Development of a simple disposable six minibioreactor system for suspension mammalian cell culture

Abstract

A simple disposable six minibioreactor system has been developed in order to perform multiple cell culture experiments in parallel, as a tool to accelerate experimentation in cell culture optimization. The system consists of a fixed part containing all instrumentation, sensors and actuators, and a disposable part, a compact unit with six minibioreactors with 10–15 mL of working volume each. This single-use unit is made of transparent biocompatible plastic material (polystyrene). Each one of the minibioreactors is equipped with agitation, headspace aeration supply and two optical probes, one for total cells measurement and pH, and another for dissolved oxygen measurement (and consequently the evaluation of Oxygen Uptake Rate, OUR). As an example of application, the performance of the system is successfully demonstrated for the culture of hybridoma cells growing in suspension under different conditions. The results allowed confirming the reproducibility of the system, and the feasibility to follow-up continuously the differences in cell growth, pH, pO2 and OUR evolution when hybridoma cells are cultured in different experimental conditions. For this, three different sets of experiments are considered. First, the use of the same culture medium DMEM supplemented with 10% fetal calf serum in all six minibioreactors. Second, the use of DMEM supplemented with three different FCS percentages (0, 1 and 10%) in two minibioreactors each. Third, the use of two different media (DMEM supplemented with 10% FCS and a chemically defined medium) in three minibioreactors each.