The early MALDI years and how "microscopy-grade" transmission-mode MALDI-2 mass spectrometry imaging was realized after a long delay: a personal retrospective and review.

Authors

Klaus Dreisewerd

Published in

Analytica chimica acta. Volume 1425. Pages 346153. Dec 01, 2026. Epub Aug 25, 2026.

Abstract

Since its invention in the mid-1980s, matrix-assisted laser desorption ionization (MALDI) mass spectrometry (MS) has developed into a key bioanalytical technique for numerous research areas in the life sciences. One remarkable application shift that began in the mid-1990s is the increasing use of the label-free MALDI technique as a molecular microscope. One holy grail of MALDI-MS Imaging (MALDI-MSI) is to reach a true single-cell or even a sub-cellular resolution to visualize the molecular content of individual cells and organelles thereof. This requires pixel sizes in the low to sub-micrometer range. These are difficult to achieve, such that new irradiation concepts are needed. Another contemporary research focus is on the advancement of multimodal imaging, especially in the combination of immunofluorescence (IF) microscopy and highly-resolved MALDI-MSI. Drawing upon four decades of active research in the MALDI field, I structured this review to offer both a personal (retro-)perspective and a comprehensive exploration of both historical and contemporary aspects. The initial chapter provides a historical overview of the development of the first laser microprobe mass analyzer (LAMMA 500), while the subsequent chapter chronicles the discovery of the MALDI technique and its initial applications in biological research. The third and fourth sections then direct the reader's attention to selected recent advancements in MALDI-imaging, highlighting pioneering contributions from both in-house and external laboratories. These developments include the utilization of laser postionization for MALDI-2 and the resurgence of the LAMMA 500 concept in the form of transmission (t-) mode MALDI-2. The recently introduced direct coupling of t-MALDI-2 with IF microscopy holds significant promise in unveiling novel avenues for cell biology research.

PMID:
42951506
Bibliographic data and abstract were imported from PubMed on 29 Oct 2026.

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