February 24, 2023
Modeling and simulation can be a powerful tool for bioprocess design. We now present InSiliCHO, an open source implementation for in silico simulation of Chinese hamster ovary cells (CHO) and a foundation for future work in DoE tools, active learning and more.
You can try InSiliCHO online in our app, or download the Python package with pip.
A good process model:
See here for a comparison of process dynamics as described by a typical response surface as obtained with DoE (left), versus a response surface from a process model (right).
The figures show cell density after 150 hours for different glucose concentrations in the starting medium and different process temperatures. While the DoE model gets the relationships directionally correct, it misses details that the process model is able to capture.
We implemented the model described in Möller et al., 2020 . This model describes the evolution of cell density, glucose, glutamine, lactate, ammonia and monoclonal antibody (mAb) concentrations. It encodes sensitivity of growth and death rates to the various chemical species, lactate metabolic shift (dependent on glucose concentration), and the inhibitive effect of ammonia on antibody production. The dynamics of the model are based on known characteristics of CHO, and the default parameters used in the model were chosen to reconstruct experimental data with good fidelity.
 Möller, Johannes, Tanja Hernández Rodríguez, Jan Müller, Lukas Arndt, Kim B. Kuchemüller, Björn Frahm, Regine Eibl, Dieter Eibl, and Ralf Pörtner. “Model Uncertainty-Based Evaluation of Process Strategies during Scale-up of Biopharmaceutical Processes.” Computers & Chemical Engineering 134 (2020): 106693.
You can try the model in our app. Use the sliders to adjust parameter values and initial conditions. The process dynamics are simulated in real time. The experimental data on which the original model was fitted is also visualized.
A fun thing to try is to optimize control and initial conditions for final mAbs concentration (can you get above 1000 mg/L?). The model can also be installed locally as a Python module via pip.
If this seems interesting or useful to you, or if you have any other thoughts or feedback, please reach out. We are very open to collaboration and would love to work with you in applying these methods productively! We can be reached at firstname.lastname@example.org
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