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大型反应器内pH不均一性对CHO细胞流加培养过程的影响

DOI: 10.13560/j.cnki.biotech.bull.1985.2015.10.003, PP. 236-241

Keywords: CHO细胞,规模缩小,pH不均一性,TNFR-Fc,反应器放大

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Abstract:

为了研究大型反应器中pH不均一性对CHO细胞流加培养过程的影响,并将培养过程顺利地放大到生产规模,根据大型反应器的混合特性,构建了搅拌式反应器与平推流反应器串联的规模缩小装置用于模拟大型反应器中的pH不均一性。结果表明停留时间为30s时,整个培养过程和对照相比并无显著的差异,这表明此时补碱所导致的pH不均一性并未对流加培养工艺造成影响。而随着停留时间的延长,反应器内pH不均一的程度越大,细胞生长和产物表达受到抑制越明显;与此同时,乳酸和氨的累积显著增加,而关键质量属性唾液酸和生物学活性也随之降低。

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