These methods are known for their high sensitivity and spatial resolution, are well-suited for single-cell analysis . However, these experiments require complex sample preparation, such as dehydration and matrix application, to facilitate ion generation through lasers or ion beams . Key single-cell MS technologies in this category include secondary ion mass spectrometry (SIMS), gas cluster ion beam (GCIB), matrix-assisted laser desorption/ionization (MALDI), and matrix-free laser desorption/ionization (LDI).