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DESI-MSI Ambient Spatial Metabolomics Imaging Service

DESI-MSI spatial metabolomics is an ambient ionization imaging method that profiles metabolites and lipids directly from native tissue surfaces without matrix coating or vacuum, at 50–200 µm practical resolution, and while preserving the section — the same slide can be H&E re-stained after imaging. A charged solvent spray desorbs molecules from the sample surface at atmospheric pressure, making DESI ideal for rapid large-area screening, delicate and native samples, and workflows that pair molecular imaging with downstream histology.

Ambient ionization — no matrix, no vacuum

Minimally destructive imaging; same section re-stained for H&E after

Rapid large-area and whole-organ screening

Native tissue, skin, and plant surface analysis

Lipid, metabolite, and drug distribution mapping

DESI-MSI ambient spatial metabolomics imaging of native tissue surface

DESI-MSI Ambient Spatial Metabolomics — Native Tissue Surface Mapping

DESI mass spectrometry imaging (DESI-MSI) is an ambient ionization method that maps lipids, abundant metabolites, and drugs directly from the surface of a tissue section, skin sample, or plant tissue — without matrix application, without vacuum, at 50–200 µm practical resolution, and while preserving the sample, so the same section can be H&E re-stained after imaging.

Vacuum-based imaging methods require matrix coating and freeze-drying, which can alter labile molecules and make the section unsuitable for subsequent histology. DESI operates at atmospheric pressure: a charged solvent micro-spray desorbs analytes from the sample surface and delivers them to the mass spectrometer, so each pixel of the ion image reflects molecules in their native state. Because the process is minimally destructive, the same section can be re-stained for H&E or IHC after imaging — molecular and morphological data from the very same tissue.

DESI-MSI ambient imaging delivers:

  • No matrix, no vacuum: direct ambient analysis with minimal sample preparation, preserving native molecular distribution
  • Minimally destructive workflow: same section can be H&E re-stained after imaging for direct molecular–morphological correlation
  • Rapid large-area coverage: fast per-unit-area acquisition suited to large sections and whole-organ screening
  • Polar analyte strength: charged-solvent desorption favors lipids, abundant metabolites, and drug compounds

DESI-MSI vs. Vacuum-Based Imaging — Choosing the Right Spatial Method

Both DESI-MSI and MALDI-MSI map molecules on tissue, but they answer different questions. The choice depends on the spatial resolution required, the analyte classes of interest, and whether the section must be preserved for downstream histology:

DESI-MSI vs. MALDI-MSI Spatial Metabolomics

DimensionDESI-MSI (Ambient)MALDI-MSI (Vacuum)
Ionization environmentAmbient, atmospheric pressureVacuum with matrix coating
Sample preparationMinimal — no matrix, direct analysisMatrix deposition required
Section preservationMinimally destructive; H&E re-staining after imagingGenerally destructive to the section
Spatial resolutionPractical 50–200 µm10–100 µm (finer pixels available)
StrengthsRapid large-area screening; polar analytes; native surfacesBroad metabolome and lipid coverage; on-tissue derivatization

The two methods are complementary rather than competing — together they cover the full spectrum of ambient mass spectrometry imaging and vacuum-based imaging. For projects requiring both high-resolution detail and rapid whole-section screening, we can design a dual-platform workflow — broad DESI-MSI screening of the full section followed by high-resolution MALDI-MSI imaging on key regions of interest — all within our spatial metabolomics service.

DESI-MSI Platform and Technical Parameters

Our DESI-MSI workflows pair a commercial DESI source with high-resolution mass spectrometry, configured per study for the surface type, analyte class, and spatial scale of your question.

