Reverse thin layer method for enhanced ion yield of oligosaccharides in matrix-assisted laser desorption/ionization

A sample preparation method that is suitable for sensitive detection of underivatized oligosaccharides by matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) has been investigated. As compared with the conventional dried-droplet or ethanol (EtOH) recrystallization method, superior mass spectra in terms of ion yield and signal-to-noise (s/n) ratio were obtained when methanol (MeOH) was used as a solvent for the mixture of matrix and oligosaccharides. Based on these results, a new sample preparation method, named the 'reverse thin layer method', was developed. This method comprises two steps: first, complete drying of the oligosaccharide solution on the MALDI target plate; and second, deposition of the matrix dissolved in a small amount of MeOH. Using this method, a relatively homogeneous matrix crystal was generated and higher yields of both positive and negative ions were obtained from oligosaccharides compared with conventional methods. Notably, the method can be applied to various matrices including both solid and liquid matrices.