Mathematical descriptions of hybridoma culture kinetics: I. Initial metabolic rates

Biotechnol Bioeng. 1988 Aug 5;32(4):491-506. doi: 10.1002/bit.260320412.


The lack of quantitative descriptions of mammalian culture kinetics limits the ability to optimally design and control cell culture bioreactors. This limitation is ad dressed by developing mathematical equations relating the initial growth rate and the antibody productivity of the hybridoma cell line, CRL-1606, to its environmental state. This initial rate approach, in contrast with steady state analysis of chemostat cultures, approximates steady state behavior, since the rates were measured over brief time intervals and at low cell concentrations (< 50,000 cells/mL). The advantage of this approach is that it is much faster than the chemostat approach.An equation for the growth rate was developed that superimposed Monod equations in serum and glutamine with "noncompetitive" -type inhibition constants were inversely proportional to the lactate and ammonium concentrations. The Monod constant is critical for relating initial, low cell level culture states to other states.Lactate was found to be the only environmental parameter that significantly inhibited antifibronectin monoclonal antibody production by the CRL-1606 hybridomas. Volumetric productivity was strictly related to culture viability, which was observed to decline at growth rates below 0.02 h(-1). Lactate was also found to significantly inhibit ammonium production.