Tubespin Process Development for Use in Cell Culture Technology

Production of proteins through suspension cell culture is a process that is both constantly changing and becoming more efficient. Through modeling of cell culture process on a small scale, large scale optimization time can be shortened and many resources conserved. Currently, shake flasks are the first method in screening of cell clones. Small scale fed-batch systems are adequate in modeling a process before moving a clone to production scale, however, these fermentors require many resources and are limited by the amount of available units and operators. Ideally, a smaller-scale system could adequately model the performance of a clone in these fermentors. In addition, the use of a smaller vessel for clone screening could decrease the amount of time from initial cloning to fermentor optimization. We propose the use of a small bioreactor manufactured by TPP and known as a TubeSpin for clone screening in place of or in addition to shake flask screening. Possibilities of using TubeSpin for direct modeling of larger bioreactors were also explored. Design of experiment (DOE) theory was applied to parameters including angle, seeding density, temperature shift, culture volume, oscillation speed, and cap modifications using five different CHO cell lines. These data were compared to previous and parallel fermentor data, and previous and parallel shake flask data to determine the best conditions to model these systems.