ParameterSpecification
IonizationDesorption electrospray ionization (DESI), ambient conditions
Spatial resolution (pixel size)Practical 50–200 µm, selected per objective and sample type
Sample preparationMinimal — no matrix, no freeze-drying; direct surface analysis
Mass accuracyHigh-resolution MS with lock-mass correction
Ionization modesPositive and negative polarity; solvent composition optimized per analyte class
Analyte focusLipids, abundant metabolites, drug compounds; polar species favored by charged-solvent desorption
Section preservationMinimally destructive — same section can be H&E or IHC re-stained after imaging
File formatsimzML + vendor raw; processed CSV/Parquet; figures PNG/TIFF/SVG
Prosolia DESI 2D ionization source

Prosolia DESI 2D Source

Ambient charged-solvent desorption at atmospheric pressure

Thermo Orbitrap Exploris 240/480 mass spectrometer

Thermo Orbitrap Exploris 240/480

High-resolution analyzer for ppm-level DESI imaging

DESI-MSI Metabolome Coverage

DESI-MSI is classically best suited to polar analytes, and its charged-solvent desorption makes it particularly strong for lipids and drug compounds on native surfaces. Typical coverage in a single study:

Compound classExamples and notes
Phospholipids and sphingolipidsPC, PE, PI, PS, SM, ceramides — strong DESI signals in both polarities
Free fatty acidsPalmitic, oleic, arachidonic acid; oxidized lipid species
Abundant small metabolitesCholine, carnitine, amino acids at moderate-to-high abundance
Drug compoundsParent drug and major metabolites; label-free distribution mapping
XenobioticsExogenous compounds and environmental contaminants on tissue surfaces

For deep metabolome coverage beyond the abundant classes, on-tissue-derivatized MALDI-MSI or homogenate-based untargeted metabolomics service on adjacent sections provides the orthogonal depth — the two approaches read the same biology from complementary angles.

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

1

Project design

We define biological hypotheses, surfaces and regions of interest, and endpoints; select polarity, solvent composition, pixel size, and spatial scale. A method sheet with acceptance criteria is finalized before sample processing.

2

Sectioning and mounting

Chain-of-custody logging; cryosectioning or microtomy to 5–20 µm thickness; slide mounting with orientation preserved for histology alignment. No matrix, no freeze-drying required.

3

Ambient acquisition

Tiled scanning at defined pixel size under ambient conditions; solvent composition and gas flow optimized for target analyte classes; lock-mass correction applied per run.

4

Processing and QC

Peak picking, deisotoping and adduct grouping, mass recalibration, intensity normalization, and image co-registration with brightfield images.

5

Annotation and statistics

Database-aided annotation, region-of-interest differential abundance, spatial autocorrelation (Moran's I), co-localization metrics, and pathway enrichment.

6

Ion image, histology, and report

Delivery of ion images overlaid on H&E from the same section, ROI tables, pathway summaries, and imzML data for re-analysis.

DESI-MSI spatial metabolomics workflow from tissue sectioning to ion image delivery

Sample Requirements for DESI-MSI (Fresh-Frozen, Skin, Plant, Native Surfaces)

DESI-MSI's minimal-preparation, ambient workflow makes it uniquely suited to samples that are delicate, native, or destined for downstream histology:

Sample typeRequirements and notes
Fresh-frozen tissuesMammalian, plant, xenografts; embedded in OCT or equivalent; 5–20 µm sections
Skin and dermatological samplesNative surface analysis with minimal handling; suited to stratum corneum and lesion studies
Plant tissues and leavesNative leaf and stem surfaces analyzed directly; no extraction required
Native surfaces (biopsies, ex vivo tissue)Direct surface mapping preserving tissue for downstream histology
Microbial biofilmsCommunity-level surface metabolomics of microbial consortia
Food matricesMethod-dependent; compatibility evaluated during project design

OCT caution: OCT embedding polymer can produce intense background in ambient imaging. When possible, avoid OCT or remove as much as possible before sectioning; CMC or FSC22 are acceptable alternatives. Our team confirms sample compatibility during project design.

