Modeling and Controller Design for Enhanced Hollow-Fiber Bioreactor Performance

Human Mesenchymal Stromal Cells (hMSC) have shown promising preclinical results by eliciting immunomodulatory effects to alleviate pathology. To obtain adequate MSC dosages for clinical use, culture expansion is needed. This process is dependent on maintaining proper levels of nutrients. Current systems rely on human intervention for nutrient measurement and regulation. Therefore, there is great potential for reducing errors through modeling and automatic control. This letter contributes to this effort by outlining a new control-centric model for hollow-fiber systems which estimates concentrations along the fibers from measurements at the input and output only. Finally, we design a feedback control system based on the model and observations which accounts for the unique constraints imposed by the bioreactor, sensors and pumps.