Ion mobility-high resolution mass spectrometry (IM-HRMS) is the next-generation analytical platform in research and industry. Unlocking its full potential across applications as varied as biotherapeutics, environment and food safety requires not only pushing back the frontiers of instrumentation, fundamental understanding and applications - but harmonisation is essential. To achieve this, current shortcomings in data collection, analysis and reporting across instrument types, laboratories and research areas need to be scrutinised and overcome. The MobiliTraIN Doctoral Network will form 10 Doctoral Candidates (DCs) who will bring a new fundamental understanding of IM- HRMS, provide reference materials and guidelines for standardisation, develop state-of-the-art methods for the application of IM- HRMS in biopharmaceutical development, biological 'omics studies, and nontarget screening of contaminants, and lay the foundations for IM-HRMS adoption in industry. Through an interdisciplinary research programme, including an open science approach and training in technical, business and transferable skills, the MobiliTraIN DCs will become leading experts in ion mobility with a unique skill set to successfully advance their careers while supporting Europe's innovation capacity. Building on existing collaborations and research excellence covering the entire innovation chain of IM-HRMS development and application, MobiliTraIN unites 8 academic institutions, 3 leading instrumentation companies, 1 regulatory agency, 1 pharma industry leader and 5 SMEs from 8 countries. With complementary expertise, know-how and mentoring experience, our consortium is ideally suited to unveil the potential of IM-HRMS as a key technology for safer therapeutics, better understanding of complex disease progression and improved monitoring of food, water and public health safety.

The flow response of 'soft materials' such as suspension, emulsions, (bio)gels and (bio)polymers, is of prime importance in a vast range of industries, e.g. foodstuffs and personal care products, and is the subject of intensive applied and fundamental research. Traditional characterization of these properties (viscosity, elasticity, creep, aging etc..) relies on rheological measurements, but it is now recognized that this alone is insufficient to fully understand, and thus optimize, the complex flow properties of soft materials. What is often required is characterization of their evolving microstructure during flow, allowing direct mapping of this evolution to their rheological response. We propose to develop a versatile module which will enable novel high quality imaging of micro-structure evolution and advanced velocimetry in rheometers in different geometries. The module will be complemented by a suite of analysis techniques. The combined capabilities will provide a new dimension in rheo-optical characterization and the module will bring these within reach of a variety of industrial and academic research laboratories.

The project is aimed at the development of new tools for the identifications of various microorganisms including bacteria causing a wide range of diseases from common cold to bloodstream infections. Knowing exactly which type of bacterium is involved in a disease is very important, since the choice of appropriate medication largely depends on it. Likewise, in case of public health or food safety, the correct classification of bacterial contaminations helps with the identification of their source and elimination of the contamination. Currently, samples containing bacterial cells are collected and sent to laboratories. Microbiologists grow the bacteria in Petri-dishes containing special nutrients. Based on the types of nutrients the bacteria can use and the results of multiple chemical tests, the bacterium is tentatively identified. If proper classification is necessary, nucleic acids are extracted from the bacterial cells, and their base-pair sequence is determined, which helps in the unambiguous identification. All of these processes are time consuming, which considerably delays the efficient intervention both in case of infectious diseases and in case of a waterborne disease outbreak. The purpose of the proposed research is to develop an alternative, much faster technique for the identification of bacteria. Mass spectrometry is an analytical technique capable of the measurement of the weight of molecules, and also the selective detection of hundreds of different molecules at the same time. We plan to use this well-established technique for looking at some special building blocks of bacterial cells. One novel aspect of the research is that mass spectrometers are not used in the traditional way, including a lengthy preparation of bacterial cells prior to analysis, but the cells are simply heated up, and electrically charged molecules formed on the boiling of cells are analysed using mass spectrometry. The idea of rapid mass spectrometric analysis by using simply heat has already been applied in case of surgery, where cancer tissue is identified in a similar way. In course of the proposed project we plan the adopt this technology (Rapid Evaporative Ionization Mass spectrometry; REIMS) for the analysis of bacteria grown in the laboratory and also for the direct analysis of liquid samples (ranging from pond water to blood) containing bacterial agents. We plan to build a large library of the spectroscopic fingerprints of the bacteria, which will be used as a training set for computer based search algorithms. The method, the database and the algorithm together will enable the unambiguous identification of bacteria in considerably shorter timeframe than the current routine. Furthermore, the proposed research can potentially lead to an approach, where bacteria are directly identified in their natural environment (e.g. in urine for a urinary infection) without growing them in the laboratory for several hours or days.

