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BIOTECHNOLOGY 59


The left and right-handed BioFlo 320 bioprocess control stations with magnetic drive glass water-jacketed vessel (left) and BioBLU single-use vessel (right)


BIOPROCESS CONTROL TECHNOLOGY Advances in


Intelligent control in cell culture process development. By Christiane Schlottbom, Stacey Willard & Ma Sha


I


n industrial production of proteins and antibodies, Chinese hamster ovary (CHO) cells have been established as the number one mammalian host. New sensor technologies and intelligent bioprocess control stations can enhance process development in the bench scale and hence pave the way for scale up.


BioFlo 320 supports 4-20 mA input/output connection with a multitude of ancillary devices including auxiliary pumps, turbidity sensors, capacitance sensors, extra scales, automatic samplers, and biochemical


Advanced bioprocess development Te recently released Eppendorf BioFlo 320 benchtop bioprocess control station can interchangeably control industry-standard autoclavable glass vessels or BioBLU Single- Use Vessels. In addition to increased versatility with respect to vessels, it offers the ability to seamlessly connect a wide variety of Mettler-Toledo ISM sensors, including dissolved oxygen (DO) and carbon dioxide (DCO2


), pH and redox. Te


analysers, which can be recorded and/or controlled within the software.


Scientists at the Eppendorf


Research & Development Lab in Connecticut, USA, have conducted CHO batch cell culture runs in which various sensors and control strategies were employed and compared. First, the capability of the control station to automatically detect and integrate sensors with ISM technology was utilised. Sensor health and maintenance was monitored using iSense software from Mettler-Toledo. In addition, the evo 200 (Fogale Nanotech) capacitance-based biomass sensor was also included for in-line growth monitoring. Te BioFlo 320 was used to control two batch suspension


CHO cultures in a three-litre glass water-jacketed vessel. Te runs differed in the automatic gassing strategy employed: one run used the three-gas algorithm and the other run used the four-gas option. In addition, to highlight the ability to integrate many different sensor types, three different DO sensors were used to monitor the DO levels in both cultures: an ISM polarographic DO sensor; an ISM optical DO sensor; and an analogue polarographic DO sensor. All three DO sensors were placed directly next to one another at the same height in the vessel. Prior to autoclaving the


vessel, an ISM gel-filled pH sensor was connected to the BioFlo 320 control station where it was automatically


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