ONLINE GAS-ANALYSIS IN ANIMAL-CELL CULTIVATION .1. CONTROL OF DISSOLVED-OXYGEN AND PH

To monitor gas reaction rates in animal cell culture at constant disso lved oxygen concentration (DO) and constant pH it was necessary to dev elop improved control methods. Decoupling of both controllers was obta ined by manipulation of molar fractions of oxygen and carbon dioxide i n the gas phase. Two pairs of DO and pH controllers were designed and tested both in simulation and experimental runs. The first controller pair was developed for headspace aeration only, whereas the second con troller pair was designed for bubble aeration using a microsparger and flushing the headspace with helium. pH was controlled by a convention al discrete PID controller in its velocity form. For DO control two li near state space feedback controllers with parameter adaptation were e stablished. In these controllers the oxygen uptake rate (OUR) was cons idered as a disturbance and was not included in the mathematical model . The feedback gain adaptation was based on the difference between the actual molar fraction of oxygen at time step n and the initial molar fraction. This difference is related to OUR and was used to increase o r decrease the state feedback controller gain (k and k(1) respectively ) in a slow manner. With these controllers it was possible to get an e xcellent online estimate of OUR. In the case of bubble aeration a simp le gas phase mass balance was sufficient, whereas during the headspace aeration a liquid phase balance was required. It has been shown that determination of OUR using gas balances requires a significantly bette r controller performance compared to just keeping DO and pH within rea sonable limits. (C) 1995 John Wiley and Sons, Inc.