A tutorial: Laserspray ionization and related laser‐based ionization methods for use in mass spectrometry

Abstract

This Tutorial is to provide a summary of parameters useful for successful outcomes of laserspray ionization (LSI) and related methods that employ a laser to ablate a matrix:analyte sample to produce highly charged ions. In these methods the purpose of the laser is to transfer matrix‐analyte clusters into the gas phase. Ions are hypothesized to be produced by a thermal process where emitted matrix:analyte gas‐phase particles/clusters are charged and loss of matrix from the charged particles leads to release of the analyte ions into the gas phase. The thermal energy responsible for the charge‐separation process is relatively low and not necessarily supplied by the laser; a heated inlet tube linking atmospheric pressure with the first vacuum stage of a mass spectrometer is sufficient. The inlet becomes the “ion source”, and inter alia, pressure, temperature, and the matrix, which can be a solid, liquid, or combinations, become critical parameters. Injecting matrix:analyte into a heated inlet tube using laser ablation, a shockwave, or simply tapping, all produce the similar mass spectra. Applications are provided that showcase new opportunities in the field of mass spectrometry.

Instrumentation development, improvement, simplification, and miniaturization: The multifunctional plate source for use in mass spectrometry

“…A heated inlet tube has been shown to improve inlet ionization. 18–31 However, even without added heat, ions are formed quite effectively using SAI with volatile matrices such as methanol and MAI with the 3-NBN matrix. Clearly, heating the inlet tube will extend the capabilities of ESI through improved desolvation and of SAI through ionization of compounds in less volatile matrices such as water.…”

“…This eliminates the necessity to use a vacuum lock, or extra pump, to introduce an entire sample plate to vacuum, as used with other commercial vacuum MALDI sources, thus essentially eliminating pumping downtime exchanging sample plates, while simplifying construction, and aiding in direct ionization. Sliding the sample plate assembly over the opening sequentially exposes samples to the vacuum of the mass spectrometer, and, for MALDI, in position to receive illumination from a laser beam (Scheme S2, Movie 2) in reflection geometry 5–13,18,22,34,71–82 or transmission geometry. 18–25,34,40,83–85 Because the sample assembly plates are at AP and only a single sample at a time is exposed to vacuum, plates are easier to load, unload, and slide by hand, or by automation, than with a plate in vacuum.…”

“…Sliding the sample plate assembly over the opening sequentially exposes samples to the vacuum of the mass spectrometer, and, for MALDI, in position to receive illumination from a laser beam (Scheme S2, Movie 2) in reflection geometry 5–13,18,22,34,71–82 or transmission geometry. 18–25,34,40,83–85 Because the sample assembly plates are at AP and only a single sample at a time is exposed to vacuum, plates are easier to load, unload, and slide by hand, or by automation, than with a plate in vacuum. We have only limited experience with vMALDI using the plate source concept, but, to date, have not detected lens element contamination.…”

“…The importance of these inventions was recognized by honoring Trimpin with the American Society for Mass Spectrometry Biemann Medal in 2019. 19 For a summary, the interested reader is referred to Trimpin et al, 19 Trimpin et al, 20 El-Baba et al, 21 and Trimpin et al 22 In this article, when an inlet tube is present to connect the AP/vacuum region, the related methods are collectively referred to as inlet ionization, and when the sample is inserted directly into vacuum on a substrate, they are referred to as vacuum ionization. Laserspray ionization (LSI), 23–25 matrix-assisted ionization (MAI), 26,27 and solvent-assisted ionization (SAI) 28,29 are some of the newer methods used to initiate the analyte ionization.…”

Direct sub‐atmospheric pressure ionization mass spectrometry: Evaporation/sublimation‐driven ionization is amazing, fundamentally, and practically

“…Manual and automated analyses from well plates to surfaces describing some representative methods and biological applications are also presented here. Summaries of the discoveries of the new ionization processes, 3 fundamentals, [4][5][6][7][8][9][10][11][12] and novel applications [13][14][15][16][17][18][19][20][21][22] have been published elsewhere; specific emphasis is to be placed on the summaries published in the Perspective in the special issue in honor of Professor Trimpin receiving the American Society for Mass Spectrometry (ASMS) Biemann Medal in Trimpin et al 3…”