Hybrid predictive modeling for control of cell culture

One or more non-transitory, computer-readable media storing instructions that, when executed by processing hardware of a computing system and for a plurality of time intervals during a cell culture process, cause the computing system to:

• obtain current values of cell culture attributes associated with a cell culture;
• generate a control value for a physical input to the cell culture process, wherein generating the control value includes
• predicting, based on the current values, future values of the cell culture attributes, at least by (i) using one or more data-driven models to predict future values of a first one or more attributes of the cell culture attributes, and (ii) using one or more first principle models to predict future values of a second one or more attributes of the cell culture attributes, and
• determining the control value by optimizing an objective function subject to the predicted future values of the cell culture attributes;
• and
• control the physical input to the cell culture process using the control value.

A system comprising:

• a bioreactor configured to hold a cell culture during a cell culture process;
• an electronically-controllable input device configured to provide physical input to the cell culture process;
• one or more analytical instruments configured to measure one or more cell culture attributes associated with the cell culture;
• and
• a computing system configured to, for one or more time intervals during the cell culture process,
• obtain, based on measurements by the one more analytical instruments, current values of cell culture attributes associated with the cell culture,
• generate a control value for the physical input to the cell culture process, wherein generating the control value includes
• predicting, based on the current values, future values of the cell culture attributes, at least by (i) using one or more data-driven models to predict future values of a first one or more attributes of the cell culture attributes, and (ii) using one or more first principle models to predict future values of a second one or more attributes of the cell culture attributes, and
• determining the control value by optimizing an function equation subject to the predicted future values of the cell culture attributes, and
• control the physical input to the cell culture process using the control value, by sending a control signal to the electronically-controllable input device.