Microcarriers

Microbond NP Microbond NP2 Microbubble flotation Microbubbles Microcarriers Microcline [12251-43-3] Micrococcin P... 

SC = suspension culture SM = stirred microcarrier. FMD = foot-and-mouth disease. 

Fig. 2. Schematic of a process for microcarrier perfusion culture using a spin filter device.

S. B. Karkare, S. T. Cole, R. Sachdev, V. Satyagal, and J. C. Eieschko, "Production of Rat Stem Cell Eactor from BRI Cells by Microcarrier Perfusion Cultuie," paper presented at the LngineeringFoundation Conference on Biochemical Lngineering FT/, Santa Baibaia, Calif., 199T,Mnnals of New YorkMcademj of Sciences, in press. 

Coating for ti ssue culture flasks, microcarriers, cell culture containers, etc. 

Scale-up to the industrial scale is only achievable and economical reasonable in stirred or airlift systems. To achieve high cell densities optimal nutrient supply is necessary. Therefore transport limitations have to be avoided by good mixing of cells (microcarrier) and medium. This movement caused by stirrer or aeration leads to mechanical forces evoking severe cell damage or cell death [3,4]. 

The main reasons for the damage to cells in a reactor are the apparent shear forces and the collision of microcarriers with themselves and with turbulent eddies. In the literature studies are mainly focused on suspension cells and there again on hybridoma cells. The work reported in the hterature can be divided into two fields studies dealing with the influence of various stirrer speeds on cell viability and those investigating the influence of defined shear forces on cells with a viscosimeter. 

Concerning adherent cells there are few studies in the literature. Some of them deal with the influence of stirrer speed on microcarrier cultures. Most studies using defined forces are from medical research. These studies, as well as those with production cells, use different types of exposure systems based on the parallel plate theory. They investigate the influence of stress on cell morphology and viability which is most important for arteriosclerosis research. 

Two different concepts are described in the literature for investigating the influence of shear stress on adherent cells Microcarrier cultures in stirred reactors and defined stress levels in flow chambers. 

Cherry and Papoutsakis [33] refer to the exposure to the collision between microcarriers and influence of turbulent eddies. Three different flow regions were defined bulk turbulent flow, bulk laminar flow and boundary-layer flow. They postulate the primary mechanism coming from direct interactions between microcarriers and turbulent eddies. Microcarriers are small beads of several hundred micrometers diameter. Eddies of the size of the microcarrier or smaller may cause high shear stresses on the cells. The size of the smallest eddies can be estimated by the Kolmogorov length scale L, as given by... 

The ratio of the Komolgorov length scale and the diameter of the microcarriers correlate with cell damage. Several researchers show that if the ratio falls below one, cell damage increases significantly [34-38]. The size of the smallest... 

ORDINARY DIFFERENTIAL EQUATION MODELS 17.3.1 Contact Inhibition in Microcarrier Cultures of MRC-5 Cells... 

Contact inhibition is a characteristic of the growth of anchorage dependent cells grown on microcarriers as a monolayer. Hawboldt et al. (1994) reported data on MRC5 cells grown on Cytodex II microcarriers and they are reproduced here in Table 17.13. 

Growth inhibition on microcarriers cultures can be best quantified by cellular automata (Hawboldt et al., 1994 Zygourakis et al., 1991) but simpler models have also been proposed. For example, Frame and Hu (1988) proposed the following model... 

Table 17.13 Growth of MRC5 Cells Cell Density versus Time for MRC5 Cells Grown on Cytodex I Microcarriers in 250 mL Spinner Flasks Inoculated at 2.26 and 4.76 cells/bead...

Figure 17.14 Growth of MRC5 Cells Measurements and model calculated values of cel density versus time for MRC5 celts grown on Cv-todex U microcarriers. Inoculation level was 2.26 cells- bead...

Vero Cells Grown on Microcarriers (Contact Inhibition)... 

Forestell, S.P., N. Kalogerakis, L.A. Behie and D.F. Gerson, "Development of the Optimal Inoculation Conditions for Microcarrier Cultures", Biotechnol. Bioeng., 39.305-313(1992). 

Kalogerakis, N. and L.A. Behie, "Oxygenation Capabilities of New Basket-Type Bioreactors for Microcarrier Cultures of Anchorage Dependent Cells", Bioprocess Eng., 17, 151-156(1997). 

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