Physical mechanisms of cell damage in microcarrier cell culture bioreactors
Article first published online: 18 FEB 2004
Copyright © 1988 John Wiley & Sons, Inc.
Biotechnology and Bioengineering
Volume 32, Issue 8, pages 1001–1014, 5 October 1988
How to Cite
Cherry, R. S. and Papoutsakis, E. T. (1988), Physical mechanisms of cell damage in microcarrier cell culture bioreactors. Biotechnol. Bioeng., 32: 1001–1014. doi: 10.1002/bit.260320808
- Issue published online: 18 FEB 2004
- Article first published online: 18 FEB 2004
- Manuscript Accepted: 30 NOV 1987
The negative effects of excessive agitation on tissue cells in microcarrier culture have often been ascribed to “shear.” Analysis of the fluid mechanics occurring suggests that there are actually three potential damage mechanisms: collisions of a cell-covered microcarrier with other beads, collisions with parts of the reactor (primarily the impeller), and interaction with turbulent eddies the size of the microcarrier beads. Review of the available quantitative information on agitation effects in cell cultures does not establish which mechanism is predominant; the range of experimental variables reported emphasizes power input over the other reactor and impeller parameters. The bead–bead collision model is tentatively supported by the available data, but the other mechanisms may still be significant in some systems. The formation of bead aggregates by cellular bridging provides a parallel means of damaging cells. Breaking of these bridges by any of the three means identified earlier can cause cell destruction and/or the net transfer of cells to formerly bare beads. High concentrations of bridges are favored by lower agitation rates, presumably because the bridges are not as quickly destroyed after formation.