Why Choose Our DESI-MSI Service

  • Minimally destructive, same-section histology
    The same slide imaged by DESI can be H&E or IHC re-stained afterward — molecular and morphological data from one tissue section.
  • No matrix, no vacuum
    Minimal sample preparation at ambient conditions preserves native molecular distribution and speeds large-area screening.
  • Native surface fidelity
    Delicate samples — skin, plant leaves, biopsies — are analyzed directly without extraction artifacts.
  • Complementary platform strategy
    Pair broad DESI screening with high-resolution MALDI-MSI imaging on key ROIs, designed within the spatial metabolomics service portfolio.
  • Auditable QC
    Lock-mass calibration, replicate regions, background controls, and acceptance criteria documented per run.

DESI-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 H&E from the same section (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 stable-isotope standards, 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
Representative DESI-MSI ion image of native tissue surface with histology overlay

Representative DESI-MSI ion image: metabolite distribution on a native tissue surface with H&E co-registration.

Region-of-interest quantitative comparison of metabolite intensities by DESI-MSI

Region-of-interest comparison: metabolite intensities across defined tissue regions with statistical markers.

Applications

  • Oncology and tumor metabolism — rapid large-area lipid and metabolite mapping across tumor sections; drug penetrance and heterogeneity screening
  • Dermatology and skin research — native surface analysis of skin sections and lesions with minimal handling
  • Plant science — direct leaf and tissue surface mapping of secondary metabolites and stress markers, no extraction required
  • Drug distribution and pharmacology — label-free mapping of parent drug and metabolites across target tissues, compatible with downstream histology
  • Pathology research — fast minimally destructive tissue profiling with the same section preserved for H&E, IHC, or other analyses after imaging

Case Study: Native Leaf Metabolomics of Extremophyte Woody Species

Physiological, transcriptomic and metabolomic insights of three extremophyte woody species living in the multi-stress environment of the Atacama Desert

Gajardo, H. A., Morales, M., Larama, G., Luengo-Escobar, A., López, D., Machado, M., Nunes-Nesi, A., Reyes-Díaz, M., et al. | Planta, 2024, 260(3)

DOI: 10.1007/s00425-024-04484-1


Background

Three woody extremophyte species of the Atacama Desert — among the harshest multi-stress environments on Earth — maintain photosynthesis and growth under extreme drought, freezing, and salinity. Understanding how their leaf metabolism supports this tolerance requires metabolomic readouts tied to the leaf tissue itself.

Challenge: Resolve the metabolic basis of stress tolerance in extremophyte leaves, integrating untargeted leaf metabolomics with physiological and transcriptomic measurements.


Analytical Approach

Untargeted leaf metabolomics was performed by LC-MS analysis at Creative Proteomics on Strombocarpa tamarugo, Neltuma alba, and Neltuma chilensis, integrated with field photosynthesis, transcriptomics, pigments, and stress physiology measurements.


Key Findings

MetricFinding
Stress toleranceS. tamarugo maintained stronger photosynthetic performance and stress tolerance under multi-stress conditions
Metabolic supportPigment, antioxidant, and stress-related metabolic differences underpinned tolerance
Non-nitrogen compoundsAccumulation of non-nitrogenous osmolytes and protective metabolites associated with adaptation

What This Means for Your DESI-MSI Study

  • Leaf tissue metabolomics drives plant stress biology. The untargeted leaf metabolome resolved tolerance-associated differences across species — the same tissue matrix DESI-MSI analyzes directly on the native leaf surface, without extraction.
  • Native surface analysis adds location. Where whole-leaf metabolomics averages the whole leaf, DESI-MSI maps metabolites across the leaf surface — revealing spatial patterns of stress markers that averaging hides.
  • Complementary depth. Conventional LC-MS provides deep coverage; DESI-MSI adds the ambient, minimally destructive spatial dimension on the native tissue.

Conclusion

This study shows how leaf metabolomics reveals the metabolic basis of extreme stress tolerance. Our DESI-MSI ambient imaging service extends this capability — mapping metabolites and lipids directly on native leaf and tissue surfaces, minimally destructively, so spatial patterns of stress and defense are seen rather than averaged.

