Friday, May 6, 2011

TFF Under Pressure

By Dr. Scott Rudge

Are there scale up issues for cross flow filtration?  In general, this step is overlooked as a scale up concern, and usually, given the primarily clean feed streams encountered in simple buffer exchange, this is warranted.  However, forewarned is forearmed when scale up is concerned.

Primarily, there is just one scale up issue with cross flow filtration, and that is the path length on the retentate side of the filter.  The flow on the retentate side of the filter is meant to continuously clean the filter surface, and prevent fouling, or at least limit it to a thin boundary layer.  The shear rate created by the fluid at the filter surface increases as the square of the linear velocity of the fluid.  The pressure drop through the filter module, from inlet to outlet, depends linearly on the length of the module, and also on the square of the linear velocity.  In many cases, a manufacturing scale module is about a meter in length.  However, on the lab scale, a module is likely to be closer to 10 cm.  Therefore, the pressure drop from the inlet to outlet on the retentate side will be 10 times higher at constant linear velocity on scale up from lab to manufacturing.  Since decreasing the flow rate will dramatically decrease the shear rate, the increased pressure will drive higher flux towards the membrane surface, increasing the thickness of the boundary layer and resulting in more surface polarization (fouling or gel formation, potentially). 

One approach taken to this predicament is to keep the pathlength constant on scale up.  This is analogous to maintaining constant bed height on chromatography scale up, an approach I disfavor.  The result of this approach is a “horizontal” scale up, where more and more units of lab proportion are lined up side by side.  This approach works, but is cumbersome and requires more and more manifolding for flow distribution, and other inconveniences.  It also assumes that the length of filter the manufacturer provides is the best and only length for every application, which is absurd.  However, this is an approach commonly pursued, and recommended by the filter manufacturers for its speed and certainty.

Another approach that is taken to this phenomenon is to increase the back pressure on the permeate.  This slows down the permeate independent of changes on the retentate side of the filter.  However, if the back pressure on the retentate side is greater than the pressure at any point along the filter on the retentate side, permeate will flow back to the retentate side.  This is clearly inefficient, it means a particular fluid element will be filtered at least three times, crossing from retentate to permeate, then back to retentate, and then eventually back to permeate on a subsequent pass.  This also means that the effective filtration area is decreased, as some portion of the filter is working in reverse, and another portion is working to correct the back flow.  The negative flow counts against filter area that is filtering in the positive direction.

Finally, employing a constant pressure gradient along the retentate side is worth trying.  Presuming the membrane geometry is essentially maintained on scale up (including spacers in the flow channel) maintaining constant pressure gradient along the retentate channel length means shear will be constant on scale up.  Pressure drop from retentate to permeate will be higher at the retentate inlet, but if the shear is appropriate and the boundary layer controlled, this will only lead to higher flux, which may be preferred.  This can be tested on the small scale by applying back pressure on the retentate and looking for leveling off of the flux vs. pressure curve.  As long as flux vs. back pressure is increasing linearly, you can get improved performance at higher pressure.  Then upon scale up, the pressure at the retentate inlet is held constant.  It is certainly worth exploring longer path lengths on scale up, performance may improve!

In the end, either horizontal scale up will be used, or some reduction in retentate flow rate will probably be required.  The result of the latter will be less shear at the membrane surface, but the payback will be in increased filtration efficiency.  Some back pressure should be applied to the retentate side on the lab scale, as more pressure due to path length will almost surely need to be applied in manufacturing.  Maintaining pressure drop on the retentate side with increased module length, along with back pressure on the permeate side usually results in successful scale up of a lab cross flow filtration procedure.

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