Improvements to the compressed-sample (CS) technique for MALDI-TOF mass spectrometry

A recently developed solvent-free compressed-sample technique for matrix-assisted laser desorption/ionization-mass spectrometry (MALDI-MS) analysis allows the reproducible analysis of synthetic polymers and peptides up to 3,500 Da. In this work, we present an improvement in resolution, an increase in intensity and a decrease of the variation coefficient, as illustrated by the analysis of PEG 2000 and MALDI imaging experiments. These advantages were achieved by homogenization of the electrical field, which was disturbed by the drills in the original MALDI target. In order to homogenize the electrical field, a new target with smaller drills was developed, metal powder was added to the matrix/analyte mixture and a round laser raster was used. Furthermore, a ball mill was implemented for the sample preparation to replace the extremely user-dependent grinding in a mortar. The new conditions were successfully applied to the quantification of several peptides of higher molecular weight and gave higher precision than had previously been achieved with the compressed-sample technique.