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

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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.