Membrane Adsorption
Membrane adsorption exploits the same mechanisms used in affinity and ion-exchange chromatography, but offers a reduced processing time and initial investment. Similar to affinity chromatography, a product yield near 100% can be achieved 35,140. In membrane adsorption, the same ligands used in affinity chromatography or resins used in ion-exchange chromatography are bound to a support medium. The use of a membrane greatly improves flow rates and nearly eliminates diffusion limitations. Membranes can be made of nylon, PVA, PEVA, PVDF, cellulose acetate and cellulose 25,100,140. The membrane capsules are single-use, meaning there is no need for eluting, cleaning, or regenerating. Benefits of single-use membranes include a decreased chance of product contamination as well as a decreased process time and buffer volume due to the decrease in required cleaning steps 38. Membrane adsorption requires a low initial investment when compared to traditional chromatographic methods, but membranes must be continually purchased, which will affect manufacturing costs 38.
In the past, membrane adsorbers have not been widely adopted because it had a lower binding capacity than that of traditional chromatography methods. Endotoxin removal efficiencies of histidine immobilized on a nylon membrane for different endotoxin concentrations have been carried out. The ligand density for the membrane adsorbers studied was 7.38 mg/g. As the initial endotoxin concentration was increased, the removal efficiency was greatly decreased. This demonstrates the limited binding capacity using membrane adsorbers. Even at the lowest endotoxin concentration of 387 EU/ml, the removal efficiency was only 65% 25. These results are consistent with those from previous studies that saw endotoxin removal efficiencies of approximately 70% with an initial endotoxin concentration of 6,000 EU/mL 141. Recently, membrane adsorbers with high efficiency endotoxin removal and binding have been synthesized. One such example of membrane adsorbers is that of amphiphilic carbonaceous particles (ACPs) incorporated in the polyvinylidene fluoride (PVDF) matrix. The absorbers have been successful at removing endotoxins from BSA protein solutions at >99.8% efficiency with >90 % protein recovery.140 Another study with PCL nanoparticle incorporated in the cellulose acetate membranes have been able to effectively remove endotoxins from water. The endotoxin binding capacity offered by the membrane adsorber was ~ \(2.7\times 10^{6}\) EU per mg particle compared to endotoxin binding capacity of ~ \(1.4\times 10^{6\ }\)EU per mg particle offered by PCL nanoparticles in suspension 100.