Effect of pore size, shear rate, and harvest time during the constant permeate flux microfiltration of CHO cell culture supernatant
Effect of pore size, shear rate, and harvest time during the constant permeate flux microfiltration of CHO cell culture supernatant
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DOI：
10.1002/btpr.4
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发表时间：
2008-07-01
影响因子：
2.9
通讯作者：
Moresoli, Christine
中科院分区：
文献类型：
--
作者：
Stressmann, Maja;Moresoli, Christine
研究了剪切速率、膜孔径和收获时培养时间对中国仓鼠卵巢（CHO）细胞培养上清微滤过程中跨膜压力（TMP）升高和膜污染的影响。采用恒渗透通量中空纤维微滤系统。当膜孔径较小（0.20 μ m），剪切速率较高（8.000 s(-1)）时，TMP随过滤时间的增加幅度最大。此外，在较小的膜孔径下观察到的高总体污染也与最高的不可逆污染和最显著的预测开孔面积减少有关。用孔隙堵塞和饼形成联合机制预测的开孔面积减少可以解释观察到的TMP剖面。基于油液经验曲线拟合得出的整体膜污染、长期不可逆污染和初始污染速率，发现采收时间对膜污染没有影响，但初始污染速率与剪切速率存在相关性。水处理污染膜时，高剪切速率下可逆污染更显著，膜孔径越小，不可逆污染越严重。建议使用大孔径膜（0.45 μ m）和低剪切速率（4000 s(-1)），以尽量减少与无血清CHO细胞培养上清的可溶性成分相关的污染。
The influence of the shear rate, the membrane pore size, and the age of the culture at time of harvest on transmembrane pressure (TMP) increase and membrane fouling during the microfiltration of a Chinese Hamster Ovary (CHO) cell culture supernatant was investigated. A hollow fiber microfiltration system operated at constant permeate flux was used. The highest TMP increase with filtration time was observed for the small membrane pore Size (0.20 mu m) operated at the higher shear rate (8.000 s(-1)). Furthermore, the high overall fouling observed with the small membrane pore size was also associated with the highest irreversible fouling and the most significant decrease of predicted open pore area. The predicted reduction in open pore area obtained with the combined pore blockage and cake formation mechanism could explain the observed TMP profiles. Based on the overall membrane fouling, the long-term irreversible fouling and the initial fouling rate, derived from oil empirical curve fitting, no effect of the time of harvest was observed but a dependence of the initial fouling rate on the shear rate was identified. Treatment of the fouled membrane with water showed the presence of a more significant reversible fouling at high shear rates and increased irreversible fouling with smaller membrane pore Size. It is recommended to use the large membrane pore Size (0.45 mu m) and the low shear rate (4,000 s(-1)) to minimize fouling associated with the soluble components of serum-free CHO cell culture supernatant.