. Low-pressure air blowdown
. Buffer displacement
. Buffer flush
. Buffer recirculation
Air Blowdown
Using air pressure to enhance volumetric recovery from a system, introduce the
pressurized line at a high point in the piping and collect the product from the
lowest point. Take care to avoid bubbling into the product, since this causes
foaming and potential product
degradation. In addition, in order to
maximize recovery the blowdown
should occur gradually, since once an
air path through the piping is formed,
further blowdown will not increase the
volumetric recovery.
Buffer Displacement
Alternatively, use buffer to push out the
remaining liquid. If this is done while
the piping is still filled with product, it
is called a buffer displacement; if it is
done after the piping has been emptied,
it is called a buffer flush. A buffer
displacement can be performed
without significantly diluting the final
product if the volume of buffer used is
only slightly larger than the volume of
piping to be cleared. Since the buffer
is being used like a plug to push the
product through the piping, in theory
no buffer should be collected in the
product tank until the product has
been completely replaced by buffer in
the piping. The effectiveness of a displacement step, however, is reduced if a
lot of mixing occurs between the buffer
displacer and the held up product.
Buffer Flush
During a buffer flush procedure, the
buffer rinses the system of residual
product. The entire amount of buffer
added to the system for the flush is
collected along with the product,
diluting the final product, so use the
minimum amount required for good
recovery. This dilution needs to be
compensated for during any
concentration steps of the process to
ensure that the final diluted product
concentration meets any specification.
Since over-concentrating a product is
often impractical because of solubility
or minimum volume reasons, a buffer
flush is not always feasible.
Buffer Recirculation
A final method for increasing the
recovery of product from the
membrane modules and piping is a
buffer recycle. For this procedure, add
buffer to the drained system,
recirculate, and then recover it in the
same manner that the product was
recovered. The buffer dilutes out any
residual product in the system. The
recirculated buffer is added to the
product, so this procedure has the
same issues of product dilution as
mentioned above. The amount of
liquid remaining in different types of
filter modules after gravity draining as
well as after draining followed by
low-pressure air blowdown compared
to the volume in the modules when full
is shown in table 2. A well-executed
Module Liquid Holdup Liquid Holdup after Liquid Holdup after
when Full Gravity Drain Drain and Blowdown
[mL m-2] [mL m-2] [mL m-2]
Pellicon 2 180 140 10
Helicon 400 20 15
Table 2. Liquid holdup in UF filter modules
Item Sanitary Consideration
Piping, Fittings Stainless Steel, 316 L or better, 20 Ra ID finish or better
buffer flush or recycle will reduce the
remaining volumes even further.
Post-Use Cleaning and Testing
After each membrane use and product
recovery, clean the TFF assembly using
the same cleaning, sanitization, and
depyrogenation protocol that was
performed before use. In addition,
perform integrity and permeability
testing. Comparing the post-use
cleaned membrane permeability with
the original value indicates the
effectiveness of the cleaning. The trend
of the value with repeated cycles can
be used to gauge expected membrane
lifetime and to set a limit on maximum
number of cycles for one set of
membranes.
Storage
If another protein processing run
doesn’t immediately follow the
cleaning, recirculate an appropriate
storage solution through the TFF
assembly to prevent organism growth.
The membrane modules must remain
filled with storage solution until the
next run to prevent drying of the
membranes. At this point, the
membranes and holder can be
isolated and removed to allow the
tank, piping, and instrumentation to be
used for other processes.
System Considerations
To implement a complete TFF process,
the piping and equipment associated
with the membrane modules must be
selected and a method for controlling
the process parameters at their
setpoints must be chosen.
Equipment Options
In addition to the membrane modules
