A multiscale metabolic model for fed batch culture process control

This project will develop a mechanistic model of cell metabolism that can be integrated with a multiscale cell growth model to predict of metabolic behavior in fed-batch culture.

Project status

100% Completed

Industry Need

Cells in culture have a high flux of glucose consumption and convert a large portion of the consumed glucose to lactate. In the late stage of fed-batch culture, the high flux metabolism may switch to low flux. The occurrence, or the lack thereof, of metabolic shift in fed-batch cultures affects the productivity and quality of therapeutic proteins.

Solution

This project will integrate a mechanistic model of cell metabolism with a multiscale cell growth model to predict of metabolic behavior in fed-batch culture.

Outputs/Deliverables

The team has generated a model to predict metabolic shift behavior. This links the metabolic model to a glycan synthesis model. The model was validated using 3 cell lines.

Impacts

Availability of a mechanistic model for cell metabolism integrated with a multiscale cell growth model to predict of metabolic behavior in fed-batch culture including productivity and quality of therapeutic proteins.

Publications

O'Brien, C. M., Zhang, Q., Daoutidis, P., & Hu, W. (2021). A hybrid mechanistic-empirical model for in silico mammalian cell bioprocess simulation. Metabolic Engineering, 66, 31-40. https://doi.org/10.1016/j.ymben.2021.03.016