Development of a novel, high‐throughput screening tool for efficient perfusion‐based cell culture process development
Development of a novel, high‐throughput screening tool for efficient perfusion‐based cell culture process development
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开发一种新型高通量筛选工具，用于高效的基于灌注的细胞培养工艺开发
DOI：
10.1002/btpr.2811
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发表时间：
2019
影响因子：
2.9
通讯作者：
Hang Yuan
中科院分区：
文献类型：
--
作者：
T. Gagliardi;Rahul Chelikani;Yang Yang;Gioia Tuozzolo;Hang Yuan
灌注技术已经成功地用于生物治疗剂的商业生产，特别是不稳定的重组蛋白，超过十年。然而，普遍缺乏专门用于基于灌注的细胞培养过程的高通量细胞培养工具。在这里，我们开发了一种高通量细胞保留操作，用于ambr® 15生物反应器系统。在24和48反应器配置中进行实验，以比较灌注模拟模型、培养基开发和克隆筛选。采用离线离心进行细胞保留和用MATLAB计算软件开发的可变体积模型，所建立的筛选模型已证明细胞培养性能、生产率和产品质量与实验室规模生物反应器相当。自动化、一次性、高通量灌注模拟物是一种强大的工具，使我们能够快速高效地开发基于灌注的细胞培养工艺。
Perfusion technology has been successfully used for the commercial production of biotherapeutics, in particular unstable recombinant proteins, for more than a decade. However, there has been a general lack of high‐throughput cell culture tools specifically for perfusion‐based cell culture processes. Here, we have developed a high‐throughput cell retention operation for use with the ambr® 15 bioreactor system. Experiments were run in both 24 and 48 reactor configurations for comparing perfusion mimic models, media development, and clone screening. Employing offline centrifugation for cell retention and a variable volume model developed with MATLAB computational software, the established screening model has demonstrated cell culture performance, productivity, and product quality were comparable to bench scale bioreactors. The automated, single use, high‐throughput perfusion mimic is a powerful tool that enables us to have rapid and efficient process development of perfusion‐based cell culture processes.