Development, Engineering and Biological Characterization of Stirred Tank Bioreactors

Abstract

Stirred tank bioreactors are still the predominant cultivation systems in large scale biopharmaceutical production. Today, several manufacturers provide both reusable and single-use systems, whereas the broad variety of designs and properties lead to deviations in biological performance. Although the methods for bioreactor characterization are well established, varying experimental conditions and procedures can result in significantly different outcomes. In order to guarantee a reliable comparison and evaluation of different single-use and reusable bioreactor types, standardized methods for their characterization are needed. Equally important is the biological capability of bioreactors, which must be accessed by standardized cultivation procedures of industrially relevant organisms (bacteria, yeasts as well as mammalian and animal cell cultures). In addition, the implementation of well-defined uniform procedures for biological and engineering characterization during the development phase can support a fast assessment of the suitability of a bioreactor system. Based on stirred bioreactors, we describe the aspects of the engineering characterization in order to discuss further the biological characterization as a valuable complement. Finally, a case study is presented.

Computational Fluid Dynamics for Advanced Characterisation of Bioreactors Used in the Biopharmaceutical Industry – Part II: Case Studies

“…In this case study, some of the methodological procedures described in part one of this series are used to numerically simulate three different stirred bioreactors to determine the specific power input and the k L a value. The specific power input was determined for two different stirrers (stirrer diameter of 20 mm and 40 mm) according to Bauer et al [1] for a bearing-free, magnetically driven 2 L benchtop system described by Schirmer et al [2], based on Levitronix's levitating impeller technology using the BPS-i30 drive (Figure 1) to validate the simulations described below. For this purpose, the torque was calculated using the known motor constant K t with 1:13 N cm A À1 using eqs (1) and ( 2) and the required current for stirring:…”

CFD modelling of a wave-mixed bioreactor with complex geometry and two degrees of freedom motion

“…The specific power input serves as an important scale-up Frontiers in Chemical Engineering frontiersin.org criterion and describes the power dissipated in the bioreactor in relation to the working volume. In stirred bioreactors and 1 DOF wave-mixed bioreactors, the power input can be determined via the torque, among other methods (Löffelholz et al, 2013a(Löffelholz et al, , 2011Schirmer et al, 2018). Because of the 2 DOF of the CELL-tainer, the specific power input was determined via the local energy dissipation rate ε, Eq.…”

A Wide Air Gap Flux Switching Bearingless Motor With Odd and Even Pole Pair Numbers

“…the ratio of active radial force F r,act,N at nominal flux bng,N and the passive radial stiffness k r 5) Minimize the cogging torque T cog 6) Minimize the variation of the nominal torque T N over the rotor angle ϕ m 7) Minimize the variation of the nominal bearing force F r,act,N over ϕ m , where a trade-off between these objectives exists (see below). This can be expressed mathematically as shown in (5), where w 1 to w 7 denote the relative weights assigned to the individual objective functions. The weights were chosen in accordance with the aforementioned priorities and based on experience from other bearingless motor designs [20], [29].…”

“…The rotor can be operated in its own containment without any mechanical contact under a wide range of environmental conditions. This is beneficial for applications such as ultra-pure, low-shear fluid handling, processing of aggressive chemicals, abrasive media, operation under extreme ambient temperatures, or single-use applications [3]- [5]. The use of a bearingless slice motor as a pump, blower, or mixer for such applications was initially proposed in [6].…”