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微生物反应器中的微传感器:新型毛细管波微生物反应器中的全生物工艺特征描述。

Microsensor in Microbioreactors: Full Bioprocess Characterization in a Novel Capillary-Wave Microbioreactor.

机构信息

Institute of Biochemical Engineering, Technische Universität Braunschweig, 38106 Braunschweig, Germany.

Center of Pharmaceutical Engineering, Technische Universität Braunschweig, 38106 Braunschweig, Germany.

出版信息

Biosensors (Basel). 2022 Jul 11;12(7):512. doi: 10.3390/bios12070512.

Abstract

Microbioreactors (MBRs) with a volume below 1 mL are promising alternatives to established cultivation platforms such as shake flasks, lab-scale bioreactors and microtiter plates. Their main advantages are simple automatization and parallelization and the saving of expensive media components and test substances. These advantages are particularly pronounced in small-scale MBRs with a volume below 10 µL. However, most described small-scale MBRs are lacking in process information from integrated sensors due to limited space and sensor technology. Therefore, a novel capillary-wave microbioreactor (cwMBR) with a volume of only 7 µL has the potential to close this gap, as it combines a small volume with integrated sensors for biomass, pH, dissolved oxygen (DO) and glucose concentration. In the cwMBR, pH and DO are measured by established luminescent optical sensors on the bottom of the cwMBR. The novel glucose sensor is based on a modified oxygen sensor, which measures the oxygen uptake of glucose oxidase (GOx) in the presence of glucose up to a concentration of 15 mM. Furthermore, absorbance measurement allows biomass determination. The optical sensors enabled the characterization of an batch cultivation over 8 h in the cwMBR as proof of concept for further bioprocesses. Hence, the cwMBR with integrated optical sensors has the potential for a wide range of microscale bioprocesses, including cell-based assays, screening applications and process development.

摘要

体积低于 1 毫升的微生物反应器 (MBR) 是替代摇瓶、实验室规模生物反应器和微量滴定板等现有培养平台的有前途的选择。它们的主要优点是简单的自动化和并行化,以及节省昂贵的介质成分和测试物质。这些优点在体积低于 10 µL 的小型 MBR 中尤为明显。然而,由于空间和传感器技术的限制,大多数描述的小型 MBR 缺乏来自集成传感器的过程信息。因此,一种新型的毛细波微生物反应器 (cwMBR) 具有 7 µL 的体积,有潜力弥补这一差距,因为它将小体积与用于生物量、pH 值、溶解氧 (DO) 和葡萄糖浓度的集成传感器结合在一起。在 cwMBR 中,pH 值和 DO 值通过 cwMBR 底部的现有发光光学传感器进行测量。新型葡萄糖传感器基于经过改良的氧传感器,该传感器在存在葡萄糖的情况下测量葡萄糖氧化酶 (GOx) 的耗氧量,最高可达 15 mM 的浓度。此外,吸光度测量允许进行生物量测定。光学传感器使在 cwMBR 中进行 8 小时批培养的表征成为进一步生物工艺的概念验证。因此,具有集成光学传感器的 cwMBR 具有广泛的微尺度生物工艺应用潜力,包括基于细胞的测定、筛选应用和工艺开发。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1ec7/9312480/013689b29414/biosensors-12-00512-g001.jpg

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