Characterization of Electrospray Drop Size Distributions by Mobility-Classified Mass Spectrometry: Implications for Ion Clustering in Solution and Ion Formation Pathways

One of the outcomes of electrospray ionization is the size distribution of the droplets, which determines, together with the solvent composition and the source gas temperature, the minimum distance from the sprayer tip to the mass spectrometer inlet and therefore the ion transfer efficiency. Even more importantly, the average number of analyte molecules and, if present, contaminant species per droplet depend on the drop size. Consequently, the drop size distribution is a key parameter in nonspecific ion clustering in solution and ion suppression. The finding that small droplet sizes improve the mass spectral quality led to the development of nanoelectrospray sources, which dispense liquid flow rates below 0.1 μL/min and can generate drops with diameters smaller than 100 nm. However, current discussions on the effect of drop size on ion formation pathways and efficiencies remain qualitative because the exact drop size distributions are unknown. Here, we show that ion mobility-classified mass spectrometry of raffinose cluster ions allows us to determine very precisely the drop size distribution generated by the electrospray source in positive- and negative-ion modes. Based on the derived drop size distributions, we can quantitatively predict nonspecific ion clustering and can extract accurate probabilities for emission of species from parent drops upon Coulomb fission.