recreate the conditions operating inside a hydrogen fuel cell (1000C) to find out how they degrade in operation leading to better fuel cells for cars and other applicationsStudy the charging and discharging of Li batteries to understand better why their performance degrades over their lifetime.Study thermal barriers that protect turbine blades from the aggressive environments inside an aeroengine to develop more efficient engines.Study the sub-surface corrosion of aircraft alloys and nuclear pressure vessels under realistic conditions improving safetyStudy in 3D how oil is removed from the pores in rocks and how we might more efficiently store harmful CO2in rocks.In the area of biomaterials it will enable us to recreate the conditions under which cells attach to new biomaterials and to follow their attachment and regeneration using a combination of imaging methods (laser, electron and x-ray) leading to:Porous hard tissue replacements (bone analogues) made from bio-active glasses with a microstructure to encourage cell attachmentSoft fibrous tissue replacements for skin, cartilage, tendon. These will involve sub-micron fibres arranged in ropes and mats.Of course the benefits of the multi-dimensional imaging we will establish at Harwell will extend much further. It will provide other academics and industry from across the UK with information across time and lengthscales not currently available. This will have a dramatic effect on our capability to follow behaviour during processing and in service.