Final Report Summary - IMAGEMS (Exploring applications of spatial-map and velocity-map imaging mass spectrometry) Mass spectrometry is a ubiquitous analytical technique used for identifying and quantifying molecules, with applications spanning areas as diverse as the identification and structural analysis of proteins, peptides, and other biological molecules; drug discovery; pharmacokinetics (the timelines over which drugs are metabolised within a patient); breath gas monitoring; quality control; reaction rate measurements; analysis of complex chemical mixtures; and geochemical and archaeological dating. Driven particularly by applications in biology, there is an ever increasing demand for innovations in instrument design that will allow molecular structures to be probed in more detail. Molecular masses are recorded by first ionizing the sample, which often leads to considerable molecular fragmentation, and then analysing the interaction of the resulting charged species with an electric or magnetic field to determine the mass. In our experiments, for example, we use time-of-flight (ToF) methods, in which the mass is determined from the time taken for the ion to fly a fixed distance under the influence of an electric field. Data is usually presented as a plot of signal intensity versus mass-to-charge ratio, m/z, with the mass-to-charge ratio identifying the molecule or molecular fragment, and the signal intensity quantifying it. The goal of the ImageMS project was to develop methods to allow images of the complete velocity or spatial distribution of the ions at their point of formation to be recorded for each mass in tandem with the mass spectrum. Our imaging methods are based on the technique of velocity-map imaging, first developed within the reaction dynamics community for studying photoinduced molecular fragmentation processes. The addition of imaging capabilities to ToF mass spectrometry offers exciting possibilities for molecular structure determination, molecular dynamics studies, surface analysis, tissue imaging for medical diagnosis and pharmacological studies, high throughput mass spectrometry, and a wide range of other applications. We have designed and built three imaging mass spectrometers over the course of the project, two of which record the velocity distributions of fragments formed when gas-phase molecules dissociate following absorption of a high energy photon or collision with an electron, and one which records spatial images of molecules at surfaces. As part of the instrument development, we have worked closely with colleagues Renato Turchetta (Rutherford Appleton Laboratory), Mark Brouard (Oxford Chemistry) and Andrei Nomerotski (Oxford Physics) to develop the pixel imaging mass spectrometry (PImMS) sensor, an ultrafast camera capable of recording the positions and arrival times of the ions with the required few-nanosecond time resolution within a single time-of-flight cycle. By some measures, the PImMS camera is the fastest camera in the world, and it is now finding many applications both in imaging mass spectrometry and in other areas. For example, in collaboration with Dan Pooley and others at the ISIS neutron facility, we have recently developed a time-resolved neutron imaging detector based on the PImMS sensor. We have already explored a number of applications for our new technology. When a molecule breaks apart, the velocity distributions of the fragment ions are highly sensitive to the detailed dynamics of the fragmentation process, and provide both a distinctive fingerprint for a given molecule, and also a great deal of insight into the detailed mechanism of one of the most fundamental processes in chemistry, the breaking of a chemical bond. We have carried out comprehensive studies into the fragmentation dynamics of a range of organic molecules which provide simple models for biological motifs (the peptide bond) or synthetic organic reactions (e.g. the retro-Diels-Alder reaction and McLafferty rearrangement), and have been able to study the competition between different reaction channels, as well as the detailed dynamics of individual channels, determining which electronic states of the molecule are involved, how the available energy is partitioned between translation, vibration, and rotation, and so on. In spatial-map imaging mode, imaging mass spectrometry has the potential to identify, with high lateral resolution, the many molecular constituents that may be present at a surface. We have demonstrated spatial-map imaging of both electrons and ions from the surfaces of carefully chosen test samples with resolutions on the micron scale, and we are now moving on to evaluate the technique for characterising a variety of 'real' samples of interest in materials science, engineering, and biology/medicine, in collaboration with a number of industrial and academic partners. The ImageMS project has been extremely successful, and has paved the way for a great deal of exciting research across a broad range of scientific fields in the future.
