Heterogeneity Studies of Mammalian Cells for Bioproduction: From Tools to Application

Quantified process parameters in pharmaceutical production and in mammalian cell fermentation process development only represent culture average values and do not portray the heterogeneity and the individual behaviour of single cells. The first studies using well-established techniques like flow cytometry or novel lab-on-a-chip systems, such as droplet microfluidics or microfluidic single-cell cultivation, indicate a substantial level of cell-to-cell heterogeneity with important implications for biotechnological processes. Understanding the reasons, degree, and dynamics of cell-to-cell heterogeneity within bioprocesses will pave the way to developing more stable cell lines and more reproducible bioprocesses. We review single-cell cultivation and analytical methods, including their application in bioprocess technology.