Novel Ionization Processes for Use in Mass Spectrometry: 'Squeezing' Nonvolatile Analyte Ions from Crystals and Droplets.

Together with my group and collaborators, I have been fortunate to have had a key role in the discovery of new ionization processes that we developed into new flexible, sensitive, rapid, reliable, and robust ionization technologies and methods for use in mass spectrometry (MS). Our current research is focused on how best to understand, improve, and use these novel ionization processes which convert volatile and nonvolatile compounds from solids or liquids into gas-phase ions for analysis by MS using e.g. mass selected fragmentation and ion mobility spectrometry to provide reproducible, accurate, and improved mass and drift time resolution. In my view, the apex was the discovery of vacuum matrix-assisted ionization (vMAI) in 2012 on an intermediate pressure matrix-assisted laser desorption/ionization (MALDI) source without the use of a laser, high voltages, or any other added energy. Only exposure of the matrix:analyte to the sub-atmospheric pressure of the mass spectrometer was necessary to initiate ionization. These findings were initially rejected by three different scientific journals, with comments related to 'how can this work?', 'where do the charges come from?', and 'it is not analytically useful'. Meanwhile, we, and others have demonstrated analytical utility without a complete understanding of the mechanism. In reality, MALDI and electrospray ionization are widely used in science and their mechanisms are still controversially discussed despite use and optimization of now 30 years. This Perspective covers applications, and mechanistic aspects of the novel ionization processes for use in MS that guided us in instrument developments, and provides our perspective on how they relate to traditional ionization processes.