The development and application of a time-lag focusing matrix-assisted laser desorption/ionisation time-of-flight mass spectrometer

Decoupling ion desorption from ion extraction in matrix-assisted laser desorption/ionisation (MALDI) on a time-of-flight mass spectrometer provides substantial benefits. Inserting the sample probe through the repeller ensures that the resultant ions are directed forward in a direction parallel to the flight axis. Spatial aberrations are minimized in this geometry. Thus, a relationship between an ion's velocity (energy) and its initial position exists before the extraction pulse is applied. Time-lag focusing can be used to compensate for the initial energy distribution of MALDI formed ions providing a significant increase in resolution. The energy deficit observed in continuous extraction MALDI was not observed with time-lag focusing. The opposite effect was seen, an energy excess that increased with mass. A method was developed to overcome the effect of the energy excess on the time-of-flight calibration curve. The dependence of ion flight time on laser power is significantly reduced in time-lag focusing. The small laser power dependent energy deficit that remains decreases slightly with increasing mass, consistent with source discharge.;A good sample preparation method is necessary to obtain consistent external mass accuracy and mass resolution. Preferably, samples should be prepared in thin layers of matrix microcrystals. The instrument is applied to the analysis of peptides, proteins, oligonucleotides, modified oligosaccharides from crude samples, and end-labelled polyethylene glycol polymers.;A technique called microspot MALDI was developed to improve the sensitivity of the MALDI method. Microcapilleries were used to deposit analyte onto a specific location on the sample probe to use the sample more efficiently. The sample preparation method is described.