Center for Advanced Sensor Technology, Department of Chemical, Biochemical and Environmental Engineering, University of Maryland, Baltimore County, 1000 Hilltop Circle, Baltimore, MD 21250, USA.
Biotechnol Bioeng. 2012 Nov;109(11):2790-7. doi: 10.1002/bit.24541. Epub 2012 May 17.
In this study, we perform mass transfer characterization (k(L) a) on a novel mechanically driven/stirred Process Scouting Device, PSD, (SuperSpinner D 1000®, SSD) and demonstrate that this novel device can be viewed as disposable bioreactor. Using patch-based optical sensors, we were able to monitor critical cell culture environmental conditions such as dissolved oxygen (DO) and pH in SSD for comparison to a 1 L standard spinner (SS) flask. We also coupled these mass transfer studies with mixing time studies where we observed relative high mixing times (5.2 min) that are typically observed in production scale bioreactors. Decreasing the mixing time 3.5-fold resulted in 30% increase in k(L) a (from 2.3 to 3.0 h(-1) ) and minimum DO level increased from 0% to 20% for our model hybridoma cell line. Finally, maximum viable cell density and protein titer stayed within ±20% of historical data, from our standard 5 L stirred bioreactor (Biostat®) operated under active DO control.
在这项研究中，我们对一种新型机械驱动/搅拌过程探索设备（PSD，SuperSpinner D1000 ® ，SSD）进行传质特性（k（L）a）测试，并证明该新型设备可以看作是一次性生物反应器。我们使用基于补丁的光学传感器，能够监测 SSD 中关键的细胞培养环境条件，如溶解氧（DO）和 pH，以便与 1L 标准搅拌瓶（SS）进行比较。我们还将这些传质研究与混合时间研究相结合，在混合时间研究中，我们观察到相对较高的混合时间（5.2min），这通常在生产规模的生物反应器中观察到。将混合时间缩短 3.5 倍，使 k（L）a 增加了 30%（从 2.3 到 3.0h（-1）），我们的模型杂交瘤细胞系的最低 DO 水平从 0%增加到 20%。最后，最大活细胞密度和蛋白滴度保持在±20%范围内，与我们在主动 DO 控制下运行的标准 5L 搅拌生物反应器（Biostat ® ）的历史数据相符。
