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Ultrafiltration of Protein Solutions

Ultrafiltration uses semi-permeable membranes to separate solution components based on selective molecular weight and structure. In ultrafiltration, the solution is contacted with the membrane under an applied pressure (Figure 1). The applied pressure forces the solvent and the smaller molecules through the membrane. The membrane retains larger molecules. The solution passed through the membrane is the permeate. The solution containing the retained molecules is the retentate (Mulder, 1991).

Figure 2 illustrates the basic structure of a spiral-wound membrane module. A permeate spacer is placed between two membranes. The two membranes and permeate spacer are glued together along three edges to form what is called a leaf. The unglued edge is connected to a perforated central collection tube. The membrane leaf along with a mesh feed spacer is spirally wound around the central collection tube. To make the leaf length shorter, several membrane leaves are wound simultaneously around the central tube. Multi-leaf designs are used to minimize the pressure drop experienced by the permeate fluid (Matsuura, 1994). The wound module is placed inside a tubular pressure vessel. Figure 3 illustrates a multi-leaf, spiral-wound module and the pressure vessel in which it is placed.

Figures 4 and 5 illustrate the fluid flow of the spiral-wound membrane module. The feed flows parallel to the central collection tube along the mesh feed spacer (Matsuura, 1994). The feed spacer acts as a turbulent generator to reduce concentration polarization. As the feed makes its way down the module, it flows across (normal to) the membrane surface (Matsuura, 1994). The crossflow of the solution to the membrane surface facilitates diffusion of the solute from the membrane surface back to the bulk flow (Long, 1999). Crossflow counteracts concentration polarization. A portion of the feed permeates the membrane. The permeate fluid flows along the permeate spacer. The direction of flow of the permeate is spiral and roughly perpendicular to the feed flow direction. The permeate is collected in the central tube.

Fouling refers to any phenomena that result in reduced transmembrane flux over time. Fouling is primarily caused by concentration polarization. Concentration polarization is the accumulation of molecules at the membrane surface (Bungay et al., 1986). Three types of fouling are cake layer formation, pore blockage, and internal pore fouling. Cake layer formation and pore blockage refer to fouling on the surface of the membrane. Deposited molecules build up on the membrane surface during cake layer formation (Figures 6) while, rejected molecules block pore openings during pore blockage (Figures 7). Internal pore fouling refers to fouling within the pores of the membrane (Figure 8). Internal pore fouling occurs when molecules are deposited within the pores of the membrane, which reduces the average membrane pore size. All three forms of fouling resist the transport of solvent and small solute molecules through the membrane pores (Mulhern, 1995). Membrane fouling models for pore blocking, cake formation and internal pore plugging are discussed in detail by Jaffrin et al. (1996).

Work by Meireles et al. (1992) shows the effects of fouling on ultrafiltration performance. Table 1 shows the permeabilities of various membranes before and after either adsorbtion or ultrafiltration with a bovine serum albumin solution. Permeabilities were determined before and after either adsorbtion or ultrafiltration to estimate the role of adsorption in fouling. In the adsorbtion process, a clean membrane was brought into contact (non pressurized) with an albumin solution for 15 hrs to reach adsorbtion equilibrium. In absence of denaturation, the permeability of each membrane was reduced by the same amount by fouling and by adsorption regardless of ultrafiltration conditions. When protein molecules are denatured, fouling was found to be more severe. Protein denaturation is sensitive to operating conditions. A possible explanation for the more severe fouling is that the denatured proteins were deposited on the membrane surface. These observations suggest that membrane fouling is primarily due to adsorption of proteins, and possibly to the deposition of denatured molecules on the membrane surface.

Meireles et al. (1992) also measured ultrafiltration fluxes and retention coefficients at the initial stage of the run and at steady state (Table 2). Since the concentrations, velocity, and transmembrane pressure remained constant in these tests, the observed decrease of permeate flux with time was due to membrane fouling. The initial retention coefficient was 100% for the 10 kDa membrane and did not change while the flux decreased. The fluxes and retention coefficients of the 40 kDa and 100 kDa membranes both varied during the run. The initial retention coefficient was 85% for the 40 kDa membrane and 20% for the 100 kDa membrane. At steady state the retention coefficients of the 40 kDa and 100 kDa membranes were 100% and 98% respectively. This increase was a result of membrane fouling. The results of Meireles et al. (1992) illustrated how fouling can induce changes, not only in the solvent flux but also in the separation potential. They also illustrated that fouling is a function of membrane properties. The least significant change occurs for smallest MWCO membrane and the most significant change occurs for the largest MWCO membrane.

In general, it is observed that high cross flow velocity and low operating pressure provide the most economical solute-solvent separations (Figure 9). A high cross flow velocity will limit concentration polarization by facilitating transport of the solute from the membrane surface back to the bulk flow. At low operating pressures, the permeate flux increases almost linearly with the applied pressure. As the pressure rises, the permeate flux increases at a steadily slower rate (i.e. the relationship is no longer linear). A pressure is reached beyond which no further increase in flux is observed. At this pressure, the limiting flux has been reached. A possible explanation for limiting flux is that higher pressure causes more severe concentration polarization and fouling. Higher crossflow velocities can reduce concentration polarization and fouling. It can be seen from Figure 9 that the higher the crossflow velocity, the higher the limiting flux. A balance of crossflow velocity and pressure must be achieved for optimal separation. The balance varies by membrane type and by feed solution characteristics. In our proposed study our experimental setup prevents us from varying the crossflow velocity. The optimum operating pressure will be determined as the pressure just below the limiting flux.

As the protein concentration in the feed solution increases, the maximum achievable flux decreases (Figure 10). At low pressures, the flux increases with applied pressure. As the pressure increases, the concentration of the protein at the membrane surface increases. The flux reaches a maximum value when the concentration of the protein at the membrane surface is so high that it forms a cake layer. The cake layer acts like a secondary membrane. Further increases in pressure increase the thickness of the cake layer but not the flux. The transmembrane flux is then determined by the rate of the diffusion of protein from the membrane surface. The more concentrated the solution, the lower the flux at which the cake layer forms. In our proposed work we will be working with dilute protein solutions 1 mg/ml to 4 mg/ml.