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Design of a Perfusion Bioreactor with Integrated Volume Expansion and Cell Retention
“Economically producing patient–specific cell therapies at commercial levels remains a challenge as it requires manufacturing separate batches per patient where the production system must be scaled–out rather than scaled–up to supply more patient doses. The current cell expansion platforms have many manual steps, open culture vessels, and multiple components rendering them laborious and contamination prone with an inefficient use of limited GMP floor space. As these systems need to be repeated for every batch, reducing the system size, process steps, component complexity, and component number enhances the scale–out potential and reduces opportunities for failure and contamination. This work therefore aims to design a bioreactor that is better suited for scale–out by consolidating cell expansion steps and components into a single mechanically-simple culture vessel.
We present a pneumatically-driven perfusion bioreactor design with internal volume expansion and internal cell retention capability. We employed in silico modeling in combination with prototype testing to design, characterize, and optimize the bioreactor design. We developed multiphase and transient computational fluid dynamic (CFD) models to simulate the gas–liquid flow patterns and predict fluid velocities, pressure, mixing, oxygen mass transfer (kLa), turbulence dissipation, and shear rate. Our models were tested in bioreactor prototypes to measure the following values: fluid velocities with particle image velocimetry, mixing times with tracer dispersion tracking, cell retention with pre-grown cell mass, and cell expansion in a full culture process. We achieved a design capable of attaining CHO cell densities exceeding 40 million cells/mL with 96% viability and 99% cell retention.”
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