**2.2 Other methods**

68 Progress in Hemodialysis – From Emergent Biotechnology to Clinical Practice

prepared from a solution with PES/PVP ratio of 18/6. Of course, PVP could also be used to modify PES hollow fiber membranes for hemofiltration (Yang et al., 2009). Gholami et al. (Gholami et al.; 2003) found that the hollow fiber membranes shrank by heat treatment, as evidenced by a decrease in flux and an increase in solute separation, although there was no visible change in the hollow-fiber dimension. However, for flat-sheet PES membranes, the membrane surface altered, and surface parameters (such as surface roughness) have been changed after non-contact heating (microwave irradiation) (Mansourpanah et al., 2009). Erlenkotter and coworkers (Erlenkotter et al, 2008) evaluated the dialysis membrane hemocompatibility. In order to compare different polymers used in the manufacturing of dialysis membranes, a set of the following hemocompatibility parameters was assessed and assembled to an overall score: generation of complement factor 5a, thrombin-antithrombin III-complex, release of platelet factor 4, generation and release of elastase from polymorphonuclear granulocytes, and platelet count. By blending polyarylate with PES, the membrane hemocompatibility improved. They also provided a score model to facilitate the selection of membrane polymers with an appropriate hemocompatibility pattern for dialysis

Membrane fouling is still a crucial problem for hollow fiber membrane. When fouling takes place on membrane surfaces, it causes flux decline, leading to an increase in production cost due to increased energy demand. Qin et al. (Qin et al., 2004) selected solvent-resistant hollow-fiber UF membranes by measurement of fiber swelling and treatability studies on spent solvent cleaning rinse. The results indicated that the membranes made of both cellulose acetate (CA) and polyacrylonitrile (PAN) materials could tolerate the solvent present and were suitable or treating the spent solvent rinses, whereas PES and PSF membranes were not suitable. The CA membrane had the lowest fouling tendency when treating the spent solvent rinse. Nakatsuka et al. (Nakatsuka et al., 1996) also found that the permeate flux for the hydrophilic CA membranes was much higher than that of the hydrophobic PES membrane, a phenomenon which was explained by membrane fouling due to the adsorption of substances in raw water on and in the pores of the membranes. Xu et al. (Xu et al., 2009) observed that the fouling layer grew faster on the inside surface of the PES hollow fiber at a lower flow rate than that at a higher flow rate due to the lower shear stress. These results suggested that PES hollow fiber membrane should be modified to

Arahman et al. (Arahman et al., 2009) modified PES hollow-fiber membrane by blending with hydrophilic surfactant Tetronic 1307. The fouling of the PES membrane with blending Tetronic 1307 was lower than that of the original PES membrane in the case of BSA filtration. A functional terpolymer of poly (methyl methacrylate–acrylic acid–vinyl pyrrolidone) (PMMA-AA-VP) was synthesized via free radical solution polymerization using DMAC as the solvent in our recent study (Zou et al., 2010). The terpolymer can be directly blended with PES using the solvent to prepare modified PES hollow fiber membrane. The hydrophilicity of the blended membranes increased, and the membranes showed good protein antifouling property. The antifouling property is always expressed as the timedependent flux during the ultrafiltration process (PBS solution and BSA solution

therapy.

**2.1.2 Improve antifouling property** 

improve antifouling property by increasing hydrophilicity.

alternatively switched), as shown in Figure 3.

Many other methods can also be used for the modification of PES hollow fiber, the following reviewed the methods. Though not all of them are discussed for hemodialysis membranes, some of the methods can be used for the modification of PES hemodialysis membranes.

### **2.2.1 Surface-coating**

Torto and coworkers (Torto et al., 2004) provided a method for the in situ modification of hollow fiber membranes used as sampling units for microdialysis probes. The method consisted of adsorption-coating of high-molecular-weight PEI onto membranes, already fitted on microdialysis probes. Modification of membranes was designed to specifically explore the so-called Andrade effects and thus enhance the interaction of membranes with enzyme. Such a procedure can be modified and employed to either promote or reduce membrane-protein interaction for hollow fibers used as microdialysis sampling units or other similar membrane applications.

