Novel ionization processes for use in mass spectrometry: ‘Squeezing’ nonvolatile analyte ions from crystals and droplets

Abstract

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.

New mass spectrometry concepts for characterization of synthetic polymers and additives

“…1,28 Limitations of both mass range and IMS separation are expressed in ionization methods that produce only singly charged ions. Novel ionization processes [29][30][31][32] were recently discovered producing multiply charged ions similar to those produced by ESI, 33 but from a solid matrix. These are similar to conditions previously associated with matrix-assisted laser desorption/ionization (MALDI), 34,35 but without the use of high voltage, laser, heat, or desolvation gases.…”

“…2,3,[58][59][60][61] Furthermore, despite several detailed studies, the use of salt additives may not have been fully explored for applications in synthetic polymer MS more generally. [62][63][64][65][66][67][68] We describe the development of new ionization processes [28][29][30][31][32]…”

“…Detailed accounts on fundamentals using biological polymers can be found in the literature. [29][30][31][32]53 hypothesized that in MAI a sublimation process is responsible for expelling matrix/analyte particles into the gas-phase charged by a triboluminescence-like process. 30,31 It is, in particular, not easily understood how gas-phase cation attachment can be associated with sublimation-driven processes.…”

“…[29][30][31][32]53 hypothesized that in MAI a sublimation process is responsible for expelling matrix/analyte particles into the gas-phase charged by a triboluminescence-like process. 30,31 It is, in particular, not easily understood how gas-phase cation attachment can be associated with sublimation-driven processes. [78][79][80] However, we have no reason to believe that the processes are fundamentally different between the synthetic and biological polymer ionization other than their basicities and therefore preferences for attaching metal cation(s) versus proton(s) as is the case with any ionization method.…”

Perspectives on the future of mass spectrometry

“…Sarah Trimpin's Perspective offers an introduction to classical and novel ionization processes, classification, and the operation of new ionization methods, characteristics of performance and applications, fundamentals and mechanisms, novel technologies enabled by new ionization processes and an outlook on a possible trajectory for these techniques …”