CFD-Based and Experimental Hydrodynamic Characterization of the Single-Use Bioreactor XcellerexTM XDR-10.

Diana Kreitmayer,Srikanth R Gopireddy,Thomas Profitlich,Koichi Nonaka,Nora A Urbanetz,Tomomi Matsuura,Takuya Nakano,Eva Gutheil,Yuichi Aki,Yuta Katayama,Takuma Eguchi,Hirofumi Kakihara

doi:10.3390/bioengineering9010022

Abstract

Understanding the hydrodynamic conditions in bioreactors is of utmost importance for the selection of operating conditions during cell culture process development. In the present study, the two-phase flow in the lab-scale single-use bioreactor Xcellerex XDR-10 is characterized for working volumes from 4.5 L to 10 L, impeller speeds from 40 rpm to 360 rpm, and sparging with two different microporous spargers at rates from 0.02 L min to 0.5 L min. The numerical simulations are performed with the one-way coupled Euler–Lagrange and the Euler–Euler models. The results of the agitated liquid height, the mixing time, and the volumetric oxygen mass transfer coefficient are compared to experiments. For the unbaffled XDR-10, strong surface vortex formation is found for the maximum impeller speed. To support the selection of suitable impeller speeds for cell cultivation, the surface vortex formation, the average turbulence energy dissipation rate, the hydrodynamic stress, and the mixing time are analyzed and discussed. Surface vortex formation is observed for the maximum impeller speed. Mixing times are below 30 s across all conditions, and volumetric oxygen mass transfer coefficients of up to 22.1 h are found. The XDR-10 provides hydrodynamic conditions which are well suited for the cultivation of animal cells, despite the unusual design of a single bottom-mounted impeller and an unbaffled cultivation bioreactor.

Highlights

Single-use bioreactors have become popular because of their lower investment costs and reduced downtime between cultivation runs [1] compared to standard stainless steel multi-use bioreactors
The bag is placed in a solid, cylindrical outer shell to which it is deemed to perfectly conform to and a cylindrical vessel shape is considered in simulations. This is in contrast to the recent study by Mishra et al [10], where a hexagonal cross-section is used for the same XDR-10 bioreactor
A strong surface vortex formation is found for the maximum impeller speed, whereas for all other conditions, the increase in liquid height remains at low values of up to 4 mm

Summary

Introduction

Single-use bioreactors have become popular because of their lower investment costs and reduced downtime between cultivation runs [1] compared to standard stainless steel multi-use bioreactors. The geometry of single-use reactors significantly deviates from classical stainless-steel reactors in the positioning of the impeller(s) and the lack of baffles [1,2]. For this type of geometry, there is less experience in optimization of the operating conditions compared to the classical reactors. Out of the XcellerexTM XDR bioreactors [5], the XcellerexTM XDR-10 is the smallest one. This cylindrical bioreactor has a flat bottom, a centered, bottom-mounted pitched-blade Computational fluid dynamics (CFD) simulations are important to investigate the hydrodynamics in single-use bioreactors [3,4].

Methods

Results

Conclusion