The Micro Reactor Research Group at Hull has now carried out over 200 man-years of research, to establish the fundamental design and operational parameters e.g. channel shape, size, flow methodology and surface functionalisation, that give micro fluidic devices significant advantages in the field of analytical chemistry. Recently this work has been extended into the field of cell biology and now features a number of ongoing collaborative projects with the Cellular Processes Group at Hull. In general the main practical advantages of micro fluidic methodology, apart from requiring small sample sizes, can be summarised as devices which offer (i) a very high degree of spatial (nano meter) and temporal (micro second) control of processes originating from diffusive mixing processes occurring within a laminar flow regime; (ii) the possibility of generating extremely high surface to volume ratios to intensify liquid/surface or surface/surface interactions and (iii) the opportunity to integrate complex processes with non-invasive analytical measurements in order to achieve significantly better temporal and spatial resolution of dynamic processes than is currently possible. At present the main thrust of the work at Hull is to develop integrated process/measurement devices for forensic/environmental and drug discovery based processes which involves approximately 28 research staff drawn from a range of scientific and engineering disciplines. Given the support at Hull to develop integrated cellular processing and measurement technology it would seem timely and advantageous to align this current proposal with ongoing work whilst developing a unique focus in tissue based research. Thus by combining new science with a significant critical mass of research and know-how considerable added value will be achieved with the proposed funding. We propose therefore to use the expertise that resides within the pool of researchers at Hull to establish (micro fluidic) and exploit (biomedical) micro fluidic methodology in the area of tissue processing and by doing so establish a unique link between research scientists and clinicians. Biological tissue obtained, for example, from a small biopsy, represents a complex aggregation of cell types arranged within an intricate non-cellular structure which supports intercellular connections. However, maintaining a stable tissue sample for study in the laboratory has proved to be very difficult as nutrient delivery, removal of waste products and gaseous exchange all need to be achieved. In nature these processes are carried out via a complex network of blood and lymphatic vessels which give dynamic perfusion of the tissue. Micro fluidic systems mimic nature with their high surface to volume ratio, inherent fast perfusion and localised (single cell) interrogation capability, and so offer an ideal microenvironment for the development of novel technology encompassing integrated measurement capability. The proposed micro fluidic devices will enable the study of cell function and the role of the extracellular (EC) matrix in normal and diseased tissues to be carried out in a novel way. This in turn will lead to significant scientific advances in the understanding of cell and tissue biology. In this project the EC environment between cells will be conditioned using a selection of reagents that will modify the chemical and biological interactions in a defined and controlled way. By then testing the conditioned tissue with a drug-like compound, the effect of conditioning (i.e. modified EC environment) can be used to identify the importance of individual cell interactions. For example, tissue could be conditioned with a calcium inhibitor e.g. EDTA which will disrupt integrin function (a family of cell surface molecules involved in cell binding) allowing the tissue, which is otherwise unchanged, to be tested for responses to cytotoxic drugs in order to identify the role of integrins in mediating drug activity.

Forensic science is an important tool in the fight against crime and this proposal will build on cutting edge research to create technology that will revolutionise the way DNA fingerprinting can be used at crime scenes to generate quick and accurate answers where they are urgently needed. Over the past decade DNA fingerprinting, together with the establishment of a national database, has becoming one of the most important forensic tools in the fight against crime, with its unique analytical capability to biometrically profile suspects. At present such analysis is carried out in the laboratory environment which requires samples to be collected from the scene of a crime, and then be transported to a central facility for subsequent analysis. This current practice clearly adds additional transport and storage time which in turn increase costs and adds unwanted delays in analysis times. Therefore the development of field-based methodology could prove to be most valuable in generating more rapid DNA-based intelligence. Such capability will not only allow DNA profiles to be obtained in say less than 30 minutes but the parallel operation of such methodology will allow reasonably large numbers of samples to be