Crossflow microfiltration of animal cells

Laminar shear is the primary mechanism of cell damage, limiting flow rate (and hence flux) in crossflow microfiltration of animal cells. Sensitivity to hydrodynamic and interfacial stress is reduced by the addition of 0.1% Pluronic polyol. A critical average wall shear rate of 3000 s−1 (above which damage occurs) is found for several cell types, including mammalian and insect cells. Hydrodynamic stress also limits the maximum tip speed in a rotary lobe pump to less than 350 cm/s. Turbulent flow in the recirculation loop piping at Reynolds numbers of up to 71,000 does not cause cell damage. Maximum sustainable flux decreases with cell concentration and increases with cell size (in qualitative agreement with the hydrodynamic lift model). A flux of 30 to 75 L/m2 h (depending on cell size) can be sustained during 20‐fold concentration from 2.5 × 106 cells/ml, while maintaining high cell viability.

[1]  ROBERT S. TUTUNJIAN.  Ultrafiltration Processes in Biotechnology , 1983, Annals of the New York Academy of Sciences.

[2]  D. Inlow,et al.  Insect cell culture and baculovirus propagation in protein-free medium , 1989 .

[3]  C. Milstein,et al.  Intracellular immunoglobulin chain synthesis in non-secreting variants of a mouse myeloma: detection of inactive light-chain messenger RNA. , 1974, Journal of molecular biology.

[4]  P. C. Chau,et al.  Serum‐free media in hybridoma culture and monoclonal antibody production , 1988, Biotechnology and bioengineering.

[5]  R. Ian Freshney,et al.  Culture of Animal Cells: A Manual of Basic Technique and Specialized Applications , 2010 .

[6]  Robert S. Cherry,et al.  Hydrodynamic effects on cells in agitated tissue culture reactors , 1986 .

[7]  R. G. Cox,et al.  The lateral migration of a spherical particle in two-dimensional shear flows , 1976, Journal of Fluid Mechanics.

[8]  J. Tramper,et al.  Shear sensitivity of insect cells in suspension , 1986 .

[9]  E. Evans,et al.  Structure and deformation properties of red blood cells: concepts and quantitative methods. , 1989, Methods in enzymology.

[10]  Eugene C. Eckstein,et al.  Self-diffusion of particles in shear flow of a suspension , 1977, Journal of Fluid Mechanics.

[11]  M P Backer,et al.  Large‐scale production of monoclonal antibodies in suspension culture , 1988, Biotechnology and bioengineering.

[12]  D. Inlow,et al.  Large-Scale Insect Cell-Culture for Recombinant Protein Production , 1988, Bio/Technology.

[13]  M S Croughan,et al.  Hydrodynamic effects on animal cells grown in microcarrier cultures , 1987, Biotechnology and bioengineering.

[14]  A red cell deformation model for hemolysis in cross flow membrane plasmapheresis , 1984 .

[15]  Georges Belfort,et al.  Membrane modules: comparison of different configurations using fluid mechanics☆ , 1988 .

[16]  G. Segré,et al.  Radial Particle Displacements in Poiseuille Flow of Suspensions , 1961, Nature.

[17]  Andrew L. Zydney,et al.  A CONCENTRATION POLARIZATION MODEL FOR THE FILTRATE FLUX IN CROSS-FLOW MICROFILTRATION OF PARTICULATE SUSPENSIONS , 1986 .

[18]  M. Jaffrin,et al.  Membrane plasma separation through small-area, hollow-fiber filters. , 1986, Artificial organs.

[19]  J. Larrick,et al.  Human monoclonal antibodies that recognize conserved epitopes in the core-lipid A region of lipopolysaccharides. , 1987, The Journal of clinical investigation.

[20]  P. Greenfield,et al.  A technique for determining the shear sensitivity of mammalian cells in suspension culture , 1987 .