Efficiency of liquid mixing and volumetric mass transfer coefficient in the CellMaker bioreactor systems.
Authors: Robert Matthew, Adam Ostrowski Cellexus International, Dundee, UK in partnership with CPI and IBioIC.
The most common reasons to move a fermentation process to a bioreactor are to provide high volume fermentation with a uniform, precisely controlled environment and even distribution of substrates. Maintaining homogeneity of all the contents of a bioreactor (cells, metabolites, nutrients, etc.) influences process control and is essential for maintaining optimal conditions. At Cellexus, we see this as a particularly important factor of our innovative airlift bioreactor design.
The CellMaker bioreactor bag does not contain mechanical devices to mix media. Instead, the unique shape of the bag is engineered to provide uniform mixing, and efficient gas and nutrient exchange, using directed flow of gas bubbles through the liquid.
The bag geometry was designed to optimise mixing of the fermentate by providing a circular motion from the conical bottom part of the bag and continuing into the wider top section, where the liquid can circulate and prevent settling of the biological material at the bottom of the bioreactor. The shape of the bioreactor bag also has a significant impact on the volumetric mass transfer coefficient (kL a). kL a is an essential parameter in all aerobic fermentation processes, as it describes how well oxygen can be delivered to the cells in the container.
In this study, we measured efficiency of mixing and oxygenation in the full range of CellMaker bioreactor bags. The CellMaker bioreactors are available in working volumes from 1.5L to 50L. The most quoted benefit of using this bioreactor is the ease of bioprocess scaling.
When up-scaling fermentation, the VVM (Volume of sparged air to Volume of liquid per Minute) is the parameter allowing to estimate the performance of the system based on air sparging. It is particularly useful in the CellMaker systems, as the air flowrate is the principle means of both mixing and aerating the media. By comparing the desired VVM to the volume of fermentate in the bioreactor bag (Figure 1), it is possible to calculate the approximate air flowrate needed to maintain the efficiency of the bioprocess. However, the relationship between the VVM and kL a, is not always directly proportional. The results presented here provide an overview of mixing and aeration efficiency, which can be expected while using the CellMaker bioreactors and scaling up fermentation.