Connected perfusion for continuous flow stirred tank reactor cell culture systems

Methods of protein production in linked culture and production bioreactor systems are provided. Such methods include a culture bioreactor (N-1 bioreactor) connected to a production bioreactor (N bioreactor). More specifically, the method comprises (a) culturing a cell having a gene encoding a protein of interest in a continuous perfusion culture bioreactor (N-1 bioreactor); inoculating a continuous stirred tank reactor (CSTR) production bioreactor (N bioreactor) with the cells obtained from step (a); and culturing the cells in the CSTR production bioreactor under conditions that allow the production of the protein of interest. 提供了在连接的培养和生产生物反应器系统中的蛋白质生产的方法。此类方法包括与生产生物反应器(N生物反应器)连接的培养生物反应器(N-1生物反应器)。更具体地，该方法包括(a)在连续灌注培养生物反应器(N-1生物反应器)中，培养具有编码目的蛋白质的基因的细胞；用从步骤(a)获得的细胞接种连续搅拌釜反应器(CSTR)生产生物反应器(N生物反应器)；并且在允许目的蛋白质产生的条件下，在CSTR生产生物反应器中培养细胞。