Single‐Photon‐Induced Post‐Ionization to Boost Ion Yields in MALDI Mass Spectrometry Imaging**

Abstract

Matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) is a rapidly growing method in many elds of the life sciences. For many analyte classes, however, its sensitivity is limited due to poor ionization e ciencies. To mitigate this problem, we here introduce a novel and cost-effective postionization scheme at high repetition rates based on the interplay of single-photon photoionization and subsequent charge transfer reactions. Importantly, the ne vacuum conditions of a dual ion-funnel ion source effectively thermalize the evolving MALDI plume and enable ample gas-phase reactions as well as the addition of chemical dopants that crucially support chemical ionization. Supported by acetone dopant, [M + H] + /[M-H] − signals of numerous glycerophospho-, sphingo-, and further lipids, registered from mammal brain and kidney sections, were boosted by up to three orders of magnitude, similar to results obtained with laser-based postionization (MALDI-2). Experiments utilizing deuterated matrix and dopant, however, indicate complex ionization pathways different from MALDI2.

Nanoliter atmospheric pressure photoionization-mass spectrometry for direct bioanalysis of polycyclic aromatic hydrocarbons

“…23 Soltwisch et al coupled single-photon ionization (SPI) with matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI). 24 Based on this interplay, numerous glycerophospho-, sphingo-, and further lipids, obtained from mammalian tissue sections, were boosted by up to three orders of magnitude, similar to the results obtained with laser-based post-ionization (MALDI-2). Pan et al combined Leidenfrost effect-assisted thermal desorption (LETD) with atmospheric pressure photoionization (APPI) to quantify free sex steroids in human serum.…”

Spatial Metabolomics and Lipidomics Reveal the Mechanisms of the Enhanced Growth of Breast Cancer Cell Spheroids Exposed to Triclosan

“…This may be because MALDI-2 involves additional fragmentation of ions during the ionization process. In some cases, the additional fragmentation may result in a loss of sensitivity for certain types of molecules . Besides, the selection of the matrix may affect the results for detecting compounds by using MALDI-2.…”

“…In some cases, the additional fragmentation may result in a loss of sensitivity for certain types of molecules. 52 Besides, the selection of the matrix may affect the results for detecting compounds by using MALDI-2. For instance, MG(18:1) and CE (18:1) could not be detected in both MALDI-2 and MALDI using the DHB matrix.…”

A Machine Learning-Driven Comparison of Ion Images Obtained by MALDI and MALDI-2 Mass Spectrometry Imaging

“…Recently, post-ionization techniques have been developed to enhance the ionization of analytes not initially ionized by MALDI to overcome these limitations, boosting sensitivities by up to 2 orders of magnitude. These techniques include low-temperature plasmas, − pulsed RF-Kr lamps, and laser-induced post-ionization (MALDI-2) . MALDI-2 is currently the most widely used post-ionization method and involves directing a second ultraviolet (UV) laser pulse (typically 260–280 nm) through the matrix/analyte plume produced by the MALDI laser pulse.…”