Chemical and Topographical Single‐Cell Imaging by Near‐Field Desorption Mass Spectrometry

Simultaneously acquiring chemical and topographical information within a single cell at nanoscale resolutions is vital to cellular biology, yet it remains a great challenge due to limited lateral resolutions and detection sensitivities. Herein, the development of near-field desorption mass spectrometry for correlated chemical and topographical imaging is reported, thereby bridging the gap between laser-based mass spectrometry (MS) methods and multimodal single-cell imaging. Using this integrated platform, an imaging resolution of 250 nm and 3D topographically reconstructed chemical single-cell imaging were achieved. This technique offers more in-depth cellular information than micrometer-range laser-based MS imaging methods. Considering the simplicity and compact size of the near-field device, this technique can be introduced to MALDI-MS, expanding the multimodal abilities of MS at nanoscale resolutions.