Page 400 - 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

Membranes, Synthetic, Applications 335

attachment to the membrane matrix, or simply confined asymmetric synthesis, which directly yields the desired
in solution form in the pores of a membrane and bound single isomer. Some work on racemic resolution contin-
externally by immiscible phases. Substrate reaching the ues today with an emphasis on the production of specialty
enzyme by convection or diffusion is converted to prod- chemicals.
uct. Alternatively, the enzyme and the substrate solution Other applications of membrane bioreactors proved
may be placed on opposite sides of the membrane so that more sustainable. The first utilizes membranes as an ad-
the reaction may occur at the membrane interface. In ei- junct to conventional bioreactors rather than their replace-
ther case, the fermentation vessel is eliminated, as is the ment. For example, as bioprocesses are scaled up to meet
need to process large volumes of dilute broth at the end increasing demands of genetically engineered products,
of the reaction. Hollow fibers are the preferred geome- every component in a bioreactor needs to be operated
try for membrane reactors because the biocatalysts can as efficiently as possible. For mammalian cell cultures,
be confined on the shell side, lumen side, or within the high cell densities can be reached by replacing traditional
macroporous fiber walls, and because circulation on both methods of gas exchange (e.g., direct sparging, surface or
sides of hollow fibers is convenient. head-space aeration) with gas exchange membranes made
Attempts at using membrane bioreactors at the process from silicone rubber or microporous polytetrafluoroethy-
scale have been successful to different extents. One early lene, both of which operate under bubble-free conditions
example of a commercial-scale operation was the enzy- that are much less disruptive to the cell culture. In a similar
matic resolution of optical isomers to produce pharma- approach, a “dialysis fermentation” system is assembled
ceutical intermediates developed in the mid-1980s. By in- by immersing tubular dialysis membrane in a conventional
corporating a stereoselective enzyme in the microporous stirred-tank fermenter (“Improved tools,” 2000). Nutrient
structure of a membrane, then supplying the racemic sub- solution containing glucose and amino acids, for exam-
strate on one side of the membrane, one of the isomers ple, is circulated through the dialysis tubing to supply the
is converted by the enzyme and diffuses to the oppo- cells in the fermenter; the same stream carries away spent
site side of the membrane where it can be recovered. media containing lactates and ammonia. In this way, cell
The membrane serves several functions simultaneously, as densities several times higher than those in a conventional
shown in Fig. 46: containing the enzyme, offering a stable fermenter may be reached, resulting in correspondingly
interface for contacting the aqueous and organic phases, higher product yield. Another benefit is that essentially no
and removing inhibitory products continuously during the fermentation product is lost to the nutrient/waste stream
reaction. This elegant process was briefly commercialized because dialysis membranes are only permeable to low-
to resolve an intermediate to the antihypertensive drug molecular-weight compounds but not to the biomolecules
diltiazem (Lopez and Matson, 1997). However, the biore- of interest. In a third example, monoclonal antibodies are
actor approach was rendered obsolete with the advent of produced by culturing hybridoma cells in a bioreactor
chamber equipped with two membrane systems: a first
hollow fiber system circulating nutrient solutions and a
second, flat-sheet membrane forming the gas exchange
interface to supply oxygen to the cells, as shown in Fig. 47.
Another noteworthy application area for membrane
bioreactors is in wastewater or industrial effluent treat-
ment. Since the early to middle 1990s, there has been a
resurgence of interest in deploying membrane systems for
waste remediation, including oily metal finishing wastes.
A combination of increasingly stringent environmental
protection regulations, the energy-efficient character of
membrane processes, and the ease with which membrane
systems may be adapted to different scale operations,
have made it attractive to design and operate customized
microbial/enzymatic digestion systems using membranes
to contain and compartmentalize the biochemical reac-
tion. (Stephenson, Brindle, Judd, and Jefferson, 2000).
Much current effort is focused on managing fouling
and sustaining reactor productivity. These applications
FIGURE 46 Membrane bioreactor in a multiphasic configuration further illustrate a gradual transition in this field.
with reversible enzyme containment. Where membrane bioreactors were once used almost