stability at high pressures help to
guide the choice of a unit operation
that will operate robustly.
Process Economics
The economics driving the success or
failure of TFF process steps are case
specific, since different applications
have very different economic goals.
For some very high value products, the
product cost is relatively insensitive to
the economics of a single process
step, while for other products every
cost must be minimized for the product
to be competitive. The costs
associated with TFF steps break down
into four categories – capital, materials,
labor, and overhead.
Typical capital costs include
membrane holders, plant floor space
requirements, utilities, pumps, valves,
instrumentation, piping, tanks, and
process automation. A unit operation
with the smallest acceptable
membrane area minimizes the cost
associated with the holders and
piping. An efficient unit operation will
have a high packing density of
membranes, requiring minimal plant
floor space for a large membrane
area. Manually operated systems
have lower instrumentation and
automation costs associated with them
than fully automated systems.
Optimizing the diafiltration step and
minimizing the number of different
buffer or cleaning solutions will
minimize tank costs. Finally, a system
that processes multiple products will
be able to split capital expenses over
a larger profit base.
Typical materials costs include
membrane modules, buffer and water
usage, cleaning chemical usage,
power consumption, and product loss.
As with the capital costs, consumable
costs are minimized if as low a
membrane area as acceptable is
installed. Choosing membranes that
are easy to clean helps to reduce the
water and chemicals used after each
run. Labor costs are reduced by using
an automated unit operation, but this
will increase capital expenditures.
The number of times a set of
membranes will be used before
installing new membranes affects the
labor and materials costs. For single
use membranes, the membrane
expense is high. However, labor,
power consumption, and
water/chemical costs associated with
cleaning are minimized. In addition,
the cost for validating the acceptability
of reuse is avoided. The labor
required for installing a new set of
membranes before each run could be
high, depending on the membrane
area and module type. On the other
hand, using membranes for multiple
runs lowers the per-run membrane cost
at the expense of higher power,
water, chemical, and validations
costs. However, if a single set of
membranes is used for an excessive
number of runs, the value gained by
not installing a new set of membranes
is negated if membrane performance
begins to degrade. This approach
also greatly increases both validation
costs and risk to the product.
Glossary of Terms
Cb: Component concentration in the bulk
solution [g L-1]
Cf: Component concentration in the filtrate
stream [g L-1]
CF: Protein concentration factor [-]
CR: Conversion ratio [-]
Crossflow: The flow of fluid through the
feed channels of the membrane modules
created by a pump
Cw: Component concentration at the
membrane surface [g L-1]
DF: Diafiltration
DV: Diavolume [-]
Feed: The fluid that flows from the recycle
tank into the feed channels of the
membrane modules
Filtrate: The fluid that passes through the
membranes, also commonly called
permeate
HPTFF: High performance tangential flow
filtration
Jf: Filtrate flux [L m-2 h-1]
Jm: Mass flux [g m-2 h-1]
kD: Kilodalton
Mass balance: The amount of the target
product in all pools compared to the total
amount put into the unit operation [%]
MF: Microfiltration
NFF: Normal flow filtration
NMWL: nominal molecular weight limit
PF: Feed pressure [bar]
Pf: Filtrate pressure [bar]
Pool: A general term denoting a total
volume of fluid
PR: Retentate pressure [bar]
QF: Feed flow rate [L h-1]
Qf: Filtrate flow rate [L h-1]
QR: Retentate flow rate [L h-1]
Rapp: Apparent or observed retention [-]
Recirculation: The flow of fluid through the
channels of the membrane modules
created by a pump
Retentate: The fluid that flows out of the
feed channels of the membrane modules
back into the recycle tank
Ri: Intrinsic retention [-]
RO: Reverse osmosis
Sapp: Apparent or observed sieving [-]
