scholarly journals Novel Carbon Dioxide-Based Method for Accurate Determination of pH and pCO2 in Mammalian Cell Culture Processes

Processes ◽  
2020 ◽  
Vol 8 (5) ◽  
pp. 520
Author(s):  
Christian Klinger ◽  
Verena Trinkaus ◽  
Tobias Wallocha

In mammalian cell culture, especially in pharmaceutical manufacturing, pH is a critical process parameter that has to be controlled as accurately as possible. Not only does pH directly affect cell culture performance, ensuring a comparable pH is also crucial for scaling and transfer of processes. A sample-based offline pH measurement is commonly used to ensure correct bioreactor pH probe signals after sterilization and as a detection measure for drifts of probe signals. However, the sample-based pH offline measurement does not necessarily deliver required accuracy. Offsets between bioreactor pH and sample pH heavily depend on equipment, local procedures and the offline measurement method that is used. This article adequately describes a novel, non-invasive method to determine pH and pCO2 in sterile bioreactors without the need to sample and measure offline. This method utilizes the chemical correlation between carbon dioxide in the gas phase, dissolved carbon dioxide, bicarbonate and dependent proton concentrations that directly affect the pH in carbonate buffered systems. The proposed carbon dioxide-based pH reference method thereby is able to accurately determine the true pH in the bioreactor without the need to sample. The proposed method is independent of scale and bioreactor configuration and does not depend on local procedures that may differ between sites, scales or operators. Applicability of the method for both stainless steel and single use bioreactors is shown. Furthermore, the very same principles are applicable for non-invasive, online pCO2 monitoring.

Author(s):  
Carlos J. Peniche Silva ◽  
Gregor Liebsch ◽  
Robert J. Meier ◽  
Martin S. Gutbrod ◽  
Elizabeth R. Balmayor ◽  
...  

2017 ◽  
Vol 114 (6) ◽  
pp. 1184-1194 ◽  
Author(s):  
Zizhuo Xing ◽  
Amanda M. Lewis ◽  
Michael C. Borys ◽  
Zheng Jian Li

2012 ◽  
Vol 59 (1) ◽  
Author(s):  
Mohd Helmi Sani ◽  
Frank Baganz

At present, there are a number of commercial small scale shaken systems available on the market with instrumented controllable microbioreactors such as Micro–24 Microreactor System (Pall Corporation, Port Washington, NY) and M2P Biolector, (M2P Labs GmbH, Aachen, Germany). The Micro–24 system is basically an orbital shaken 24–well plate that operates at working volume 3 – 7 mL with 24 independent reactors (deep wells, shaken and sparged) running simultaneously. Each reactor is designed as single use reactor that has the ability to continuously monitor and control the pH, DO and temperature. The reactor aeration is supplied by sparging air from gas feeds that can be controlled individually. Furthermore, pH can be controlled by gas sparging using either dilute ammonia or carbon dioxide directly into the culture medium through a membrane at the bottom of each reactor. Chen et al., (2009) evaluated the Micro–24 system for the mammalian cell culture process development and found the Micro–24 system is suitable as scaledown tool for cell culture application. The result showed that intra-well reproducibility, cell growth, metabolites profiles and protein titres were scalable with 2 L bioreactors.


In Vitro ◽  
1973 ◽  
Vol 8 (5) ◽  
pp. 375-378 ◽  
Author(s):  
Arthur H. Intosh ◽  
K. Maramorosch ◽  
C. Rechtoris

1999 ◽  
Vol 34 (2) ◽  
pp. 159-165 ◽  
Author(s):  
J. Feuser ◽  
M. Halfar ◽  
D. Lütkemeyer ◽  
N. Ameskamp ◽  
M.-R. Kula ◽  
...  

1983 ◽  
Vol 1 (4) ◽  
pp. 102-108 ◽  
Author(s):  
M.W. Glacken ◽  
R.J. Fleischaker ◽  
A.J. Sinskey

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