Abstract: A method to determine the molecular weights of femtomole or smaller quantities of small molecules, such as peptides, oligonucleotides, or heterocyclics, covalently attached to polystyrene beads on a grid, is presented using imaging time-of-flight secondary ion mass spectrometry (TOF-SIMS). The determination is made possible by selectively clipping the bond linking the small molecule to the bead, followed directly by a TOF-SIMS assay of the bead on the grid. The method can be applied to large numbers of polystyrene beads having different small molecules attached thereto for direct characterization of massive combinatorial libraries.