This proposal is a Platform Grant renewal. Our previous grant allowed us to develop the key characterisation facilities and enabled us to understand fully the materials that were the study of the grant. These materials were low loss microwave dielectrics, ferroelectric materials and thin films of these materials. The Platform renewal will build upon some remarkable discoveries that the team, including the key PDRAs, has made over the last 4 years and centre around functional materials for devices operating from microwave to millimetre wave or from MHz to THz. First it is important to explain the Materials Science progress that forms the underpinning technologies that will enable us to use the Platform grant to build new devices. At the heart of microwave devices are resonators that require low dielectric loss or very high Q factor and the target is to aim for very high Q dielectrics. Our previous Platform grant and indeed prior support from EPSRC allowed us to discover very low loss, high Q materials. This culminated in two significant discoveries. 1 First we were able to use low loss resonators as sensors for liquid sensing 2 Second, we demonstrated that by using a very high Q resonator we could achieve maser action at room temperature and in Earth's field - published in Nature 2012. This platform grant will enable us to build upon these discoveries. 1) Advanced Characterisation: In the first theme the aim will be to carry out a series of qualifying experiments to determine the best possible conditions and materials for sensing over the wide range of frequencies available to us (Hz to THz) 2) Microwave and mm wave sensors: The third theme takes the science to application. We will use the resonators for analysis of ions, biomolecules, proteins and cells. The sensitivity of the resonators allows nanolitre quantities to be analyzed very rapidly for possible cancer cell detection in blood and bacteria in water. 3) "UMPF" and "HEP" Cavities: In the second theme we aim to make UMPF (Ultrahigh Magnetic Purcell Factor) and "HEP" (High Electric Purcell) cavities. These are small resonant cavities with a very high Q given the very small mode volume and success here will enable us to improve electron paramagnetic sensing dramatically and enable single cell detection. Success in these new themes for the Platform would represent a remarkable step-change in technology.

The research, which will be carried out in the School of Engineering at the University of Glasgow, will underpin a completely new paradigm in the handling of liquids. It involves the control of the mechanical interactions between fluids and microfabricated structures, with acoustic waves. Notwithstanding its potential impact on a wide range of areas (e.g. physics and chemistry), my focus in this Fellowship will be in enabling advanced diagnostics both in remote areas in developing countries and in the developed world, by integrating complex biological sample processing on low cost portable devices. Acoustic waves carry a mechanical energy that has been successfully used to actuate a wide range of liquid functions. In particular, Surface Acoustic Waves (SAW) propagated on piezoelectric surfaces, using transducers commonly found in electronics, can refract in a liquid, leading to recirculation flows. I have pioneered and enhanced a technique to control SAW and their interactions with the liquid and particles, enabling more complex manipulations. The new platform is based on micromanufactured, disposable phononic lattices, that scatter or reflect the acoustic waves in a frequency dependent manner. These structures shape the acoustic waves, in a manner analogous to that of holograms shaping light. The structures rely on mechanical contrast when holograms are based on refractive index. Geometric aspects of the hologram's design provide colours of different frequencies; here, the phononic lattice geometry determines the frequency at which the sound is scattered. The different frequencies of ultrasound interact with different phononic structures to give different functions, providing a "tool-box" of different diagnostic processes (sample processing, cell separation, detection), which, when combined, form a fluidic circuit, a complete diagnostic assay. Contrary to the established microfluidic systems used in point-of-care devices, which rely on flow through channels to carry out different functions at different positions within the channels, I will design, fabricate, characterise and use new phononic lattices to combine different functions in the frequency domain, on a stationary sample. Others involved in the research include Professor Miles Padgett (School of Physics), Professor Andy Waters (Welcome Centre for Molecular Parasitology), Dr Andrew Winters (Consultant in Sexual Health & HIV Medicine and Joint Clinical Director at The Sandyford Clinic, NHS Greater Glasgow and Clyde) and Dr Mhairi Copland (Paul O'Gorman Leukaemia Research Centre and the Beatson Cancer Research. My research will have three potential outcomes in diagnostics and sensing, namely the development of new Microsystems technologies for: 1. Drug resistant malaria diagnostics. I will develop phononic geometries to carry out a complete nucleic acid based test, including sample preparation, amplification, and detection in whole blood. These will be fabricated in low cost materials (e.g. glass, composites) and could transform malaria diagnostics in the Developing World. 2. Multiplexed detection of a panel of sexually transmitted diseases, working with the NHS. The ability to perform complex sample preparation has the potential to integrate multiplexed analysis in an expert system, where instead of a diagnostic test centered around a pathogen, the test has the capability to analyse a set of symptoms, a decisive shift in diagnostics. 3. Stratification of leukemia cells' aggressiveness. I will explore how the combination of the cells mechanical information probed using acoustics, and coupled with electrical information on cell membranes, could enable a multidimensional analysis of cells. This research will have the potential to create devices to carry out diagnostics anywhere.

