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哺乳动物细胞补料分批培养中营养物浓度的自适应模糊控制。

Adaptive fuzzy control of nutrients concentration in fed-batch culture of mammalian cells.

出版信息

Cytotechnology. 1997 Nov;25(1-3):9-15. doi: 10.1023/A:1007950002663.

DOI:10.1023/A:1007950002663
PMID:22358875
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3466750/
Abstract

An adaptive fuzzy controller was developed to control the glucose and glutamine concentrations in the reactor constant at the desired level. The parameter values of the controller change during the cultivation according to the culture phase which was detected by the lactate concentration. Cultivations with different glucose and glutamine set point concentrations of a recombinant BHK anchorage-dependent cell line were performed in a fed-batch reactor on-line connected with an HPLC system. Glucose and glutamine concentrations were satisfactorily controlled at each set point during all cultivation periods. Ammonia had a determining effect on productivity since it inhibited cell growth and protein specific production. Ammonia production increased with an increase of glutamine or a decrease of glucose set point concentrations, indicating the importance of glucose to glutamine ratio for the optimization of productivity in mammalian cell cultures.

摘要

开发了一种自适应模糊控制器,以将反应器中的葡萄糖和谷氨酰胺浓度控制在所需水平。根据通过乳酸浓度检测到的培养阶段,控制器的参数值在培养过程中发生变化。在与 HPLC 系统在线连接的分批进料式反应器中,对重组 BHK 贴壁依赖性细胞系进行了不同葡萄糖和谷氨酰胺设定点浓度的培养。在所有培养期间,葡萄糖和谷氨酰胺浓度都能令人满意地控制在每个设定点。氨对生产力有决定性影响,因为它抑制细胞生长和蛋白质特异性生产。随着谷氨酰胺或葡萄糖设定点浓度的增加或降低,氨的产量增加,表明葡萄糖与谷氨酰胺的比值对优化哺乳动物细胞培养中的生产力非常重要。

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引用本文的文献

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本文引用的文献

1
Improvement of cloned alpha-amylase gene expression in fed-batch culture of recombinant Saccharomyces cerevisiae by regulating both glucose and ethanol concentrations using a fuzzy controller.通过使用模糊控制器调节葡萄糖和乙醇浓度来提高重组酿酒酵母补料分批培养中克隆的α-淀粉酶基因表达。
Biotechnol Bioeng. 1994 Nov 5;44(9):1055-63. doi: 10.1002/bit.260440906.
2
Catabolic control of hybridoma cells by glucose and glutamine limited fed batch cultures.葡萄糖和谷氨酰胺限制补料分批培养对杂交瘤细胞的分解代谢控制
Biotechnol Bioeng. 1994 Sep 20;44(7):808-18. doi: 10.1002/bit.260440706.
3
Growth characteristics in fed-batch culture of hybridoma cells with control of glucose and glutamine concentrations.通过控制葡萄糖和谷氨酰胺浓度对杂交瘤细胞进行补料分批培养的生长特性
Biotechnol Bioeng. 1994 Jun 5;44(1):95-103. doi: 10.1002/bit.260440114.
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Continuous production of prourokinase in feed harvest and perfusion cultures.在收获饲料和灌注培养中连续生产尿激酶原。
Biotechnol Bioeng. 1990 Sep;36(6):623-9. doi: 10.1002/bit.260360610.
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Glutamine-limited batch hybridoma growth and antibody production: experiment and model.谷氨酰胺限制的分批培养杂交瘤生长及抗体产生:实验与模型
Biotechnol Bioeng. 1990 Jun 5;36(1):74-82. doi: 10.1002/bit.260360110.
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A model for density-dependent growth of anchorage-dependent mammalian cells.一种贴壁依赖型哺乳动物细胞密度依赖性生长的模型。
Biotechnol Bioeng. 1988 Oct 5;32(8):1061-6. doi: 10.1002/bit.260320813.
7
Reduction of waste product excretion via nutrient control: Possible strategies for maximizing product and cell yields on serum in cultures of mammalian cells.通过营养控制减少废物排泄:在哺乳动物细胞培养中最大化血清中产物和细胞产量的可能策略。
Biotechnol Bioeng. 1986 Sep;28(9):1376-89. doi: 10.1002/bit.260280912.
8
The importance of ammonia in mammalian cell culture.氨在哺乳动物细胞培养中的重要性。
J Biotechnol. 1996 May 15;46(3):161-85. doi: 10.1016/0168-1656(95)00196-4.
9
Fractional factorial study of hybridoma behavior. 2. Kinetics of nutrient uptake and waste production.杂交瘤细胞行为的部分因子试验研究。2. 营养物质摄取及废物产生的动力学
Biotechnol Prog. 1993 May-Jun;9(3):309-16. doi: 10.1021/bp00021a010.
10
Effect of glucose on the cultivation of mammalian cells.葡萄糖对哺乳动物细胞培养的影响。
Dev Biol Stand. 1987;66:279-90.