Scale-up issues for commercial depth filters in bioprocessing

Negin Nejatishahidein, Minyoung Kim, Seon Y. Jung, Ehsan E. Borujeni, Lara Fernandez-Cerezo, David J. Roush, Ali Borhan, Andrew L. Zydney

Research output: Contribution to journalArticlepeer-review


Significant increases in cell density and product titer have led to renewed interest in the application of depth filtration for initial clarification of cell culture fluid in antibody production. The performance of these depth filters will depend on the local pressure and velocity distribution within the filter capsule, but these are very difficult to probe experimentally, leading to challenges in both process design and scale-up. We have used a combination of carefully designed experimental studies and computational fluid dynamics (CFD) to examine these issues in both lab-scale (SupracapTM 50) and pilot-scale (StaxTM) depth filter modules, both employing dual-layer lenticular PDH4 media containing diatomaceous earth. The SupracapTM 50 showed a more rapid increase in transmembrane pressure and a more rapid DNA breakthrough during filtration of a Chinese Hamster Ovary cell culture fluid. These results were explained using CFD calculations which showed very different flow distributions within the modules. CFD predictions were further validated using measurements of the residence time distribution and dye binding in both the lab-scale and pilot-plant modules. These results provide important insights into the factors controlling the performance and scale-up of these commercially important depth filters as well as a framework that can be broadly applied to develop more effective depth filters and depth filtration processes.

Original languageEnglish (US)
Pages (from-to)1105-1114
Number of pages10
JournalBiotechnology and bioengineering
Issue number4
StatePublished - Apr 2022

All Science Journal Classification (ASJC) codes

  • Biotechnology
  • Bioengineering
  • Applied Microbiology and Biotechnology


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