High-performance tangential flow filtration (HPTFF) is an emerging technology that enables the separation of proteins with similar size. HPTFF technology has become possible by exploiting several new discoveries. It has been demonstrated that optimum selectivity and throughput are obtained in the pressure-dependent flux regime. Selectivity and throughput can also be enhanced through module design and process configurations that reduce the transmembrane pressure gradient. Optimization of buffer pH and ionic strength have a significant impact on the sieving behavior of proteins in membrane systems. 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 both selectivity and throughput were obtained by selecting the appropriate membrane charge at an optimum pH. The high selectivity and throughput values enabled protein purification using a small number of diavolumes (N=4-12), reasonable membrane area per mass of product (17m2kg-1), and short processing times (1-3h). Purification factors up to 990-fold were obtained with 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 methods. Copyright (C) 1999 Elsevier Science B.V.
All Science Journal Classification (ASJC) codes
- Materials Science(all)
- Physical and Theoretical Chemistry
- Filtration and Separation