MALDI-MSI Spatial Metabolomics Imaging Service

MALDI-MSI Spatial Metabolomics — In Situ Metabolite and Lipid Mapping on Tissue

MALDI-MSI spatial metabolomics is a label-free tissue imaging method operating at 10–100 µm resolution, combining on-tissue derivatization, dual-polarity acquisition, and histology co-registration for in situ metabolite and lipid mapping.

Conventional metabolomics homogenizes tissue and averages away spatial information. Where a tumor meets its stroma, where a drug accumulates versus where it clears, which brain regions rewire their metabolism — these questions require data that keeps the location attached to the measurement. MALDI mass spectrometry imaging (MALDI-MSI) generates a mass spectrum at every pixel of a tissue section, producing ion images in which each metabolite or lipid is mapped back to its anatomical position.

MALDI-MSI spatial metabolomics delivers:

• Micrometer spatial resolution: pixel sizes of 10–100 µm selected per study objective, with histology co-registration for region-of-interest analysis
• Metabolite and lipid coverage in one run: amino acids, TCA and energy metabolites, neurotransmitters, free fatty acids, phospholipids, sphingolipids, and more across dual polarity
• On-tissue derivatization options: carbonyl, amine, and carboxylate chemistry extends sensitivity to polar metabolite classes that ionize poorly without derivatization
• Spatial statistics: region-of-interest differential abundance, co-localization, and spatial autocorrelation (e.g., Moran's I) for decision-grade comparisons

What MALDI-MSI Adds Over Conventional Metabolomics

Conventional LC-MS answers "how much is in the whole sample." MALDI-MSI answers "where is it, and how does that differ between regions?" The two are complementary — conventional methods provide sensitive global quantification, while imaging reveals the spatial biology that averaging hides:

Conventional Metabolomics vs. MALDI-MSI Spatial Metabolomics

For deep quantitative confirmation of imaging hits, our untargeted metabolomics service provides homogenate-based LC-MS profiling on adjacent sections — the two approaches read the same biology from complementary angles.

MALDI-MSI Platform and Technical Parameters

Our MALDI-MSI workflows run on high-resolution mass spectrometry platforms with MALDI ionization sources, configured per study for the pixel size, mass range, and chemical coverage your question requires.

Spatial Metabolome and Lipidome Coverage

On-tissue derivatization spatial metabolomics extends MALDI-MSI beyond lipids into polar primary metabolites — the class most customers worry is undetectable by MALDI. Combined with lipid imaging, coverage spans the full small-molecule landscape in a single section:

MALDI-MSI Workflow — A Step-by-Step Guide

Sample Requirements for MALDI-MSI (Fresh-Frozen, FFPE, Organoids)

MALDI-MSI is compatible with a wide range of sample types. Because imaging preserves tissue architecture, sample orientation and section quality directly affect data quality:

FFPE guidance: Formalin fixation and paraffin embedding can deplete small molecules, but optimized deparaffinization followed by on-tissue derivatization extends FFPE compatibility beyond lipid-focused imaging to defined metabolite classes — including amines and carbonyls. If you are working with FFPE blocks and are unsure whether your analyte of interest survives the workflow, contact us with the target list before submission; we will confirm feasibility during project design.

Why Choose Our MALDI-MSI Service

• Metabolome-forward coverage
  We integrate spatial lipidomics and metabolomics in a single acquisition — amino acids, TCA intermediates, and neurotransmitters via on-tissue derivatization, alongside full lipid imaging.
• Dual-polarity acquisition
  Positive and negative modes in a single study maximize coverage across lipid, metabolite, and xenobiotic classes.
• Histology co-registration
  Ion images are aligned to H&E and IHC so molecular findings stay anchored to real tissue morphology.
• Orthogonal validation
  Imaging hits can be confirmed by LC-MS on adjacent sections or serial extracts, adding deep quantitative confirmation to imaging data.
• Auditable QC
  Lock-mass calibration, replicate regions, background and matrix-only controls, and acceptance criteria documented per slide set.

