Continuous Online Protein Quality Monitoring during Perfusion Culture Production Using an Integrated Micro/Nanofluidic System.
Continuous Online Protein Quality Monitoring during Perfusion Culture Production Using an Integrated Micro/Nanofluidic System.
复制标题
使用集成微/纳流体系统在灌注培养生产过程中连续在线监测蛋白质质量。
DOI：
10.1021/acs.analchem.9b05835
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发表时间：
2020
影响因子：
7.4
通讯作者：
Han,Jongyoon
中科院分区：
文献类型：
--
作者：
Kwon,Taehong;Ko,SungHee;Hamel,Jean-FrançoisP;Han,Jongyoon
我们展示了一种新的微/纳流体系统，用于在高细胞浓度CHO细胞灌注培养期间直接从培养上清液连续和自动监测蛋白质产物的大小和数量。微流控装置能够使无堵塞的细胞保留用于连续产生含有单克隆抗体（IgG 1）的培养上清液的实验室规模（350 mL）灌注生物反应器。纳米流体装置直接监测培养上清液中的蛋白质大小和数量。这种纳米流体蛋白质分析的连续流动和全自动操作降低了设计复杂性，并提供了比离线和批量模式传统分析更详细的蛋白质产品信息。此外，纳米流体装置的化学和机械鲁棒性使得能够连续监测数天至一周。这种连续和在线的蛋白质质量监测可以部署在生物制造的不同步骤和规模，以提高产品质量和制造效率。
We demonstrate a new micro/nanofluidic system for continuous and automatic monitoring of protein product size and quantity directly from the culture supernatant during a high-cell-concentration CHO cell perfusion culture. A microfluidic device enables clog-free cell retention for a bench-scale (350 mL) perfusion bioreactor that continuously produces the culture supernatant containing monoclonal antibodies (IgG1). A nanofluidic device directly monitors the protein size and quantity in the culture supernatant. The continuous-flow and fully automated operation of this nanofluidic protein analytics reduces design complexity and offers more detailed information on protein products than offline and batch-mode conventional analytics. Moreover, chemical and mechanical robustness of the nanofluidic device enables continuous monitoring for several days to a week. This continuous and online protein quality monitoring could be deployed at different steps and scales of biomanufacturing to improve product quality and manufacturing efficiency.