Application of periodic backpulsing to reduce membrane fouling during ultrafiltration of plasmid DNA

• Backpulsing reduces fouling during plasmid ultrafiltration.
• Plasmids removed from blocked pores primarily by tangential flow.
• Simple fouling model developed based on plasmid trapping and release.
• Model calculations in good agreement with data for plasmid transmission.
• Diafiltration process with backpulsing provides good plasmid recovery.

There is considerable interest in using ultrafiltration for the purification of plasmid DNA, but membrane fouling remains an issue. The objective of this work was to examine the use of periodic backpulsing to reduce fouling during plasmid ultrafiltration by “releasing” previously trapped plasmids from the membrane pores. Experiments were performed using hollow fiber ultrafiltration membranes over a range of backpulse frequency, amplitude, and duration. Plasmid removal under typical conditions was dominated by the shear / drag associated with the tangential flow, with good recovery of plasmid transmission obtained by periodically closing the permeate exit line (without any backpressure). Data were analyzed using a simple fouling model that accounts for the partial blockage of pores by trapped plasmids that are then released during backpulsing. The results clearly demonstrate that this type of pulsed operation can provide much greater plasmid recovery in the permeate solution with a nearly constant filtrate flux during a diafiltration process.

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