The individualization of dialysis treatment using a customized dialysate composition usually requires a continuous measurement of electrolytes and urea in blood. The current practices are spot measurements of blood samples either with blood gas analyzers or in the laboratory, involving considerable personnel effort. Furthermore, the measured values are time delayed and not available in a continuous fashion. In this paper we investigate an in-line concept for continuous monitoring of important blood parameters such as sodium, potassium, calcium and urea concentrations in blood serum using ion-selective electrodes. This concept is evaluated in a preclinical study with human packed red blood cells as a test medium over a period of 7 h. It has been shown that the electrolytes can be well monitored. In addition, we present first measurements with ion-sensitive field-effect transistors in a miniaturized sensor assembly. Therefore, new low-cost electronics for such ion-sensitive field-effect transistors have been developed.