Page 396 - 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 331

B. Process Bioseparation 1. Separation by Size or Charge Discrimination
At the end of successful discovery and clinical trial phases Whenever a large difference in size exists among species
of a biopharmaceutical development program, the goal to be separated, the task of selecting membrane processes
is production on a scale large enough to be commer- and materials is relatively simple. Often the choice is gov-
cially attractive. Through a series of scale-up operations, erned by the characteristic size of the species to be re-
a laboratory-scale procedure is transformed to process- tained. For example, microfilters and ultrafilters are gen-
scale equipment and protocols. Membrane processes have erally used to retain and purify particulates and soluble
been shown to be readily scalable—i.e., the performance macromolecules, respectively, as discussed in previous
of large systems may be accurately predictable from sections. Experience over several decades of laboratory-
the behavior of small systems—and economically com- and process-scale practice has led to some rules-of-thumb.
petitive with other means of separation such as chro- For example, hydrophobic membranes are prone to inter-
matography. Today, membrane processes have become a action with various proteinaceous materials. Nonspecific
broadly adopted unit operation in the biotechnology in- binding of solutes reduces the likelihood of a clean sep-
dustry in which as much as 90% of the overall manufac- aration; it also increases the risk of fouling and conse-
turing cost may be attributed to separation and purifica- quent loss of flux. Hydrophilic membranes are therefore
tion operations. A number of membrane processes that preferred for most bioseparations. Similarly, membranes
are suitable alternatives to conventional processing tech- bearing functional groups undergo acid–base equilibrium
niques are listed in Table XI. A recent reference focusing in response to the pH and ionic strength of its aqueous en-
on filtration in biopharmaceutical production covers the vironment. The resultant charge on the membrane surface
use of membranes and depth filters, including detailed interactswiththenetchargeonsolutesrangingfromamino
monographs on various sectors of this regulated industry acids to proteins whose electrochemical signatures are de-
(Meltzer and Jornitz, 1998). termined by their isoelectric points. A widely accepted

TABLE XI Conventional Bioseparation Technologies and their Membrane-Based Alternatives
Conventional
Unit operation bioseparation process Membrane process Membrane process feature

Cell harvesting Centrifugation Crossflow microfiltration (MF) Separation does not rely on density differences
Ultrafiltration (UF) High cell densities obtainable
Whole-broth clarification Rotary vacuum drum filtration Crossflow MF, UF Maintains high throughput
Centrifugation Does not require filter aids
Protein concentration Electrolyte/solvent UF Recovery and purification performance
and purification precipitation Diafiltration controllable via membrane selection
Membrane-modulated Some fractionation possible
precipitation
Affinity column Membrane-based affinity Much higher throughput
chromatography separation Smaller investment in expensive ligands
Reduced hold-up volume; thus lower product
loss risks
Economical scale-up
Ion-exchange column Membrane-based ion exchange High volumetric efficiency
chromatography chromatography
Desalting Size-exclusion Electrodialysis Higher throughput for given size of equipment
(gel-permeation) Dialysis
chromatography Economical even at large scale
UF
Acid/base recovery Chemical treatment Bipolar membrane synthesis Requires no chemical additive; products may
Ion exchange be directly recycled
Microsolute concentration Vacuum evaporation Reverse osmosis Reduced loss of volatile products
Pervaporation
Membrane distillation Less damage to heat-sensitive substances
Solvent extraction Podbielniak extraction Membrane solvent extraction Minimum emulsification and associated
entrainment loss
Coupled transport Enhanced selectivity and concentration