THERMOMETER IONS, INTERNAL ENERGIES, AND AMBIENT IONIZATION IN-SOURCE FRAGMENTATION

Ionization and fragmentation are at the core of mass spectrometry. But they are not separated in space, as in-source fragmentation can also occur. Here we survey the literature published since our 2005 review on the internal energy and fragmentation in electrospray ionization sources (Gabelica & De Pauw, Mass Spectrom. Rev. 2005, 24, 566). We present new thermometer molecules to diagnose and quantify source heating, provide tables of recommended threshold (E0) and appearance energies (Eapp) for the survival yield method, and systematically compare the softness of a variety of ambient pressure ionization methods. The droplet size distribution and desolvation dynamics play a major role: lower average internal energies are obtained when the ions remain protected by a solvation shell and spend less time nakedly exposed to activating conditions in the transfer interface. Methods based on small droplet formation without electrophoretic charging can thus be softer than electrospray. The tuning of the entire source interface often has an even greater influence on ion internal energies and fragmentation than on the ionization process itself. We also highlight new dielectric barrier discharge sources that can gas-phase ionize small molecules while conferring barely more internal energy than electrospray ionization. We hope that this review will facilitate the control and standardization of in-source ion activation conditions, to ensure the transferability of data and research results in mass spectrometry.