run before the crime scene becomes contaminated or corrupted. Whilst the basic analytical methodology required to carry out DNA analysis is well established (i.e. extraction and purification of the DNA from the biological sample, amplification of the target DNA by polymerase chain reaction (PCR) and electrophoretic size separation and fluorescent detection of the DNA fragments) the development of a portable device which integrates these hitherto separate functions is a unique challenge which form the basis of this proposal.In order to achieve true hand-held portability the technology needs to be mechanically and chemically/biochemically robust and have low power requirements for battery-based operation. In this proposed project the combined expertise of the applicants will be focused on generating a prototype instrument that will meet the portability requirements outlined above. The work builds on early encouraging research in which micro fluidic methodology coupled with efficient microwave-based heating has been demonstrated to be suitable for the PCR amplification of DNA samples. The micro fluidic approach, which offers small sample capability (microlitres), has already been shown by number of researchers, including the applicants, to offer a rapid approach to the thermal PCR cyclic process suggesting realistic processing times of around 20 minutes. Following amplification of the target DNA, analysis can effectively be performed using capillary electrophoresis-based separations with fluorescence detection and once again the micro fluidic approach has proved advantageous in offering an efficient and rapid separation process within a few minutes. The prototype developed in this application will be based on an integrated micro fluidics manifold or chip that will enable sample extraction/preconcentration, PCR amplification and DNA fragment separation to be achieved whilst exploiting low power requirements by using manual and electrokinetic fluidic pumping, low power solid state microwave-based heating and low power fluorescent detection. Whilst all of the sample processing stages indicated have been demonstrated separately, it is important to stress that there is a real scientific challenge in bringing them all together in an integrated unit with compatible functions and requirements at each stage. If successful, the product will be an example of novel low-cost but highly functional technology, which will be of immediate benefit in the fight against crime. We know this is not going to be easy but we believe the research team assembled around this proposal can get the job done and break the integration barrier to success that currently exists.

Quantum mechanics tells us how the world works at its most fundamental level. It predicts very strange behaviour that can typically only be observed when things are very cold and very small. It has an inbuilt element of chance, allows superpositions of two different states, and admits super-strong correlations between objects that would be nonsensical in our everyday world / entanglement . Despite this strange behaviour, quantum mechanics is the most successful theory that we have ever had / it predicts what will happen almost perfectly!Although the theory of quantum mechanics was invited at the beginning of the last century, quantum information science has only emerged in the last decades to consider what additional power and functionality can be realised by specifically harnessing quantum mechanical effects in the encoding, transmission and processing of information. Anticipated future technologies include quantum computers with tremendous computational power, quantum metrology which promises the most precise measurements possible, and quantum cryptography which is already being used in commercial communication systems, and offers perfect security.Single particles of light / photons / are excellent quantum bits or qubits, because they suffer from almost no noise. They also have great potential for application in future quantum technologies: schemes for all optical quantum computers are a leading contender, and photons are the obvious choice for both quantum communication and for quantum metrology schemes for measuring optical path lengths. There have already been a number of impressive proof-of-principle demonstrations of photonic information science.However, photonic quantum technologies have reached a roadblock: they are stuck in the research laboratory. All of the demonstrations to date have relied on imperfect, unscalable and bulky elements with single photons travelling in air. This is not suitable for future technologies. In addition there has been no integration of these critical components which will be essential for the realisation of scalable and practical technologies. This project aims to address these problems by developing single photon sources based on diamond nanocrystals, optical wires on optical chips, and superconducting single photon detectors, to the high performance levels required. It also aims to integrate all of these components on a single optical chip, and thus bring photonic quantum technologies out of the laboratory towards the marketplace.

