High throughput automated microbial bioreactor system used for clone selection and rapid scale-down process optimization.
High throughput automated microbial bioreactor system used for clone selection and rapid scale-down process optimization.
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DOI：
10.1002/btpr.2534
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发表时间：
2018-01
影响因子：
2.9
通讯作者：
Keshavarz-Moore E
中科院分区：
文献类型：
--
作者：
Velez-Suberbie ML;Betts JPJ;Walker KL;Robinson C;Zoro B;Keshavarz-Moore E
高通量自动化发酵系统已成为早期生物过程开发的有用工具。在这项研究中，我们研究了一种专为微生物培养而设计的24×15毫升一次性使用的微生物反应器系统AMBR 15F。我们比较了该系统对两个大肠杆菌菌株BL21(DE3)和MC4100以及两个工业相关分子hGH和scFv的补料分批生长和生产能力。此外，使用团注、线性或指数投料策略对不同碳源进行了测试，显示了AMBR 15F系统处理自动投料的能力。我们以单位体积功率(P/V)作为衡量标准，将AMBR 15F与1个L搅拌生物反应器进行比较，后者以前扩大到20个L，但具有不同的生物系统，因此在生长和产品产量方面都显示出潜在的1300倍的规模可比性。通过将在AMBR 15F系统中生长的细胞暴露在工业离心机预期的剪切水平下，我们确定这些细胞与实验室规模的生物反应器中的细胞一样健壮。这些结果表明，AMBR15F系统是一种高效的高通量微生物系统，可用于菌株和分子的选择以及快速放大。©2017作者生物技术进展，由Wiley期刊，Inc.代表美国化学工程师学会生物技术出版。计划，34：58-68,2018
High throughput automated fermentation systems have become a useful tool in early bioprocess development. In this study, we investigated a 24 x 15 mL single use microbioreactor system, ambr 15f, designed for microbial culture. We compared the fed‐batch growth and production capabilities of this system for two Escherichia coli strains, BL21 (DE3) and MC4100, and two industrially relevant molecules, hGH and scFv. In addition, different carbon sources were tested using bolus, linear or exponential feeding strategies, showing the capacity of the ambr 15f system to handle automated feeding. We used power per unit volume (P/V) as a scale criterion to compare the ambr 15f with 1 L stirred bioreactors which were previously scaled‐up to 20 L with a different biological system, thus showing a potential 1,300 fold scale comparability in terms of both growth and product yield. By exposing the cells grown in the ambr 15f system to a level of shear expected in an industrial centrifuge, we determined that the cells are as robust as those from a bench scale bioreactor. These results provide evidence that the ambr 15f system is an efficient high throughput microbial system that can be used for strain and molecule selection as well as rapid scale‐up. © 2017 The Authors Biotechnology Progress published by Wiley Periodicals, Inc. on behalf of American Institute of Chemical Engineers Biotechnol. Prog., 34:58–68, 2018
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