Controlled shear filtration: A novel technique for animal cell separation.
A novel rotary microfiltration technique specifically suited for the separation of animal cells has been developed. The concept allows the independent adjustment of wall shear stress, transmembrane pressure, and residence time, allowing straightforward optimization of the microfiltration process. By using a smooth, conically shaped rotor, it is possible to establish a controlled shear field in which animal cells experience a significant hydrodynamic lift away from the membrane surface. It is shown in preliminary experiments that shear-induced cell-rupture speeds up membrane clogging and that cell debris poses the most significant problem in harvesting of BHK cell cultures by dynamic microfiltration. However, a threshold value of shear stability exists which depends on the frequency of passing the shear field, the residence time in the shear field, as well as on cell status. By operating close to this threshold value, cell viability can be maintained while concentration polarization is efficiently minimized. By applying this concept, it is possible to attain flux rates several times higher compared to conventional crossflow filtration. Controlled shear filtration (CSF) can be used for batch harvesting as well as for cell retention in high cell density systems. In batch harvesting of hIL-2 from rBHK cell culture, a constant flux rate of 290 L h-1 m-2 has been adjusted without indication of membrane clogging or fouling.
Gesellschaft für Biotechnologische Forschung mbH, Biochemical Engineering Division, Mascheroder Weg 1, D-38124 Braunschweig, Germany.
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JH
Vogel
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Kroner
D000818:Animals; D002462:Cell Membrane / Q000737:chemistry; D002469:Cell Separation / Q000295:instrumentation / Q000379:methods*; D006224:Cricetinae; D005374:Filtration / Q000295:instrumentation* / Q000379:methods*; D008452:Maximum Allowable Concentration; D013997:Time Factors