Experts in science (chemistry, physics, statistics), heritage science and sensor technology will drive an ambitious but realistic proposal to develop diagnostic olfactory tools for heritage science. The new devices will be non-invasive, non-contact, portable and simple to use providing real-time data; making them well suited to address cultural heritage questions and survey collections, particularly for objects where potential hazards, access issues or sampling restrictions have precluded study to date. Implementation of energy efficient sensors to tackle heritage problems (rather than large equipment) will also help reduce the U.K.'s environmental footprint. Indeed, there is an overall lack of capacity in the heritage sector both in organic material analysis and volatile organic compound (VOC) monitoring; this research addresses such issues.\n\nBy merely 'sniffing' the air, questions regarding the environmental and conservation history, composition, condition or stability of objects will be answered. This will empower collections custodians and allow informed decisions about the acquisition, storage, conservation, display and long-term preservation of items, whilst also ensuring the health of those accessing public and private collections. \n\nThree key interconnected challenges have been identified where timely research will give the UK a leading position providing new knowledge, expertise and technical developments, informing practitioners in heritage-user defined problem areas. \n\n1: The past use of hazardous chemicals to disinfect/disinfest objects presents risks to those handling or accessing objects. Within this challenge objects will be 'sniffed' to determine if they have undergone such treatments. The data will allow informed conservation /research decisions regarding handling, display, loan and access. Key deliverables include: improvement of scholarly, public and native community use and engagement with cultural heritage and collection preservation, and development of new knowledge data bases that will be used to train portable sensing systems designed for high-throughput object screening.\n\n2: Since the beginning of last century observation and analyses have established that paper is unstable. A by-product of the deterioration process is the production of VOCs. In this challenge a well characterized set of papers will be 'sniffed' to identify target indicators that imply paper instability. A key deliverable will be the development and application of non-invasive portable sampling tools for paper-based collections that can be used to provide rapid on-site analysis of stability and risk. \n\n3: Heritage institutions are continually acquiring objects that contain synthetic, complex and inherently unstable modern materials. The composition and condition of such objects are extremely difficult to characterise and assess. A unique approach will be taken to tackle this problem: measurement of VOCs emitted by modern materials. The data will be used to inform heritage users of object composition and materials instability; interpretation of 'object smell' has not previously been exploited in this way. A key deliverable is development of a new tool for the identification of modern materials at risk allowing mitigation methods to be implemented to retard chemical and/or biological deterioration.\n\nThis proposal therefore seeks to develop VOC sampling tools to address these challenges without the need for complex or costly instrumentation. Indeed very few heritage institutions have access to laboratory equipment and such studies are impossible to implement. The outcome of this research (development of hand held portable low cost sensors) will be of wide benefit to heritage-users and open the research door to thousands of smaller institutions (museums, galleries, libraries, historic houses) and private collectors.\n

This is an extension of the Fellowship: 'NISA: Novel approaches for in situ analysis of biomolecules' (EP/L023490/1). The aim of the original research was to develop novel approaches for in situ biomolecular analysis, i.e., the analysis of biomolecules directly from their natural (or actual) environment. The principal focus has been on the in situ analysis of proteins. Proteins are the work-horses of the cell and perform all the functions required for life. They also find uses as therapeutics and in consumer products. To gain insight into the roles of proteins in life processes, it is necessary to analyse proteins at a molecular level. Mass spectrometry, in which ionised molecules are characterised according to their mass-to-charge, is ideally suited to this challenge, offering high sensitivity, broad specificity (all molecules have a mass), and the capability for chemical structure elucidation. The majority of research within the original fellowship has concentrated on development of mass spectrometry tools for in situ analysis of INTACT, but UNFOLDED, proteins. Significant advances in sensitivity have been achieved through hyphenation of mass spectrometry with gas-phase separation techniques and modifications to the mass spectrometry instrumentation. These tools enable identification of unknown proteins, identification and localisation of sites of protein modification or mutation, and spatial profiling (mass spectrometry imaging) of proteins within the substrate. Those tools do not, however, provide information on the overall 3-D structure of proteins. It is the 3-D structure of proteins that dictate their function. Knowledge of protein structure is therefore vital in deciphering the roles of protein in health and disease. In order to fully interrogate the relationship between protein structure, function and environment, it is necessary to develop tools incorporating native mass spectrometry in which proteins remain in their FOLDED form and their inter- and intra-molecular noncovalent