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 spectrometry (MALDI TOF) is becoming a standard tool in mass spectrometry in general and protein analysis in particular. Its advantages include high sensitivity, tolerance to buffers, fast data acquisition, and simple and robust instrumentation. Disadvantages have been relatively low resolution and mass accuracy and have mainly been caused by factors related to sample preparation. Here we describe a simple new sample preparation procedure in which matrix and sample handling are completely decoupled. Fast evaporation of a matrix solution based on, e.g,, acetone produces a thin layer, presumably consisting of microcrystals. In a second 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 the prepared samples; (iii) sample surfaces become much more homogeneous, allowing very fast data acquisition; (iv) spectra show a more linear mass scale and higher resolution, especially when a reflector is used. In examples, a sensitivity of 5 amol and a resolution of up to 5700 (fwhm) could be achieved for peptides.