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蛋白质与抗体的生产:下游加工技术章节

Manufacturing of Proteins and Antibodies: Chapter Downstream Processing Technologies.

作者信息

Turner Richard, Joseph Adrian, Titchener-Hooker Nigel, Bender Jean

机构信息

MedImmune LLC Gaithersburg Headquarters, One MedImmune Way, Gaithersburg, MD, 20878, USA.

The Advanced Centre of Biochemical Engineering, Department of Biochemical Engineering, University College London, Bernard Katz Building, London, WC1E 6BT, UK.

出版信息

Adv Biochem Eng Biotechnol. 2018;165:95-114. doi: 10.1007/10_2016_54.

DOI:10.1007/10_2016_54
PMID:28776064
Abstract

Cell harvesting is the separation or retention of cells and cellular debris from the supernatant containing the target molecule Selection of harvest method strongly depends on the type of cells, mode of bioreactor operation, process scale, and characteristics of the product and cell culture fluid. Most traditional harvesting methods use some form of filtration, centrifugation, or a combination of both for cell separation and/or retention. Filtration methods include normal flow depth filtration and tangential flow microfiltration. The ability to scale down predictably the selected harvest method helps to ensure successful production and is critical for conducting small-scale characterization studies for confirming parameter targets and ranges. In this chapter we describe centrifugation and depth filtration harvesting methods, share strategies for harvest optimization, present recent developments in centrifugation scale-down models, and review alternative harvesting technologies.

摘要

细胞收获是指从含有目标分子的上清液中分离或截留细胞及细胞碎片。收获方法的选择很大程度上取决于细胞类型、生物反应器操作模式、工艺规模以及产品和细胞培养液的特性。大多数传统收获方法采用某种形式的过滤、离心或两者结合来进行细胞分离和/或截留。过滤方法包括常规流深层过滤和切向流微滤。能够可预测地缩小所选收获方法的规模有助于确保生产成功,对于开展小规模表征研究以确定参数目标和范围至关重要。在本章中,我们描述了离心和深层过滤收获方法,分享收获优化策略,介绍离心缩小模型的最新进展,并综述其他收获技术。

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本文引用的文献

1
A scale-down mimic for mapping the process performance of centrifugation, depth and sterile filtration.一种用于映射离心、深层和无菌过滤工艺性能的缩小模拟装置。
Biotechnol Bioeng. 2016 Sep;113(9):1934-41. doi: 10.1002/bit.25967. Epub 2016 Mar 16.
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Development of a novel and efficient cell culture flocculation process using a stimulus responsive polymer to streamline antibody purification processes.利用响应性聚合物开发新型高效的细胞培养絮凝工艺,简化抗体纯化工艺。
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Modeling industrial centrifugation of mammalian cell culture using a capillary based scale-down system.
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Recent advances in large-scale production of monoclonal antibodies and related proteins.近年来,单克隆抗体和相关蛋白的大规模生产取得了新进展。
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Ultra scale-down prediction using microwell technology of the industrial scale clarification characteristics by centrifugation of mammalian cell broths.使用微孔技术对哺乳动物细胞培养液进行离心以实现工业规模澄清特性的超微缩预测。
Biotechnol Bioeng. 2009 Oct 1;104(2):321-31. doi: 10.1002/bit.22393.
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Industrial scale harvest of proteins from mammalian cell culture by tangential flow filtration.切向流过滤法从哺乳动物细胞培养物中工业规模提取蛋白质。
Biotechnol Bioeng. 1991 Aug 5;38(4):413-22. doi: 10.1002/bit.260380411.
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Micro biochemical engineering to accelerate the design of industrial-scale downstream processes for biopharmaceutical proteins.微生化工程以加速生物制药蛋白质工业规模下游工艺的设计。
Biotechnol Bioeng. 2008 Jun 15;100(3):473-87. doi: 10.1002/bit.21788.
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Advances in primary recovery: centrifugation and membrane technology.一次采油技术进展:离心法与膜技术
Biotechnol Prog. 2008 May-Jun;24(3):488-95. doi: 10.1021/bp070414x. Epub 2008 Apr 15.
10
The use of chitosan as a flocculant in mammalian cell culture dramatically improves clarification throughput without adversely impacting monoclonal antibody recovery.壳聚糖作为絮凝剂在哺乳动物细胞培养中的应用显著提高了澄清通量,且不会对单克隆抗体回收率产生不利影响。
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