5 Conclusion
This work has successfully demonstrated the use of mixing time as a suitable criterion for scale translation between a microwell model and bench scale STRs. The DISMT technique was used to characterise mixing time in both vessels. The mixing data showed good correlation with the power law function proposed by Rodriguez et al., 2014, confirming its applicability as a scaling law for OSR’s of different sizes and geometries. At matched mixing time, comparable HEK293T stable lentiviral vector producer cell line growth kinetics and LVV productivity profiles were achieved in 24-DSW plate and 2 L STR cultures. However, lack of pH control in the microwells may have contributed to differences in glucose and lactate concentrations post-induction. Overall, the microwell approach offers many advantages in terms of reduction in scale of operation (by over 10-fold compared to 50 mL shake flask, and 300-fold compared to 2 L STR), reduced cost and increased experimental throughput. Given its many advantages, as well as proven scalability with STR’s, the 24-DSW scale down model provides an ideal platform for rapid upstream process development of LVV production.