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Background Fed-batch cultivation is currently the most prominent process for the production of Biologics using mammalian cell lines such as CHO cells. Performance of fedbatch processes greatly depends on the feeding strategy. One important aspect of feeds is the nutrient concentration, which should be as high as possible. However, for some nutrients, there are solubility and/or stability limitations in aqueous solution. Thus, alternative systems for liquid feed manufacturing were considered. Deep Eutectic Solvents (DES) are salts in liquid state with a melting point under 100°C in the absence of water that form a eutectic system with a lower melting point than either of the individual components. The result is a highly concentrated, water free liquid system. A common component of DES is choline chloride (ChCl), a quaternary ammonium salt. For cell culture applications, ChCl is particularly well suited, since it is already widely used as cell culture medium component. We have experimentally manufactured deep eutectic solvents (DES) for application as cell culture feeds containing tyrosine and cysteine, which are challenging due to their weak solubility and/or stability in aqueous solution.

Manufacturing ultra-concentrated liquid feeds: Transitioning the aqueous solubility barrier of the feed amino acids cysteine and tyrosine