Modern mass spectrometry (MS) can be compared to microscopy with its impact on analysing nature and materials down to the molecular (individual molecule) level, including the analysis of the cellular processes of life and the structure of molecules. These analytical tools have frequently been the key to major breakthroughs in science. MS in particular, has been at the forefront of recent advances in areas like biomedicine and healthcare. In this project we will develop a new instrument and the associated methodologies for another major step forward in MS and its application. MS requires the production of gas phase ions. The two major ionisation techniques in modern MS are electrospray ionisation (ESI) and matrix-assisted laser desorption/ionisation (MALDI). There are fundamental differences between these two techniques. ESI enables ion formation exclusively out of a liquid while MALDI uses predominantly solid samples. Another significant difference can be found in their ability to produce multiply charged ions. For peptides, MALDI typically generates singly charged while ESI easily provides multiply charged ions. Importantly, the production of highly charged ions is desirable as it allows the use of high-performance mass spectrometers, which typically cannot analyse the larger singly charged ions. It also facilitates more informative controlled fragmentation of the ions, thus helping to obtain further information such as their molecular structure. Consequently, there is a clear advantage of using ESI. Nonetheless, MALDI with its higher tolerance to contaminants, ease-of-operation, potential for high-speed automated analysis as well as its MS imaging capabilities makes it an ionisation technique that can cover (bio)analytical areas where ESI is less suitable. If these strengths could be combined with the analytical power of multiply charged ions, new instrumental configurations and new large-scale (bio)analyses using MALDI MS would become feasible. The proposed instrument and method development will lead to a new technology that will enable the production of stable and high yields of multiply charged MALDI ions at high sensitivity, i.e. low analyte concentration and low sample consumption. It is based on a new ion source design, using a heated ion transfer tube to transfer the produced ions into the analyser of the mass spectrometer, and novel liquid sample preparation methods, ensuring stable and high yields of ESI-like multiply charged ions. Thus, the two main disadvantages of MALDI (no/low yield of multiply charged ions and highly variable ion yield and signal quality) will be addressed within this project. Ultimately, the newly developed technology should not only become a real competitor for ESI but also open up new areas of analysis that have previously been inaccessible. In short, this project will develop a new MS technology that will significantly widen the application range of MALDI MS and thus MS in general, enabling new and more powerful analytical strategies. The project will result in a prototype instrument and methodology that can easily be commercialised. As MALDI MS is already making great strides within the (bio)analytical field it can be anticipated that this project will have significant impact in many areas from academia and industry to the public health sector and thus society at large.

Life sciences research is increasingly being performed using high-tech instrumentation, producing vast quantities of data. In turn, the science as a whole is being transformed from a knowledge-based discipline, into a Big Data discipline. Some of these techniques are called "omics" - from genomics (studying genes on a large scale), proteomics (proteins) and metabolomics (metabolites). Proteins are the functional molecules in cells, and by studying the levels at which different proteins are present in cells (for example comparing healthy versus diseased cells), we can understand how the system as a whole is behaving (or going wrong) and we can begin to understand the function played by the individual proteins. The pervasive technique used for proteomics is mass spectrometry (MS), which is capable of measuring many thousands of proteins from a single sample. One of the biggest challenges in omics research is the interplay between often complex and noisy data produced by the instrument and the requirement for bespoke software for data analysis. Both areas are under active development in academic research groups and by industrial organisations (commercial instrument and software manufacturers) - and it is indeed a major challenge ensuring that academic research and development has maximum impact on industry. In proteomics, there are various software packages, both commercial and free/open source, capable of analysing the raw data collected from MS to give a list of proteins identified, along with an abundance value in or between samples of interest. One popular package is called Progenesis QI - marketed internationally by instrument manufacturer Waters. Waters are a large global corporation, with headquarters near Manchester, UK. However, in proteomics, there is currently a shortage of good software for taking the quantified protein list, and performing downstream data analysis to arrive at a real understanding of the biological system, as required by scientists that make use of proteomics techniques in their research. These downstream analyses include visualising the large data set to check the data quality, and starting to understand which groups of proteins may be changing in the system of interest. It is also necessary to perform specialised statistical analyses to ensure that only significant results are taken for further study and published. In this project, an academic biologist and data analyst (Dr Dean Hammond) will take part in an industry interchange, to work directly with Waters, to develop new software for proteomics data analysis, developing a package called ProteoAnalytics. The package will be able to take input from Progenesis QI (and other suitable upstream packages), enabling biologists easy access to cutting-edge methods for data interpretation (such as mapping proteins to biological pathways), performing specialised statistical analyses, creating unique and powerful visualisations of large data sets, and assisting users to prepare high-quality figures and charts for scientific publications. The software will enable Waters to understand very rapidly the features that work for users, and will assist proteome scientists to perform large scale data analyses. The interchange will allow Dr Hammond to take his knowledge of academic proteomics data analysis to Waters, and gain experience of the industry perspective in software development. The interchange also enables the creation of a collaborative partnership between the principal investigator (Dr Andy Jones, who leads an academic software development group) with the commercial software development team at Waters.