Biomedical Engineering Reference
In-Depth Information
is especially critical to robust and consistent design. Hence, an understanding of both the
membrane and the operating conditions are necessary in TFF to determine the solute
separation. Fortunately, given the well-developed fundamentals of fluid flow and mass
transfer, proven approaches have been developed and are summarized and presented here
to provide a “Quality by Design” understanding of TFF system operation. These design
approaches enable reliable specification of the transmembrane pressure driving force
and the compensating tangential flow to optimally balance the complex and competing
mass transport effects seen with TFF.
6.4 TFF DESIGN OBJECTIVES
In designing a TFF operation, the major design objectives in order of importance are as
follows:
1. Product recovery
2. Membrane recovery
3. Filtrate flux rate
Designing for product recovery ensures cost-effective operation and involves
evaluating factors such as membrane selectivity, membrane adsorption, and shear
degradation. Membrane recovery enables cost-effective reuse of membranes, reduces
change-out time, and aids in lot-to-lot consistency. Optimizing filtrate flux rate mini-
mizes the membrane area and operating time. Since the operating parameters impact
each of the above objectives, they must be simultaneously addressed during the design
process. A clear set of QbD principles is thus critical to the optimal and robust
specification of the TFF process.
6.5 MEMBRANE SELECTION
The first step to designing a TFF step is to select the membrane that will give the best
separation performance for a given feed stream. Cellulose acetate, polyvinylidene
difluoride (PVDF), polysulfone (PS), and polyether sulfone (PES) are the most common
membrane types of membrane media employed in biotechnology applications [15].
Asymmetric membranes generally offer the best performance and consist of a thin skin
(
m
0.1-0.5
m) that serves as the solute barrier on top of a polymeric substrate layer
m
(
m) that supports the thin skin [16]. The thin skin of the membrane largely
determines the rejection of solutes in the feed stream. The composite structure of
asymmetric membranes provides both excellent retention and permeate flux. While the
membrane itself is the dominant factor in determining retention of solutes, retention also
depends on several operating factors. For example, protein transport across an ultrafil-
tration membrane has been modeled as the transport of a colloidal particle through a
liquid-filled pore [17]. Since the size and shape of a protein is influenced by its pI
(isoelectric point), solvent, pH, and ionic strength, these factors will affect the retention
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