Monday, November 7, 2011
Capri Ballroom (Marriott Marco Island)
Process analytical technology tools, such as online nutrient and metabolite analysis, can significantly increase process understanding while improving process control and performance. In this study, a SEG-FLOW™ automated bioreactor sampling and feed system was evaluated for its impact on Chinese Hamster Ovary (CHO) cell culture process performance. Cell-free samples were obtained from a bench-scale bioreactor through a FISP® sampling probe and subsequently delivered to a YSI 2700 biochemistry analyzer for glucose analysis. Glucose concentration data were communicated from the YSI 2700 to the SEG-FLOW™ system for feed algorithm calculation and feed pump control. Media glucose levels were maintained at the desired setpoint using a semi-continuous feed scheme programmed by the SEG-FLOW™ software. A second batch, using a daily manual sampling and bolus feed protocol, was performed as a control. The SEG-FLOW™ system, as compared to the control, provided a more optimal glucose feeding regimen for the CHO cell culture, which provided a greater carbon conversion efficiency. This, in turn, resulted in reduced glucose uptake requirements, higher peak and total viable cell concentrations, reduced lactate production and increased protein yield. Additionally, lower media osmolality was achieved due to less base required for the lower lactate production. The SEG-FLOW™ automated online sampling and feed control system can benefit upstream process development by, first, improving cell culture performance through better process monitoring and control, and, second, increasing process knowledge and understanding through real-time sample analysis.
Key words: automated sampling, cell culture, feed control, nutrient monitoring, process analytical technology