A research team led by scientists from the Dalian Institute of Chemical Physics (DICP) of the Chinese Academy of Sciences, in collaboration with partners, has developed a novel high-spatial-resolution mass spectrometry imaging (MSI) instrument using a single-mode fiber image relay. The system delivers a spatial resolution of 800 nm, allowing researchers to resolve lipid metabolism heterogeneity during drug-induced cell apoptosis at the single-cell level.
Their findings were recently published in Journal of the American Chemical Society .
Dysregulation of apoptosis represents a hallmark of tumorigenesis, and numerous anticancer agents induce tumor cell apoptosis via interactions with the cell membrane. During this process, alterations in the cell membrane microenvironment and metabolic reprogramming can be profiled using lipidomics. Yet due to the minute size of individual cells and the compositional complexity of lipids, conventional liquid chromatography–mass spectrometry (LC-MS) techniques generally yield only bulk-averaged data, making it challenging to resolve lipid heterogeneity at the single-cell level.
To overcome these limitations, the team proposed an integrated strategy combining instrument development and MSI methodology. Leveraging the mode-filtering characteristics of single-mode fibers paired with a custom-designed optical image relay system, they developed a new high-spatial-resolution laser desorption/ionization source.
The device achieved a spatial resolution of approximately 800 nm while preserving a long working distance (>25 mm), helping to reduce contamination of the fiber probe. Building on this platform, the team constructed a reflectron time-of-flight mass spectrometer with a mass resolving power greater than 10,000, enabling high-resolution MSI of both mouse brain tissue sections and single cells.
Moreover, the researchers combined high-resolution MSI, cell morphological analysis, and LC-MS to establish a new approach that simultaneously captures bulk compositional information and single-cell, phenotype-specific lipidomic data. Using this method to study apoptosis in HeLa and HepG2 cells triggered by various drugs, they observed that drug-induced lipid metabolic changes displayed clear dose- and time-dependent patterns.
In addition, the team generated drug-specific single-cell lipid fingerprints in a multidrug treatment model, uncovering metabolic variations linked to distinct pharmacological mechanisms.
These findings provide a feasible approach for characterizing apoptosis‑related lipid metabolic changes at single-cell resolution using MSI.
Journal of the American Chemical Society
Single-Mode Fiber Image Relay Mass Spectrometry Imaging Reveals Lipid Heterogeneity during Drug-Induced Apoptosis
13-Mar-2026