Figure 1: Image photograph of the 2mag bioREACTOR 8 in the Multifermenter system

Figure 2: The Multifermenter is part of an automated process chain supplemented by a laboratory information management system (LIMS) for data management to enable systematic data analysis and design of experiment approaches by software tools

Figure 3: 8-fold parallelized stirred-tank reactor system – 2mag bioREACTOR 8. Besides a block part (1) with 8 positions for single use

reactor vessels and an integrated inductive drive the bioREACTOR 8 is equipped with a lid consisting of a gassing unit (3) for headspace

gassing with sterile air, nitrogen and oxygen and 8 stirring elements on hollow axles. The special geometry of the gas-inducing stirring

elements (4) produces a tangential and axial flow of the media and therewith excellent mixing and gassing of the suspension. This allows

for high oxygen input (kLa > 0.4 s-1). The headspace cooling block (2) minimizes evaporation loss during the cultivation. pH and DO can be

measured non-invasive with fluorescence detection spots in the disposable vessels (5). Sampling ports (6) in the gassing unit allow for

automation (e.g. sampling, feeding, pH control) with a liquid handling robot.

Figure 4: Multifermenter system at Boehringer Ingelheim RCV – 2mag bioREACTOR 8 in a laboratory robot system

Figure 5: Overview - Multifermenter operation workflow

Figure 6: (A) Scheme of the Multifermenter system online curves, displaying different durations of the exponential phases (I – IV), carbon source feed rate (line); cumulative inducer feed (dots); pH (line/dots) (B) Product variant relative abundance compared to main mass peak for durations of the exponential phases (I – IV) and drug substance as reference standard (Ref. Std.).

A B

Janzen, N.H., Striedner, G., Jarmer, J., Voigtmann, M., Abad, S., Reinisch, D.: Implementation of a fully automated microbial

cultivation platform for strain and process screening. Biotechnol. J. 2019, DOI: 10.1002/biot.201800625