Liquid chromatography-mass spectroscopy (LC-MS) is a technique that allows separation and precise identification of a wide range of biologically-important molecules. The LC-MS will supplement gas chromatography-mass spectrometers and nuclear magnetic resonance spectrometers housed in the School of Biosciences at Exeter University, to provide an analytical facility for biomolecules. The LC-MS will be used to support a wide range of research projects in the area of plant and microbial sciences. The projects to be supported and enabled include the following. 1. Investigations of the synthesis and function of vitamin C in plants and of the genetic control of metabolism. 2. The response of plants to fungal and bacterial pathogens: what kinds of chemical signals and defensive chemicals are involved in disease resistance. 3. Toxin production by pathogenic bacteria. 4. Algal metabolism: algae (phytoplankton) are important for photosynthesis and productivity in the oceans and are key in absorbing carbon dioxide from the atmosphere. Studies of algal metabolism in conjunction with new genome sequence information will provide new information on their response to climate change.

Cancer is the leading cause of death in developed countries and there is a major desire to pivot towards preventative rather than curative based medicine. Currently, effective treatment heavily relies on early stage detection and an accurate diagnosis of the cancer through molecular profiling. Liver cancer is the third most common cause of death due to cancer and has a global incidence of 1 million new cases annually. The prognosis for patients is poor and even worse in resource-poor settings such as sub-Saharan Africa, and Central and Far-East Asia. For example, liver cancer, linked to hepatitis B infection, currently kills nearly four times as many people as HIV/AIDS in Africa, however early detection could have a significant impact on survival rates. In both the developed and developing world, there is a critical need for new tools and technology for the routine detection and diagnosis of cancer and diseases in general. The goal of this project is to develop a handheld device that can detect biomarkers in urine that will be able to diagnose liver cancer at the point-of-care. It will be assessed using validated patient urine samples. The technology upon which this is based is high performance liquid chromatography (HPLC). Like how a glass prism separates white light into its component colours, HPLC separates a liquid into its component analytes. HPLC is a gold standard analytical technique crucial to many industries worldwide in its ability to separate and identify chemicals in a complex mixture. HPLC is ideally suited to detecting and quantifying biomarkers in urine; however, it is not currently portable or suited to point-of-care analyses due to its size, cost and complexity. As part of this project, we will miniaturise the technology to a handheld device. Point-of-care or on-site HPLC analysis would provide results that could be acted on within minutes that otherwise would take weeks. Due to the crisis in healthcare provision, such technology would ideally be suited to monitoring any individual, not only patients, in the home in order to realise the vision of next generation precision healthcare. Such a device has the potential to monitor us on a daily basis and act as an early warning system for doctors. Such person-specific molecular data may be used to detect or even predict the onset of disease."

Applications such as hydrogen storage, separation, catalysis, delivery of poorly soluble drugs all demand internally micro- or meso-porous inorganic materials, with specific requirements for pore size and available surface area, which can be produced reliably, easily and cheaply. Therefore there is a great need to improve existing methods for production of porous materials. The proposal aims to investigate, by experiment, entirely novel micro- and meso-porous silica particles using nano/microbubbles as templating material. Recently published developments on the stability and long life of nano/microbubbles in aqueous and organic solvents have paved the way for their application in various fields and the proposed research intends to use stable nano/microbubbles to tune the internal porosity/architecture of an inorganic material. The work aims to identify the main parameters influencing the nano/microbubble size and relate it to the resulting internal structure as well as those influencing the silica particle size and uniformity. An efficient method (ultrasound sonicator and cavitation venturi tube) will be used to generate the nano/microbubbles and their size and stability will be validated allowing their use as templating material within the silica droplets to tailor the internal structure of spherical silica particles. Improved production of silica droplets containing nano/microbubbles using membrane emulsification will be a significant leap toward reducing surfactant templating methods and slow batch operation to grow silica particles. The aim is to facilitate the development of an eco-friendly process (that does not rely on templating surfactants) for the production of highly uniform porous spherical silica particles. Although silica will be used as a case study material, the process has the potential to be applied to tailor the internal architecture of both inorganic and polymeric nanostructures. Such nanostructures have great potential for applications in drug delivery, energy (e.g. hydrogen) storage as well as catalyst supports.

