EFFECT OF SOLUTION PH AND IONIC-STRENGTH ON THE SEPARATION OF ALBUMINFROM IMMUNOGLOBULINS (IGG) BY SELECTIVE FILTRATION

Although protein fractionation by selective membrane filtration has nu merous potential applications in both the downstream processing of fer mentation broths and the purification of plasma proteins, the selectiv ity for proteins with only moderately different molecular weights has generally been quite poor. We have obtained experimental data for the transport of bovine serum albumin (BSA) and immunoglobulins (IgG) thro ugh 100,000 and 300,000 molecular weight cutoff polyethersulfone membr anes in a stirred ultrafiltration device at different solution pH and ionic strength. The selectivity was a complex function of the flux due to the simultaneous convective and diffusive solute transport through the membrane and the bulk mass transfer limitations in the stirred ce ll. Under physiological conditions (pH 7.0 and 0.15 M NaCl) the maximu m selectivity for the BSA-IgG separation was only about 2.0 due primar ily to the effects of protein adsorption. In contrast, BSA-IgG selecti vities as high as 50 were obtained with the same membranes when the pr otein solution was at pH 4.8 and 0.0015 M NaCl. This enhanced selectiv ity was a direct result of the electrostatic contributions to both bul k and membrane transport. The membrane selectivity could actually be r eversed, with higher passage of the larger IgG molecules, by using a 3 00,000 molecular weight cutoff membrane at pH 7.4 and an ionic strengt h of 0.0015 M NaCl. These results clearly demonstrate that the effecti veness of selective protein filtration can be dramatically altered by appropriately controlling electrostatic interactions through changes i n pH and/or ionic strength. (C) 1994 John Wiley & Sons, Inc.