AVT, Biochemical Engineering, RWTH Aachen University, Worringerweg 1, Aachen 52074, Germany.
J Biol Eng. 2013 Dec 2;7(1):28. doi: 10.1186/1754-1611-7-28.
Among disposable bioreactor systems, cylindrical orbitally shaken bioreactors show important advantages. They provide a well-defined hydrodynamic flow combined with excellent mixing and oxygen transfer for mammalian and plant cell cultivations. Since there is no known universal correlation between the volumetric mass transfer coefficient for oxygen kLa and relevant operating parameters in such bioreactor systems, the aim of this current study is to experimentally determine a universal kLa correlation.
A Respiration Activity Monitoring System (RAMOS) was used to measure kLa values in cylindrical disposable shaken bioreactors and Buckingham's π-Theorem was applied to define a dimensionless equation for kLa. In this way, a scale- and volume-independent kLa correlation was developed and validated in bioreactors with volumes from 2 L to 200 L. The final correlation was used to calculate cultivation parameters at different scales to allow a sufficient oxygen supply of tobacco BY-2 cell suspension cultures.
The resulting equation can be universally applied to calculate the mass transfer coefficient for any of seven relevant cultivation parameters such as the reactor diameter, the shaking frequency, the filling volume, the viscosity, the oxygen diffusion coefficient, the gravitational acceleration or the shaking diameter within an accuracy range of +/- 30%. To our knowledge, this is the first kLa correlation that has been defined and validated for the cited bioreactor system on a bench-to-pilot scale.
在一次性生物反应器系统中,圆柱形轨道摇床生物反应器具有重要优势。它们为哺乳动物和植物细胞培养提供了明确的流体动力学流动,同时具有出色的混合和氧气转移性能。由于在这种生物反应器系统中,体积传质系数 kLa 与相关操作参数之间没有已知的通用相关性,因此本研究的目的是通过实验确定通用的 kLa 相关性。
使用呼吸活性监测系统 (RAMOS) 在圆柱形一次性摇床生物反应器中测量 kLa 值,并应用 Buckingham 的 π 定理来定义 kLa 的无量纲方程。通过这种方式,开发并验证了一种与规模和体积无关的 kLa 相关性,该相关性适用于从 2 L 到 200 L 体积的生物反应器。最终的相关性用于计算不同规模下的培养参数,以确保烟草 BY-2 悬浮细胞培养有足够的氧气供应。
所得方程可普遍应用于计算任何七个相关培养参数(如反应器直径、摇床频率、填充体积、粘度、氧气扩散系数、重力加速度或摇床直径)的传质系数,精度范围为 +/- 30%。据我们所知,这是首次在从实验室到中试规模的引用生物反应器系统中定义和验证的 kLa 相关性。