High density multiplexing assays for proteins, nucleic acids, and other molecules are described based upon using mass spectrometry detection. A solid-state support assay format is utilized, whereby, the bead carries both a coding molecule to track the sample or analyte and the molecule(s) necessary to perform an affinity-based assay. After the necessary reactions are complete, all of the components, e.g., coding molecule, binding molecule, analyte, and/or label are dissociated for analysis in a mass spectrometer. Various means of performing detection for the assays include different types of mass spectrometers with different types of sampling systems, including MALDI-TOF and ESI.