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Peer-reviewedCC BYJournal of the American Society for Mass Spectrometry

Ionic Solid Matrices Applied via Low-Temperature Evaporation Enable High-Resolution and Sensitive MALDI Imaging of Metabolites.

  • Toufik Mahamdi1,2
  • Nadia Moltó1,2
  • Mireia Arasa1
  • Roger Giné1,2
  • Jordi Rofes1,2
  • María García-Altares1
  • Maria Vinaixa1,2,3
  • Oscar Yanes1,2,3
  1. 1Universitat Rovira i Virgili , Department of Electronic Engineering, Tarragona43007, Spain.
  2. 2CIBER de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Instituto de Salud Carlos III, Madrid28029, Spain.
  3. 3Metabolomics Platform, Institut de Recerca Biomèdica Catalunya Sud, Hospital Universitari Sant Joan de Reus, Reus43204, Spain.
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Abstract

Matrix-Assisted Laser Desorption/Ionization Mass Spectrometry Imaging (MALDI-MSI) enables spatially resolved molecular analysis of biological tissues. However, imaging low-molecular-weight metabolites remains challenging because conventional organic matrices generate intense background signals in the low m/z region. Ionic matrices can reduce matrix-related interferences, improve spectral reproducibility, and enhance sensitivity. However, their application in MALDI-MSI has remained limited, largely due to the need for additional matrix preparation and the challenging wet deposition of viscous ionic liquid matrices, and has mainly focused on lipid imaging above m/z 500. Here, we present a novel approach combining ionic solid matrices (ISMs) with low-temperature thermal evaporation (LTE) to enhance MALDI-MSI performance for small metabolites. ISMs based on α-cyano-4-hydroxycinnamic acid (CHCA) and 2,5-dihydroxybenzoic acid (DHB) provided superior sensitivity and reduced matrix background. In particular, CHCA + N,N-diethylaniline enabled the detection and annotation of 69 metabolites with m/z < 500 in mouse brain tissue at 20 μm spatial resolution. When applied to mouse pancreas, this ISM allowed the first specific localization of melatonin and 3-iodotyrosine within the islets of Langerhans, opening new avenues for spatial metabolomics in endocrine research.

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Cite

BibTeXRIS
BibTeX
@article{mahamdi2026ionic,
  title = {{Ionic Solid Matrices Applied via Low-Temperature Evaporation Enable High-Resolution and Sensitive MALDI Imaging of Metabolites.}},
  author = {Toufik Mahamdi and Nadia Moltó and Mireia Arasa and Roger Giné and Jordi Rofes and María García-Altares and Maria Vinaixa and Oscar Yanes},
  journal = {Journal of the American Society for Mass Spectrometry},
  year = {2026},
  month = oct,
  doi = {10.1021/jasms.6c00219},
  url = {https://europepmc.org/article/MED/42916751},
  note = {CC BY},
}
RIS
TY  - JOUR
TI  - Ionic Solid Matrices Applied via Low-Temperature Evaporation Enable High-Resolution and Sensitive MALDI Imaging of Metabolites.
AU  - Toufik Mahamdi
AU  - Nadia Moltó
AU  - Mireia Arasa
AU  - Roger Giné
AU  - Jordi Rofes
AU  - María García-Altares
AU  - Maria Vinaixa
AU  - Oscar Yanes
PY  - 2026
DA  - 2026/10/01
JO  - Journal of the American Society for Mass Spectrometry
DO  - 10.1021/jasms.6c00219
UR  - https://europepmc.org/article/MED/42916751
AB  - Matrix-Assisted Laser Desorption/Ionization Mass Spectrometry Imaging (MALDI-MSI) enables spatially resolved molecular analysis of biological tissues. However, imaging low-molecular-weight metabolites remains challenging because conventional organic matrices generate intense background signals in the low m/z region. Ionic matrices can reduce matrix-related interferences, improve spectral reproducibility, and enhance sensitivity. However, their application in MALDI-MSI has remained limited, largely due to the need for additional matrix preparation and the challenging wet deposition of viscous ionic liquid matrices, and has mainly focused on lipid imaging above m/z 500. Here, we present a novel approach combining ionic solid matrices (ISMs) with low-temperature thermal evaporation (LTE) to enhance MALDI-MSI performance for small metabolites. ISMs based on α-cyano-4-hydroxycinnamic acid (CHCA) and 2,5-dihydroxybenzoic acid (DHB) provided superior sensitivity and reduced matrix background. In particular, CHCA + N,N-diethylaniline enabled the detection and annotation of 69 metabolites with m/z < 500 in mouse brain tissue at 20 μm spatial resolution. When applied to mouse pancreas, this ISM allowed the first specific localization of melatonin and 3-iodotyrosine within the islets of Langerhans, opening new avenues for spatial metabolomics in endocrine research.
SN  - 1044-0305
SN  - 1879-1123
ER  -