Andrew L. Zydney

The behavior of suspensions and macromolecular solutions in crossflow microfiltration

Abstract Although microfiltration is one of the oldest pressure-driven membrane processes, it is probably the least understood when it comes to the filtration of suspensions and macromolecules. Microfiltration is characterized by operation at low pressures, by high permeation fluxes, and by crossflow mode in flat or cylindrical geometries. The major limitation of microfiltration is membrane fouling due to the deposition and intrusion of macromolecules, colloids and particles onto and into the microporous membrane. In this review, we analyze the various components of this problem by focusing on the formation of cakes, the behavior of suspension flows and particle transport in simple geometry ducts, and on the formation and behavior of fouling layers including those resulting from macromolecules, colloids and particles. Some of the work we report on is very recent or is still in progress and needs independent verification. With this understanding, we hope that the reader will be able to use these concepts for analyzing other systems and for investigating new module designs.

Membrane separations in biotechnology.

Membranes have always been an integral part of biotechnology processes. The sterile filtration of fermentation media, purification buffers, and protein product pools is standard practice in industry. Microfiltration is also used extensively for medium exchange and harvest. Ultrafiltration can be found in virtually every biotechnology process. A significant number of mammalian cell processes use filtration as an integral part of the overall strategy for viral clearance. Depth filters have also seen widespread use for the clarification of both mammalian and bacterial feed streams. Improvements in membrane technology are now focused on high-resolution applications, including improved protein-virus separation, protein purification by high-performance tangential flow filtration and enhanced membrane chromatography. These developments will allow membranes to play an important role in the evolution of the next generation of biotechnology processes.

HUMIC ACID FOULING DURING MICROFILTRATION

Recent studies have shown that natural organic matter (e.g., humic and fulvic acids) is a major foulant during ultrafiltration of surface water. The objective of this study was to develop a more complete understanding of the mechanisms governing humic acid fouling, including the effects of humic acid adsorption, concentration polarization, and aggregate deposition on the rate and extent of fouling. Data were obtained with Aldrich and Suwannee River humic acids using ultrafiltration membranes with a broad range of molecular weight cutoffs. Fouled membranes were also examined using streaming potential and contact angle measurements. The extent of flux decline was greatest for the largest molecular weight cutoff membranes due to the greater relative hydraulic resistance of the humic acid deposit formed on the surface of these membranes. This humic acid deposit reduced the apparent zeta potential and increased the membrane contact angle. Simple static adsorption and concentration polarization caused relativel...

Humic acid fouling during ultrafiltration

Recent studies have shown that natural organic matter (e.g., humic and fulvic acids) is a major foulant during ultrafiltration of surface water. The objective of this study was to develop a more complete understanding of the mechanisms governing humic acid fouling, including the effects of humic acid adsorption, concentration polarization, and aggregate deposition on the rate and extent of fouling. Data were obtained with Aldrich and Suwannee River humic acids using ultrafiltration membranes with a broad range of molecular weight cutoffs. Fouled membranes were also examined using streaming potential and contact angle measurements. The extent of flux decline was greatest for the largest molecular weight cutoff membranes due to the greater relative hydraulic resistance of the humic acid deposit formed on the surface of these membranes. This humic acid deposit reduced the apparent zeta potential and increased the membrane contact angle. Simple static adsorption and concentration polarization caused relatively little flux decline. Humic acid aggregates had a significant effect on fouling only for the larger molecular weight cutoff membranes. The rate and extent of humic acid fouling increased at low pH, high ionic strength, and in the presence of calcium due to changes in intermolecular electrostatic interactions. These results provide important insights into the mechanisms of humic acid fouling during ultrafiltration.

A CONCENTRATION POLARIZATION MODEL FOR THE FILTRATE FLUX IN CROSS-FLOW MICROFILTRATION OF PARTICULATE SUSPENSIONS

Cross-flow filtration with microporous membranes is increasingly used in the separation and concentration of particulate suspensions. Existing models for the filtrate flux are inadequate for correlating experimental observations and are based on contradictory physical mechanisms. We propose that the flux is limited by the formation of a dynamic concentration polarization boundary layer consisting of a high concentration of retained particles. A simple model is developed incorporating a shear-enhanced diffusivity of the large particles which arises from mutually induced velocity fields in the shear flow of the concentrated suspension. Predictions of the model agree well with experimental data for a variety of particulate suspensions. The model provides both a fundamental understanding of the physical phenomena governing flux and a rational basis for design of improved cross-flow filters.

