Limitations of Mass Spectrometry Imaging Technology: A List of Samples Suitable for Different Ionisation Imaging Sources

Mass spectrometry imaging is not a ‘one-size-fits-all’ approach. Imaging sources utilising different ionisation methods each have their own limitations in terms of sample type, spatial resolution and molecular coverage. Choosing the wrong source can result in either weak signals, insufficient resolution or the sample being ruined during pre-treatment. This article compiles a list of suitable samples to help you quickly identify the right source for different research questions.

Let us be clear from the outset: there is no ‘one-size-fits-all’ source.

Imaging sources—whether atmospheric pressure desorption, laser-based, vacuum matrix-assisted, or ion beam—differ significantly in principle and are naturally suited to different samples. Rather than striving for ‘universal coverage’, it is better to select the source that best matches the sample’s characteristics. The following section focuses on the capabilities of Xinceyuan’s MSI DPI / LDPI systems, whilst also highlighting their complementary relationship with other approaches.

List 1: Plant and food samples

Leaves, seeds, fruit pulp, tea leaves, olive oil, etc., with a focus on the spatial distribution of flavour compounds, contaminants and metabolites. These samples have a relatively loose structure, so matrix-free analysis and zero pre-treatment are priorities. The DESI/PI dual-mode of MSI DPI (20–200 μm) is suitable for: the dual-mode gain clearly visualises theanine, caffeine and other compounds (approximately 61-fold for caffeine and 14.5-fold for theanine), whilst the localisation of contaminants preserves in situ information. For resolution at the cellular level, consider MSI LDPI (2–3 μm).

List 2: Animal Tissues and Neural Sections

Sections of the brain, liver, tumours, etc., focusing on the regional distribution of metabolites and lipids. MSI DPI’s matrix-free approach prevents matrix background from suppressing signals at the low-mass end; for lipids such as cholesterol in mouse brain, post-electron ionisation provides approximately 205-fold gain, enabling the visualisation of even faint distributions. When examining gradients at the subcellular level (such as tissue junctions and nerve endings), the 2–3 μm resolution of LDPI is more suitable, with a minimum detectable m/z of approximately 70.

List 3: Forensic and physical evidence samples

For physical evidence such as bloodstains, fingerprints and fibres, the principle is that the less pre-treatment required, the better, in order to preserve the integrity of the chain of evidence. The matrix-free, zero-pre-treatment characteristics of MSI DPI meet this requirement, allowing direct imaging of the surface of physical evidence to localise the distribution of chemical components. In such scenarios, the priority is on ‘non-destructive analysis’ rather than extreme resolution; the DPI’s ability to map surface distributions is generally sufficient.

List 4: Scenarios Requiring Complementary Elemental or High-Resolution Analysis

If a study requires both elemental distribution (e.g. metals, silicon) and molecular distribution, a single ambient-pressure source cannot cover the elemental aspect and must be complemented by a plasma beam approach such as SIMS; if extremely high spatial resolution is required for small-molecule mapping, MALDI-type approaches have their place under matrix-assisted conditions. The value of MSI DPI/LDPI lies in the ‘distribution’ capabilities of atmospheric pressure, matrix-free analysis and broad coverage; it complements rather than replaces the elemental and matrix-assisted analysis approaches.

List 5: Precious, irreplaceable samples

Clinical surgical specimens and rare samples are particularly vulnerable to damage during pre-treatment. Matrix-free sources (DPI / LDPI) do not involve the application of chemical matrices, preserving the sample in its original state and allowing for subsequent analysis such as haematoxylin and eosin (HE) staining. For such samples, ‘non-destructive analysis’ takes precedence over all other parameters.

How to use this checklist

Match your samples to the appropriate category: loose structure, focus on distribution → DPI dual-mode; Requires cell-level resolution → LDPI; Precious and non-destructible → Matrix-free; Requires elemental or ultra-high resolution → Consider complementary approaches. The purpose of this checklist is to narrow down the selection; the final decision must still be based on instrument compatibility (Agilent, AB SCIEX and Thermo instruments in stock can be retrofitted with DPI/LDPI) and budget constraints.

Summary

The application boundaries of mass spectrometry imaging are defined by sample type, spatial scale and molecular coverage. The list of suitable applications for MSI DPI/LDPI focuses on plant-based foods, tissue and neural sections, forensic evidence and precious samples, with the core features being ambient pressure, matrix-free analysis and broad coverage. Only by understanding these boundaries can the right technology be applied to the right samples.