and holder, at minimum a working TFF
operation requires a recycle vessel, a
feed pump, a retentate control valve,
and pressure sensors for the feed and
Connections Tri-Clamp. style retentate lines. Many systems also
include feed and filtrate flow meters, a
Elastomers EPDM, silicone filtrate pressure sensor, and sensors for
Valves Diaphragm preferred temperature, pH, conductivity, or UV
absorbance.
Pumps Circumferential piston displacement, rotary lobe, centrifugal Most TFF systems used for protein
Instrumentation Sanitary fluid flow path (materials and design) processing are operated in a sanitary
manner. Table 3 lists the primary
Table 3. Acceptable components and materials for sanitary systems
sanitary design considerations for
different system components.
Finally, consider the process
requirements for volume reduction,
buffer exchange, and product
recovery when choosing equipment
design and layout. In a typical
ultrafiltration process, the maximum
practical VCF is approximately
50 – 100 before the limitation of
minimum recirculation volume in a
single tank becomes a significant
problem, even when more novel tank
designs are used. Examples of tank
features that can reduce the minimum
recirculation volume are a conical
bottom, a reduced-diameter lower
section, and a low side-entry retentate
return port. Likewise, diafiltration of
non-retained species is typically limited to a maximum of approximately
14 diavolumes, since beyond this any
incomplete mixing or deadlegs in the
system will significantly reduce the
effectiveness of further buffer exchange
or contaminant removal.
Postprocessing recovery of a retentate
product is enhanced when a system
has minimal deadlegs, minimal piping
length, and piping that is sloped to a
recovery port at the lowest point.
Process Control Options
Throughout a TFF process, as protein
is concentrated or exchanged into
different buffers, the process
parameters need to be adjusted so
that they remain at their setpoints.
Several methods of process control are
used to accomplish this. The tangential
flow can be controlled to maintain
either
. Constant crossflow rate
. Constant pressure drop
The applied pressure can be
controlled to maintain a constant
. Retentate pressure
. TMP
. Flux
. Cwall
. Mixed mode control
Fully automated 80 m2 Pellicon system for concentration and diafiltration.
Constant Crossflow Rate
To control the tangential flow based
on crossflow rate, install a flow meter
on the unit operation downstream of
the feed pump and prior to the membrane modules. The benefit of this type
of control is that the crossflow rate is
known to be constant even if the
resistance to flow through the feed
channels changes. Constant crossflow
control is especially useful when
processing solutions that experience
viscosity changes during processing
and to facilitate accurate pump sizing
during scale-up.
Constant Pressure Drop
Alternatively, control the tangential
flow by setting a constant feed
pressure or pressure drop. A flowmeter
is not required for this type of control,
only pressure gauges are needed, so
the instrumentation is simpler and less
expensive. However, pressure drop
often changes throughout a process
due to changes in solution viscosity or,
occasionally, restriction of feed
channels by foulants. In addition,
variability in membranes and feedstock cause lot to lot pressure drop
changes. When choosing a method
of tangential flow control, consider the
characteristics of the process fluid as
well as the precision required to
achieve process objectives.
Constant Retentate Pressure
The simplest way to control the
applied pressure is to set a constant
retentate pressure by adjusting a valve
on the retentate line. For unit
operations where the tangential flow is
controlled based on a crossflow rate,
the TMP changes slightly throughout
the process. For unit operations where
the tangential flow is controlled based
on a pressure drop, the TMP remains
constant.
Constant TMP
Alternatively, set a constant TMP for
crossflow rate controlled operations by
changing the retentate pressure
setpoint throughout the process as the
feed pressure changes. This is slightly
more complicated and there is usually
no significant benefit.
Constant Flux
Change the retentate pressure
throughout a process in response to
changes in the filtrate rate to maintain
