Nanoscale Single-Cell Mass Spectrometry Imaging via Tapered Fiber Projection Laser Desorption/Ionization Mass...

Area of Science:

• Chemical imaging
• Mass spectrometry
• Cell biology

Background:

• Subcellular chemical mapping of endogenous biomolecules without labeling is challenging due to limited resolution and sensitivity.
• Existing techniques struggle to provide nanoscale insights into cellular chemical composition.

Purpose of the Study:

• To develop a novel platform for nanoscale single-cell mass spectrometry imaging (SC-MSI).
• To achieve high lateral and imaging resolution for detailed chemical analysis within individual cells.
• To enable the study of drug effects and lipid alterations at the subcellular level.

Main Methods:

• Development of tapered fiber projection laser desorption/ionization mass spectrometry (TFPLDI-MS).
• Integration of tapered fiber laser delivery with a telescopic projection system.
• Utilizing plasmonic nanoparticles to enhance ion yields for improved detection sensitivity.

Main Results:

• Achieved 570 nm lateral resolution and 400 nm imaging resolution with a 6 amol detection limit.
• Demonstrated simultaneous nanoscale mapping of drugs and phospholipids within single cells.
• Revealed drug-specific lipid alterations during apoptosis in HeLa cells, elucidating heterogeneous therapeutic responses.

Conclusions:

• TFPLDI-MS offers superior imaging resolution and sensitivity for SC-MSI compared to existing laser-based techniques.
• The platform enables spatially resolved lipidomics and the study of therapeutic responses at the single-cell level.
• TFPLDI-MS is a transformative tool for next-generation SC-MSI, bridging nanoscale chemical imaging and biomedical applications.