(592d) Scaling up and Down Cylindrical Orbshake Bioreactors: Engineering and Use of Osrs for High Density CHO Cell Cultures - 5 Ml to 2500 L

Impeller-free mixing of a liquid is possible: “Shaken, not stirred!” reflects this. However, technical parameters of shaking processes, such as vessel geometry, direction and frequency of vessel displacement, gas transfer, power input, shear stress impact, etc. have only been explored by a few groups recently. Mixing by stirring, in contrast, has been studied extensively over more than 5 decades and impeller driven technology remains industry gold standard, particularly when animal cells, such as Chinese Hamster Ovary (CHO) cells are cultivated in large-scale bioreactors. 5-10 ml suspension cultures of CHO were shaken “orbitally” for the first time by MdJ in the late 1990s in slim, cylindrical vessels (OrbShake Tubes). Today hundreds of thousands of these 50 ml plastic tubes, ventilated passively by diffusion through a sterility membrane and endowed with a conical bottom for easy harvest of cells after centrifugation, are used widely. Over more than 10 years now we established key engineering data and studied the culture performance of orbitally shaken cylinders from 300 ml to 50 L, to 250 L and eventually to 2500 L. We found superior cell growth and productivity in these reactors, solidified by very short mixing times, high gas transfer rates, and low shear stress. The talk will cover the essentials of our research over the last 15 years and will present surprising data of so far unpublished case studies with CHO cells and their performance.