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

Abstract

Orbitally shaken bioreactors (OSRs) are commonly used for the cultivation of mammalian cells in suspension. To aid the geometry designing and optimizing of OSRs, we conducted a three‐dimensional computational fluid dynamics (CFD) simulation to characterize the flow fields in a 10 L cylindrical OSR with different vessel diameters. The liquid wave shape captured by a camera experimentally validated the CFD models established for the cylindrical OSR. The geometry size effect on volumetric mass transfer coefficient (kLa) and hydromechanical stress was analyzed by varying the ratio of vessel diameter (d) to liquid height at static (hL), d/hL. The highest value of kLa about 30 h−1 was observed in the cylindrical vessel with the d/hL of 6.35. Moreover, the magnitudes of shear stress and energy dissipation rate in all the vessels tested were below their minimum values causing cells damage separately, which indicated that the hydromechanical‐stress environment in OSRs is suitable for cells cultivation in suspension. Finally, the CFD results suggested that the d/hL higher than 8.80 should not be adopted for the 10 L cylindrical OSR at the shaking speed of 180 rpm because the “out of phase” state probably will happen there.

Metabolic profiling of Chinese hamster ovary cell cultures at different working volumes and agitation speeds using spin tube reactors

“…9 Low growth and rapid viability loss have been reported in CHO cell cultures due to high working volumes and low agitation rates using larger orbitally shaken bioreactors. [9][10][11] Using a design of experiment approach, Strnad et al (2010) determined that the maximal r-EPO production in CHO cells resulted from low working volumes and high agitation rates in STR50s, although this conclusion resulted from a statistical modeling approach rather than an experimental approach. 6 It is clear that identification of the optimal operational setting conditions are linked with a combination of appropriate oxygen supply and mixing conditions.…”

Fluid dynamics of a pilot‐scale OrbShake bioreactor under different operating conditions

“…The O 2 level in the liquid was recorded continuously by a noninvasive optical sensor spot (PreSens GmbH, Regensburg, Germany) while executing the experiments under the various shaking speeds and filling volumes. The value of k L a was calculated by the mass balance equation [Eqn (1)] 22 where C L is the DO concentration in the liquid phase, C * is the DO concentration at saturation and t is the time.…”

Mass Transfer in a Liter-Scale Wave Mixed Single-Use Bioreactor: Influence of Viscosity and Antifoaming Agent

“…Despite the already substantial amount of experimental data regarding wave mixed single-use bioreactors, given the wide interest from researchers and broad applicability in modern areas of biopharmacy, bioengineering, and novel medical therapies, characterization of rocking bioreactors is still desired, as it has been discussed in reports about, e.g., stirred single-use and multi-use reactors (10 –1 to 10 0 dm 3 volume, − 10 1 to 10 2 dm 3 volume, − and 10 3 dm 3 volume − ). Similar to other bioreactor types, such as orbitally shaken single-use bioreactors − and shake flasks − or airlift bioreactors, − it is valuable and relevant to further supplement the base of experimental data about wave mixed devices, including those regarding the mass transfer. The data will subsequently enable researchers to derive empirical correlations for predicting values of important parameters (e.g., mixing time, volumetric mass transfer coefficient) as a function of process variables, such as those defining the wave mixing (rocking angle α, rocking frequency ω, headspace gas flow rate Q G ) or the properties of the liquid phase (temperature T , viscosity μ, volume of liquid phase V L ).…”