Advanced In Situ Microscopy for On-Line Monitoring of Animal Cell Culture

Cell concentration is one of the key parameters to be monitored during cell cultivation processes. This is very often done off-line by sterile sampling and subsequent counting using a hemocytometer or an electronic cell counter. A direct optical measurement of cell density via an in situ microscope (ISM) eliminates the need for sampling and allows for continuous monitoring of this key parameter. Two such systems have been described in the literature, one of them has been developed at Mannheim University of Applied Sciences. This system has the advantage of not using any moving mechanical parts within or outside the fermentation vessel. Here we show two examples of advanced applications of a new version of this ISM with unprecedented resolution and frame rate: Adaptation to double glass jacket equipped bench top reactors and longer term application in a perfused 30 L steel reactor. Results in both cases show the performance of the ISM, the comparability of cell culture data obtained by ISM and traditional methods and the potential for further development of the ISM.