A. Oeggerli et al., ONLINE GAS-ANALYSIS IN ANIMAL-CELL CULTIVATION .1. CONTROL OF DISSOLVED-OXYGEN AND PH, Biotechnology and bioengineering, 45(1), 1995, pp. 42-53
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.