Chapter

Characterisation of Shake Flasks for Cultivation of Animal Cell Cultures

Boehringer Ingelheim Veterinary Research Center Gmbh & Co. Kg, Hanover, Lower Saxony, Germany
DOI: 10.1007/978-1-4020-5476-1_131

ABSTRACT This study investigated the oxygen transfer processes and general correlations between culture performance and the operating
conditions for shake flask fermentations of animal cell cultures. This involved both the online measurement of the oxygen
transfer rate and the continuous recording of measurements for the dissolved oxygen concentration in the shake flask.

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    ABSTRACT: Though cell culture-based protein production processes are rarely carried out under batch mode of operation, cell line and initial process development operations are usually carried out in batch mode due to simplicity of operation in widely used scale down platforms like shake flasks. Nutrient feeding, if performed, is achieved by bolus addition of concentrated feed solution at different intervals, which leads to large transient increases in nutrient concentrations. One negative consequence is increased waste metabolite production. We have developed a hydrogel-based nutrient delivery system for continuous feeding of nutrients in scale down models like shake flasks without the need for manual feed additions or any additional infrastructure. Continuous delivery also enables maintaining nutrient concentrations at low levels, if desired. The authors demonstrate the use of these systems for continuous feeding of glucose and protein hydrolysate to a suspension Chinese Hamster Ovary (CHO) culture in a shake flask. Glucose feeding achieved using the glucose-loaded hydrogel resulted in a 23% higher integral viable cell density and an 89% lower lactate concentration at the end of the culture when compared with a bolus-feed of glucose.
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