@article { ISI:000312157100027,
	title = {In situ pH maintenance for mammalian cell cultures in shake flasks and tissue culture flasks},
	journal = {Biotechnology Progress},
	volume = {28},
	number = {6},
	year = {2012},
	month = {NOV},
	pages = {1605-1610},
	publisher = {WILEY-BLACKWELL},
	address = {111 RIVER ST, HOBOKEN 07030-5774, NJ USA},
	abstract = {<p>pH in animal cell cultures decreases due to production of metabolites like lactate. pH control via measurement and base addition is not easily possible in small-scale culture formats like tissue-culture flasks and shake flasks. A hydrogel-based system is reported for in situ pH maintenance without pH measurement in such formats, and is demonstrated to maintain pH between 6.8 and 7.2 for a suspension CHO cell line in CD CHO medium and between 7.3 and 7.5 for adherent A549 cells in DMEM:F12 containing 10\% FBS. This system for pH maintenance, along with our previous report of hydrogels for controlled nutrient delivery in shake flasks can allow shake flasks to better mimic bioreactor-based fed batch operation for initial screening during cell line and process development for recombinant protein production in mammalian cells. (C) 2012 American Institute of Chemical Engineers Biotechnol. Prog., 2012</p>},
	keywords = {high throughput screening, pH control for cell culture, pH control in shake flask, pH control in tissue culture flasks, small scale platforms for cell culture},
	issn = {8756-7938},
	doi = {10.1002/btpr.1614},
	author = {Pradhan, Ketaki and Pant, Tejal and Gadgil, Mugdha}
}
@article { ISI:000345845400022,
	title = {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},
	journal = {Journal of Chemical Technology and Biotechnology},
	volume = {90},
	number = {1},
	year = {2015},
	month = {JAN},
	pages = {166-175},
	publisher = {WILEY-BLACKWELL},
	address = {111 RIVER ST, HOBOKEN 07030-5774, NJ USA},
	abstract = {<p>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</p>},
	keywords = {clone screening, clone selection, culture duration, high throughput screening, lactate consumption, mathematical model with pH effects, pH control for animal cell culture},
	issn = {0268-2575},
	doi = {10.1002/jctb.4302},
	author = {Gadgil, Mugdha}
}
