Banik G G, Heath C A
Thayer School of Engineering, Dartmouth College, Hanover, New Hampshire 03755, USA.
Biotechnol Prog. 1995 Sep-Oct;11(5):584-8. doi: 10.1021/bp00035a013.
Suspended mammalian cells can be cultivated in a variety of operational modes (pure chemostat, total cell retention, or partial cell retention) in a homogeneous perfusion bioreactor by varying the cell bleed rate. Hybridomas were grown in the reactor at a perfusion rate of 2.0 day-1 for over 10 weeks at different specific growth rates and viable cell densities achieved by varying the extent of cell retention. Cell metabolism in the reactor was found to vary with the extent of cell retention, which determined both cell density and specific growth rate. With partial cell retention, the nutrient consumption and metabolite production rates decreased with both increasing growth rate and increasing cell density. The specific and volumetric antibody production rates, however, increased dramatically with cell density (and to a lesser extent with decreasing growth rate). The specific MAb production rate was lower with total cell retention than with partial retention at the same growth rate. Since the reactor can be operated over a range of perfusion rates and extents of cell retention, the system can be used to culture cell lines with widely different productivity patterns.
通过改变细胞排放速率，悬浮的哺乳动物细胞可以在均质灌注生物反应器中以多种操作模式（纯恒化器、全细胞保留或部分细胞保留）进行培养。杂交瘤细胞在反应器中以2.0天-1的灌注速率培养超过10周，通过改变细胞保留程度实现不同的比生长速率和活细胞密度。发现反应器中的细胞代谢随细胞保留程度而变化，细胞保留程度决定了细胞密度和比生长速率。在部分细胞保留的情况下，营养物质消耗和代谢产物生成速率随生长速率和细胞密度的增加而降低。然而，比抗体生成速率和体积抗体生成速率随细胞密度显著增加（在较小程度上随生长速率降低而增加）。在相同生长速率下，全细胞保留时的特异性单克隆抗体生成速率低于部分细胞保留时的速率。由于该反应器可以在一系列灌注速率和细胞保留程度下运行，该系统可用于培养具有广泛不同生产力模式的细胞系。
