New Technique Maps Molecule Distribution Within Single Cells

Understanding the biological functions of tissues is challenging due to their heterogeneous mix of cell types. A research team led by The University of Osaka has introduced a new technology that enables visualization of molecular distribution within individual cells, offering new insights into disease mechanisms in complex biological samples.

The technique, called t-SPESI (tapping-mode scanning probe electrospray ionization), analyzes the spatial arrangement of molecules in a cell. It works by taking multiple micro-samples from different regions of a single cell and transferring them for mass spectrometry analysis, which identifies the precise chemical components in each sampled area. According to Yoichi Otsuka, first  author of the study published in Communications Chemistry, “We have developed a new t-SPESI unit that allows us to visualize the microscopy sample in multiple modes. We can also directly observe the sampling process as the micro-samples are taken for mass spectrometry analysis.”

The team modified their earlier t-SPESI technology so the analytical unit could be positioned above an inverted fluorescence microscope. This setup enables observation of both the sample and the sampling process. The sample can be imaged in different modes, allowing researchers to detect fluorescently tagged molecules, map features on the cell surface, and locate chemical components within the cell. 

The technology is particularly useful for visualizing intracellular lipids, which are important in metabolic processes and often linked to disease when distributed abnormally. Senior author Michisato Toyoda notes, “When we applied our technology to model cells, we were able to observe the lipids within each individual cell using mass spectrometry imaging, directly visualize the cell by fluorescence microscopy, and also determine the surface shape of the cell.” The team could also distinguish between different cell types based on their molecular composition. 

This approach enables a deeper understanding of the molecular complexity within diseased tissue samples, supporting future advances in therapies and diagnostics.