Biotechnology Laboratory, University of British Columbia, Vancouver, BC, Canada.
Cytotechnology. 2003 May;42(1):35-45. doi: 10.1023/A:1026192228471.
Consistent perfusion culture production requires reliable cell retention and control of feed rates. An on-line cell probe based on capacitance was used to assay viable biomass concentrations. A constant cell specific perfusion rate controlled medium feed rates with a bioreactor cell concentration of approximately 5 x 10(6) cells mL(-1). Perfusion feeding was automatically adjusted based on the cell concentration signal from the on-line biomass sensor. Cell specific perfusion rates were varied over a range of 0.05 to 0.4 nL cell(-1) day(-1). Pseudo-steady-state bioreactor indices (concentrations, cellular rates and yields) were correlated to cell specific perfusion rates investigated to maximize recombinant protein production from a Chinese hamster ovary cell line. The tissue-type plasminogen activator concentration was maximized ( approximately 40 mg L(-1)) at 0.2 nL cell(-1) day(-1). The volumetric protein productivity ( approximately 60 mg L(-1) day(-1) was maximized above 0.3 nL cell(-1) day(-1). The use of cell specific perfusion rates provided a straightforward basis for controlling, modeling and optimizing perfusion cultures.
持续灌流培养生产需要可靠的细胞保留和控制进料速率。一种基于电容的在线细胞探头用于检测活生物质浓度。通过在线生物量传感器的细胞浓度信号，以大约 5×10(6)个细胞/mL 的生物反应器细胞浓度控制恒定的细胞比灌流速率来控制培养基进料速率。根据细胞浓度信号自动调整细胞比灌流速率。细胞比灌流速率在 0.05 到 0.4 nL 细胞(-1)天(-1)的范围内变化。将假稳态生物反应器指数（浓度、细胞速率和产率）与所研究的细胞比灌流速率相关联，以最大限度地从中国仓鼠卵巢细胞系生产重组蛋白。组织型纤溶酶原激活剂浓度在 0.2 nL 细胞(-1)天(-1)时达到最大值（约 40 mg/L）。在细胞比灌流速率高于 0.3 nL 细胞(-1)天(-1)时，体积蛋白生产率（约 60 mg/L 天(-1)）达到最大值。使用细胞比灌流速率为控制、建模和优化灌流培养提供了一个直接的基础。