Mechanisms for BSA fouling during microfiltration

Although protein fouling is one of the critical factors governing the effectiveness of many microfiltration processes, the underlying chemical and physical mechanisms that influence the initiation and growth of the fouling layer have not yet been clearly established. We have obtained data for the flux decline during the stirred cell microfiltration of bovine serum albumin (BSA) preparations with different physical and/or chemical characteristics through isotropic polyvinylidene fluoride microfiltration membranes. The initial fouling in this system was caused by the convective deposition of protein aggregates onto the membrane surface. Native (non-aggregated) BSA only fouled the membrane by chemical attachment to an existing protein deposit via the formation of intermolecular disulfide linkages. A mathematical model was developed to describe this dual-mode fouling process, with the model calculations being in very good agreement with the experimental data. These results provide important new insights into the physical and chemical interactions governing protein fouling during microfiltration.

Protein separations using membrane filtration : New opportunities for whey fractionation

There is considerable commercial interest in the preparation of individual whey proteins for food, nutraceutical, and therapeutic applications. Recent developments in membrane filtration have provided exciting new opportunities for large-scale protein fractionation. This manuscript provides an overview of the previous work on protein separations using membrane filtration, including the importance of solution pH and ionic strength to obtain very high resolution separations. Specific data are shown for the separation of hemoglobin from BSA and for the purification of immunoglobulins from a complex feed stream using a gradient diafiltration process. The potential applications of membrane systems for whey protein fractionation are also examined.

Analysis of humic acid fouling during microfiltration using a pore blockage-cake filtration model

Fouling by natural organic matter, such as humic substances, is a major factor limiting the use of microfiltration for water purification. The objective of this study was to develop a fundamental understanding of the underlying mechanisms governing humic acid fouling during microfiltration using a combined pore blockage–cake filtration model. Data were obtained over a range of humic acid concentrations, transmembrane pressures, and stirring speeds. The initial flux decline was due to pore blockage caused by the deposition of large humic acid aggregates on the membrane surface, with a humic acid deposit developing over those regions of the membrane that have first been blocked by an aggregate. The rate of cake growth approaches zero at a finite filtrate flux, similar to the critical flux concept developed for colloidal filtration. The data were in good agreement with model calculations, with the parameter values providing important insights into the mechanisms governing humic acid fouling during microfiltration. In addition, the basic approach provides a framework that can be used to analyze humic acid fouling under different conditions.

Stagnant film model for concentration polarization in membrane systems

The stagnant film model is used almost universally to describe bulk mass transfer (concentration polarization) in pressure-driven membrane systems. However, the mathematical justification for this model, and in particular the logarithmic dependence on the solute concentration and the form of the mass transfer coefficient, remains a point of considerable confusion. This communication presents a more rigorous development of the stagnant film model, providing a much firmer mathematical justification for this approach as well as a more quantitative description of the limitations of this model. Specific calculations are provided for fully developed laminar flow in a parallel plate device and for unsteady mass transfer in an unstirred batch system. In addition, the effects of a concentration-dependent viscosity and diffusivity on the stagnant film analysis are examined, yielding new insights into the proper form of the stagnant film model under these conditions.

Effect of membrane morphology on the initial rate of protein fouling during microfiltration

Protein fouling remains a major problem in the use of microfiltration for many bioprocessing applications. Experiments were performed to evaluate the effect of membrane morphology and pore structure on protein fouling using different track-etched, isotropic, and asymmetric microfiltration membranes. Fouling of membranes with straight-through pores occurred by pore blockage caused by deposition of large protein aggregates on the membrane surface. However, the rate of blockage was a function of the membrane porosity due to the possibility of multiple pore blockage by a single protein aggregate on high porosity membranes. Membranes with interconnected pores fouled more slowly since the fluid could flow around the blocked pores through the interconnected pore structure. This behavior was quantified using model membrane systems with well-defined pore morphology constructed from track-etch and isotropic membranes in a layered series combination. These results provide important insights into the effects of membrane pore structure and morphology on protein fouling.