A. A. Öncül

Characterization of flow conditions in 2 L and 20 L wave bioreactors using Computational Fluid Dynamics.

Characterization of flow conditions is of great importance to control cell growth and cell damage in animal cell culture because cell viability is influenced by the flow properties in bioreactors. Alternative reactor types like Wave Bioreactors® have been proposed in recent years, leading to markedly different results in cell growth and product formation. An advantage of Wave Bioreactors® is the disposability of the Polyethylenterephthalet‐bags after one single use (fast setup of new production facilities). Another expected advantage is a lower shear stress compared to classical stirred‐tank reactors, due to the gentle liquid motion in the rocking cellbag. This property would considerably reduce possible cell damage. The purpose of the present study is to investigate in a quantitative manner the key flow properties in Wave Bioreactors®, both numerically and experimentally. To describe accurately flow conditions and shear stress in Wave Bioreactors® using numerical simulations, it is necessary to compute the unsteady flow applying Computational Fluid Dynamics (CFD). Corresponding computations for two reactor scales (2 L and 20 L cellbags) are presented using the CFD code ANSYS‐FLUENT®. To describe correctly the free liquid surface, the present simulations employ the Volume of Fluid (VOF) method. Additionally, experimental measurements have been carried out to determine liquid level, flow velocity and liquid shear stress, which are used as a validation of the present CFD simulations. It is shown that the obtained flows stay in the laminar regime. Furthermore, the obtained shear stress levels are well below known threshold values leading to damage of animal cells.

Experimental characterization of flow conditions in 2- and 20-L bioreactors with wave-induced motion.

Quantifying the influence of flow conditions on cell viability is essential for a successful control of cell growth and cell damage in major biotechnological applications, such as in recombinant protein and antibody production or vaccine manufacturing. In the last decade, new bioreactor types have been developed. In particular, bioreactors with wave‐induced motion show interesting properties (e.g., disposable bags suitable for cGMP manufacturing, no requirement for cleaning and sterilization of cultivation vessels, and fast setup of new production lines) and are considered in this study. As an additional advantage, it is expected that cultivations in such bioreactors result in lower shear stress compared with conventional stirred tanks. As a consequence, cell damage would be reduced as cell viability is highly sensitive to hydrodynamic conditions. To check these assumptions, an experimental setup was developed to measure the most important flow parameters (liquid surface level, liquid velocity, and liquid and wall shear stress) in two cellbag sizes (2 and 20 L) of Wave Bioreactors®. The measurements confirm in particular low shear stress values in both cellbags, indicating favorable hydrodynamic conditions for cell cultivation.

CFD model of a semi-batch reactor for the precipitation of nanoparticles in the droplets of a microemulsion

Abstract Precipitation inside the droplets of a microemulsionis a promising technology for the production of nanoparticles with tailored properties, like particle size or shape [1]. In this work, a water-in-oil (w/o)-microemulsion consisting of water, cyclohexane and the non-ionic technical surfactant Marlipal O13/40 is used to synthesise BaSO 4 nanoparticles. The reaction is initiated by the mixing of two microemulsions, one containing the first reactant BaCl 2 and the other containing the second reactant K 2 SO 4 , in semi-batch operation mode in a standard Rushton tank (V=300 ml). A narrow particle size distribution (Fig. 1) and particle sizes between 4 and 40 nm have been achieved by experiments [2].

Flow Characterization in Wave Bioreactors Using Computational Fluid Dynamics

Quantifying and optimizing the flow conditions in cultivation systems is essential for successful cell growth in major biotechnological applications, like vaccine production processes. Recently, disposable wave bioreactors have been proposed for manufacturing of biologics, leading to markedly different mixing properties compared to stirred tank reactors, i.e. lower shear stress. To describe accurately the conditions in wave bioreactors using numerical simulations, it is first necessary to compute the unsteady flow employing Computational Fluid Dynamics (CFD). Simultaneously, the Volume of Fluid (VOF) method is employed to simulate motion of the free liquid surface. Experimental measurements have been carried out in order to determine liquid surface height, flow velocity and shear stress, which are used as a validation of CFD simulations. The obtained results confirmed low shear stress levels, well below known threshold values leading to cell damage. Recent simulations take additionally into account microcarriers through Population Balance Model (PBM), needed for adherent cell growth.