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Updated: Jul 22, 2025

Fluorescence-Guided Matrix-assisted Laser Desorption/Ionization with Laser-Induced Postionization Mass Spectrometry of Individual Rat Neural Cells
Published on: May 23, 2025
Microlensed fiber allows subcellular imaging by laser-based mass spectrometry
Yifan Meng1,2, Wei Hang3, Richard N Zare4
1Ministry of Education (MOE) Key Laboratory of Spectrochemical Analysis and Instrumentation, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen, China.
A novel microlensed fiber enables subcellular resolution in mass spectrometry imaging (MSI). This universal, economic technique enhances chemical mapping of molecules and elements in biological samples, improving spatial resolution for laser-based MSI platforms.
Area of Science:
- Analytical Chemistry
- Biotechnology
- Microscopy
Background:
- Mass spectrometry imaging (MSI) provides label-free, high-throughput chemical mapping.
- Rapid analysis in MSI allows for monitoring of dynamic chemical changes.
- Current MSI techniques face limitations in achieving subcellular spatial resolution.
Purpose of the Study:
- To develop a protocol for mass spectrometry imaging (MSI) with subcellular spatial resolution.
- To introduce a universal and economic microlensed fiber technique for laser-based MSI.
- To demonstrate the adaptability of the microlensed fiber across various mass spectrometry methods.
Main Methods:
- Fabrication of a microlensed fiber by grinding an optical fiber.
- Utilizing the microlensed fiber to focus laser radiation for sample ablation.
- Mass spectrometric analysis of the ablated plume.
- Integration with matrix-assisted laser desorption ionization, laser desorption ionization, laser ablation electrospray desorption ionization, and laser ablation inductively coupled plasma.
Main Results:
- Achieved subcellular spatial resolution in MSI.
- Demonstrated the universal applicability of the microlensed fiber with multiple laser-based MSI platforms.
- The experimental setup can be completed in approximately 2 hours by a trained graduate student.
- The technique is adaptable to most laser-based mass spectrometry methods, including atmospheric pressure applications.
Conclusions:
- The microlensed fiber is a cost-effective and universal tool for enhancing spatial resolution in MSI.
- This method enables submicroscale imaging of single cells and biological tissues.
- Existing laser-based MSI platforms can achieve significant breakthroughs in spatial resolution by incorporating the microlensed fiber module.
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