生物反应器
过程开发
实验室烧瓶
工艺工程
再现性
吞吐量
生物过程
可扩展性
色谱法
生物医学工程
计算机科学
材料科学
化学
化学工程
工程类
电信
数据库
物理化学
有机化学
无线
作者
Ashraf Amanullah,José M. Otero,Mark Mikola,Amy Hsu,Jinyou Zhang,John G. Auniņš,H. Brett Schreyer,James Hope,A. Peter Russo
摘要
Abstract With increasing timeline pressures to get therapeutic and vaccine candidates into the clinic, resource intensive approaches such as the use of shake flasks and bench‐top bioreactors may limit the design space for experimentation to yield highly productive processes. The need to conduct large numbers of experiments has resulted in the use of miniaturized high‐throughput (HT) technology for process development. One such high‐throughput system is the SimCell™ platform, a robotically driven, cell culture bioreactor system developed by BioProcessors Corp. This study describes the use of the SimCell™ micro‐bioreactor technology for fed‐batch cultivation of a GS‐CHO transfectant expressing a model IgG4 monoclonal antibody. Cultivations were conducted in gas‐permeable chambers based on a micro‐fluidic design, with six micro‐bioreactors (MBs) per micro‐bioreactor array (MBA). Online, non‐invasive measurement of total cell density, pH and dissolved oxygen (DO) was performed. One hundred fourteen parallel MBs (19 MBAs) were employed to examine process reproducibility and scalability at shake flask, 3‐ and 100‐L bioreactor scales. The results of the study demonstrate that the SimCell™ platform operated under fed‐batch conditions could support viable cell concentrations up to least 12 × 10 6 cells/mL. In addition, both intra‐MB (MB to MB) as well as intra‐MBA (MBA to MBA) culture performance was found to be highly reproducible. The intra‐MB and ‐MBA variability was calculated for each measurement as the coefficient of variation defined as CV (%) = (standard deviation/mean) × 100. The % CV values for most intra‐MB and intra‐MBA measurements were generally under 10% and the intra‐MBA values were slightly lower than those for intra‐MB. Cell growth, process parameters, metabolic and protein titer profiles were also compared to those from shake flask, bench‐top, and pilot scale bioreactor cultivations and found to be within ±20% of the historical averages. Biotechnol. Bioeng. 2010; 106: 57–67. © 2010 Wiley Periodicals, Inc.
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