Get access

Optimization of an Acoustic Cell Filter with a Novel Air-Backflush System

Authors

  • Volker M. Gorenflo,

    Corresponding author
    1. Biotechnology Laboratory, University of British Columbia, 237–6174 University Boulevard, Vancouver, British Columbia, Canada V6T 1Z3
    • Biotechnology Laboratory, University of British Columbia, 237–6174 University Boulevard, Vancouver, British Columbia, Canada V6T 1Z3. Phone: (604) 822–6974. Fax: (604) 822–2114
    Search for more papers by this author
  • Sumitra Angepat,

    1. Biotechnology Laboratory, University of British Columbia, 237–6174 University Boulevard, Vancouver, British Columbia, Canada V6T 1Z3
    2. Department of Chemical and Biological Engineering, University of British Columbia, 2216 Main Mall, Vancouver, British Columbia, Canada V6T 1Z4
    Search for more papers by this author
  • Bruce D. Bowen,

    1. Department of Chemical and Biological Engineering, University of British Columbia, 2216 Main Mall, Vancouver, British Columbia, Canada V6T 1Z4
    Search for more papers by this author
  • James M. Piret

    1. Biotechnology Laboratory, University of British Columbia, 237–6174 University Boulevard, Vancouver, British Columbia, Canada V6T 1Z3
    2. Department of Chemical and Biological Engineering, University of British Columbia, 2216 Main Mall, Vancouver, British Columbia, Canada V6T 1Z4
    Search for more papers by this author

Abstract

Increasing worldwide demand for mammalian cell production capacity will likely be partially satisfied by a greater use of higher volumetric productivity perfusion processes. An important additional component of any perfusion system is the cell retention device that can be based on filtration, sedimentation, and/or acoustic technologies. A common concern with these systems is that pumping and transient exposure to suboptimal medium conditions may damage the cells or influence the product quality. A novel air-backflush mode of operating an acoustic cell separator was developed in which an injection of bioreactor air downstream of the separator periodically returned the captured cells to the reactor, allowing separation to resume within 20 s. This mode of operation eliminated the need to pump the cells and allows the selection of a residence time in the separator depending on the sensitivity of the cell line. The air-backflush mode of operating a 10L acoustic separator was systematically tested at 107 cells/mL to define reliable ranges of operation. Consistent separation performance was obtained for wide ranges of cooling airflow rates from 0 to 15 L/min and for backflush frequencies between 10 and 40 h−1. The separator performance was optimized at a perfusion rate of 10 L/day to obtain a maximum separation efficiency of 92 ± 0.3%. This was achieved by increasing the power setting to 8 W and using duty cycle stop and run times of 4.5 and 45 s, respectively. Acoustic cell separation with air backflush was successfully applied over a 110 day CHO cell perfusion culture at 107 cells/mL and 95% viability.

Ancillary