The vision of the proposed EPSRC Centre for Innovative Manufacturing (CIM) is to break new ground by creating the concept of the factory on the machine to deliver to UK industry disruptive solutions in advanced manufacturing for the next generation of high added-value products. Embracing and developing the factory on the machine concept will be a critical step in enabling a sustainable manufacturing sector for the next generation of engineered products dependent on precision and micro/nano scale geometrical accuracy and functionally optimised surfaces.Key challenges to achieving the concept of the factory on the machine are: Challenge I: Elevation of machine tool accuracies beyond the present formidable barriers to those currently only achievable by advanced metrology equipment in stable operating environments, through embodiment of our leading research in machine error modelling and reduction. Challenge II: Building sound foundations for the factory on the machine by developing new metrology instrumentation, used within the machine environment and a novel toolkit, for geometrical characterisation (size, geometry and texture) for the next generation of engineering products.In order to answer the challenges and vision of the CIM, the overall research programme is divided into key research themes and platform type activities. The two major thematic areas of research within the CIM are:Theme I - factory on the machine : to create a configurable and scalable platform for implementing advanced manufacturing and measurement technologies on machines ranging from nano, micro to large volume capability. Analogous with the lab on a chip concept, the delivered system will fuse production capability with high-precision metrology to provide an automatic quality control feedback loop for both product quality and machining process sustainability. Theme II - underlying techniques for factory on the machine : The aim here is to create new measurement and specification methodologies and products (smart software and hardware systems) and to deliver an underpinning new technology in measurement science for micro/nano scale surfaces on macro/meso dimensioned objects with Euclidean or non-Euclidean (non-rotational and non-translational symmetry) geometry and deterministic texture all to be applied within the factory on the machine environment. Platform activities will encompass: (i) Retention and recruitment of key identified research and technique staff; (ii) Generation of new knowledge and instrumentation derived from fundamental EPSRC, EU and TSB funded research projects (iii) Support blue sky research and feasibility studies in machine tool/surface technology and (iv) Knowledge exchange to key partners through specific projects, collaboration agreements, licensing, workshops, training, national networks, sand pits and open days. Platform activities will be targeted towards key partners firstly, their supply chains/end users, then secondly wider sectors of UK industry, as well as national and international standardisation bodies. Overall, this CIM research will link measurement and production in a unique way to minimise cost whilst at the same time enabling the manufacturing base to meet the challenge of ever increasing complexity and quality in manufacture. It will provide coherent research solutions to the manufacturing sector to ensure that advanced UK manufacture is at the forefront of emerging technologies. Partnership with UK industry will provide a research focal point, a national network to disseminate the outcomes and a link with other networks, CIMs and IKCs to ensure that the research provides the required outputs to drive industry forward. This would boost the capabilities of the project proposers to an unrivalled and unique position within the field of machine tool accuracy and surface metrology, allowing the research team to command a global leading role in the foreseeable future.

Dramatic progress has been made in the past few years in the field of photonic technologies, to complement those in electronic technologies which have enabled the vast advances in information processing capability. A plethora of new screen and projection display technologies have been developed, bringing higher resolution, lower power operation and enabling new ways of machine interaction. Advances in biophotonics have led to a large range of low cost products for personal healthcare. Advances in low cost communication technologies to rates now in excess of 10 Gb/s have caused transceiver unit price cost reductions from >$10,000 to less than $100 in a few years, and, in the last two years, large volume use of parallel photonics in computing has come about. Advances in polymers have made possible the formation of not just links but complete optical subsystems fully integrated within circuit boards, so that users can expect to commoditise bespoke photonics technology themselves without having to resort to specialist companies. These advances have set the scene for a major change in commercialisation activity where photonics and electronics will converge in a wide range of systems. Importantly, photonics will become a fundamental underpinning technology for a much greater range of users outside its conventional arena, who will in turn require those skilled in photonics to have a much greater degree of interdisciplinary training. In short, there is a need to educate and train researchers who have skills balanced across the fields of electronic and photonic hardware and software. The applicants are unaware of such capability currently.This Doctoral Training Centre (DTC) proposal therefore seeks to meet this important need, building upon the uniqueness of the Cambridge and UCL research activities that are already focussing on new types of displays based on polymer and holographic projection technology, the application of photonic communications to computing, personal information systems and indeed consumer products (via board-to-board, chip to chip and later on-chip interconnects), the increased use of photonics in industrial processing and manufacture, techniques for the low-cost roll-out of optical fibre to replace the copper network, the substitution of many conventional lighting products with photonic light sources and extensive application of photonics in medical diagnostics and personalised medicine. Many of these activities will increasingly rely on more advanced systems integration, and so the proposed DTC includes experts in computer systems and software. By drawing these complementary activities together, it is proposed to develop an advanced training programme to equip the next generation of very high calibre doctoral students with the required expertise, commercial and business skills and thus provide innovation opportunities for new systems in the future. It should be stressed that the DTC will provide a wide range of methods for learning for students, well beyond that conventionally available, so that they can gain the required skills. In addition to lectures and seminars, for example, there will be bespoke experimental coursework activities, reading clubs, roadmapping activities, secondments to collaborators and business planning courses.Photonics is likely to become much more embedded in other key sectors of the economy, so that the beneficiaries of the DTC are expected to include industries involved in printing, consumer electronics, computing, defence, energy, engineering, security, medicine and indeed systems companies providing information systems for example for financial, retail and medical industries. Such industries will be at the heart of the digital economy, energy, healthcare and nanotechnology fields. As a result, a key feature of the DTC will be a developed awareness in its cohorts of the breadth of opportunity available and a confidence that they can make impact therein.