IMPROVED RESOLUTION AND VERY HIGH-SENSITIVITY IN MALDI TOF OF MATRIX SURFACES MADE BY FAST EVAPORATION

Matrix-assisted laser desorption/ionization time-of-flight mass spectr ometry (MALDI TOF) is becoming a standard tool in mass spectrometry in general and protein analysis in particular. Its advantages include hi gh sensitivity, tolerance to buffers, fast data acquisition, and simpl e and robust instrumentation. Disadvantages have been relatively low r esolution and mass accuracy and have mainly been caused by factors rel ated to sample preparation. Here we describe a simple new sample prepa ration procedure in which matrix and sample handling are completely de coupled. Fast evaporation of a matrix solution based on, e.g,, acetone produces a thin layer, presumably consisting of microcrystals. In a s econd step a drop of analyte solution is deposited on the layer. Some of the features of this new procedure are as follows: (i) there is an improvement in sensitivity; peptides can routinely be analyzed in the attomole range; (ii) salts and impurities are more easily washed off t he prepared samples; (iii) sample surfaces become much more homogeneou s, allowing very fast data acquisition; (iv) spectra show a more linea r mass scale and higher resolution, especially when a reflector is use d. In examples, a sensitivity of 5 amol and a resolution of up to 5700 (fwhm) could be achieved for peptides.