Ultrafiltration is commonly used in the dairy and biotechnology industries for protein concentration, buffer exchange and desalting. Conventional ultrafiltration suffers from an inherent trade-off between permeability (flux) and selectivity (protein retention). According to this trade-off, membranes that have a high permeability have low protein retention and vice versa. The purpose of the present work was to show that that this rule of thumb can be broken by using charged ultrafiltration membranes. The hypothesis of the work was that, by placing a charge on the membrane and adjusting the solution conditions in such a way that the protein is charged similar to the membrane, it is possible to reject proteins based on electrostatic repulsion compared to simply size-based sieving. Thus, wide-pore size membranes can be used for protein concentration at a higher flux compared to tighter membranes. This mechanism of protein sieving also enables protein fractionation from mixtures and expands the utility of ultrafiltration beyond simple protein concentration.;In the present work, positively charged membranes were developed to fractionate the dairy proteins that differed somewhat in isoelectric points but not much in size from natural feed streams. Placing a charge on the membrane, adjusting the solution pH to the isoelectric point of one of the proteins and operating in stages allowed fractionation of proteins that were 15 - 20 times smaller than the membrane molecular weight cut-off and gave chromatographic purity without chromatography. Negatively charged membranes were developed to concentrate whey proteins and milk proteins at higher fluxes compared to industry standard tight membranes for a complete 40-fold concentration process with diafiltration. A new method of scale-up based on constant concentration polarization index was proposed and validated for a 70-fold scale-up across geometry for whey protein concentration.;Mass balance models were developed and validated in the present work for concentration and diafiltration. Single-stage sieving coefficients at total recycle could predict the performance of a multi-stage concentration and diafiltration accurately. The experimental methods and mathematical models developed in this work can be used to design, simulate and optimize different process flow sheets, and explore the effect of various operating conditions on the membrane processing of proteins.
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