A new read-out method for antibody arrays using laser desorption ionisation mass spectrometry (LDI-MS) is presented. Small, photocleavable reporter molecules with a defined mass called "mass tags" are used for detection of immunocaptured proteins from human plasma. Using prostate specific antigen (PSA), a biomarker for prostate cancer, as a model antigen a high sensitivity generic detection methodology based immunocapture with a primary antibody and detection with a biotin labelled secondary antibody coupled to mass tagged avidin is demonstrated. As each secondary antibody can bind several avidin molecules each having a large number of mass tags, signal amplification can be achieved. The developed PSA sandwich mass tag analysis method provided a limit of detection below 200 pg/mL (6 pM) for a 10 µL plasma sample, well below the clinically relevant cut-off value of 3-4 ng/mL. This brings the LOD for detection of intact antigens with MALDI-MS down to levels comparable with SISCAPA SRM and ELISA), as 6 pM corresponds to a maximal amount of 60 amol PSA captured on-spot. We propose the potential use of LDI (laser desorption/ionization) with mass tag read-out implemented in a sandwich assay format for, low abundant and/or early disease biomarker detection.