What is it about?

Production of secreted proteins from recombinant mammalian cells can be maximized easily by culturing these cells in high cell density perfusion bioreactors, using cell retention devices such as membrane filters or inclined settlers. With a novel, more efficiently scalable design of inclined settlers into compact cell settlers, we have now demonstrated the increased power of these cell retention devices by culturing the smaller (and more challenging) yeast Pichia pastoris cells in high cell density perfusion bioreactors. Further, we demonstrate that there is no protein sieving in these membrane-free cell retention devices, as is common with membrane filters.

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Why is it important?

As secreted protein overexpression is increasingly achieved in yeast Pichia and Saccharomyces cells, it is now feasible to maximize their production in high cell density continuous perfusion bioreactors using the novel compact cell settlers. Even for the mammalian cells secreted overexpressed therapeutic glycoproteins, the novel compact design reduces the size and footprint of inclined settlers required for selectively recycling live and productive cells back into the bioreactor, while continuously removing the smaller dead cells and cell debris, to maintain high quality (by design) of the secreted products in the harvest stream.

Perspectives

Unlike our previous publications on inclined settlers, wherein we published the algebraic equations necessary for scaling them up for commercial production of therapeutic biologics by others, we are now manufacturing these more efficiently scalable compact cell settlers as larger scale settlers in stainless steel and as single use disposable plastic devices and plan to commercialize them for industrial scale production of secreted proteins.

Dhinakar Kompala
Sudhin Biopharma Co.

Read the Original

This page is a summary of: Compact Cell Settlers for Perfusion Cultures of Microbial (and Mammalian) Cells, Biotechnology Progress, July 2017, Wiley,
DOI: 10.1002/btpr.2533.
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