Cell death from bursting bubbles: Role of cell attachment to rising bubbles in sparged reactors

Bursting bubbles are thought to be the dominant cause of cell death in spar ged animal or insect cell cultures. Cells that die during the bubble burst can come from three sources: cells suspended near the bubble; cells trapped in the bubble lamella; and cells that attached to the rising bubble. This article examines cell attachment to rising bubbles using a model in which c ell attachment depends on cell radius, bubble radius, and cell-bubble attac hment time. For bubble columns over 1 m in height and without protective ad ditives, the model predicts significant attachment for 0.5- to 3-mm radius bubbles, but no significant attachment in the presence of protective additi ves. For bubble columns over 10 cm in height, and without protective additi ves, the model predicts significant attachment for 50- to 100-mu m radius b ubbles, but not all protective additives prevent attachment for these bubbl es. The model is consistent with three sets of published data and with our experimental results. Using hybridoma cells, serum-free medium with antifoa m, and 1.60 +/- 0.05 mm (standard error) radius bubbles, we measured death rates consistent with cell attachment to rising bubbles, as predicted by th e model. With 1.40 +/- 0.05 mm (SE) radius bubbles and either 0.1% w/v Plur onic-F68 or 0.1% w/v methylcellulose added to the medium, we measured death rates consistent with no significant cell attachment to rising bubbles, as predicted by the model. (C) 1999 John Wiley & Sons, Inc.