Potential of cell retention techniques for large-scale high-density perfusion culture of suspended mammalian cells.
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.
Voisard
D
D
Bioprocess Technology Development, Serono Biotech Center, CH-1809 Fenil-sur-Corsier, Switzerland. damien.voisard@serano.com
Meuwly
F
F
Ruffieux
P-A
PA
Baer
G
G
Kadouri
A
A
D000818:Animals; D019149:Bioreactors; D018929:Cell Culture Techniques / Q000295:instrumentation* / Q000379:methods*; D002469:Cell Separation / Q000295:instrumentation* / Q000379:methods*; D002478:Cells, Cultured; D002498:Centrifugation / Q000295:instrumentation / Q000379:methods; D004867:Equipment Design; D005434:Flow Cytometry / Q000295:instrumentation / Q000379:methods; D006801:Humans; D008322:Mammals; D010477:Perfusion / Q000295:instrumentation* / Q000379:methods*; D014462:Ultrafiltration / Q000295:instrumentation / Q000379:methods