High-performance tangential flow filtration using charged membranes

High-performance tangential flow filtration (HPTFF) is an emerging technolo gy that enables the separation of proteins with similar size. HPTFF technol ogy has become possible by exploiting several new discoveries. It has been demonstrated that optimum selectivity and throughput are obtained in the pr essure-dependent flux regime. Selectivity and throughput can also be enhanc ed through module design and process configurations that reduce the transme mbrane pressure gradient. Optimization of buffer pH and ionic strength have a significant impact on the sieving behavior of proteins in membrane syste ms. Finally, a novel set of design equations and diagrams have been derived which provide a rational means for determining the optimum combination of selectivity and throughput for any given process. The current study focused on exploring the effects of membrane charge, in combination with buffer pH , on protein separation using HPTFF. Order-of-magnitude improvements in bot h selectivity and throughput were obtained by selecting the appropriate mem brane charge at an optimum pH. The high selectivity and throughput values e nabled protein purification using a small number of diavolumes (N = 4-12), reasonable membrane area per mass of product (17 m(2) kg(-1)), and short pr ocessing times (1-3 h). Purification factors up to 990-fold were obtained w ith yields of 94%. These results were obtained in linear scale-down systems representative of existing industrial scale systems, currently in use for ultrafiltration of human pharmaceuticals produced by recombinant DNA method s. (C) 1999 Elsevier Science B.V. All rights reserved.