Among the variables that are appropriate for direct feedback control of the perfusion rate in mammalian cell cultures, high priority should be given to the glucose concentration. Here we describe the application of a closed-loop control scheme for the long-term cultivation of CHO cells in a high cell density (35 – 40 million cells/ml) perfusion process. The monitoring and control system worked successfully for 2.5 months without any signs of performance degradation. In targeting industrial applications, issues such as reliability, sterility and accuracy are given high priority. The implementation of the glucose monitoring system, which is the main part of the control complex, is addressed. The performance of the perfusion culture was evaluated at four different glucose set points, providing essential information about process optimization. The on-line glucose concentration was used by an embedded expert system which drove the process through the batch and the perfusion phases, achieving total SCADA control of the feed rate. In summary, the proposed glucose monitoring and control technique proved to be a reliable tool which can be applied with confidence at an industrial scale for either microbial or mammalian cell cultures.
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