Laser ablation rapid evaporative ionisation mass spectrometry imaging with few-micrometer sampling pixels
Year: 2026
Type: preprint
Abstract: Achieving sub-cellular resolution in ambient, matrix-free mass spectrometry imaging (MSI) remains challenging because reducing the sampling area often compromises ion yield and image fidelity. Here, we demonstrate an infrared laser–driven ambient MSI platform that mitigates these limitations through low-fluence, picosecond pulsed, highrepetition-rate laser ablation with a custom 2.94 μm light source with near-diffraction limited beam quality. This approach produces well-confined ablation features with diameters of 5μm to 10 μm. Coupling the laser ablation plume to a rapid evaporative ionisation mass spectrometry (LA-REIMS) interface and a commercial time-of-flight mass analyser provides multiplexed ion maps of metabolites, phospholipids, and other small molecules in a single acquisition. This configuration enables routine 3 μm-pixel size imaging of fresh-frozen tissue sections, as well as imaging of formalin-fixed, paraffin embedded biopsy samples, all without additional preparation steps. Oversampled images preserve sub-cellular morphology and yield molecular distributions that correlate with fluorescence and histological features. Together, these results define a robust operational regime for high-fidelity, matrix-free MSI in the few-μm pixel range, where high infrared beam quality and stable, low-fluence, high repetition rate picosecond laser sampling underpin gentle ablation and efficient ion formation via REIMS, enabling sub-cellular molecular mapping in a clinically compatible, fully ambient format.
Source: ChemRxiv
Institutions: Imperial College London, University of Regensburg
Language: English
Subfield: Spectroscopy
Field: Chemistry
Domain: Physical Sciences
Open Access status: green
OpenAlex ID: W7220725414