The sensitivity of biosensors is often not sufficient to detect diagnostically relevant biomarker concentrations. In this paper we have utilized a Quartz Crystal Microbalance with Dissipation monitoring (QCM-D) to detect dissipative losses induced by the attachment of intact vesicles. We modified a sandwich assay by coupling the secondary antibodies to vesicles. This resulted in an increase of detection sensitivity, achieving a diagnostically relevant detection limit of 5 ng/ml or 30 pM antigens. In addition, we could combine the individual assay steps to decrease the total time to result in about 30 minutes.