Damage mechanisms of suspended animal cells in agitated bioreactors with and without bubble entrainment

Abstract

We show that when freely suspended hybridoma cells are cultured in an agitated bioreactor, two fluid-mechanical mechanisms can cause cell damage and growth retardation. The first is present only when there is a gas phase, and is associated with vortex formation accompanied by bubble entrainment and breakup. In the absence of a vortex and bubble entrainment, cells can be damaged only at very high agitation rates, above approximately 700 rpm, by stresses in the bulk turbulent liquid. Cell damage then correlates with Kolmogorov eddy sizes similar to or smaller than the cell size. In the absence of a vortex, the entrainment and motion of very fine bubbles cause no growth retardation even at agitation rates as high as 600 rpm.

Production of Adenoviral Vectors in 293 Cells: A Case Study of the Adaptation of Attached Cells to Grow in Suspension

“…This is due to the fragile nature of animal cells, which can be damaged under conditions of high turbulence [26,27]. Hence, in mammalian cell culture the objectives of maximizing oxygen transfer rates must be balanced with the maintenance of the integrity of the cell membrane [28,29].…”

“…These cells are shear sensitive due to the protection from the environment by the cell membrane only. The major physical forces during cell culture that can cause cell damage include shear forces and bubble energy [28,30,31].…”

Transfection of Spodoptera frugiperda Insect Cell and Production of Recombinant Protein

“…Süspanse hücreler gaz-sıvı ara yüzey ortadan kaldırıldığı zaman sıklıkla yüksek karıştırma hızlarını tolere edebilmektedir. Karıştırma kaynaklı hücre zararı Kolmogorov girdaplarının oluşumu nedeniyle meydana gelebilmektedir [93], [94]. Hücre zararını önlemek için biyoreaktör havalandırma ve karıştırma hızlarının kullanılan karıştırıcı dikkate alınarak optimize edilmesi ve oluşan kayma geriliminin hücre zararına yol açmayacak bir aralıkta tutulması gerekmektedir.…”

Collection of collapsing bubble driven phenomena found in champagne glasses

“…Nevertheless, only quite recently, much interest has been devoted to characterize each and every parameter involved in its bubbling process. 6 From a strictly physicochemical point of view, Champagne wines are multicomponent hydroalcoholic systems, with a density close to unity, a surface tension -1 m mN 50 , and a viscosity about 50 % larger than that of pure water. 6 Champagne wines are also supersaturated with CO 2 dissolved gas molecules formed together with ethanol during the second fermentation process (called prise de mousse, and promoted by adding yeasts and a certain amount of sugar inside bottles filled with a base wine and sealed with a cap).…”