Characterization of flow conditions in 2 L and 20 L wave bioreactors® using computational fluid dynamics

Abstract

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.

Fluid dynamic characterization of a laboratory scale rocked bag bioreactor

“…As the platform rotates upward again (Figure H) the fluid accelerates in the horizontal direction to achieve the velocity field shown in Figure A. Similarly, to what was observed in this work, Oncul et al (2009) measured velocities using a hot‐film velocity probe at various positions within a 2 L bag, at a rocking speed N = 15 rpm and 7° rocking angle, and reported higher velocities in the middle of the bag at x/L = 0.5 compared to the bag edges.…”

“…Fluid velocities measured by Oncul et al in a 2 L rocked bag at N = 15 rpm showed a similar trend, with maximum average velocities of 0.1–0.2 ms −1 reported at various locations in the bag at an inclination of α = 0°, and minimum average velocity values around or less than 0.02 ms −2 obtained at α = 8°. The volumetric flow rate estimation described by Eq.…”

“…Only a handful of experimental and computational fluid dynamics (CFD) studies have been carried out, which aimed at characterising the flow pattern present inside a rocked bag. Velocity measurements, obtained by Oncul et al (2009) at single points in the flow with a hot‐film anemometer, were used to validate CFD simulations at 2 and 20 L scales . Oncul et al described laminar conditions at rocking rate N = 15 rpm and reported mean velocities between 0 and 0.2 ms −1 in a 2 L bag and between 0 and 0.6 ms −1 in a 20 L bag over the course of one rock.…”

Single-Use Bioreactors for Animal and Human Cells

“…14.3, where Δx represents the maximum fluid element displacement in the vessel during one rocking cycle, which is hard to determine experimentally. It has been stated that turbulent conditions appear in oscillating flows when β exceeds 700 for Wo greater than 8.5 (Oncül et al 2009). …”

“…In contrast, the non-dimensional Womersley number (Wo), a classical non-dimensional number, and a parameter β were used to quantify the unsteady nature of the flows (Oncül et al 2009). Wo is expressed by Eq.…”