Biomedical Engineering Reference
In-Depth Information
Figure 6.8. Effect of TMP on % transmission for r-hGH. Initial concentration 0.83mg/mL on
5 kDa membrane.
pressure/membrane controlled region and delaying the onset of the gel layer controlled
region to a higher TMP. Cross-flow turbulence can be used to characterize the TFF
system and can be expressed in terms of cross-flow rate, shear rate, or Reynolds number.
Assuming that product retention is acceptable, the optimal operating point is in the
transition region just prior to the gel layer controlled region. The transition point provides
the optimal balance between flux performance and external pressure. The plot in Fig. 6.7
can be used to determine the transition region and the optimal TMP that maximizes
permeate flux.
Higher cross-flow also results in greater product shear and heat generation and
requires large pumps and piping. A suitable cross-flow flux is selected to give the desired
permeate flux while balancing these other effects. To enable comparison with other
membrane configurations and to aid in scale-up, the cross-flow rate is specified in terms
of the cross-flow flux.
In addition, since TMP affects the gel layer, it is in effect a dynamic membrane. As
TMP increases, the gel layer restricts solute transmission increasing the rejection
coefficient. While this has a beneficial effect for product recovery as shown in Fig. 6.8,
the retention of unwanted (contaminant) species also increases, which could result in
longer diafiltration cycles to achieve the needed purity. Retention should again be
assessed and the operating TMP adjusted as necessary to achieve the desired product
retention and contaminant clearance.
Temperature influences fluid viscosity and density and solute diffusivity. As a result,
increasing the operating temperature increases permeate flux. However, in biotechnol-
ogy applications, temperature generally has detrimental effects on the product. It is thus
important to assess the effects of temperature on the product and specify the highest
possible temperature within product and membrane stability constraints.
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