生物反应器
吞吐量
工艺工程
灌注
生物医学工程
生物系统
稳态(化学)
计算机科学
工艺优化
过程开发
足迹
化学
材料科学
色谱法
生化工程
化学工程
生物
工程类
医学
无线
电信
古生物学
有机化学
物理化学
心脏病学
作者
Marie Dorn,Kerensa Klottrup‐Rees,Ken Lee,Martina Micheletti
摘要
The promise of continuous processing to increase yields and improve product quality of biopharmaceuticals while decreasing the manufacturing footprint is transformative. Developing and optimizing perfusion operations requires screening various parameters, which is expensive and time-consuming when using benchtop bioreactors. Scale-down models (SDMs) are the most feasible option for high-throughput data generation and condition screening. However, new SDMs mimicking perfusion are required, enabling experiments to be run in parallel. In this study, a method using microwell plates (MWP) operating in semi-perfusion mode with an implemented cell bleed step is presented. A CHO cell line was cultivated in a 24-well MWP (Vw = 1.2 mL) and grown at four high cell density (HCD) setpoints. Quasi steady-state condition was obtained by manually performing cell bleeds followed by a total medium exchange after centrifugation. Further, two HCD setpoints were scaled up (VW = 30 mL), comparing a squared six-well deepwell plate (DWP) to shake flasks (SF). This evaluation showed comparable results between systems (DWP vs. SF) and scales (MWP vs. DWP + SF). The results show that the well-plate-based methods are suitable to perform HCD and quasi steady-state cultivations providing a robust solution to industrially relevant challenges such as cell clone and media selection.
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