Laser ablation rapid evaporative ionisation mass spectrometry imaging with few-micrometer sampling pixels
6 affiliations
- 1Department of Physics, Imperial College London, Prince Consort Road, London, United Kingdom, SW7 2BW
- 2Department of Metabolism, Digestion and Reproduction, Imperial College London, Du Cane Road, London, United Kingdom, W12 0NN
- 3Institute for Multimodal Imaging of Intercellular Communication
- 4Universität Regensburg
- 5Department of Brain Sciences, Imperial College London, Du Cane Road, London, United Kingdom, W12 0NN
- 6Department of Surgery and Cancer, Imperial College London, Ayrton Road, London, United Kingdom, SW7 5NH
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.
Related
- Deep Ultraviolet Laser Ablation Surface Sampling for Native Mass Spectrometry.
- Continuous-wave laser ablation enables high-resolution ambient mass spectrometry imaging
- Analysis of Additive Distributions in Rigid PVC by Laser Ablation Inductively Coupled Plasma Mass Spectrometry
- Unifying Passive Air Sampling with Paper Spray Ionization Mass Spectrometry for the Detection of Third-Hand Cigarette Smoke.
- Modulation of Crystal Habit and Preferred Orientation of Aspirin: Combined Effects of Solvent and a Metallic Mesh Template during Evaporative Crystallization
BibTeX
@misc{wang2026laser,
title = {{Laser ablation rapid evaporative ionisation mass spectrometry imaging with few-micrometer sampling pixels}},
author = {Yu Wang and Ronan Battle and William Francis and Lucy Noyes and Daniel Simon and Yayue Song and Yuchen Xiang and Stefania Maneta-Stavrakaki and Duncan Roberts and Timothy H. Runcorn and Stefan Antonowicz and Simone Di Giovanni and Lauren Ford and Zoltan Takats and Robert T. Murray},
howpublished = {ChemRxiv},
year = {2026},
month = oct,
doi = {10.26434/chemrxiv.15009965/v1},
url = {https://chemrxiv.org/doi/full/10.26434/chemrxiv.15009965/v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - Laser ablation rapid evaporative ionisation mass spectrometry imaging with few-micrometer sampling pixels
AU - Yu Wang
AU - Ronan Battle
AU - William Francis
AU - Lucy Noyes
AU - Daniel Simon
AU - Yayue Song
AU - Yuchen Xiang
AU - Stefania Maneta-Stavrakaki
AU - Duncan Roberts
AU - Timothy H. Runcorn
AU - Stefan Antonowicz
AU - Simone Di Giovanni
AU - Lauren Ford
AU - Zoltan Takats
AU - Robert T. Murray
PY - 2026
DA - 2026/10/06
PB - ChemRxiv
DO - 10.26434/chemrxiv.15009965/v1
UR - https://chemrxiv.org/doi/full/10.26434/chemrxiv.15009965/v1
AB - 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.
ER -