Estimation of Chinese hamster ovary cell density in packed-bed bioreactor by lactate production rate

Abstract

A method is described for estimating recombinant Chinese hamster ovary (rCHO) cell density in a packed-bed bioreactor by lactate production rate. The lactate production rate, which depended on both the cell numbers and cell growth rate, was modeled by segregating the cell population into two parts: one growing at a maximum specific growth rate and another non-growing. The individual cell in each part had the same lactate production rate. The established rate equation of lactate production matched the experimental data reasonably well and could be used to estimate the cell growth in the batch culture with microcarriers. Furthermore, in the perfusion culture of rCHO cells in a packed-bed bioreactor, the final cell density, 1.3×10¹⁰ cells l⁻¹, estimated by lactate production rate, was comparable to the direct sample counting of 1.2×10¹⁰ cells l⁻¹, showing that lactate production rate method would be useful in tracing the cell growth in packed-bed bioreactors.