DEVELOPMENT OF FUNCTIONALIZED MEMBRANE BASED TECHNOLOGY FOR ISOLATION OF VIRUS

Abstract

Virus filtration is a critical component of the downstream purification process during the production of important biotherapeutics. However, it is a challenging and economically expensive process. This study has been directed towards the development of reusable and efficient functionalized polymeric membrane for the isolation of virus from process stream. Theoretical analysis of the commercially available virus filters revealed that despite high LRV value, these membranes compromise in terms of permeability, which is in the order of 10-11 m3/(m2-s-Pa). This ultimately decreases the productivity and consequently increases the processing cost. In this work, functionalized membrane was developed using Layer-by-Layer technique, which offered 2 fold increase in permeability with additional benefit of flux recovery. MS2 was used as a surrogate virus model. Studies have shown that bacteriophages are similar to some human viruses, which occur naturally in the human and animal intestinal tract and grow faster. Therefore, they are well suited as model system for experiments. Quantitative data for the virus filtration was obtained through the functionalized membrane. In addition, flux recovery was also examined by mitigating the fouling in the membrane with Triton X detergent. Results show LRV value of 1.1 with permeability value of 2×10-10 m3/(m2-s-Pa) at 34.5 kPa (5psi). Flux recovery was achieved by dislodging the two bilayers of PEI-PSS form the functionalized membrane, keeping the PAA backbone intact. This, in turn enables the reusability of the membrane. In addition, the number of bilayers within the membrane can be chosen based on the size of target virus.