Liquid matrix-assisted laser desorption/ionization (MALDI) allows the generation of predominantly multiply
charged ions in atmospheric pressure (AP) MALDI ion sources for mass spectrometry (MS) analysis.
The charge state distribution of the generated ions and the efficiency of the ion source in generating such
ions crucially depend on the desolvation regime of the MALDI plume after desorption in the AP-tovacuum
inlet. Both high temperature and a flow regime with increased residence time of the desorbed
plume in the desolvation region promote the generation of multiply charged ions. Without such measures
the application of an electric ion extraction field significantly increases the ion signal intensity of
singly charged species while the detection of multiply charged species is less dependent on the extraction
field. In general, optimization of high temperature application facilitates the predominant formation and
detection of multiply charged compared to singly charged ion species. In this study an experimental setup
and optimization strategy is described for liquid AP-MALDI MS which improves the ionization effi-
ciency of selected ion species up to 14 times. In combination with ion mobility separation, the method
allows the detection of multiply charged peptide and protein ions for analyte solution concentrations
as low as 2 fmol/lL (0.5 lL, i.e. 1 fmol, deposited on the target) with very low sample consumption in
the low nL-range
