| Bioprocess optimization is experiment-driven, requiring large numbers of culture conditions to be evaluated. These can be time and labor intensive and expensive due to the high cost of equipment and consumables. Shake flask experiments allow many experiments to be performed in parallel at low cost, but little information can be gathered from each experiment because of the lack of process monitoring and control. A small reactor platform allowing simultaneous low cost experiments with the high information value of a fully instrumented fermenter would be beneficial.; First, a small reactor was built around a disposable cuvette; with a working volume of 2.5 mL. This reactor was equipped with optical sensors for pH, oxygen, and cell mass. The cuvette was operated with 2VVM of air sparged into the reactor and 300 RPM agitation to achieve a kLa of about 28 h-1. An E. coli culture was grown in the cuvette at room temperature. An identical culture was grown in a 1 L bench-scale fermenter that was operated at 300 RPM with 1 VVM air sparged into the fermenter (kLa of 21 h-1) and temperature controlled at 25°C. The fermentation results were almost identical between the two reactors, showing the potential of using a mL bioreactor as a scaled down model of bench-scale fermenters.; Because the results from the cuvette reactor were so promising, a parallel bioreactor platform was built around a standard 24 well plate. Each well provides a working volume of about 1 mL, and was equipped with optical sensors for pH, oxygen, and cell mass. With air sparged at 1 VVM, the reactors had k La values ranging from 50 to 500 h-1 for agitation between 100 and 2800 RPM, showing the capacity for controlling dissolved oxygen. Mixing times under these conditions were 0.4 to 10 seconds. Hardware was also designed and constructed to allow for control of culture temperature and pH.; Simultaneous fermentations were performed in the parallel bioreactor platform, and results were comparable between individual wells. While minor differences between the reactors causes some variation, the system successfully demonstrates proof of concept and holds promise for future work. |
