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

Abstract

Batch-to-batch reproducibility of animal cell cultures can significantly be enhanced using process control procedures. Most informative signals for advanced process control can be derived from the volume fractions of oxygen and carbon dioxide in the vent line of the reactors. Here we employed simple low-cost sensors, previously not considered for off-gas analysis at a laboratory-scale cell cultures, and compared them with a simultaneously used quadrupole mass spectrometer, i.e., the standard equipment. A decisive advantage is that the sensors did not need any calibration and are easy to use. We show that monitoring and advanced control of cell cultures can significantly be simplified using the devices tested here and that the same batch-to-batch reproducibility can be obtained with much less effort than before.

Online monitoring of the respiratory quotient reveals metabolic phases during microaerobic 2,3‐butanediol production with Bacillus licheniformis

“…Thus, with the observed pH profile the measured CTR would rather be decreased than increased. Apart from equilibrium changes of the bicarbonate buffer, the specific aeration rate has a predominant influence on the carbon dioxide release from the culture broth . As the specific aeration rate is not changed during the cultivation, this does not explain the formation of an RQ peak.…”

Mini‐review: soft sensors as means for PAT in the manufacture of bio‐therapeutics

“…Partly, this can be ascribed to reliability, durability, stability, and the low price of these sensors. Other common low‐cost alternatives are gas analysers and dip‐stick methods for metabolites and nutrient components . The latter are not commercially available so far for on‐line use but may technically be realized.…”

Soft sensors in bioprocessing: A status report and recommendations

“…Table 2 lists some of these. The soft sensors are mostly based on on‐line measurements from off‐gas analyzers [31]. Quite common is the simple calculation of derived variables such as the oxygen uptake rate, the carbon dioxide evolution rate, the respiratory quotient and the oxygen transfer coefficient (k L a).…”