Soft matter and functional interfaces are ubiquitous! Be it manufactured plastic products (polymers), food (colloids), paint and other decorative coatings (thin films and coatings), contact lenses (hydrogels), shampoo and washing powder (complex mixtures of the above) or biomaterials such as proteins and membranes, soft matter and soft matter surfaces and interfaces touch almost every aspect of human activity and underpin processes and products across all industrial sectors - sectors which account for 17.2% of UK GDP and over 1.1M UK employees (BIS R&D scoreboard 2010 providing statistics for the top 1000 UK R&D spending companies). The importance of the underlying science to UK plc prompted discussions in 2010 with key manufacturing industries in personal care, plastics manufacturing, food manufacturing, functional and performance polymers, coatings and additives sectors which revealed common concerns for the provision of soft matter focussed doctoral training in the UK and drove this community to carry out a detailed "gap analysis" of training provision. The results evidenced a national need for researchers trained with a broad, multidisciplinary experience across all areas of soft matter and functional interfaces (SOFI) science, industry-focussed transferable skills and business awareness alongside a challenging PhD research project. Our 18 industrial partners, who have a combined global work force of 920,000, annual revenues of nearly £200 billion, and span the full SOFI sector, emphasized the importance of a workforce trained to think across the whole range of SOFI science, and not narrowly in, for example, just polymers or colloids. A multidisciplinary knowledge base is vital to address industrial SOFI R&D challenges which invariably address complex, multicomponent formulations. We therefore propose the establishment of a CDT in Soft Matter and Functional Interfaces to fill this gap. The CDT will deliver multidisciplinary core science and enterprise-facing training alongside PhD projects from fundamental blue-skies science to industrially-embedded applied research across the full spectrum of SOFI science. Further evidence of national need comes from a survey of our industrial partners which indicates that these companies have collectively recruited >100 PhD qualified staff over the last 3 years (in a recession) in SOFI-related expertise, and plan to recruit (in the UK) approximately 150 PhD qualified staff members over the next three years. These recruits will enter research, innovation and commercial roles. The annual SOFI CDT cohort of 16 postgraduates could be therefore be recruited 3 times over by our industrial partners alone and this demand is likely to be the tip of a national-need iceberg.

