MALDI and SIMS microscope mode imaging mass spectrometry

Mass spectrometry imaging (MSI) is a powerful tool, mapping the spatial distribution of molecules with micron or sub-micron resolutions using their molecular mass. Microscope MSI is a great technique with a high throughput, but is used less commonly than microprobe MSI as it achieves lower mass and spatial resolution. This thesis presents methods for improving the mass and spatial resolution with a microscope MSI instrument, as well as expanding the imaging field of view. A new microscope MSI instrument is also presented, utilising secondary ion mass spectrometry (SIMS). Using a reflectron ToF mass spectrometer, by generating a stronger field, the spatial resolution can be increased from 13 ± 1 μm o 8 ± 1 μm experimentally, and could potentially reach <7 μm according to simulations. Variable magnification has been explored in simulation, and the application of an additional einzel lens proved capable of changing the magnification from ×92 to ×20, which can expand the field of view from 270 μm to 1242 μm. This can increase the scope of the instrument by acquiring larger images first, with a <50 μm spatial resolution and ~ 2,500 mass resolution, before increasing the magnification on a region of interest and attaining higher resolution data. Such a feature would be very desirable in commercial applications and improve the throughput of the instrument. Using a Timepix3 camera, the timing precision can be improved by using a more intense trigger, reaching a 4.5 ns full width half maximum (FWHM). Through the use of time-over-threshold data, mass peaks can be reduced from a FWHM of 50 μm to 32 μm, improving the attainable mass resolution with the Timepix3 camera, bringing it closer to the true mass resolution of the instrument. A SIMS ToF mass spectrometer has been presented, taking a similar design to the reflectron ToF instrument. Work was done to characterise this instrument in order for it to be used in tandem with the reflectron ToF mass spectrometer.