Novo Nordisk A/S, Måløv, Denmark.
LEO Pharma A/S, Ballerup, Denmark.
Biotechnol Lett. 2022 Jul;44(7):813-822. doi: 10.1007/s10529-022-03258-7. Epub 2022 Jun 1.
Hydrodynamics, mixing and shear are terms often used when explaining or modelling scale differences, but other scale differences, such as evaporation, can arise from non-hydrodynamic factors that can be managed with some awareness and effort.
We present an engineering approach to the prediction of evaporation rates in bioreactors based on gHO/Nm of air entering and leaving the bioreactor and confirm its usefulness in a 28-run design of experiments investigating the effects of aeration rate (0.02 to 2.0 VVM), condenser temperature (10 to 20 °C), fill (2.5 to 5 kg), broth temperature (25 to 40 °C) and agitator speed (25 to 800 rpm). Aeration rate and condenser temperature used in the engineering prediction provided a practically useful estimate of evaporation; the other factors, while statistically identified as having some influence, were of negligible practical usefulness. Evaporation rates were never found to be zero, and could be at least 10% different to those expected at scale.
An assessment of evaporation rates for any project is encouraged, and it is recommended that the effects are accounted for by measurements, modelling or by tuning the exhaust cooling device temperature to minimize scale differences.
在解释或建模规模差异时,经常使用流体动力学、混合和剪切等术语,但蒸发等其他规模差异可能源于非流体动力学因素,通过一些意识和努力可以加以管理。
我们提出了一种基于进入和离开生物反应器的空气的 gHO/Nm 预测生物反应器中蒸发速率的工程方法,并通过 28 次实验设计证实了其在研究通气速率(0.02 至 2.0 VVM)、冷凝器温度(10 至 20°C)、填充量(2.5 至 5 千克)、培养基温度(25 至 40°C)和搅拌器速度(25 至 800 rpm)影响的实验中的有用性。工程预测中使用的通气速率和冷凝器温度提供了蒸发的实际有用估计;其他因素虽然在统计学上被确定为具有一定影响,但实际上用处不大。从未发现蒸发速率为零,并且实际蒸发速率与预期规模的差异至少为 10%。
鼓励对任何项目进行蒸发速率评估,并建议通过测量、建模或通过调整排气冷却装置温度来最小化规模差异来考虑这些影响。