Acoustic edge effect: Novel acoustophoretic cell retention to enable continuous bioprocessing

Abstract

There is currently a shift in Bioprocessing towards continuous manufacturing of monoclonal antibodies or recombinant proteins in perfusion mammalian cell cultures (Konstantinov & Cooney, Journal of Pharmaceutical Sciences, 2015). A cell retention device is the key technology component that enables the shift to continuous production. A novel acoustic cell retention device operates by continuously drawing off a harvest flow, equal to the perfusion rate of the bioreactor, while recirculating the retained cells back to the bioreactor. The harvest flow path is tangent and significantly smaller than the recirculation rate. The device utilizes a novel acoustophoretic effect known as an “acoustic edge/interface” effect in conjunction with a recirculating flow beneath the acoustic harvest chamber which collects and returns cells to the bioreactor. This interface effect operates by creating a radiation pressure/force field at the interface between cell-free harvest and cell-laden circulating fluids. Numerical results show an insight into the mechanism of the acoustic edge effect. Experimental results confirm the existence of this novel acoustic edge effect. CHO cell perfusion cultures were operated continuously for >15 days. This technology delivers continuous cell retention and steady unhindered product transmission enabling continuous production of biopharmaceuticals unlike traditional hollow-fiber tangential flow filtration.