IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v16y2025i1d10.1038_s41467-025-59839-3.html
   My bibliography  Save this article

Deep MALDI-MS spatial omics guided by quantum cascade laser mid-infrared imaging microscopy

Author

Listed:
  • Lars Gruber

    (Technische Hochschule Mannheim
    Heidelberg University)

  • Stefan Schmidt

    (Technische Hochschule Mannheim)

  • Thomas Enzlein

    (Technische Hochschule Mannheim)

  • Huong Giang Vo

    (Mainz University)

  • Tobias Bausbacher

    (Technische Hochschule Mannheim
    Heidelberg University)

  • James Lucas Cairns

    (Technische Hochschule Mannheim
    Heidelberg University)

  • Yasemin Ucal

    (Technische Hochschule Mannheim)

  • Florian Keller

    (Technische Hochschule Mannheim)

  • Martina Kerndl

    (Medical University of Vienna
    Christian Doppler Laboratory for Arginine Metabolism in Rheumatoid Arthritis and Multiple)

  • Denis Abu Sammour

    (Technische Hochschule Mannheim)

  • Omar Sharif

    (Medical University of Vienna
    Christian Doppler Laboratory for Immunometabolism and Systems Biology of Obesity-Related Diseases (InSpiReD))

  • Gernot Schabbauer

    (Medical University of Vienna
    Christian Doppler Laboratory for Arginine Metabolism in Rheumatoid Arthritis and Multiple)

  • Rüdiger Rudolf

    (Technische Hochschule Mannheim
    Heidelberg University)

  • Matthias Eckhardt

    (University of Bonn)

  • Stefania Alexandra Iakab

    (Technische Hochschule Mannheim)

  • Laura Bindila

    (Mainz University)

  • Carsten Hopf

    (Technische Hochschule Mannheim
    Heidelberg University
    Heidelberg University)

Abstract

In spatial’omics, highly confident molecular identifications are indispensable for the investigation of complex biology and for spatial biomarker discovery. However, current mass spectrometry imaging (MSI)-based spatial ‘omics must compromise between data acquisition speed and biochemical profiling depth. Here, we introduce fast, label-free quantum cascade laser mid-infrared imaging microscopy (QCL-MIR imaging) to guide MSI to high-interest tissue regions as small as kidney glomeruli, cultured multicellular spheroid cores or single motor neurons. Focusing on smaller tissue areas enables extensive spatial lipid identifications by on-tissue tandem-MS employing imaging parallel reaction monitoring-Parallel Accumulation-Serial Fragmentation (iprm-PASEF). QCL-MIR imaging-guided MSI allowed for unequivocal on-tissue elucidation of 157 sulfatides selectively accumulating in kidneys of arylsulfatase A-deficient mice used as ground truth concept and provided chemical rationales for improvements to ion mobility prediction algorithms. Using this workflow, we characterized sclerotic spinal cord lesions in mice with experimental autoimmune encephalomyelitis (EAE), a model of multiple sclerosis, and identified upregulation of inflammation-related ceramide-1-phosphate and ceramide phosphatidylethanolamine as markers of white matter lipid remodeling. Taken together, widely applicable and fast QCL-MIR imaging-based guidance of MSI ensures that more time is available for exploration and validation of new biology by default on-tissue tandem-MS analysis.

Suggested Citation

  • Lars Gruber & Stefan Schmidt & Thomas Enzlein & Huong Giang Vo & Tobias Bausbacher & James Lucas Cairns & Yasemin Ucal & Florian Keller & Martina Kerndl & Denis Abu Sammour & Omar Sharif & Gernot Scha, 2025. "Deep MALDI-MS spatial omics guided by quantum cascade laser mid-infrared imaging microscopy," Nature Communications, Nature, vol. 16(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-59839-3
    DOI: 10.1038/s41467-025-59839-3
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-025-59839-3
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-025-59839-3?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    References listed on IDEAS

    as
    1. Yeran Bai & Carolina M. Camargo & Stella M. K. Glasauer & Raymond Gifford & Xinran Tian & Andrew P. Longhini & Kenneth S. Kosik, 2024. "Single-cell mapping of lipid metabolites using an infrared probe in human-derived model systems," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    2. Denis Abu Sammour & James L. Cairns & Tobias Boskamp & Christian Marsching & Tobias Kessler & Carina Ramallo Guevara & Verena Panitz & Ahmed Sadik & Jonas Cordes & Stefan Schmidt & Shad A. Mohammed & , 2023. "Spatial probabilistic mapping of metabolite ensembles in mass spectrometry imaging," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    3. Kevin Yeh & Ishaan Sharma & Kianoush Falahkheirkhah & Matthew P. Confer & Andres C. Orr & Yen-Ting Liu & Yamuna Phal & Ruo-Jing Ho & Manu Mehta & Ankita Bhargava & Wenyan Mei & Georgina Cheng & John C, 2023. "Infrared spectroscopic laser scanning confocal microscopy for whole-slide chemical imaging," Nature Communications, Nature, vol. 14(1), pages 1-12, December.
    Full references (including those not matched with items on IDEAS)

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. Le Wang & Haonan Lin & Yifan Zhu & Xiaowei Ge & Mingsheng Li & Jianing Liu & Fukai Chen & Meng Zhang & Ji-Xin Cheng, 2024. "Overtone photothermal microscopy for high-resolution and high-sensitivity vibrational imaging," Nature Communications, Nature, vol. 15(1), pages 1-13, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-59839-3. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.