Development of a feed-forward control system for medium in shake-flask culture

Abstract

Shake-flask culture is used in various applications and is one of the most widely used aerobic culture methods at the laboratory scale. Most shake-flask cultures used upstream of bioprocess development use a batch mode strategy, necessitating the expansion of culture conditions in upstream bioprocess development not limited to batch mode. Hence, the development of convenient small-scale fed-batch culture methods is necessary. The aim of this study was to develop a system that can provide a feed strategy for shaking cultures using an Erlenmeyer flask with a breathable culture stopper. The developed system comprises commercial products, is equipped with a sampling unit that does not interfere with the feeding strategy when collecting culture broth during shaking culture, and is applied to a shake-flask culture of Saccharomyces cerevisiae. The set values for bacterial yield and specific growth rate were fixed at 0.5 g-dry cell/g-D-glucose and 0.2 /h, respectively, whereas the measured values were observed to be 0.55 g-dry cell/g-D-glucose and 0.22 /h, respectively (batch mode: 0.22 g-dry cell/g-D-glucose and 0.45 /h, respectively). These results indicate that the developed system enables highly accurate feed-forward control of the feeding solution without changing the conventional components used in the shake-flask culture methods.