(389g) Scaling Down to Scale up: Mass Transport for Aqueous Two-Phase Separation of Viral Vaccines

The pursuit of continuous processing to reduce costs, labor, and plant footprints presents special challenges for the manufacturing of viral vaccines that already suffer from poor stability and recovery in traditional unit operations. A potential solution is aqueous two-phase systems (ATPS) that have high capacity and low shear and are readily adapted to continuous operation. Bench-scale batch and continuous purification have produced over 80% recovery of porcine parvovirus (PPV) with high host cell protein and DNA removal. However, during expansion to new molecules, recoveries in a mixer-settler system have been inconsistent and a strong dependence on mixing intensity has emerged during optimization. To provide necessary understanding for scale up of our continuous ATPS process, we quantified diffusion of fluorescently tagged protein (BSA) and virus (PPV) in the bulk and across the ATPS interface using a Y-channel microdevice. From this, we determined diffusion coefficients and mass flux values useful for modelling separations of these products. Understanding the limitations of mass flux in ATPS will allow us to design equipment that can mix and settle these interesting biphasic systems for continuous manufacturing.