### **2.2.2 Photo-induced surface grafting**

To modify PES membranes, photochemical surface technique is attractive, and has several advantages. Mild reaction conditions and low temperature may be applied; and high selectivity is possible by choosing the reactive groups or monomers and respective excitation wavelength; and it can be easily incorporated into the end stages of a

Polyethersulfone Hollow Fiber Membranes for Hemodialysis 71

Hollow fiber scaffolds that compartmentalize axonal processes from their cell bodies can enable neuronal cultures with directed neurite outgrowth within a three-dimensional (3-D) space for controlling neuronal cell networking in vitro. Controllable 3-D neuronal networks in vitro could provide tools for studying neurobiological events. In order to create such a scaffold, PES micro-porous hollow fibers were ablated with a KrF excimer laser to generate specifically designed channels for directing neurite outgrowth into the luminal compartments of the fibers. These hollow fiber scaffolds can potentially be used in combination with perfusion and oxygenation hollow fiber membrane sets to construct a hollow fiber-based 3-D bioreactor for controlling and studying in vitro neuronal networking

The same as other methods mentioned above, few study was reported on the modification of PES hollow fiber membranes by plasma treatment or plasma-induced grafting method. Only one study on the modification of PES hollow fibres by O2 plasma treatment (Batsch et al., 2005) was reported. After about one month of stable operation, the membrane samples were taken and also cleaned with chemical solutions, and the fouling could be prevented by

Thermal induced graft polymerization is a facile way to modify PES membranes. The method always uses chemical initiator or cleavage agent. Furthermore, many kinds of biomolecules, such as enzyme, protein and amino acid, could be covalently immobilized

Kroll et al. (Kroll et al., 2007) chemically modified commercially available PES and PSF hollow fiber membranes by reacting terminal hydroxyl groups with ethylene glycol diglycidyl ether (EGDGE) to produce terminal epoxy groups. For increasing loading capacity hydroxyethyl cellulose polymers were bound to the epoxy groups. Second epoxidation produced final polymers containing reactive epoxy groups on the hollow fiber surface. From this modified PES and PSF, respectively, a wide variety of N-containing reagents (e.g. iminodiacetic acid (IDA)) can be bound to the epoxy groups. The different reactions were proved by acid orange II assay and phenol sulfuric assay. The chelating IDAmembranes were complexed with different divalent metal ions (Cu2+, Ni2+, Co2+, and Zn2+). Immobilized metal ion affinity PES hollow fiber membranes were used for purification of a recombinant protein (GFP-His) from Escherichia coli, which carried a polyhistidine

**3. Biocompatibility and separation performance of the membrane in vitro** 

The biocompatibility and separation performance of PES-based hemodialysis membranes in vitro are discussed. Protein adsorption on material surface is a common phenomenon during thrombogenic formation. Thus, the amount of protein adsorbed on the PES membrane is considered to be one of the important factors in evaluating the blood compatibility of the membrane. The adhesion of platelets to blood-contacting medical devices is a key event in thrombus formation on material surface. Thus, protein adsorption and platelet adhesion on PES membrane surface are studied. In addition, the clearance and

in three dimensions between compartmentalized cultures (Brayfield et al., 2008).

**2.2.3 Plasma treatment and plasma-induced grafting polymerization** 

**2.2.4 Thermal-induced grafting and immobilization** 

onto PES membranes by a simple chemical reaction.

the modification.

sequence.

manufacturing process (Zhao et al., 2003). However, the method is always applied to modify flat-sheet membrane; it is difficult to modify hollow fiber membranes, especially to modify the internal surface of hollow fiber membrane.

Few studies focused on the modification of PES hollow fiber membranes by photo-induced grafting method, since it is difficult to apply irradiation on internal surface of hollow fiber membrane. Bequet and coworkers (Bequet et al., 2002) developed a way to prepare nanofiltration hollow fiber from ultrafiltration membranes, consisting of in-line external modification of the skin of a polysulfone (PSF) ultrafiltration hollow fiber by grafting AA under UV irradiation. The continuous photo-grafting set-up is shown in Figure 4. As shown in the figure, the modification is applied on the outer surface of the hollow fiber membrane. As mentioned above, AA and MA could be grafted on the surfaces of PES membranes by the photochemical method. It should be noticed that due to the present of carboxyl groups, these modified membranes showed pH-sensitivity.

