Viable cell estimation of mammalian cells using off-gas-based oxygen uptake rate and aging-specific functional

Abstract

This study developed an estimation routine for counting the viable cells in an in vitro fed-batch Chinese hamster ovary cultivation that relies on off-gas information and inlet gas mixture knowledge. We computed the oxygen uptake rate bound to the bioreactor exhaust gas outlet when the inlet gas mixture was stationary. Our mammalian biosynthesis analysis determined the stoichiometric parameters as a function of the average population age. We cross-validated an identical algorithm for mammalian and microbial cultivations and found that the' 99% confidence band of the model generally overlapped with the error bars defined from observations. The resulting RMSE and MAE averages were 0.188 and 0.14e⁹cells L^-1, respectively, when estimating the viable mammalian cell count. The validation for the estimation of total bacterial biomass yielded an MAE and RMSE of 1.78 g L^-1 and 2.53 g L^-1, respectively. Moreover, our proposed approach provides an online estimation of the average population age for both aerobically cultivated microorganisms.

Keywords: Aging; Mammalian cells; Online estimation; Soft sensor; Stoichiometry; Viable cells.