Designing a Strategy for pH Control to Improve CHO Cell Productivity in Bioreactor

Background: Drastic pH drop is a common consequence of scaling up a mammalian cell culture process, where it may affect the final performance of cell culture. Although C[O.sub.2] sparging and base addition are used as common approaches for pH control, these strategies are not necessarily successful...

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Bibliographic Details
Published in:Avicenna journal of medical biotechnology 2021-07, Vol.13 (3), p.123
Main Authors: Ahleboot, Zohreh, Khorshidtalab, Mahdi, Motahari, Paria, Mahboudi, Rasoul, Arjmand, Razieh, Mokarizadeh, Aram, Maleknia, Shayan
Format: Article
Language:English
Subjects:
Analysis
Cells
Hydrogen-ion concentration
Immunoglobulin G
Online Access:Get full text
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Summary:Background: Drastic pH drop is a common consequence of scaling up a mammalian cell culture process, where it may affect the final performance of cell culture. Although C[O.sub.2] sparging and base addition are used as common approaches for pH control, these strategies are not necessarily successful in large scale bioreactors due to their effect on osmolality and cell viability. Accordingly, a series of experiments were conducted using an IgG1 producing Chinese Hamster Ovary (CHO-S) cell culture in 30 L bioreactor to assess the efficiency of an alternative strategy in controlling culture pH. Methods: Factors inducing partial pressure of C[O.sub.2] and lactate accumulation (as the main factors altering culture pH) were assessed by Plackett-Burman design to identify the significant ones. As culture pH directly influences process productivity, protein titer was measured as the response variable. Subsequently, Central Composite Design (CCD) was employed to obtain a model for product titer prediction as a function of individual and interaction effects of significant variables. Results: The results indicated that the major factor affecting pH is non-efficient C[O.sub.2] removal. C[O.sub.2] accumulation was found to be affected by an interaction between agitation speed and overlay air flow rate. Accordingly, after increasing the agitation speed and headspace aeration, the culture pH was successfully maintained in the range of 6.95-7.1, resulting in 51% increase in final product titer. Similar results were obtained during 250 L scale bioreactor culture, indicating the scalability of the approach. Conclusion: The obtained results showed that pH fluctuations could be effectively controlled by optimizing C[O.sub.2] stripping. Keywords: Carbon dioxide, Cell survival, Hydrogen-ion concentration (pH), Immunoglobulin G, Lactic acid
ISSN:2008-2835
DOI:10.18502/ajmb.v13i3.6369