Studies on fluid dynamics of the flow field and gas transfer in orbitally shaken tubes

Abstract

Orbitally shaken cylindrical bioreactors [OrbShake bioreactors (OSRs)] without an impeller or sparger are increasingly being used for the suspension cultivation of mammalian cells. Among small volume OSRs, 50-mL tubes with a ventilated cap (OSR50), originally derived from standard laboratory centrifuge tubes with a conical bottom, have found many applications including high-throughput screening for the optimization of cell cultivation conditions. To better understand the fluid dynamics and gas transfer rates at the liquid surface in OSR50, we established a three-dimensional simulation model of the unsteady liquid forms (waves) in this vessel. The studies verified that the operating conditions have a large effect on the interfacial surface. The volumetric mass transfer coefficient (k a) was determined experimentally and from simulations under various working conditions. We also determined the liquid-phase mass transfer coefficient (k ) and the specific interfacial area (a) under different conditions to demonstrate that the value of a affected the gas transfer rate more than did the value of k . High oxygen transfer rates, sufficient for supporting the high-density culture of mammalian cells, were found. Finally, the average axial velocity of the liquid was identified to be an important parameter for maintaining cells in suspension. Overall these studies provide valuable insights into the preferable operating conditions for the OSR50, such as those needed for cell cultures requiring high oxygen levels. © 2016 American Institute of Chemical Engineers Biotechnol. Prog., 33:192-200, 2017.

Establishment of a CFD‐based kLa model in microtiter plates to support CHO cell culture scale‐up during clone selection

“…A similar numerical setup to Salek et al was used by Zhang et al, who present a method of simulating the volumetric power input and k L a values. Another k L a model for CFD was presented by Zhu et al They use the turbulent dissipation rate for the estimation of the k L by using a two equation k − ɛ turbulence model in contrast to other CFD studies that use laminar modeling. In this work, a method of calculating local mass transfer coefficients for the estimation of global k L a coefficients in shaken microtiter plates is presented.…”

Characterizing the fluid dynamics of the inverted frustoconical shaking bioreactor

“…Under the effect of gravity and centrifugal forces, the shape of the liquid wave remained unchanged after a short acceleration, which is considered favorable to predict the oxygen transfer rate (OTR). The stable shape of liquid waves was also found in the unbaffled Erlenmeyer‐type flask and OSR50 . The distribution of liquid height ( H ) along the wall of the vessel in a complete circle was obtained from simulated and experiment results respectively.…”

“…However, CFD tools have only recently been applied to model the flow field in OSRs . We have recently applied CFD tools to study the interaction of the gas and liquid phases and gas transfer in the OSR50 . However, there is still a lack of fluid dynamics information in the IFSB, especially for the modeling of the engineering parameters.…”

Characterizing the fluid dynamics in the flow fields of cylindrical orbitally shaken bioreactors with different geometry sizes

“…τ yy = 2μ ∂u y ∂y (16) τ zz = 2μ ∂u z ∂z (17) The distribution of was calculated in the cylindrical OSR with the d/h L of 1.76 at 10 L filling volume and 100 rpm shaking speed (Fig. 8).…”

“…Recently, the advanced model, population balance model (PBM), has been validated in simulating bubble breakage and coalescence in STRs [15]. We have recently investigated the interaction of the gas and liquid phases and gas transfer in the OSR50 by using the CFD method [17]. Unfortunately, the results from studies with STRs cannot be applied to OSRs, due to the difference of agitating principle and oxygen supply.…”