Development of scalable functionalized membranes for bioprocessing applications
In the recent years pharmaceutical and biomedical fields have emerged to become a huge market for the membrane technology. Hydrophilized polyether sulfone (PES) and polyvinylidene fluoride (PVDF) membranes are currently most abundantly used for the bio-pharmaceutical applications. Various surface functionalization techniques have been remarkably evolved over the past decades towards developing membranes for such applications. Functional membranes such as ion-exchange membranes or membrane absorbers are widely used to increase the separation efficiencies; stimuli responsive membranes, e.g., to pH or temperature, are explored. Despite these developments, many functionalization techniques are limited to lab-scale implementation. Moreover, there is still limited separation performance due to poor selectivity as a result of different types of fouling. This project therefore focuses on industrial production of functionalized microfiltration (MF) PVDF membranes for bio-pharmaceutical applications. The functionalization is carried out via scalable two-step graft coating polymerization involving redox initiation of radical reactions with ethylene glycol dimethacrylate (EGDMA) as the cross-linker. Either vinyl monomers or hydrophilic polymers were added in order to introduce specific functionality in the coating. EGDMA dominated the polymerization due to higher reactivity, higher local concentration at the interface and efficient homopolymerization. Vinyl monomers drove the thermodynamics and kinetics towards more efficient functionalization compared to the long chain polymers. Acrylic acid and 2-hydroxyethyl methacrylate (HEMA) as functional monomers presented a promising platform to obtain superior anti-fouling surface properties. The EGDMA-monomer ratio played an integral role in influencing the final membrane properties. EGDMA governed the structural changes while monomer defined the surface properties obtained upon modification. Polyacrylic acid formed pH-responsive dangling chains which could repel particles from entering the membrane pores through electrostatic repulsions. Poly(HEMA) formed a hydration layer on the surface reducing the particle adhesion onto the membrane surface. Acrylic acid and HEMA functionalized flat sheet membranes were industrially produced in a roll-to-roll process. The membrane demonstrated compatibility towards wide range of chemicals, high thermal and mechanical stability, and retained their properties after sterilization. Furthermore, in addition to the very low protein binding ability (< 2 µg/cm2 ), the membranes showed higher particle retention than the competitor membrane with smaller pore sizes due to the reduced membrane-particle adhesion. Furthermore, a relationship between the membrane pore size and polymerization efficiency was established to extend the functionalization to base membranes with varying pore sizes. The results revealed a gradient of polymerization in the cross-section of the membrane which reduced with increasing pore size. Commercial MF membranes have been successfully functionalized via developed methodology at an industrial scale to obtain desired surface properties to minimize fouling and enhance the separation performance. The preliminary performance and characterization results for the developed prototypes show considerable potential to implement developed membranes for bioprocessing applications.