Characterization and application of a miniature 10 mL stirred-tank bioreactor, showing scale-down equivalence with a conventional 7 L reactor
Characterization and application of a miniature 10 mL stirred-tank bioreactor, showing scale-down equivalence with a conventional 7 L reactor
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DOI：
10.1021/bp050369y
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发表时间：
2006-06-01
影响因子：
2.9
通讯作者：
Baganz, Frank
中科院分区：
文献类型：
--
作者：
Betts, Jonathan I.;Doig, Steven D.;Baganz, Frank
本研究的目的是表征仪器化 10 mL 微型搅拌罐生物反应器的工程环境，并评估其作为微生物发酵过程缩小设备的潜力。多个研究小组和公司已经开发了微型生物反应器，例如本工作中详述的微型生物反应器，旨在解决当前生物工艺开发筛选阶段的瓶颈。微型生物反应器的特征是在各种叶轮速度下的总体积氧传递系数和混合时间。直接测量微型生物反应器的功率输入，并据此计算每个叶轮的功率数并估计比功率输入，从而可以将微型生物反应器的性能直接与传统的 7 L 生物反应器的性能进行比较。还研究了微型生物反应器进行微生物发酵的能力。在完全需氧和限氧条件下，以相同的比功率输入对产生质粒 DNA 的大肠杆菌 DH5 α 进行重复分批发酵。结果表明，两种量表在生长和产物动力学方面具有高度相似性。在两种操作规模下获得的相同的最大比生长速率和相同的生物质特定 DNA 产物产量强调了这一点，证明了在等效比功率输入的基础上缩小至 10 mL 的可行性。
The aim of this study was to characterize the engineering environment of an instrumented 10 mL miniature stirred-tank bioreactor and evaluate its potential as a scale-down device for microbial fermentation processes. Miniature bioreactors such as the one detailed in this work have been developed by several research groups and companies and seek to address the current bottleneck at the screening stage of bioprocess development. The miniature bioreactor was characterized in terms of overall volumetric oxygen transfer coefficient and mixing time over a wide range of impeller speeds. Power input to the miniature bioreactor was directly measured, and from this the power number of each impeller was calculated and specific power input estimated, allowing the performance of the miniature bioreactor to be directly compared with that of a conventional 7 L bioreactor. The capability of the miniature bioreactor to carry out microbial fermentations was also investigated. Replicate batch fermentations of Escherichia coli DH5 alpha producing plasmid DNA were performed at equal specific power input, under fully aerobic and oxygen-limiting conditions. The results showed a high degree of equivalence between the two scales with regard to growth and product kinetics. This was underlined by the equal maximum specific growth rate and equal specific DNA product yield on biomass obtained at the two scales of operation, demonstrating the feasibility of scaling down to 10 mL on the basis of equivalent specific power input.