S25: Establishment Of A New Platform For High Cell Density Screening And Early Process Development In Mini-Bioreactors

During microbial strain development, screening of the best performing strains is commonly carried out in shake flasks. However, the data is usually not representative relative to data from fermentors, and selected strains may not be the best performers. Additionally, high cell density is a prerequisite to increase productivity; therefore, high cell density fermentation is typically performed during early stage development. Due to the multitude of variables required for each strain, the time and cost can pose a bottle neck in current development processes.

To overcome the shake flask constraints of non-representative data and the throughput limitation, efforts to combine the strain screening and early process development in high cell density mode were carried out using the 250mL DASbox system. Volumetric oxygen mass transfer coefficient, power consumption, mixing time, tip speed, and cooling capacity were characterized on the DASbox and 1L DASGIP to establish a scale-down correlation between both systems. An existing 1L DASGIP process with well-proven scalability was scaled down and further developed to form a new platform process in the DASbox. The new platform process was used to screen 18 strains, and subsequently 4 promising strains were successfully scaled back up to the 1L DASGIP.

The results indicated that the new DASbox platform process provided a bench top fermentor equivalent. This strategy overcame the common limitations of batch mode screening in shake flasks, and the chosen strains showed a good correlation for success at larger scales. Considerable reduction in time and cost was recognized by using the Mini-Bioreactor platform.