Chemical speciation of trace metals in mammalian cell culture media: looking under the hood to boost cellular performance and product quality

Upstream process development seeks to optimize media formulations to promote robust cell culture conditions and regulate product quality attributes such as glycosylation, aggregation, and charge variants. Transition metal ions Mn, Fe, Cu, and Zn present in cell culture media have a significant impact on cell growth, metabolism and product quality. These metals and other media components can have different chemical associations or speciation in media that are poorly characterized but may significantly impact their properties and effect on cellular performance. Computer-based equilibrium models are a good starting point for exploring metal speciation, bioavailability and conditions where precipitation may occur. However, some equilibrium constants, especially for newly introduced medium components, have not been experimentally determined. Owing to concurrent physical and biological processes, speciation may also be controlled by reaction kinetics rather than by equilibrium. These factors highlight the importance of analytically interrogating medium speciation to gain insights into the complex interconnections between media components and bioprocess performance.

Automated summary

Upstream process development focuses on optimizing media formulations to enhance cell culture conditions and regulate product quality attributes. Transition metal ions in cell culture media, such as Mn, Fe, Cu, and Zn, have significant impacts on cell growth, metabolism, and product quality, but their associations and effects are not well characterized. Equilibrium models can be used to explore metal speciation, but experimental determination of equilibrium constants and consideration of reaction kinetics are also necessary to fully understand the complex interactions between media components and bioprocess performance.