In this current work, we performed MSI studies using a DESI XS source (Waters Inc., Milford, MA, USA) integrated with a Waters Synapt G2-Si mass spectrometer and a Waters ACQUITY UPLC M-Class system (Waters Inc., Milford, MA, USA). Without conducting complex instrumentation modification, we achieved single-cell resolution MSI by optimizing experimental parameters such as the temperature of the ion transfer capillary, sprayer-surface distance, voltage, and solvent flowrate.