Ammonia adsorption by L-type zeolite and Prussian blue from aqueous and culture solutions

Abstract Modern regenerative medicine and pharmaceutical manufacturing require a large-scale culture of cells. Consequently, cells must be suspension-cultured at high densities, which is challenging because more metabolites, especially ammonia, are produced that inhibit cell proliferation. To address this problem, we tested four zeolites (L-type zeolite, ferrierite, mordenite, and Y-type zeolite) and Prussian blue for their ability to adsorb NH4+ (the predominant form of ammonia in a culture-solution pH) from an aqueous solution and a culture solution. The L-type zeolite and Prussian blue effectively adsorbed NH4+ from aqueous solutions, while the other absorbents were ineffective. Notably, neither adsorbent removed glucose, a representative nutrient, from the aqueous solution. Kinetics and equilibrium studies revealed that both adsorbents (L-type zeolite and Prussian blue) obey pseudo-second-order kinetics and are well fitted by the Langmuir isotherm model. The L-type zeolite also exhibited a high NH4+-adsorption in the culture solution. Further, while the L-type zeolite exhibited minimal cytotoxicity, Prussian blue was cytotoxic. Using the L-type zeolite for adsorption is simple and cost-effective, thus making it a suitable NH4+ adsorbent for culture solutions. Furthermore, reusing an expensive culture solution on a large scale can effectively lower costs of producing cell cultures intended for pharmaceutical manufacturing and regenerative medicine purposes. Thus, it is expected that this method will be used to regenerate culture solutions on a large-scale.