Fourier Transform Ion Cyclotron Resonance Mass Spectrometry. Development of instrumentation, data aquisition software and processing methods

Abstract

This thesis describes, the use of a Fourier Transform Ion Cyclotron (FTICR) mass spectrometer in the study of biological samples with, imaging mass spectrometry (MS). To achieve this goal experiments were performed on an in-house modified FTICR-MS instrument (for which special acquisition software was developed) as well as on a commercial instrument. Data processing tools were developed in-house to be able to process the FTICR data and construct the resulting images. To test whether imaging MS experiments were feasible on a FTICR-MS, the first experiments were performed on a commercial instrument containing a MALDI ionization source. In this thesis imaging FTICR-MS experiments on a rat brain tissue section are shown for the first time. Advantages, disadvantages and further improvements in this respect are evaluated. The developed acquisition software consists of a workflow-based method that controls the experiments on the FTICR mass spectrometer, or any other type of scientific instrument, and includes on-the-fly decision-making tools. This allows for example switching between the appropriate fragmentation technique in the mass spectrometer depending on the sample under investigation, performed on-the-fly. Furthermore the developed acquisition method is flexible and user-friendly. The amount and the size of the data provided by modern mass spectrometers are not compatible with manual analysis. Therefore to be able to post-process data fast and accurately a parallel processing technique for large data sets in a distributed computing environment was developed. Another objective described in this thesis is the modification of the FTICR instrument to perform both electrospray (ESI) and matrix assisted laser desorption ionisation (MALDI) (work in progress). The simulations and the experimental results of a new designed ESI ion source are described. Here, our goal is to increase the detection sensitivity by designing a linear accumulation octopole with enhanced ion ejection capabilities. The octopole design and implementation was the first step in the development of the instrument in order to combine ESI with MALDI imaging.