In optimizing the properties of functional materials it is essential to understand in detail how structure influences properties. Identification of the most important structural parameters is time-consuming and usually investigated by preparing many different chemical modifications of a material, determining their crystal structures, measuring their physical properties and then looking for structure-property correlations. It is also necessary to assume that the chemical modifications have no influence other than to distort the structure, which is often not the case. High pressure offers a way around these difficulties. Pressure can be used to distort a material without the need for chemical modification. Both crystal structures and physical property measurements can be conducted at high pressure, so that the properties of the same material can be studied in different states of distortion, providing the most direct way to study correlations between structure and properties. In this proposal we focus on structure-property relationships in molecule-based magnets connected into extended chains, networks or frameworks using a combination of high pressure crystallography, magnetic measurements, spectroscopy and simulation which will exploit the UK's unique capabilities in extreme conditions research. Extended materials are of great interest because a small distortion at one site is propagated throughout the material by the strong chemical links between the magnetic centres, making the magnetic properties very sensitive to structural changes. We will design and build new instruments for magnetic susceptibility and diffraction measurements at high pressure and low temperature and we will exploit these new instruments and methodology to study two important classes of magnetic material. 1-D magnetic materials represent a fertile playground for discovering and understanding exotic physical phenomena. The magnetic behaviour of Single-Chain Magnets (SCMs) is fundamentally governed by the magnitude of nearest neighbour exchange interactions (intra-chain exchange), the extent of inter-chain interactions, and Ising-like anisotropy - all of which are sensitive to pressure. We have already shown that these parameters can be pressure-tuned in Single-Molecule Magnets (SMMs) and the same should be true for SCMs In 3-D frameworks magnetism can be combined with porosity, so that inclusion of different guest molecules provides another means for controlling magnetic properties. Prussian Blue Analogues consist of different metal cations linked by cyanide anions, while metal carboxylates build diamond-like frameworks. In both cases guest molecules influence magnetic ordering temperatures. Some metal-organic frameworks show spin-crossover behaviour, where different electronic configurations of the metal ions are stable under different conditions. The transition from one form to another is influenced by guest molecules which occupy the pores of the framework. High pressure will enable us to control the structure of the framework itself, the interactions between the host and the guest, and the number of guest molecules incorporated into the pores, providing a quantitative link between host-guest interactions and magnetism.

Cancer is the leading cause of death in developed countries and there is a major desire to pivot towards preventative rather than curative based medicine. Currently, effective treatment heavily relies on early stage detection and an accurate diagnosis of the cancer through molecular profiling. Liver cancer is the third most common cause of death due to cancer and has a global incidence of 1 million new cases annually. The prognosis for patients is poor and even worse in resource-poor settings such as sub-Saharan Africa, and Central and Far-East Asia. For example, liver cancer, linked to hepatitis B infection, currently kills nearly four times as many people as HIV/AIDS in Africa, however early detection could have a significant impact on survival rates. In both the developed and developing world, there is a critical need for new tools and technology for the routine detection and diagnosis of cancer and diseases in general. The goal of this project is to develop a handheld device that can detect biomarkers in urine that will be able to diagnose liver cancer at the point-of-care. It will be assessed using validated patient urine samples. The technology upon which this is based is high performance liquid chromatography (HPLC). Like how a glass prism separates white light into its component colours, HPLC separates a liquid into its component analytes. HPLC is a gold standard analytical technique crucial to many industries worldwide in its ability to separate and identify chemicals in a complex mixture. HPLC is ideally suited to detecting and quantifying biomarkers in urine; however, it is not currently portable or suited to point-of-care analyses due to its size, cost and complexity. As part of this project, we will miniaturise the technology to a handheld device. Point-of-care or on-site HPLC analysis would provide results that could be acted on within minutes that otherwise would take weeks. Due to the crisis in healthcare provision, such technology would ideally be suited to monitoring any individual, not only patients, in the home in order to realise the vision of next generation precision healthcare. Such a device has the potential to monitor us on a daily basis and act as an early warning system for doctors. Such person-specific molecular data may be used to detect or even predict the onset of disease."