Simple adaptive pH control in bioreactors using gain-scheduling methods

Abstract

A simple well-performing adaptive control technique for pH control in fermentations of recombinant protein production processes is described and its design procedure is explained. First, the entire control algorithm was simulated and parameterized. Afterwards it was tested in real cultivation processes. The results show that this simple technique leads to significant reductions in the fluctuations of the pH values in microbial cultures at a minimum of expenditures. The signal-to-noise ratio and thus the information captured by the pH signal were increased by about an order of magnitude. This leads to a substantial improvement in the noise of many other process signals that are used to monitor and control the process. For instance, respiratory off-gas data of CO(2) and its derived carbon dioxide production rate signals from the cultures carry much less noise as compared to those values obtained with conventional pH control. Detailed process analysis revealed that even very small pH jumps of 0.03 values during the fermentation were shown to result in pronounced deflections in CO(2)-volume fraction of 8% (peak to peak). The proposed controller, maintaining the pH within the interval of 0.01 around the setpoint, reduces the noise considerably.

Simplified off-gas analyses in animal cell cultures for process monitoring and control purposes

“…Although, the noise on the CPR signal is smaller than that on the OUR signal, the latter is to be preferred for process control applications since the carbon dioxide transfer rate may be distorted by changes in the bicarbonate mole fraction, particularly at small pH changes (Royce 1992;Gnoth et al 2010).…”

Bioreactor control improves bioprocess performance

“…In a large number of validation runs with many different cultivations it was shown, that increasing the controller gain proportional to the current CPR or substrate feed rate improves the quality of the feedback control system significantly. Evidence for this finding can be found in [44] and [45], which was based on data sets from more than 50 microbial and animal cell cultivations. This is also shown in Fig.…”

On the solution of biomass growth rate control in anaerobic fermentation process with quality constraint insight

“…Although most industrial fermentations are still instrumented in basic measurements (such as temperature and pressure), it becomes quite common to utilize CO 2 measurements in gas vent line. For batch fermentation, pH measurement is rather uncommon, despite the advantages it brings [11]. The alcoholic fermentation can be described by fermentable sugar consumption, ethanol production, wort density or CO 2 evolution [12].…”