Cell Lysis


It may be necessary to reformulate the cell balance if the cell population is significantly differentiated; examples include mixed cultures, mammalian cell culture, and recombinant fermentations with plasmid instability (see "Selection/Mutation and Contamination"). If we assume the system is operating at steady state and there is no accumulation of fluid or cells in the vessel, then the time derivative can be set to zero. Under normal bioprocessing conditions, cell death is assumed to be negligible (i.e., i > a). Bacterial and yeast cells maintain approximately complete viability except in suboptimal environments and at very low dilution rates, whereas in mammalian cell culture, viability and cell lysis may vary significantly with time.

Assuming that the feed to the reactor is sterile (X0 = O), the material balance reduces to equation 2, in which the specific growth rate is equal to the liquid flow rate from the vessel divided by the liquid volume. This quantity is called the dilution rate D (the inverse residence time for the CSTR) and has units of h-1.

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