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Potential of cell retention techniques for large-scale high-density perfusion culture of suspended mammalian cells

Authors

  • D. Voisard,

    Corresponding author
    1. Bioprocess Technology Development, Serono Biotech Center, CH-1809 Fenil-sur-Corsier, Switzerland; telephone: +41 21 923 22 53; fax: +41 21 923 20 16
    • Bioprocess Technology Development, Serono Biotech Center, CH-1809 Fenil-sur-Corsier, Switzerland; telephone: +41 21 923 22 53; fax: +41 21 923 20 16
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  • F. Meuwly,

    1. Bioprocess Technology Development, Serono Biotech Center, CH-1809 Fenil-sur-Corsier, Switzerland; telephone: +41 21 923 22 53; fax: +41 21 923 20 16
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  • P.-A. Ruffieux,

    1. Bioprocess Technology Development, Serono Biotech Center, CH-1809 Fenil-sur-Corsier, Switzerland; telephone: +41 21 923 22 53; fax: +41 21 923 20 16
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  • G. Baer,

    1. Bioprocess Technology Development, Serono Biotech Center, CH-1809 Fenil-sur-Corsier, Switzerland; telephone: +41 21 923 22 53; fax: +41 21 923 20 16
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  • A. Kadouri

    1. Bioprocess Technology Development, Serono Biotech Center, CH-1809 Fenil-sur-Corsier, Switzerland; telephone: +41 21 923 22 53; fax: +41 21 923 20 16
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Abstract

This review focuses on cultivation of mammalian cells in a suspended perfusion mode. The major technological limitation in the scaling-up of these systems is the need for robust retention devices to enable perfusion of medium as needed. For this, cell retention techniques available to date are presented, namely, cross-flow filters, hollow fibers, controlled-shear filters, vortex-flow filters, spin-filters, gravity settlers, centrifuges, acoustic settlers, and hydrocyclones. These retention techniques are compared and evaluated for their respective advantages and potential for large-scale utilization in the context of industrial manufacturing processes. This analysis shows certain techniques have a limited range of perfusion rate where they can be implemented (most microfiltration techniques). On the other hand, techniques were identified that have shown high perfusion capacity (centrifuges and spin-filters), or have a good potential for scale-up (acoustic settlers and inclined settlers). The literature clearly shows that reasonable solutions exist to develop large-scale perfusion processes. © 2003 Wiley Periodicals, Inc. Biotechol Bioeng 82: 751–765, 2003.

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