Segmented flow generation by chip reactors for highly parallelized cell cultivation

Segmented flow generation by chip reactors for highly parallelized cell cultivation
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DOI:
10.1016/j.bios.2003.12.021
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发表时间:
2004-06-15
影响因子:
12.6
通讯作者:
Köhler, JM
Köhler, JM
中科院分区:
工程技术1区
文献类型:
--
作者:
Grodrian, A;Metze, J;Köhler, JM

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微系统技术为生产可用于细胞培养的小液体量处理装置提供了便利的工具。这里,提出了一种用于快速生成细胞悬浮液等分试样的模块化系统。该系统用于生产和分析大量分离良好的培养物体积。可以从系统中检索选定的克隆。因此,采用了分段流的原理。含有一个细胞或非常小的细胞群的水性培养基的部分通过不混溶的液体(如十二烷、十四烷或矿物油)彼此分离。此外,烷烃将培养液滴与芯片通道和毛细管壁的内侧分离。这样,就可以排除细胞壁表面和细胞壁化学特性之间的相容性问题。分离的培养液滴由不同通道和室拓扑中的微流传输引导。整个系统具有串行操作的细胞处理系统的特征。每个微通道中等分试样的生成速度可加快至约 30 Hz。这意味着每小时可生产约 105 册文化卷,每天可生产约 200 万册。模型生物体以及天然样品(土壤)中的生物体都显示出微生物的生存和生长。 (C) 2004 Elsevier B.V. 保留所有权利。
Micro system technology offers convenient tools for the production of handling devices for small liquid volumes which can be used in cell cultivation. Here, a modular system for the rapid generation of cell suspension aliquots is presented. The system is used to produce and analyze high numbers of well-separated culture volumes. Selected clones may be retrieved from the system. Therefore, the principle of segmented flow is applied. Portions of aqueous culture medium containing one cell or very small cell ensembles are separated from each other by a nonmiscible liquid like dodecane, tetradecane or mineral oil. In addition, the alkane separates the culture droplets from the innerside of the walls of chip channels and capillaries. This way, compatibility problems between cell wall surfaces and the chemical character of walls are excluded. The separated culture droplets are guided by micro flow transportation in different channel and chamber topologies. The whole system has the character of a serially operating cell processing system. The aliquot generation can be sped up to frequencies of about 30 Hz in each microchannel. That means, that about 105 individual cultural volumes can be produced per hour or about 2 million per day. The survival and the growth of microorganisms has been shown for model organisms as well as for organisms from a natural sample (soil). (C) 2004 Elsevier B.V. All rights reserved.