High density culture of mammalian cells with dynamic perfusion based on on-line oxygen uptake rate measurements

Yun Seung Kyung, Madhusudan V. Peshwa, David M. Gryte, Wei Shou Hu

Research output: Contribution to journalArticlepeer-review

57 Scopus citations

Abstract

In a continuous culture with cell retention the perfusion rate must be adjusted dynamically to meet the cellular demand. An automated mechanism of adjusting the perfusion rate based on real-time measurement of the metabolic load of the bioreactor is important in achieving a high cell concentration and maintaining high viability. We employed oxygen uptake rate (OUR) measurement as an on-line metabolic indicator of the physiological state of the cells in the bioreactor and adjusted the perfusion rate accordingly. Using an internal hollow fiber microfiltration system for total cell retention, a cell concentration of almost 108 cells/mL was achieved. Although some aggregates were formed during the cultivation, the viability remained high as examined with confocal microscopy after fluorescent vital staining. The results demonstrate that on-line OUR measurement facilitates automated dynamic perfusion and allows a high cell concentration to be achieved.

Original languageEnglish (US)
Pages (from-to)183-190
Number of pages8
JournalCytotechnology
Volume14
Issue number3
DOIs
StatePublished - Jan 1994

Keywords

  • Cell culture
  • bioreactor
  • high cell density
  • oxygen consumption

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