The efficiency of matrix assisted laser desorption/ionization mass spectrometry (MALDI) has been shown to be highly sensitive to the sample preparation procedure. Every single choice during sample preparation can affect the outcome of the MALDI measurements. The matrix/solvent system is considered one of the most important sample preparation parameters; however, other choices such as substrate material, sample purification, and sample crystallization technique are just as important.
Users new to the field can be easily overwhelmed by the number of sample preparation procedures available in the mass spectrometry literature. It seems that every MALDI practitioner has a different opinion of what constitutes the best sample preparation protocol. Many experienced MALDI users refer to sample preparation as an art form, which is mastered only through practice and experimentation. Trial and error, a frequent component of any MALDI optimization effort, is the consequence of the current lack of detailed understanding of the processes that lead to desorption and ion formation from MALDI samples.
The method used to prepare the protein-doped matrix crystals on the MALDI target can be the key to a successful MALDI experiment. This application note is designed to guide MALDI users through some of the available sample preparation options, with particular emphasis on the selection criteria for the best sample crystallization method