Secondary strain screening is usually carried out in a number of shake flask studies. However, the limitations are that the data is usually not representative relative to data from fermentors and selected strains may not be the best performers. In addition, since high cell density is the prerequisite to productivity, a number of high cell density experiments in fermentors must be performed during early stage development. Due to the number of variables that require investigation per strain, time and cost involved in screening and early stage development pose as a bottle neck in current development processes.
To overcome the limitations and bottle neck mentioned above, efforts to combine secondary screening and early process development in high cell density mode was carried out. To establish correlation between the minibioreactor and 1L DASGIP, characterization for their volumetric oxygen mass transfer coefficient, power consumption, mixing time, cooling capacity and tip speed was performed. From the data, an existing DASGIP process was scaled down and developed to form a new platform process in the minibioreactor.
The results showed that the new minibioreactor platform process provided bench top fermentor equivalent cultivation environment. The data obtained overcame the common limitations of secondary screening in shake flasks. The chosen strains showed higher correlation rate for success at larger scales. Considerable reduction in time and cost was seen.