The unique feature of the label-free measurement techniques for screening specific binding molecules against a certain ligand is that knowledge about the analyte is not required. Due to the direct monitoring of the binding event, no further detection step, e.g., by a fluorescently labeled antibody, is necessary. This technique enables not only the analysis of binding properties, but also applications in serodiagnosis and in primary screening in drug discovery. Especially when complex biological solutions such as blood serum are used as sample fluids, the minimization of unspecific attachment is the crucial point of the assay. In this chapter, the basic handling of the grating coupler as an example of a label-free transducer is described, together with a simple protocol to minimize unspecific attachment when measuring undiluted blood serum.