What is DESI-MSI spatial metabolomics?

DESI-MSI (desorption electrospray ionization mass spectrometry imaging) uses a charged solvent spray at atmospheric pressure to desorb molecules directly from a sample surface, generating ion images that map lipids, metabolites, and drugs to their locations without matrix coating, vacuum, or tissue homogenization.

How does DESI-MSI differ from MALDI-MSI?

DESI-MSI operates at ambient conditions with no matrix and no vacuum, requires minimal sample preparation, and is minimally destructive — the same section can be H&E re-stained afterward. MALDI-MSI offers finer spatial resolution and broader metabolome coverage with on-tissue derivatization, at the cost of matrix coating and vacuum. The methods are complementary, and we can design dual-platform workflows.

What spatial resolution can you achieve?

Practical spatial resolution of 50–200 µm, selected per study objective and sample type — well suited to large-area screening and tissue-scale mapping.

Can the same section still be used for histology?

Yes. DESI-MSI is minimally destructive, so the same section can be H&E or IHC re-stained after imaging. You receive ion images co-registered to histology from the very same tissue.

Which compounds can DESI-MSI detect?

DESI-MSI is classically best suited to polar analytes: phospholipids, sphingolipids, free fatty acids, abundant small metabolites (choline, carnitine, amino acids), drug compounds, and xenobiotics.

Do I need any special sample preparation?

No. DESI-MSI requires minimal preparation — no matrix, no freeze-drying. Fresh-frozen sections are mounted and analyzed directly. OCT should be avoided or removed where possible due to background signal.

Can you image skin and plant samples?

Yes. DESI-MSI is particularly well suited to native surfaces — skin sections, plant leaves and tissues, and delicate biopsies — analyzed directly without extraction artifacts.

Can I combine DESI-MSI with other spatial technologies?

Yes. Broad DESI-MSI screening can be combined with high-resolution MALDI-MSI on key regions of interest, and with spatial transcriptomics, all within the spatial metabolomics service portfolio.

Can DESI-MSI quantify metabolites?

DESI-MSI provides relative quantification with robust normalization. Semi-absolute quantification of defined targets using stable-isotope standards is possible, with feasibility assessed per study.

What data do I receive?

Ion images co-registered to H&E (presentation-ready), ROI-level statistics tables, co-localization and pathway summaries, full imzML and vendor raw data, peak lists, metadata, and analysis notebooks for re-analysis.

Publications

GPC3-mediated metabolic rewiring of diabetic mesenchymal stromal cells enhances their cardioprotective functions via PKM2 activation

Joladarashi, D., Thej, C., Mallaredy, V., et al.

Journal: iScience, 2024, 27(10), 111021

Untargeted metabolomics of diabetic mesenchymal stromal cells linking GPC3-mediated rewiring to cardioprotective function via PKM2. Demonstrates tissue-relevant metabolic readouts in a disease context.

Comparative metabolite profiling of salt sensitive Oryza sativa and the halophytic wild rice Oryza coarctata under salt stress

Tamanna, N., Mojumder, A., Azim, T., et al.

Journal: Plant-Environment Interactions, 2024, 5(3)

Comparative leaf metabolomics of salt-sensitive and halophytic rice under salt stress, resolving tolerance-associated metabolic differences. Demonstrates plant tissue metabolomics workflows.

The effects of anthropogenic stressors on above- and belowground phytochemical diversity of the wetland grass, Phragmites australis

Glassmire, A. E., Salgado, A. L., Diaz, R., et al.

Journal: Plants, 2024, 13(22), 3133

Untargeted metabolomics of above- and belowground plant tissues revealing phytochemical diversity responses to environmental stressors. Demonstrates native plant tissue metabolomics.

For Research Use Only. Not for use in diagnostic procedures.
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