Forced dried droplet method for MALDI sample preparation

A forced dried droplet method (FDD) is developed to overcome the drawbacks of the conventional dried-droplet (DD) method for matrix assisted laser desorption/ionization (MALDI) sample preparation. The crystals produced by the DD method are heterogeneous and irregularly distributed, and thus many methods have tried to solve the problems. However, most of them spend more time or need additional instruments to generate homogeneous microcrystals. The FDD sample preparation method can produce uniform microcrystals with homogeneous size distribution in few minutes without additional instruments. Stirring the sample spot solution (an agitation process) with a pipette tip can change the crystal size distribution which is observed by the microscope. Mass spectrometric analysis shows that the smaller the crystal size is, the better the ion signal intensity is. The formation of microcrystals can be explained with the effective rate of secondary nucleation. The relative standard deviation (RSD) of the FDD method is ∼16% which is comparable to the two-layer (TL) method and is better than the DD method.