Journal article
Kinetic Simulation of a Centrifugal Bioreactor for High Population Density Hybridoma Culture
Biotechnology progress, Vol.25(6), pp.1650-1659
2009
Handle:
https://hdl.handle.net/2376/114639
PMCID: PMC2796705
PMID: 19806634
Abstract
Demand for increasingly complex post-translationally modified proteins, such as monoclonal antibodies (mAbs), necessitates the use of mammalian hosts for production. The focus of this paper is a continuous centrifugal bioreactor (CCBR) capable of increasing volumetric productivity for mAb production through high density hybridoma culture, exceeding 10
8
cells/mL. At these extreme densities environmental conditions such as substrate and inhibitor concentrations rapidly change, dramatically affecting growth rate. The development of a kinetic model predicting glucose, mAb, lactate, and ammonium concentrations based on dilution rate and cell density is shown in this paper. Additionally, it is found that pH affects both growth rate and viability, and a range of 6.9 to 7.4 is needed to maintain growth rate above 90% of the maximum. Modeling shows that operating an 11.4 mL CCBR inoculated with 2.0 × 10
7
cells/mL at a dilution rate of 1.3 h
−1
, results in a predicted growth rate 82% of the maximum value. At the same dilution rate increasing density to 6.0 × 10
7
cells/mL decreases the predicted growth rate to 60% of the maximum; however, by increasing dilution rate to 6.1 h
−1
the growth rate can be increased to 86% of the maximum. Using the kinetic model developed in this research the concentration of glucose, mAb, lactate, and ammonium are all predicted within 13% of experimental results. This model and an understanding of how RPM impacts cell retention serve as valuable tools for maintaining high density CCBR cultures, ensuring maximum growth associated mAb production rates.
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Details
- Title
- Kinetic Simulation of a Centrifugal Bioreactor for High Population Density Hybridoma Culture
- Creators
- Christopher J Detzel - School of Chemical Engineering and Bioengineering, Washington State University, P.O. Box 642710, Pullman, Washington 99164-2710, USADerek J Mason - School of Chemical Engineering and Bioengineering, Washington State University, P.O. Box 642710, Pullman, Washington 99164-2710, USAWilliam C Davis - Department of Veterinary Microbiology and Pathology, Washington State University, P.O. Box 647010, Pullman, WA 99164-7010Bernard J Van Wie - School of Chemical Engineering and Bioengineering, Washington State University, P.O. Box 642710, Pullman, Washington 99164-2710, USA
- Publication Details
- Biotechnology progress, Vol.25(6), pp.1650-1659
- Academic Unit
- Veterinary Microbiology and Pathology, Department of; Chemical Engineering and Bioengineering, School of
- Identifiers
- 99900547467601842
- Language
- English
- Resource Type
- Journal article