Implementation of a Fully Automated Microbial Cultivation Platform for Strain and Process Screening.,Biotechnology Journal

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Implementation of a Fully Automated Microbial Cultivation Platform for Strain and Process Screening.
Biotechnology Journal ( IF 3.2 ) Pub Date : 2019-06-26 , DOI: 10.1002/biot.201800625
Nils H Janzen _{1,

2} , Gerald Striedner ₂ , Johanna Jarmer ₁ , Martin Voigtmann _{1,

2} , Sandra Abad ₁ , Daniela Reinisch ₁

Affiliation

Advances in molecular biotechnology have resulted in the generation of numerous potential production strains. Because every strain can be screened under various process conditions, the number of potential cultivations is multiplied. Exploiting this potential without increasing the associated timelines requires a cultivation platform that offers increased throughput and flexibility to perform various bioprocess screening protocols. Currently, there is no commercially available fully automated cultivation platform that can operate multiple microbial fed-batch processes, including at-line sampling, deep freezer off-line sample storage, and complete data handling. To enable scalable high-throughput early-stage microbial bioprocess development, a commercially available microbioreactor system and a laboratory robot are combined to develop a fully automated cultivation platform. By making numerous modifications, as well as supplementation with custom-built hardware and software, fully automated milliliter-scale microbial fed-batch cultivation, sample handling, and data storage are realized. The initial results of cultivations with two different expression systems and three different process conditions are compared using 5 L scale benchmark cultivations, which provide identical rankings of expression systems and process conditions. Thus, fully automated high-throughput cultivation, including automated centralized data storage to significantly accelerate the identification of the optimal expression systems and process conditions, offers the potential for automated early-stage bioprocess development.

中文翻译：

用于筛选菌株和过程的全自动微生物培养平台的实现。

分子生物技术的进步导致了许多潜在生产菌株的产生。由于可以在各种工艺条件下筛选每种菌株，因此潜在的栽培数量成倍增加。在不增加相关时间表的情况下开发这种潜力需要一个培养平台，该平台提供更高的通量和灵活性以执行各种生物过程筛选方案。当前，尚无可用于操作多种微生物补料分批过程的商用全自动培养平台，包括在线采样，深度冷冻离线样品存储以及完整的数据处理。为了实现可扩展的高通量早期微生物生物工艺开发，将市售的微生物反应器系统和实验室机器人结合起来，以开发出一个全自动的培养平台。通过进行大量修改，以及添加定制的硬件和软件，可以实现全自动毫升级微生物补料分批培养，样品处理和数据存储。使用5 L规模的基准培养比较了使用两种不同表达系统和三种不同处理条件的培养的初步结果，这提供了对表达系统和处理条件相同的排名。因此，全自动的高通量培养，包括自动的集中式数据存储，可显着加快最佳表达系统和工艺条件的鉴定，

更新日期：2019-06-26

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