Fig. 4. Schema for the experimental continuous photo-grafting set-up. (From reference, Bequet et al., 2002)

Shen et al. (Shen et al., 2005) modified the inner-surface of PSF hollow fiber UF membranes by using gas-initiation under UV and liquid-polymerization, which aimed to adjust the diameter of the pores in the membranes. Benzophenone (BP) was in a gaseous condition as photo-initiator, AM as graft monomer, the polyacrylamide (PAM) chain was grafted on the surface of the membranes. After the membrane surface being modified, the water flux and retention altered, and thus it could be seen that the diameter of the pores in the membrane was altered. Of course, the method could also be used to produce the PES hollow fiber membrane with small pore size.

Goma-Bilongo and co-workers (Goma-Bilongo et al., 2006) developed a numerical model to represent the process by which hollow-fiber membranes could undergo continuous surface modification by UV photo-grafting, which was the same as reported by Bequet (Bequet et al., 2002). The model took into account the coupled effects of radiation, mass transfer with polymerization reaction and heat transfer with evaporation. Then, they modified PSF hollow fiber membranes using sodium p-styrene sulfonate (NaSS) as a vinyl monomer, for treatment of anionic dye solutions (Akbari et al., 2007). However, till now, no report for the modification of PES hollow fiber membranes was found.

manufacturing process (Zhao et al., 2003). However, the method is always applied to modify flat-sheet membrane; it is difficult to modify hollow fiber membranes, especially to modify

Few studies focused on the modification of PES hollow fiber membranes by photo-induced grafting method, since it is difficult to apply irradiation on internal surface of hollow fiber membrane. Bequet and coworkers (Bequet et al., 2002) developed a way to prepare nanofiltration hollow fiber from ultrafiltration membranes, consisting of in-line external modification of the skin of a polysulfone (PSF) ultrafiltration hollow fiber by grafting AA under UV irradiation. The continuous photo-grafting set-up is shown in Figure 4. As shown in the figure, the modification is applied on the outer surface of the hollow fiber membrane. As mentioned above, AA and MA could be grafted on the surfaces of PES membranes by the photochemical method. It should be noticed that due to the present of carboxyl groups,

the internal surface of hollow fiber membrane.

these modified membranes showed pH-sensitivity.

Hollow fiber

Fig. 4. Schema for the experimental continuous photo-grafting set-up.

modification of PES hollow fiber membranes was found.

Shen et al. (Shen et al., 2005) modified the inner-surface of PSF hollow fiber UF membranes by using gas-initiation under UV and liquid-polymerization, which aimed to adjust the diameter of the pores in the membranes. Benzophenone (BP) was in a gaseous condition as photo-initiator, AM as graft monomer, the polyacrylamide (PAM) chain was grafted on the surface of the membranes. After the membrane surface being modified, the water flux and retention altered, and thus it could be seen that the diameter of the pores in the membrane was altered. Of course, the method could also be used to produce the PES hollow fiber

UV Lamps

Tricylinder

Monomer solution

Goma-Bilongo and co-workers (Goma-Bilongo et al., 2006) developed a numerical model to represent the process by which hollow-fiber membranes could undergo continuous surface modification by UV photo-grafting, which was the same as reported by Bequet (Bequet et al., 2002). The model took into account the coupled effects of radiation, mass transfer with polymerization reaction and heat transfer with evaporation. Then, they modified PSF hollow fiber membranes using sodium p-styrene sulfonate (NaSS) as a vinyl monomer, for treatment of anionic dye solutions (Akbari et al., 2007). However, till now, no report for the

(From reference, Bequet et al., 2002)

Bobbin

membrane with small pore size.

Hollow fiber scaffolds that compartmentalize axonal processes from their cell bodies can enable neuronal cultures with directed neurite outgrowth within a three-dimensional (3-D) space for controlling neuronal cell networking in vitro. Controllable 3-D neuronal networks in vitro could provide tools for studying neurobiological events. In order to create such a scaffold, PES micro-porous hollow fibers were ablated with a KrF excimer laser to generate specifically designed channels for directing neurite outgrowth into the luminal compartments of the fibers. These hollow fiber scaffolds can potentially be used in combination with perfusion and oxygenation hollow fiber membrane sets to construct a hollow fiber-based 3-D bioreactor for controlling and studying in vitro neuronal networking in three dimensions between compartmentalized cultures (Brayfield et al., 2008).
