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.