Techniques for monitoring cell cultures and fermentation processes not only enable prompt feedback to variations in critical parameters (e.g., media composition and metabolites) but further improve our understanding of the processes themselves. In this context, surface plasmon resonance (SPR) spectroscopy is one of the methods of choice. This technique exploits angle shifting to follow molecular interactions in real-time. Therefore, it allows samples to be characterized without additional molecular labels and time-consuming sample preparation. The immobilization of receptors onto the chip surface is one of the most challenging requirements in SPR. Especially for measurements in crude samples, it is crucial to achieve a sufficient immobilization level and block the remaining sensitive area to prevent nonspecific binding.In this article, we present a SPR-based detection system for human serum albumin (HSA). As HSA is exclusively synthesized in the liver, it can be used to characterize the specific activity of in vitro cultivated human hepatocytes. These can be cultivated in so-called multi-organ-chips, which have been developed by groups at the TU Berlin and Fraunhofer IWS for predictive preclinical substance evaluation.