Secondary ion mass spectrometry (SIMS) is a technique similar to DESI, but while DESI is an ambient ionization technique, SIMS happens in vacuum. The solid sample surface is bombarded by a highly focused beam of primary ions. As they hit the surface, molecules are emitted from the surface and ionized. The choice of primary ions determines the size of the beam and also the extent of ionization and fragmentation. Pareek et al. performed metabolomics to trace how purines are synthesized within purinosomes and used isotope labeling and SIMS imaging to directly observe hotspots of metabolic activity within frozen HeLa cells.