Macroscopic Dynamic Modeling of Sequential Batch Cultures of Hybridoma Cells: An Experimental Validation

杂交瘤细胞序贯分批培养的宏观动态建模:实验验证

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作者:Laurent Dewasme, François Côte, Patrice Filee, Anne-Lise Hantson, Alain Vande Wouwer

Abstract

Hybridoma cells are commonly grown for the production of monoclonal antibodies (MAb). For monitoring and control purposes of the bioreactors, dynamic models of the cultures are required. However these models are difficult to infer from the usually limited amount of available experimental data and do not focus on target protein production optimization. This paper explores an experimental case study where hybridoma cells are grown in a sequential batch reactor. The simplest macroscopic reaction scheme translating the data is first derived using a maximum likelihood principal component analysis. Subsequently, nonlinear least-squares estimation is used to determine the kinetic laws. The resulting dynamic model reproduces quite satisfactorily the experimental data, as evidenced in direct and cross-validation tests. Furthermore, model predictions can also be used to predict optimal medium renewal time and composition.

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