Page 399 - Academic Press Encyclopedia of Physical Science and Technology 3rd Chemical Engineering

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Encyclopedia of Physical Science and Technology EN009K-419 July 19, 2001 20:57

334 Membranes, Synthetic, Applications

ogyfromtheperspectiveofmembranematerials,chemical
and biochemical functionalization strategies, module de-
sign, and engineering considerations. Some applications
in biotechnology are mentioned peripherally.
Ion exchange membranes exhibit certain attributes of
affinity membranes with respect to bioseparations. Since
proteins and other biomolecules carry characteristic
charges, it is possible to manipulate the acid–base balance
of the environment to cause the species in solution to bind
to the membrane, or to release them by shifting away
from those conditions. Indeed, ion exchange membranes
may be deployed in ways analogous to those for ion
exchange chromatography. Engineering considerations
similar to those for affinity membranes also apply to ion
exchange membrane systems. It is useful to consider all
membrane processes, whether they operate largely by
sieving or by reversible adsorption, as complementary
unit operations in the overall manufacturing scheme and
optimized accordingly.

D. Membrane Bioreactors
Harnessing biochemical conversions to yield valuable
products requires careful control of the environment such
that the viability of the catalytic microorganism, enzyme,
or cell culture is sustained, plus balanced supplies of re-
actants and products. Conventional stirred-tank reactors
FIGURE 45 Affinity membrane separation of proteins represents
represent the standard configuration of this unit operation,
the most advanced support for affinity sites.
but there are some advantages to using membranes for
the same purpose while overcoming some shortcomings
mechanisms. Both mechanisms could complement each of conventional reactor design. As a physical substrate,
other in enhancing the purity of the product if the sepa- membranes confine the catalytic species at high packing
ration process is optimized. Typically, the performance density and help organize the supply and retrieval of re-
of an affinity membrane system is governed by several actants and products, respectively, into separate streams.
independent factors: fluid dynamics, ligand–ligate inter- In addition, the permselective properties of the membrane
action, membrane morphology and ligand distribution, permit both the conversion and separation functions to be
the configuration of the device, and operating conditions. integrated into a single device.
It is possible to achieve very high resolving power using Fermentation is typically conducted in dilute suspen-
affinity membranes in a stack configuration provided flow sion culture. The low concentration in such systems limits
through such a stack is controlled to simulate plug flow. reaction efficiency, and the presence of particulate and
Despite these advantages, membrane affinity processes colloidal solids poses problems for product recovery and
have not been widely adopted commercially to date for purification. By circulating the fermentation broth through
several reasons: affinity chromatography offers a famil- an ultrafiltration system, it is possible to recover product
iar, high-resolution approach to separating complex pro- continuously as they are generated while minimizing loss
tein mixtures to the biotechnology industry, in which of enzyme or cells and keeping product concentration in
changes even to a comparable membrane process would the bioreactor below the self-inhibition level for the bio-
requirecomplexandexpensiverevalidation;scale-upfrom catalyst. This process is referred to as perfusion. As the
the laboratory to the process level also requires a se- ultrafiltration unit is part of the production process, the
ries of well-engineered devices and system support, both entire system is often considered a membrane reactor.
of which are still at the development stage for affinity A more appropriate definition of membrane bioreactors
membranes. confines them to devices in which biochemical conversion
A comprehensive review of affinity membrane separa- actually occurs. For example, an enzyme may be immo-
tions (Klein, 2000) traces the development of this technol- bilized in the membrane by physical sorption or covalent