Improvements in instrumentation and methods for matrix-assisted laser desorption ionization Fourier transform mass spectrometry

The high resolution and mass accuracy inherent to Fourier transform ion cyclotron resonance mass spectrometry (FTICR) have established the method as a premier analytical tool. Emerging techniques for the analysis of both biological and synthetic analytes greatly benefit from these advantages. Presented here are several advances in instrumental techniques and methods targeted at increasing the accuracy of information provided by FTICR in general, as well as improving several aspects of instrumental performance for matrix assisted laser desorption ionization (MALDI) FTICR.; A 4.7 tesla internal MALDI instrument based on an open-ended, capacitively coupled cell, is presented. The unique integration of capacitive coupling and amplified gated trapping allows these methods to be used within the same experiments. These advantages provided narrowband remeasurement efficiency of 100% for more than 200 remeasurement cycles, and a resolution (FWHH) of about 1.5 million for a small peptide of m/z 1164.; Several methods for the improvement of synthetic polymer analysis with MALDI FT-ICR are presented. Using the open cylindrical geometry to trap ions allowed large mass ranges to be collected from a MALDI event, with reduced dependance on gated trapping timing compared to the cubic cell. Consideration of the isotope beating effect for polymer analysis is also shown to be important as improper sampling of beat periods can cause error greater than 5% in the assignment of molecular weight averages. Using theoretical models of time domain transients, sampling for a minimum of 2 beat periods for the frequencies corresponding to isotopic masses for the center mass of the polymer distribution is advised for proper determinations of molecular weight averages.; Corrections for the total ion density for analyte and calibrant ions used for external calibration are shown to be crucial for high mass accuracy. Using broadband quadrupolar excitation for ion remeasurement, a linear correlation between the total ion density and mass shift was shown. Average mass measurement errors of less than 2 ppm are shown for an externally calibrated peptide at m/z 3495, and a polymer distribution with an average mass around 6500 Da.