Membrane Bioseparations

A. L. Zydney, University of Delaware, Newark, DE, USA Copyright © 2000 Academic Press

Membrane processes are particularly well suited to the separation and purification of biological molecules since they operate at relatively low temperatures and pressures and involve no phase changes or chemical additives. Thus, these processes cause minimal denaturation, deactivation and/or degradation of highly labile biological cells or macromolecules. Although essentially all membrane processes (Figure 1) have been used for bioseparations, the greatest interest has been in the application of the pressure-driven processes of ultrafiltration (UF) and microfiltration (MF). Ultrafiltration membranes have pore sizes between 1 and 50 nm and are used for protein concentration, buffer exchange, desalting, clarification of antibiotics and virus clearance. There is also growing interest in the use of ultrafiltration for protein purification using high performance tangential flow filtration (HPTFF). Microfiltration membranes have a pore size between 0.05 and 10 |im and are thus used for initial clarification of protein solutions, cell harvesting and sterile filtration. In addition, ultrafiltration and microfiltration of blood are used for the treatment of a variety of metabolic and immunolo-gical disorders.

The development of membrane processes for bioseparations is very similar to the design of membrane systems for nonbiological applications. However, there are some important differences including:

1. increased concerns about deactivation or de-naturation of biological molecules and cells

2. very high value (on a per unit mass basis) of most biological products (particularly recombinant therapeutic proteins)

3. tendency of biological macromolecules and cells to cause significant fouling of both ultrafiltration and microfiltration membranes

4. critical importance of validation and integrity testing in bioprocessing applications

This article provides a brief review of the historical development of membrane systems for bioseparations. This is followed by a general discussion of the

Mierofiltration Virus filtration

HPTFF

Ultrafiltration IManofiltralion

Components retained by membrane

Components passed through membrane

Reverse osmosis

Mierofiltration Virus filtration

HPTFF

Ultrafiltration IManofiltralion

Reverse osmosis

Components retained by membrane

Components passed through membrane

Intact cells Cell debris Bacteria

Viruses

Proteins

Proteins

Nucleic acids Antibiotics

Sugars Salts

Viruses

Proteins

Nucleic acids

Sugars

Salts

Proteins Nucleic acids Sugars Salts

Proteins Nucleic acids Sugars Salts

Nucleic acids Surfactants Sugars Salts

Salts Water

Water

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Noble RD and Douglas Way J (eds) (1996) Liquid Membranes. Theory and Application. American Chemical Society Symposium Series no 347. Washington, DC: American Chemistry Society .

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