PhD Defense by Bryan Wang
BioE PhD Defense Presentation
Monday, December 4th at 2 p.m.
EBB CHOA room
Advisor: Krishnendu Roy, PhD – School of Biomedical Engineering, GT
Stephen Balakirsky, PhD – Georgia Tech Research Institute
Fani Bukouvala, PhD – School of Chemical and Biomolecular Engineering, GT
Johnna Temenoff, PhD – School of Biomedical Engineering, GT
Carolyn Yeago, PhD – Institute of Bioengineering and Bioscience, GT
Process Development and Process Analytical Technology Integration for Cell Therapy Manufacturing
Biomanufacturing of cell therapies involves highly complex and labor-intensive processes, where the process parameters and biological variabilities can significantly influence product quality, reproducibility, and therapeutic efficacy of the products. The complexity and largely manual unit operations contribute to product variability and high cost. To address these manufacturing challenges, we designed a digital-twin-enabled closed-loop cell manufacturing platform with automation and feedback controls. This platform integrates process analytical technologies (PAT) to enable deeper process understanding and provide real-time control of process variables. Specifically, we designed bench-scale bioreactors with automated sampling, at-line and in-line monitoring, digital twin-enabled media nutrients estimation, and feedback-controlled feeding capabilities. Human umbilical cord tissue-derived MSCs (CT-MSCs) and T cells were used as the example cell therapy product. At-line glucose and lactate monitoring confirmed the accuracy of the digital twin estimations. Spent media samples and detailed functional characterizations of the MSCs and T cells end-products generated from the automation-controlled bioreactor demonstrated that high expansion and functions of the MSCs and T cells were maintained in these closed-loop bioreactors. Real-time imaging with quantitative oblique back illumination microscopy showed high-resolution images of cells in-process in a dynamic 3D environment. Overall, the digital twin-enabled bioreactor platform reduced costs, labor, time, and, more importantly, perturbations; and could improve yield while maintaining the phenotype and quality of cell therapy products. Our integrated automation system provides a blueprint for multiplexed PAT integration, process optimization, feedback-controlled intelligent automation to enable the discovery, monitoring, and control of critical quality attributes and critical process parameters for cell therapy manufacturing.
- Workflow Status:Published
- Created By:Tatianna Richardson
- Modified By:Tatianna Richardson