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TMP

In a TFF unit operation, filtrate flux
increases with increasing TMP up to a
point and then it levels off. The first
part of the curve, where the flux
increases with pressure, is the pressure
dependent regime. Here, the primary

membrane resistance. The second,
level part of the curve is the pressure
independent regime. In this section,
the concentration of protein at the
membrane surface is high and a
significant portion of the applied
pressure is working against the protein
osmotic pressure. As protein
concentration increases or feed flow
rate decreases, the TMP at which the
flux plateaus decreases. A typical
trend of flux with increasing TMP,
protein concentration, and feed flow
rate is shown in figure 9.

If the process is run with a TMP
setpoint in the pressure independent
regime, maximum flux is achieved,
and this minimizes the required
membrane area. However, the protein
wall concentration is high and could
exceed a solubility limitation, leading
to yield losses. On the other hand, if a
TMP setpoint is chosen in the pressure
dependent regime, fluxes are lower
and more membrane area is required.
Therefore, for a standard UF/DF
process, the optimum TMP at which to
run a process is at the knee of the
curve, where nearly the highest flux is
achieved without exerting excessive
pressure or reaching exceedingly high
protein wall concentrations. For HPTFF
processes, where two similarly-sized
components are being separated, the
optimum operating point is determined
differently.

Transmembrane Pressure (bar)
Flux(L m-2 h -1 )
Optimum
Operating Point
High Protein Concentration
or Low Feed Flow
Filtrate Control

Many TFF applications apply a
crossflow and pressure setpoint and
the filtrate flows uncontrolled and
unrestricted out of the module. This is
the simplest type of operation and
most concentration and/or diafiltration
processes where the target product is
in the retentate operate in this manner.
For other applications, however, it is
helpful to use some type of filtrate
control beyond that achieved by
simply adjusting the pressure with the
retentate valve.

When using very open UF
membranes, the membrane
permeability is so high that nearly all
of the crossflow is converted to filtrate
with very little applied TMP. Although
this results in high fluxes, it is similar to
operating in an NFF mode and the
benefits of the tangential flow are lost.
Often, very high wall concentrations
and high membrane fouling occur,
especially during the startup of the
process. To reduce the filtrate rate and
enable the TMP to be controlled at the
low values required for robust TFF
operations the filtrate flow must be
controlled.

In a controlled flow filtrate
operation, a pump or valve on the
filtrate line restricts filtrate flow to a set
value, as shown in Figure 10. In
addition to reducing the filtrate flow to
maintain adequate tangential flow, it
creates pressure in the filtrate line to
reduce the TMP while the feed and
retentate pressures remain fixed.

Low Protein Concentration
or High Feed Flow

factor limiting flux is the fouled

Figure 9. A typical trend of flux versus transmembrane pressure for a TFF process

Diafiltration Retentate Valve to
Buffer Return Apply Pressure
Retentate
Pressure

Filtrate
Pump

Filtrate
Stream

Feed
Tank Feed
Pressure
Filtration
ModuleFeed
Pump
Figure 10. Schematic of a TFF system using a pump for a filtrate control

Membrane Area

After determining the process flux and the total volume to be processed, the
membrane area required for the final unit operation can be determined.
However, since flux is filtrate flow rate divided by both area and time, the
membrane area is also a function of the total process time. Choosing a longer
process time leads to lower membrane area requirements. This is beneficial
because membrane and capital costs are reduced. In addition, unrecoverable
holdup volume is lower in smaller unit operations, minimizing yield losses.
However, excessively long process times put the product at risk for quality
degradation and/or bioburden contamination. Interestingly, product pump
passes do not change significantly because a low-area operation has a low