Automated Vertical Wheel Bioreactor Integrated with Process Analytics for T-Cell Manufacturing

This publication describes the development of an automated Vertical-Wheel bioreactor platform for closed-system manufacturing of T cells and CAR-T cells. The study integrates process analytical technologies including in-line pH and dissolved oxygen sensors, real-time imaging, automated sampling, hollow-fiber perfusion, and data-driven process control. Process development experiments evaluated agitation rate, feeding strategy, activation methods, and cytokine supplementation to identify critical process parameters affecting expansion, viability, and memory T-cell phenotypes. Symbolic regression analysis linked media metabolites and cytokines to culture outcomes and identified factors predictive of stem cell memory and central memory T-cell populations. The platform successfully expanded unmodified and BCMA-directed CAR-T cells while demonstrating the potential for automated monitoring, adaptive process optimization, and scalable manufacturing workflows for cell therapy production.