Bioseparations via Coupled TPP and Electrostatic Forces

CTS-0091552

Bioseparations using Coupled TPP and Electrostatic Forces

Victor G.J. Rodgers (University of Iowa)

Andrew L. Zydney (University of Delaware)

Abstract

Membrane processes have great potential for use in the downstream purification of a wide range of biological products. However, current devices are limited by a lack of selectivity and problems associated with protein fouling. The goal of this work is to examine the development of an enhanced membrane separation technology that combines the use of interfacial electrical interactions to enhance the overall selectivity with transmembrane pressure pulsing (TPP) to reduce membrane fouling and increase flux. Initial experimental studies are using well-defined protein solutions containing either one or two proteins and standard ultrafiltration membranes with well characterized properties. Batch-cell and crossflow ultrafiltration (UF) experiments will be performed to evaluate the transport of model single-component solutions and binary mixtures of proteins with and without TPP. Data obtained over a range of buffer conditions indicate the efficacy of using membranes with different surface-charge characteristics to exploit electrostatic interactions on the separation. Protein charge is determined by capillary electrophoresis, and the membrane charge is analyzed both before and after each run by measuring the streaming potential. Post-operative solution analysis and membrane hydraulic permeability data are used to determine quantitatively the extent of membrane fouling as a function of operating conditions, membrane surface characteristics, and protein properties. The data analysis employs factorial design and analysis of variance (ANOVA) to discern the most significant factors in improving solute sieving, solute flux, and overall purification factor. These experimental studies are complimented by theoretical analyses of bulk and membrane transport phenomena, including the effects of both the electrostatic interactions and the transmembrane pressure pulsing.

The combination of dynamic TPP with the proper exploitation of electrostatic interactions has the potential to provide significant enhancements in protein-separation membrane performance. In particular, the use of electrical interactions to repel selectively like-charged species should enable very high resolution separations to be accomplished with commercially available membrane materials. Transmembrane pressure pulsing will allow these devices to be operated at much higher throughput while minimizing membrane fouling. The net result is that this technology should be able to improve dramatically the overall yield, purification factor, and throughput characteristics of membrane systems, allowing these devices to be used for an entirely new range of applications in the biotechnology and biomedical industries. For example, because membrane processes are inherently cost effective and cause little damage to fragile biological components, successful implementation of this technology could enable processes for the production of new therapeutic proteins and nutraceuticals from natural sources like milk and plasma, the development of new biomedical devices for removal of auto-antibodies from plasma, or the treatment of life-threatening diseases with dynamic mass-transfer-based artificial organs.