In bioprocess development for the production of pharmaceuticals, proteins, or nutritional additives, scale-down models are used to save time and costs when testing for suitable cell lines, media composition, and process conditions.
However, it is often difficult to determine critical parameters for scale-up of processes at small scale. Shake flasks are commonly used in biotech research and production. They represent a low-cost alternative to expensive larger-scale bioreactor systems and are a lot easier to handle.
On the other hand there is no established system for online monitoring and control of important culture parameters at this scale. A reliable method for automated feeding and the elimination of manual sampling is needed to improve bioprocess development at shake-flask scale.
In these experiments, a feedback-controlled system was tested that could be applied to shake-flask cultures. A feed with carbon source was triggered by the DO content in the cultures and measured online with chemical optical sensor technology from PreSens.
The oxygen sensors were integrated at the bottom of glass Erlenmeyer flasks and read out noninvasively through the transparent flask wall. The sensor signal was transferred to the OXY-10 mini, a 10-channel oxygen meter allowing simultaneous online measurements in up to 10 shake flasks. Using peristaltic pumps the glucose solution was added to the cultures automatically on demand.
Tests with pulsed feed on demand in cultures of Saccharomyces cerevisiae were carried out and results compared to values gained at bioreactor scale (20 L). Furthermore, the system was used to test a carbon-limited process and to enhance biomass and product yield, where the goal was to keep DO at about 20%.