Wave characterization for mammalian cell culture: residence time distribution

The high dose requirements of biopharmaceutical products led to the development of mammalian cell culture technologies that increase biomanufacturing capacity. The disposable Wave bioreactor is one of the most promising technologies, providing ease of operation and no cross-contamination, and using an innovative undulation movement that ensures good mixing and oxygen transfer without cell damage. However, its recentness demands further characterization. This study evaluated the residence time distribution (RTD) in Wave, allowing the characterization of mixing and flow and the comparison with ideal models and a Stirred tank reactor (STR) used for mammalian cell culture. RTD was determined using methylene blue with pulse input methodology, at three flow rates common in mammalian cell culture (3.3 × 10−5 m3/h, 7.9 × 10−5 m3/h, and 1.25 × 10−4 m3/h) and one typical of microbial culture (5 × 10−3 m3/h). Samples were taken periodically and the absorbance read at 660 nm. It was observed that Wave behavior diverted from ideal models, but was similar to STR. Therefore, the deviations are not related to the particular Wave rocking mechanism, but could be associated with the inadequacy of these reactors to operate in continuous mode or to a possible inability of the theoretical models to properly describe the behavior of reactors designed for mammalian cell culture. Thus, the development of new theoretical models could better characterize the performance of these reactors.

► Residence time distribution in Wave and Stirred tank bioreactors was evaluated.
► Wave behavior diverts from ideal models.
► Wave and Stirred tank reactors behave similarly.
► New models need to be developed to describe mammalian cell culture reactors behavior.