Correlation between mass transfer coefficient kLa and relevant operating parameters in cylindrical disposable shaken bioreactors on a bench-to-pilot scale
Correlation between mass transfer coefficient kLa and relevant operating parameters in cylindrical disposable shaken bioreactors on a bench-to-pilot scale
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DOI：
10.1186/1754-1611-7-28
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发表时间：
2013-01-01
影响因子：
5.6
通讯作者：
Buechs, Jochen
中科院分区：
文献类型：
--
作者：
Kloeckner, Wolf;Gacem, Riad;Buechs, Jochen
背景：在一次性生物反应器系统中，圆柱形轨道振荡生物反应器显示出重要的优势。它们为哺乳动物和植物细胞培养提供了良好的流体动力学流动以及出色的混合和氧转移。由于在这样的生物反应器系统中氧气的体积传质系数k（L）a和相关操作参数之间没有已知的普遍相关性，因此本研究的目的是通过实验确定普遍的k（L）a相关性。使用呼吸活性监测系统（拉莫斯）测量圆柱形一次性摇动生物反应器中的k（L）a值，并使用Buckingham的PI-1000测定k（L）a值。定理被应用于定义k（L）a的无量纲方程。以这种方式，在体积为2 L至200 L的生物反应器中开发并验证了与规模和体积无关的k（L）a相关性。最终的相关性用于计算不同规模的培养参数，以允许烟草BY-2细胞悬浮培养物的充足氧气供应。所得方程可普遍应用于计算七个相关培养参数中的任何一个的传质系数，所述七个相关培养参数例如反应器直径、振荡频率、填充体积、粘度、氧扩散系数，重力加速度或摇动直径在± 30%的精度范围内。据我们所知，这是第一个在实验室到中试规模上针对所引用的生物反应器系统定义和验证的kLa相关性。
Background: 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 k(L)a and relevant operating parameters in such bioreactor systems, the aim of this current study is to experimentally determine a universal k(L)a correlation.Results: A Respiration Activity Monitoring System (RAMOS) was used to measure k(L)a values in cylindrical disposable shaken bioreactors and Buckingham's pi-Theorem was applied to define a dimensionless equation for k(L)a. In this way, a scale- and volume-independent k(L)a 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.Conclusion: 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.