Effect of ionic strength on membrane fouling during ultrafiltration of plasmid DNA

Recent studies have demonstrated that the selectivity of membrane systems for DNA purification can be enhanced by proper selection of solution ionic strength, but these data were all obtained in dilute solutions where fouling is negligible. The objective of this work was to evaluate the effect of solution conditions on the fouling characteristics of both supercoiled and linear plasmid DNA isoforms with different length. Data were obtained using Biomax polyethersulfone ultrafiltration membranes with 300 and 1000 kDa nominal molecular weight cutoffs. Sieving coefficient and filtrate flux data were analyzed using a model based on the partial blockage of the membrane pores by trapped plasmids. Fouling increased dramatically at low ionic strength, with the flux decline parameter for the 3.0 kbp plasmid in a 1 mM NaCl solution being an order of magnitude greater than that in a 10 mM solution. Fouling was also most pronounced for the larger 16.8 kbp plasmid, consistent with the greater probability of plasmid trapping at the pore entrance. These results provide important insights into the development of membrane systems for plasmid DNA filtration in different solution conditions.