TY - JOUR T1 - Development of a mathematical model for animal cell culture without pH control and its application for evaluation of clone screening outcomes in shake flask culture JF - Journal of Chemical Technology and Biotechnology Y1 - 2015 A1 - Gadgil, Mugdha KW - clone screening KW - clone selection KW - culture duration KW - high throughput screening KW - lactate consumption KW - mathematical model with pH effects KW - pH control for animal cell culture AB -

BACKGROUNDCurrently used mathematical models for animal cell growth and metabolism cannot simulate changing culture pH and its effect on metabolism, and hence cannot accurately model cultures lacking pH control. Animal cell cultures are however widely cultured at a small scale without pH control, e.g. for clone screening during cell line development. A mathematical model for animal cell growth without pH control is developed and applied to design optimal conditions for clone screening without pH control. RESULTSThe mathematical model successfully simulates published data for suspension CHO culture in shake flasks. It is further used to simulate clonal heterogeneity and predict relative clone performance in different culture conditions. Predictions of correlation coefficients between clone titers in batch and fed batch screening conditions and pH controlled fed batch agree with published values. Fed batch mode is predicted to give better screening outcomes than batch, but only for clones able to consume lactate. Simulations reveal that culture duration of the screening assay has a large effect on the screening outcome and optimal durations differ based on the ability or inability of clones to consume lactate. CONCLUSIONThis study presents a tool for optimal design of screening assay for clone selection without pH control. (c) 2014 Society of Chemical Industry

PB - WILEY-BLACKWELL CY - 111 RIVER ST, HOBOKEN 07030-5774, NJ USA VL - 90 IS - 1 U3 -

Foreign

U4 - 2.738 ER -