MALDI-MSI Data Deliverables and Spatial Bioinformatics

Our histology-guided spatial metabolomics workflow delivers presentation-ready assets and the raw data to re-analyze:

• Ion images for prioritized features, co-registered to histology (presentation-ready)
• ROI-level tables with mean, median, variance, effect sizes, and FDR-controlled p-values
• Spatial statistics — co-localization matrices, gradient analysis, neighborhood enrichment, Moran's I
• Quantitative spatial metabolomics options — semi-absolute quantification of defined targets using on-tissue stable-isotope internal standards (SIL-IS), with feasibility assessed per study
• Pathway panels summarizing localized pathway activity trends
• Full data package — imzML, vendor raw files, peak lists, metadata JSON, and analysis notebooks

Applications

• Oncology and tumor metabolism — map metabolic reprogramming across tumor boundaries, hypoxic cores, and invasive fronts; study drug penetrance and resistance microenvironments
• Neuroscience — regional metabolome rewiring in brain sections; neurotransmitter localization; neuropathology models
• Drug distribution and pharmacology — label-free drug distribution imaging of parent compounds and metabolites across target tissues, without radiolabeling or fluorescent tags
• Plant and food science — spatial localization of secondary metabolites and defense compounds in tissue sections
• Microbiome and biofilm — community-level metabolite mapping in microbial consortia

As part of the broader spatial metabolomics service portfolio, MALDI-MSI can be combined with DESI-MSI, nano-DESI, and spatial transcriptomics for multi-modal tissue analysis.

Case Study: Tumor Drug Penetration Measured by Targeted Metabolomics in Cholangiocarcinoma

Pan-lysyl oxidase inhibition disrupts fibroinflammatory tumor stroma, rendering cholangiocarcinoma susceptible to chemotherapy

Burchard, P. R., Ruffolo, L. I., Ullman, N. A., Dale, B. S., Dave, Y. A., Hilty, B. K., Ye, J., Georger, M., Jewell, R., Miller, C., et al. | Hepatology Communications, 2024, 8(8), e0502

DOI: 10.1097/hc9.0000000000000502

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Background

Cholangiocarcinoma (CCA) is characterized by a highly desmoplastic, fibroinflammatory stroma that compresses tumor vasculature and limits chemotherapeutic penetration. Pan-lysyl oxidase (pan-LOX) inhibition was proposed to reverse this mechanical barrier and restore drug access to the tumor.

Challenge: Quantify how effectively chemotherapy reaches the tumor interior when stromal remodeling is disrupted — a measurement that requires tissue-level drug quantification, not just plasma levels.

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Analytical Approach

In a mouse model of cholangiocarcinoma treated with pan-LOX inhibition plus chemotherapy, intratumoral 5-fluorouracil (5FU) concentration was determined by UPLC-MS analysis performed at Creative Proteomics — a tissue-level quantitative readout of drug penetrance into the tumor.

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Key Findings

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What This Means for Your MALDI-MSI Study

• Tissue-level drug quantification is the question. The 5FU penetrance readout that drove this study is exactly the measurement class MALDI-MSI visualizes in situ — drug and metabolite distribution mapped across the tumor, no homogenization required.
• Regional heterogeneity matters. Whole-tissue quantification answered "how much drug reached the tumor." MALDI-MSI answers "where did it reach" — core vs. periphery, viable vs. stromal zones — adding the spatial dimension to penetration studies.
• Orthogonal confirmation. Where imaging identifies candidate accumulation regions, LC-MS on adjacent sections confirms identity and quantity — the same combined workflow we support.

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Conclusion

This study demonstrates how tissue-level drug and metabolite quantification drives mechanism-of-action research in oncology. Our MALDI-MSI spatial metabolomics service extends this capability — visualizing drug and metabolite distribution across tissue sections at micrometer resolution, so penetration, heterogeneity, and regional response are seen, not averaged.

Publications