Page 397 - Academic Press Encyclopedia of Physical Science and Technology 3rd Chemical Engineering

P1: GLQ Final Pages
Encyclopedia of Physical Science and Technology EN009K-419 July 19, 2001 20:57

332 Membranes, Synthetic, Applications

notion is that at least one to two orders of magnitude dif- membrane separator is an example of this approach. It
ference in molecular weight between the retained species consists of a membrane mounted on a porous rotor in-
and the permeated species is required to achieve “clean” side a concentric cylinder. In operation, a suspension is
separation, as in protein solutions containing electrolytes introduced into the annular space between the membrane
and small organic molecules. and the outer cylinder while the rotor is driven at high
Clearance of viruses from biopharmaceuticals, blood angular velocity. Taylor vortices formed inside the annu-
components, and plasma derivatives is essential for safe- lar space help prevent the suspended solids from adhering
guarding against transmission of pathogenic agents. Ef- to the membrane. The solid components thus collected
fective validation of inactivation or removal of viruses is in the annular space exit in a concentrated stream while
also a regulatory requirement. Membrane filtration is used the liquid portion passes through the membrane and the
routinely, both for preventing entry of viruses into biopro- core of the rotor. In principle this design can be applied
cesses as well as clearing them prior to final packaging to various separations where concentration polarization is
of the product (Levy, Phillips, and Lutz, 1998; Aranha, a serious concern, such as cell cultures or fermentation
2001). broths (Belfort, Davis, and Zydney, 1994). In practice,
Virus particles range in size from about 20 to 300 nm the most successful application is in plasmapheresis (See
in diameter. Since they are larger in size than most pro- Section VII.B.)
teins, viruses may be segregated by size discrimination
using membranes similar to those used for ultrafiltration
3. High-Performance Tangential Flow Filtration
or nanofiltration. Depending on the concentration of the
protein, the virus targets and their sizes, dead-end filtration In biotechnology, one often encounters mixtures of pro-
(also referred to as “normal-flow filtration” or “direct-flow teins whose molecular weights differ by less than an order
filtration,”) or crossflow (tangential-flow) filtration may of magnitude. Fractionating such mixtures had not been
be more effective. Commercial membranes designed for considered feasible by traditional ultrafiltration methods.
virus removal may be isotropic or asymmetric; they are However, by the mid-1990s a strategy was developed that
used primarily for normal-flow and tangential-flow con- combinestheeffectsofsizediscrimination,chargeinterac-
figurations, respectively. Although they exhibit a range tions, management of hydrodynamics, and module design
of characteristic pore structures and sizes, virus filtration to yield exceptional selectivity in separating mixtures of
membranes are usually rated by their ability to reduce the biomoleculeswhosemolecularweightsdifferbyassmalla
titerofgivenvirusesundergivenconditionsbyalogreduc- factor as two or even less. Referred to as high-performance
tion value, LRV = log(C i /C p ), where C i and C p are the tangential-flow filtration (HPTFF), this technique begins
virus concentrations within the feed and permeate steams, with a detailed profiling of the electrochemical proper-
respectively. Regulatory guidelines usually recommend a ties of each protein to be separated, and then selecting
cumulative LRV of 12, or a twelve-log reduction in virus an operating pH to maximize the difference in the net
titer, in most protein purification processes. This is usually charge—hence accentuating the difference in the coiled
accomplished by a combination of chromatographic and or extended conformation—of the proteins. A membrane
membrane processes. is chosen whose overall pore size distribution offers the
most effective size discrimination between the dimensions
of the coiled and extended species. In operation, the feed
2. Concentration Polarization and
solution and a sweep solution are pumped tangentially
Hydrodynamic Countermeasures
across opposite sides of the membrane in co- current fash-
Other important considerations in process bioseparations ion, as shown schematically in Fig. 44 (Zydney and van
are fluid management and membrane rejuvenation meth- Reis, 2000; van Reis, 2000). Transmembrane pressure is
ods. Crossflow, or flow tangential to the membrane sur- regulated such that filtration occurs at a rate low enough to
face, induces shear at the membrane surface and helps re- prevent the rejected solute from accumulating irreversibly
duce concentration polarization. This flow pattern also on the membrane surface. To help maintain a constant lin-
creates lift forces that counteract the deposition of ear velocity of the feed and sweep streams as they tra-
particulate matter on the membrane resulting from verse the membrane surface, the flow channels are sized
permeation flow normal to the membrane surface. (See with a progressively diminishing cross section and a pro-
Section I.A.) gressively enlarged cross section on the feed and perme-
An effective method of controlling concentration po- ate sides of the membrane module respectively. The rate
larization and sustaining productivity involves inducing of cross-sectional-area change corresponds to the volu-
turbulent vortices on the membrane surface to counteract metric changes of those streams due to filtration. To con-
the forces of solute or particle deposition. The rotating serve buffer consumption, HPTFF systems are preferably