Point of care testing is fundamental in delivering health and economic sustainability in the Global South. Our project will enable low cost, effective and accurate diagnosis of, in the first instance, two infectious diseases, namely malaria and schistosomiasis. This will be achieved using a novel very low cost paper diagnostic method that is able to quantify the infectious agent's DNA in a patient sample in a multiplexed assay. The platform will allow the measurement of several diseases at the same time, thereby increasing the efficiency of healthcare provision in often hard to reach settings, as well as establishing the species of the infectious agent (e.g. malaria), which will provide actionable information to healthcare professionals, where drugs have different levels of activity for different species, thus helping in reducing the potential emergence/increase of drug resistance. We have already demonstrated the potential for these low cost assays as being both sensitive and specific and we now wish to develop new engineering approaches to improve their performance (in terms of their speed and ease of use) and evidence their impact so that they can find widespread application in both rural and urban environments in Uganda and Sierra Leone, and other endemic countries. As the assays are sensitive and quantitative, they have the potential to be used not only in the treatment of individuals, but also in eradication programmes, such as those advocated by the London 2020 accord, enabling the surveillance of disease re/emergence. To help communicate the value of repeated treatments, we plan to develop new engagement tools based upon a novel mobile phone imaging platform that enables patients to visualise the infectious agent in a sample, and to see the outcome of interventions (whether these be through drug administration or physical/cultural changes such as access to improved sanitation or bed nets). We also propose to measure the impact of our novel diagnostic and imaging platforms by collection of suitable, realistic, logistically feasible metrics, and the potential impacts (including resources, health outcomes, employment, income) of the interventions. We will also feed these into newly developed and parameterised economic models to predict the long-term benefits specific interventions may have. Finally, integral to the proposed research is an ambitious programme of impact, which includes public engagement over infectious disease diagnosis and STEM and capacity strengthening. We will also explore routes to delivery of the technologies both in the UK, where the provision of low-cost point-of-care diagnostics is of significant interest (through our industrial partners), and in LMICs. Our ambition is to explore whether, through not-for-profit business planning, we can develop the correct interactions with Governments, Hospitals and Charities/NGOs, to test whether we are able to scale the manufacturing of these devices, such that they can be made in Africa, for Africa, by Africans.

Colorectal Cancer (CRC) is the third most common cancer in the UK, with approximately 32,300 new cases diagnosed and 14,000 deaths in England and Wales each year. Occurrence of colorectal cancer is strongly related to age, with 83% of cases arising in people older than 60 years. It is anticipated that as our elderly population increases, CRC will increase in prevalence (National Institute for Clinical Excellence, www.nice.org.uk). This raises important questions relating to treatment in elderly patients balanced with quality-of-life and health economics considerations. The challenge to nanotechnology and engineering is to deliver cost-effective, less invasive treatments with fewer side-effects and potential benefits for quality of life in patients. This is particularly important in CRC at the present time as the NHS bowel-screening programme is rolled out for all individuals aged 60 to 69. This raises important issues for rapid, accurate, and acceptable, safe and cost-effective investigation and treatment of older symptomatic patients. Ultrasound has a clear and growing role in modern medicine and there is increasing demand for the introduction of ultrasound contrast agents such as microbubbles (MBs). These MBs are typically less than one hundredth of a millimetre in size, so that they can pass through the vasculature, and lead to imaging enhancements by scattering of the ultrasound signal. So-called third generation MBs will not only perform functional imaging with greatly enhanced sensitivity and specificity but will also carry therapeutic payloads for treatment or gene therapy. These will most likely be released by destroying the bubbles at the targeted site and their effect enhanced further by sonoporation (sound induced rupture of the cell walls to allow drugs in). Although the focus of our proposal is therapeutic delivery for cancer treatment, the basic technologies for MB development and ultrasound technology are equally applicable to other conditions e.g. cardiovascular and musculoskeletal disease where there is an unmet clinical need, particularly in ageing populations. As such this is a generic technology development relevant to different diseases.Our programme of research addresses several key issues central for the successful development of these 3rd Generation MBs. Firstly, we propose to develop a machine, based on microfluidics, for the creation of MBs of uniform size (necessary for human application). This instrument will also allow us to put suitable coatings on the MBs to target them specifically at cancerous cells. Secondly, we will develop novel coatings to allow control over the way bubbles respond to ultrasound signals. We will then add payloads of the required drug to be delivered onto the micro-bubble surface. At the same time we will develop novel methods of generating ultrasound signals which can be used to selectively destroy the MBs and simultaneously create holes in the cells to which the drugs should be delivered. A necessary part of such a programme of research is the full testing and evaluation of the MBs developed for targeted therapy of CRC using a combination models. Firstly, against cancer cells grown in test tubes and secondly, against mice infected with the relevant cancer. At the conclusion of our research project we will have enhanced our understanding of how MB and ultrasound technologies can be combined to yield new routes for therapeutic delivery/gene therapy. This will provide a platform to launch the next stage of research, required before such an approach could be used clinically.