Mass spectrometry imaging for biology and biotechnology

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Mass spectrometry is a 'broadband' technology - everything has a mass. Mass spectrometers have developed over the past 15 years to attack more and more problems in biology, addressing the issue of complexity of the sample and the subtleties of the biomolecular domain. However, it is only recently that there have been significant developments in the ability to acquire a mass spectrum from a biological material in a spatially defined fashion - 'MS imaging'. The instruments designed for this application can generate an image in which the measured signal is not simply a colour (as in optical imaging) but a mass spectrum. We propose to establish an MS imaging platform at the University of Liverpool that is accessible to other scientists within and outside the University. The system will couple a high resolution, high sensitivity mass spectrometer with two different imaging modalities - a matrix assisted laser desorption ionisation method (MALDI) and a laser activated electrospray ionisation method (LAESI). In MALDI, the sample is coated with a matrix molecule that absorbs the ultraviolet laser energy and which directs that energy to activation and charge addition to generate ions from the tissue or sample. In LAESI, an infrared laser is used to effect localised heating and volatilisation of the sample in close proximity to a probe that generates the ions for analysis. MALDI is preferred for small biomolecules, whereas LAESI is preferred for biological macromolecules. The two different sources permit the entire range of biological molecules, from low molecular weight metabolites to macromolecules such as proteins to be analysed.The mass spectrometer we propose to install has several advantages. First, it is a high resolution instrument and the exquisite sensitivity is enhanced by a new design within the ion optics that steers informative ions into the mass analyser and away from contamination and background - this greatly increases sensitivity. Secondly, the instrument includes an ion mobility device that can further resolve ions according to their cross sectional area. This is particularly advantageous in imaging applications, where the complexity of the sample can compromise signal to noise and thus, sensitivity.The main application for this platform has traditionally been in tissue visualisation - the exemplar project here is in the spatial mapping of damage to joints, or particular relevance to the biology of ageing. Whilst tissue imaging will be a major demand on instrument time, we will also explore new applications for one or the other ionisation methods. These include interrogation of proteins or carbohydrates that have been captured on arrays, rapid screening of metabolites in microorganisms that are engineered to generate new chemicals, for rapid phenotyping of proteins in biological fluids and for the direct visualisation of scent marks deposited in the environment. Thus, the new capacity will have broad applicability to a large set of BBSRC-funded projects.To our knowledge, there is no system of comparable sophistication and scope that is in the UK and openly available to UK researchers. By establishing this platform at Liverpool, it will be under the management of the University of Liverpool Technology Directorate. The Technology Directorate has the mission of providing access to the very best research facilities for the maximal number of users, both inside and outside the University. It has the mechanisms and structures to ensure full time operation and to ensure access, as well as providing financial support for properly open facilities such as this, and by awarding access grants to allow academics, and particularly early career staff, to be able to use such facilities in advance of winning substantive funding.