Center for Advanced Sensor Technology, Dept. of Chemical and Biochemical Engineering, University of Maryland, Baltimore County, Baltimore, MD 21250, USA.
Biotechnol Prog. 2011 May-Jun;27(3):803-10. doi: 10.1002/btpr.578. Epub 2011 Apr 26.
The bioprocess development cycle is a complex task that requires a complete understanding of the engineering of the process (e.g., mass transfer, mixing, CO(2) removal, process monitoring, and control) and its affect on cell biology and product quality. Despite their widespread use in bioprocess development, spinner flasks generally lack engineering characterization of critical physical parameters such as k(L)a, P/V, or mixing time. In this study, mass transfer characterization of a 250-mL spinner flask using optical patch-based sensors is presented. The results quantitatively show the effect of the impeller type, liquid filling volume, and agitation speed on the volumetric mass transfer coefficient (k(L)a) in a 250-mL spinner flask, and how they can be manipulated to match mass transfer capability at large culture devices. Thus, process understanding in spinner flasks can be improved, and these devices can be seamlessly integrated in a rational scale-up strategy from cell thawing to bench-scale bioreactors (and beyond) in biomanufacturing.
生物工艺开发周期是一项复杂的任务，需要全面了解工艺的工程学（例如传质、混合、CO2 去除、过程监测和控制）及其对细胞生物学和产品质量的影响。尽管在生物工艺开发中广泛使用，但搅拌瓶通常缺乏对关键物理参数（如 k(L)a、P/V 或混合时间）的工程特性描述。本研究使用基于光学补丁的传感器对 250 毫升搅拌瓶的传质特性进行了描述。结果定量显示了搅拌器类型、液体填充体积和搅拌速度对 250 毫升搅拌瓶体积传质系数（k(L)a）的影响，以及如何操纵它们以匹配大容量培养设备的传质能力。因此，可以提高搅拌瓶中的工艺理解，并可以将这些设备无缝集成到从细胞解冻到台式生物反应器（及更高级别）的生物制造中的合理放大策略中。
