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一种完全在线、配备传感器的、一次性多相微生物反应器,可用作生物技术应用的筛选平台。

A fully online sensor-equipped, disposable multiphase microbioreactor as a screening platform for biotechnological applications.

机构信息

Institute of Biochemical Engineering, Technische Universität Braunschweig, Braunschweig, Germany.

Center of Pharmaceutical Engineering (PVZ), Technische Universität Braunschweig, Braunschweig, Germany.

出版信息

Biotechnol Bioeng. 2019 Jan;116(1):65-75. doi: 10.1002/bit.26831. Epub 2018 Nov 6.

Abstract

A new disposable, multiphase, microbioreactor (MBR; with a working volume of 550 μl) equipped with online sensors is presented for biotechnological screening research purposes owing to its high-throughput potential. Its design and fabrication, online sensor integration, and operation are described. During aerobic cultivation, sufficient oxygen supply is the most important factor that influences growth and product formation. The MBR is a microbubble column bioreactor (μBC), and the oxygen supply was realized by active pneumatic bubble aeration, ensuring sufficient volumetric liquid-phase mass transfer (k a) and proper homogenization of the cultivation broth. The μBC was equipped with miniaturized sensors for the pH, dissolved oxygen, optical density and glucose concentration that allowed real-time online monitoring of these process variables during cultivation. The challenge addressed here was the integration of sensors in the limited available space. The MBR was shown to be a suitable screening platform for the cultivation of biological systems. Batch cultivations of Saccharomyces cerevisiae were performed to observe the variation in the process variables over time and to show the robustness and operability of all the online sensors in the MBR.

摘要

介绍了一种新型一次性、多相、微生物反应器(MBR;工作体积为 550μl),由于其高通量的潜力,可用于生物技术筛选研究。描述了其设计和制造、在线传感器集成和操作。在好氧培养过程中,充足的氧气供应是影响生长和产物形成的最重要因素。MBR 是一种微泡柱生物反应器(μBC),通过主动气动鼓泡曝气实现氧气供应,确保了足够的体积液相传质(k a)和培养物的适当均化。μBC 配备了用于 pH 值、溶解氧、光密度和葡萄糖浓度的小型化传感器,可在培养过程中实时在线监测这些过程变量。这里解决的挑战是在有限的可用空间内集成传感器。MBR 被证明是一种适合生物系统培养的筛选平台。进行了酿酒酵母的分批培养,以观察过程变量随时间的变化,并展示 MBR 中所有在线传感器的稳健性和可操作性。

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