High resolution localized surface plasmon resonance (HR-LSPR) sensors were combined with matrix assisted laser desorption ionization mass spectrometry (MALDI-MS) for the first time. LSPR sensors provide real-time label-free detection of molecular adsorption. Subsequent MALDI-MS analysis enables identification of the adsorbed molecules. This synergistic LSPR-MS approach was applied to the detection and identification of amyloid beta oligomers which play an important role in the molecular pathogenesis of Alzheimer's Disease.