interactions are maintained. To address that need, preliminary research undertaken as part of the original fellowship has focused on developing methods for NATIVE AMBIENT MASS SPECTROMETRY in which folded proteins, protein complexes and protein assemblies are sampled directly from their physiological environment. To date, our research in this area has focused on a single sampling technique, i.e., liquid extraction surface analysis; however, there are many ambient sampling approaches which may prove suitable, each offering different specifications in terms of sensitivity, speed, and spatial resolution. The aim of the fellowship extension is to establish NATIVE AMBIENT MASS SPECTROMETRY as a broad discipline for the in situ analysis of folded proteins and their complexes. The goal is to develop a suite of tools which will be capable of providing information on protein function in health and disease. Each potential application of native ambient mass spectrometry will come with its own unique challenges. For example, spatial resolution i.e., intricate mapping of the protein distribution in the tissue, may be the crucial requirement. Alternatively, high throughput (speed of analysis) may be the key to success, or it may be that the sensitivity of the technique that is vital. By widening the scope of native ambient mass spectrometry to encompass a full range of sampling techniques, we will enable each of these challenges to be addressed. Moreover, a range of ion mobility spectrometry techniques, which enable measurement of protein structure as well as improving sensitivity, will be integrated with native ambient mass spectrometry allowing spatial profiling of 3D protein structure. The impact of the research will be demonstrated by application to Alzheimer's disease, a disease associated with protein misfolding and aggregation, and non-alcoholic fatty liver disease, a disease associated with unusual binding between proteins and lipids.

The aim of the research is to develop novel approaches for the analysis of biomolecules, and in particular proteins, directly from their natural (or actual) environment, i.e., to develop approaches for in situ biomolecular analysis. Proteins are the work-horses of the cell and perform all the functions required for life. They also find uses as therapeutics and in consumer products. To gain insight into the various and specific roles of proteins in life processes, or to determine the therapeutic efficacy of protein drugs, or to establish the environmental fate of protein additives in consumer products, it is necessary to be able to analyse proteins at a molecular level. Mass spectrometry, in which ionised molecules are characterised according to their mass-to-charge, is ideally suited to this challenge, offering high sensitivity, broad specificity (all molecules have a mass), and the capability for chemical structure elucidation. The ultimate goal is to link molecular analysis directly to molecular environment. Much like a forensics officer tasked with determining the presence of an illicit substance, there is much greater reliability and credibility afforded to an analysis performed at the scene of the crime than to one performed following removal of the sample to a separate location and alternative surroundings. Growing evidence suggests in situ protein analysis has groundbreaking roles to play in biomarker discovery, diagnosis & early detection of disease, targeting therapeutics (personalised medicine) and assessment of therapeutic efficacy. The benefits of in situ protein analysis can be illustrated by considering a thin tissue section through a drug-treated tumour. In principle, in situ analysis would inform on drug-target interactions (i.e., is the drug binding to the correct protein?). Moreover, with in situ protein analysis the capacity for artefact introduction as a result of sample preparation (e.g., application of a matrix) or sample damage is eliminated. Nevertheless, a number of challenges exist. Proteins are large molecules associated with a vast array of chemical modifications, and which form loosely-bound complexes with themselves, other proteins and other molecule types. It is not only their chemical structure but also their overall 3-D structure which dictate their function. Other molecular classes that are hugely important in biological processes also have an intricate relationship with proteins. Any in situ mass spectrometry approach needs to be able to meet these analyte-driven challenges, i.e., it must be capable of (a) measuring proteins and characterising any modifications, (b) detecting protein complexes and determining their constituents, (c) providing information on 3-D structure, and (d) detecting other relevant molecular classes. Moreover, there are technique-driven challenges for in situ analysis including inherently high sample complexity and wide ranging concentrations, and opportunities for quantitation. The research will meet these challenges by developing a newly emerging in situ approach, liquid extraction surface analysis mass spectrometry, in combination with two complementary types of ion mobility spectrometry (which can either provide information on 3-D structure, or separate ionised molecules in the mass spectrometer on the basis of their 3-D shape) and a structural elucidation strategy known as electron-mediated dissociation mass spectrometry. The research will be undertaken primarily at the University of Birmingham in the Advanced Mass Spectrometry Facility in the School of Biosciences and the School of Chemistry mass spectrometry facility. The programme involves a number of academic and industrial collaborators and additional research will be carried out during scientific visits to National Physical Laboratory (NPL), Thermo Fisher Scientific, Waters, Owlstone, Florida State University, Texas A&M University and Université d'Aix-Marseille.

