Figure 1. Schematic Illustration of a Tangential Flow Filtration System
Membrane Evaluation
The experimental set-up should mimic the large-scale installation in its essential elements (Figure 1). Choose the smallest
membrane module that is a true linear scale-down version of the full-scale modules with identical flow-path length, channel
height, and ports.2 Use a lab-scale rotary lobe pump as the recirculation pump since these pumps produce relatively low shear and provide constant
flow rate against varying pressure and are typically used in production-scale systems. Peristaltic pumps, however, produce
flow with significant pressure fluctuations, especially when operated at high pressure, and the results obtained in the lab
may not be readily scalable. It is useful to install flow meters on the retentate and permeate streams. Simple in-line rotameter-type
flow meters (with a suspended float and a transparent tube with a variable area of cross-section) are effective for this purpose
except for very turbid feed streams.
Determine the volume of product required per experiment based on estimates of membrane flux (see "Calculation of Product Volume")
and obtain the estimated volume of representative feedstream. Assemble the membrane cartridge and measure the initial water
permeability as recommended by the manufacturer. The membrane manufacturer usually provides a range of recirculation flow
rate for a given type of cartridge. Run the recirculation pump to generate a flow rate in the middle of the range recommended
by the manufacturer. Partially close the retentate valve (V1 in Figure 1) to generate a retentate back-pressure (P2 of 5-15 psig for microfiltration, 20-40 psig for ultrafiltration). Keep the permeate valve (V2) open for the initial experiment. Monitor permeate flow rate during the experiment by collecting permeate in a vessel placed
on a balance. Collect samples of permeate and retentate at intervals to assay for product concentration. As the operation
proceeds, the volume of material in the feed tank will decrease, and the concentration of retained species (in this case,
cells and cell debris) will increase. Continue processing until the feed volume is close to the system hold-up volume or
until the permeate flow drops to less than 25% of the initial value. Obtain a sample of the permeate pool and the retentate
at the end of the process. Drain the system and rinse and clean the membrane as recommended by the manufacturer. Measure the
water permeability after cleaning. Calculate the average permeate flux. Evaluate product transmission (ratio of product concentration
in permeate to that in the retentate) at different points in the run and plot against product load (L/ft2) as shown in Figure
3.
Significant fouling of the membrane will be indicated by a sharp drop in product transmission and permeate flux. Figure 3
shows the product transmission during the clarification of cell harvest for two types of membranes. Product transmission drops
off more quickly for membrane A compared to that for membrane B, suggesting that the product may be binding to membrane A
or that significant membrane fouling occurs with membrane A .
Calculate overall product recovery as:
Measure key quality attributes of the product in the permeate pool. For example, if the product is known to aggregate, fragment,
or lose biological activity under high shear, compare these attributes in the feed and permeate samples to ensure that the
product is not adversely affected.
Anurag S. Rathore, PhD, is a consultant, Biotech CMC Issues, and a member of the faculty in the department of chemical engineering at the Indian Institute of Technology. Rathore is also a member of BioPharm International's Editorial Advisory Board.
Articles by Anurag S. Rathore, PhD
Jerold Martin is the senior vice president of global scientific affairs at Pall Life Sciences. He also is the chairman of the Board and Technology Committee at Bio-Process Systems Alliance.
Articles by Jerold Martin
