Date of Award

Fall 2020

Project Type

Thesis

Program or Major

Chemical Engineering

Degree Name

Master of Science

First Advisor

Kang Wu

Second Advisor

Young Jo Kim

Third Advisor

Nan Yi

Abstract

Bioreactors for cell culture or fermentation are widely used for the production of proteins and other value-added products. Operation of bioreactors at large scale involves progressively increasing the culture volume in 4 to 10 folds increments to inoculate the culture and scale it up stepwise. To initiate the cell growth in a typical bioreactor of 20,000L, it often requires a train from benchtop scale at 1L to 10L, 100L, 1000L, 4000L and finally the 20,000L bioreactor. The transfer of cells from one bioreactor to the next one inevitably involves “lag phase” at the beginning of each culture, during which cells do not grow but adapt to the new environment. The existing of multiple lag phases increases the time cost of the production process. In addition, the use of multiple bioreactors leads to more operational problems such as higher contamination risk, higher cleaning costs, and more cleanroom space and equipment footprint, all of which further increase the overall production costs. To solve this problem, Lonza’s facility in Portsmouth designed a novel variable diameter bioreactor (VDB) which has variable diameter sections utilizing a novel continuous impeller. It is capable of operating from 1000L to 20,000L, which will eliminate the need of the 1000L and 4000L bioreactors in the train. Using CFD modeling, Lonza optimized the design of the VDB and the continuous impeller, which is comparable to conventional stir tank bioreactors based on simulation results. However, experimental characterization is needed to compare VDB with traditional bioreactors and further optimize the operational parameters before implementing it at large scale.

In this study, the mixing time and mass transfer coefficient (kLa) of VDB, the conventional reactor with conventional impeller and the conventional reactor with continuous impeller in different volumes, agitation speed and airflow rate were experimentally characterized. From the experiment, the mixing time of VDB and conventional reactor with continuous impeller was found to be higher than that of the conventional reactor with conventional, which is constant with the CFD prediction. The mass transfer coefficients of VDB and conventional reactor with continuous impeller was found to be higher than conventional reactor with conventional impeller when the reactors were full filled. When the reactor was filled 20L, the mass transfer coefficients of VDB and conventional reactor with continuous impeller have similar mass transfer coefficients. When the reactor was filled 40L, the mass transfer coefficients of VDB and conventional reactor with conventional impeller have similar mass transfer coefficients. Besides, it is found that at higher airflow rates, increase the agitation cannot reduce the mixing time significantly. It is also found that higher airflow rates, higher agitation speeds, and smaller volumes led to higher mass transfer coefficients (kLa), and the influence of airflow rate on mass transfer coefficients is more significant. The combined effect of these factors on the mixing time and mass transfer coefficients were evaluated. The results will provide insights on determining the operational parameters of VDB at different volumes in the scaled-up operations.

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