The impact of road traffic on local air quality is a major public policy concern and has stimulated a substantial body of research aimed at improving underlying vehicle and traffic management technologies and informing public policy action. Recent work has begun to exploit the capability of a variety of vehicle-based, person-based and infrastructure-based sensor systems to collect real time data on important aspects of driver and traffic behaviour, vehicle emissions, pollutant dispersion, concentration and human exposure. The variety, pervasiveness and scale of these sensor data will increase significantly in the future as a result of technological developments that will enable sensors to become cheaper, smaller and lower in power consumption. This will open up enormous opportunities to improve our understanding of urban air pollution and hence improve urban air quality. However, handing the vast quantities of real time data that will be generated by these sensors will be a formidable task and will require the application of advanced forms computing, communication and positioning technologies and the development of ways of combining and interpreting many different forms of data. Technologies developed in EPSRC's e-Science research programme offer many of the tools necessary to meet these challenges. The aim of the PMESG project is to take these tools and by extending them where necessary in appropriate ways develop and demonstrate practical applications of e-Science technologies to enable researchers and practitioners to coherently combine data from disparate environmental sensors and to develop models that could lead to improved urban air quality. The PMESG project is led by Imperial College London, and comprises a consortium of partners drawn from the Universities of Cambridge, Southampton, Newcastle and Leeds who will work closely with one another and with a number of major industrial partners and local authorities. Real applications will be carried out in London, Cambridge, Gateshead and Leicester which will build on the Universities' existing collaborative arrangements with the relevant local authorities in each site and will draw on substantial existing data resources, sensor networks and ongoing EPSRC and industrially funded research activities. These applications will address important problems that to date have been difficult or impossible for scientists and engineers working is this area of approach, due to a lack or relevant data. These problems are of three main types; (i) measuring human exposure to pollutants, (ii) the validation of various detailed models of traffic behaviour and pollutant emission and dispersion and (iii) the development of transport network management and control strategies that take account not just of traffic but also air quality impacts. The various case studies will look at different aspects of these questions and use a variety of different types of sensor systems to do so. In particular, the existing sensor networks in each city will be enhanced by the selective deployment of a number of new sensor types (both roadside and on-vehicle/person) to increase the diversity of sensor inputs. The e-Science technologies will be highly general in nature meaning that will have applications not only in transport and air quality management but also in many other fields that generate large volume of real time location-specific sensor data.Each institution participating in this project will be submitting their resource summary individually to Je-s. The resources listed within this Je-S Proposal are solely those of Imperial College with other institutions submitting their costs seperately, with one case for support.

We will mount sensors on pedestrians and cyclists to monitor their exposure to pollution from transport. This will be an addition to the TIME-EACM project, which is about to use Cambridge City as a test bed for a variety of ways to gather data about traffic flow, and is writing middleware to analyse the data in real time.The initial part of the study will be to confront the technical challenges associated with sensors that need to be highly portable. Sensor technologies are now advancing to the point where parts per billion sensitivities are becoming achievable in small low power devices for species relevant to local air quality including ozone, nitrogen dioxide and a range of hydrocarbons. The challenge will be to link such sensors to effective mobile systems to broadcast data back to central points for analysis and presentation, and to locate their wearers sufficiently accurately. The TIME-EACM project will log and store data and integrate databases with information flow from its sensors, and the data stream from the pervasive environmental sensors will be added to this. The TIME-EACM middleware will be compatible with data on pollution from pervasive environmental sensors. All data will be time-stamped and location-stamped and correlated with TIME-EACM data on traffic flow.