Date of Award

2009

Degree Type

Dissertation

Department

Chemical and Biomedical Engineering

First Advisor

Belovich, Joanne

Subject Headings

Cell culture, Biotechnology, Cell culture, Perfusion culture, Cell retention, Gravity settler, Settling velocity, Algae concentration, Ultrasonic filter, Particle separation

Abstract

A lack of efficient, economical, and reliable cell retention devices has limited the application of perfusion culture systems in the biopharmaceutical industry. Two types of cell retention devices were developed in this work for long-term perfusion culture systems: a modification of an inclined gravity settler and a variation of an ultrasonic filter. Both bench-top and large-scale tests showed that the gravity settler can effectively retain viable cells and preferentially remove nonviable cells in perfusion culture systems. The viable cell retention rate can be maintained well above 90 during long-term perfusion culture period while the nonviable cell retention rate is 20-30 lower than that of viable cells. The design of this settler enables its manufacture as a single-use device to be used in conjunction with disposable bioreactors. An apparatus for measuring the settling velocities of both the viable and nonviable cells, which is both simple and inexpensive to use, was developed in order to predict optimal operation parameters of the gravity settler. The gravity settler was also effective in an algae dewatering process. The ultrasonic filter has a cell retention capacity 21-fold greater than that of the gravity settler for the same working surface area. Due to its unique design, this ultrasonic filter can operate continuously, as opposed to the currently available ultrasonic filters that need on-off intervals for removal of retained cells

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