Researchers have developed a physics-based framework for predicting how molecules are extracted from samples during impingement-based mass spectrometry imaging. The model is intended to help scientists understand the trade-offs among spatial resolution, molecular coverage, and ionization softness when selecting or optimizing an imaging method.
Mass spectrometry imaging maps the spatial distribution of lipids, metabolites, peptides, proteins, and other molecules within cells and tissues. Several MSI techniques use droplets, particles, or liquid probes to remove analytes from a sample before ionization and mass analysis.
John C. Sentmanat and Andrei G. Fedorov of the Georgia Institute of Technology divided these extraction processes into two main regimes: thermodynamic, or passive, desorption, and kinematic, or active, extraction.
Thermodynamic desorption occurs when molecules move into a solvent because of favorable chemical interactions. Desorption electrospray ionization is one example. Its liquid film can reduce molecular fragmentation, making the method suitable for fragile biomolecules. However, extraction depends on analyte solubility and solvent choice, while surface wetting can restrict spatial resolution.
Kinematic extraction uses the energy from high-speed particles or droplets to overcome the forces holding molecules within the sample. Techniques operating mainly in this regime include electrospray droplet impact, gas cluster ion beam, and massive cluster impact secondary ion mass spectrometry.
The researchers created a dimensionless parameter, Πσ, that compares the stress generated during particle impact with the cohesive forces binding molecules to the sample. The model predicts that kinematic extraction can begin when Πσ is equal to or greater than 1. Below this threshold, extraction is expected to be primarily thermodynamic. Values close to 1 indicate a mixed regime in which both mechanisms may contribute.
The framework also considers particle charge and mass, accelerating voltage, travel distance, aerodynamic drag, and inertia. The analysis indicated that active extraction becomes possible only when the electric force accelerating a particle exceeds the combined effects of drag and inertia.
When applied to representative operating conditions reported for existing MSI methods, the model placed atmospheric-pressure DESI within the thermodynamic regime. Vacuum-based electrospray droplet impact and cluster-ion techniques were assigned mainly to the kinematic regime. Nano-DESI and liquid microjunction surface sampling were also estimated to operate thermodynamically, although the authors cautioned that the model provides only a qualitative approximation for methods without impinging particles.
High Πσ values were associated with a greater likelihood of molecular fragmentation. However, the parameter does not directly predict ionization softness because fragmentation also depends on ionization chemistry, molecular structure, energy redistribution, and the local sample environment.
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