Ultra-Thin Channel Filtration (UTF™)

UTF™ is a new modality for the concentration of biomolecules and buffer exchange by ultrafiltration. It relies on dead-ended filtration to deliberately build a concentrated boundary layer on the surface of the membrane – in that sense, it can be thought of as the anti-TFF. Once the boundary layer is built it is removed from the channel by a combination of reverse permeation and displacement with the feed stream. It is, therefore, a repetitive cycling process.

The UTF™ Concentration Process comprises two steps executed continuously in rapid succession:

  1. Loading: the feed stream is loaded into the UTF™ channels in dead-ended mode, building the boundary layer on the surface of the membrane.

  2. Recovery: the boundary layer is removed by a combination of reverse permeation and displacement with the feed stream.

These two steps – Loading & Recovery – are repeated every 30~120 seconds, e.g., Loading for 60 seconds and Recovery taking 5 seconds.

A graph titled 'Dead-ended Flux Decay: 10 grams per liter IgG
						 at 55 psi'. The x-axis is time in minutes between x=0 and x=2, and
						 the y-axis is volumetric flux in liters per square meter per hour
						 between y=0 and y=100. A rough exponential decay function is
						 graphed, running through the approximate points (0, 67), (1, 31),
						 and (2, 23). The section of the graph bounded by points (0, 67)
						 and (1, 31) is boxed in by a rectangle whose sides are arrows
						 pointing in a counter-clockwise manner. The bottom arrow, pointing
						 in the positive x direction, is labeled 'Load: 60 seconds'. The
						 top arrow, pointing in the negative x direction, is labeled
						 'Recovery: 5 seconds'.
Flux Decay and UTF™ Steps

As expected, the instantaneous flux during the loading step decreases with time. However, once the boundary layer is removed, the flux recovers fully for the next cycle, delivering a high average stable flux for the duration of the process.

Since the permeation flux – the productivity – of an ultrafiltration membrane in dead-ended mode decreases with time, the UTF™ process requires thin channels to obtain a practical flux: at the end of the Load Step the boundary layer almost completely fills the channel. UTF™ channels are microfluidic channels with channel heights on the order of 50~100 µm.

UTF™ can also be used for buffer exchange. In this case the UTF™ Process comprises an additional Washing Step between the Load and Recovery steps. After the boundary layer is built during the Load Step, a wash buffer is fed to the UTF™ channel to displace the feed buffer through the concentrated boundary layer.

Similarly to Single-pass TFF, the UTF™ modality is a single-pass process with all the advantages of single-pass operation: simpler system and low residence time (low protein exposure time). However, in contrast to Single-pass TFF, UTF™ processes are simpler having only a single degree of freedom – the load time. Furthermore, UTF™ modules are more versatile than Single-pass TFF modules – the same UTF™ module can be used for many applications.

The UTF™ module and process are covered by US Patent 9,511,326 “Cycling ultra-thin channel filtration” and pending international patents.


Ultrafiltration (UF) and microfiltration (MF) membranes have become essential to the separation and purification in manufacture of biomolecules. Biomolecular manufacturing, regardless of its scale, generally employs one or more steps using filtration. The attractiveness of these membrane separations rests on several features including, for example, 25 high separation power, and simplicity, requiring only the application of pressure differentials between feed and permeate. This simple and reliable one-stage filtering of the sample into two fractions makes membrane separation a valuable approach to separation and purification.


A need still exists for MF and UF processes suitable for bioprocessing which are able to yield high conversion, high productivity, and lower buffer consumption without the need of recirculation loops, intermediate pumps, and without the complexity of the systems and the modules of the single-pass processes developed to date. It would be desirable to operate a bio-processing separation process in a single pass mode without a recirculation loop while providing a high conversion with a relatively low hold up volume and simple separation modules.

It would be further desirable to operate the separation without the requirement of a high capacity feed pump and associated system interconnections. Operation of a diafiltration process in a single pass mode with simple separation modules would also be desirable especially when the technique does not require high buffer consumption. It would also be desirable to reduce bioprocessing system cost by reducing the complexity of the system and by using simpler more versatile separation modules.

Commercial Applications

A commercially important area for UF separations and purification is the purification of biomolecules for therapeutic drugs. Both naturally derived and genetically engineered biomolecules require multiple TFF steps to concentrate the biomolecule and to purify the biomolecule, including a process to wash the biomolecule by a process known as diafiltration. These TFF steps require custom systems to carry out batch processes that last several hours requiring large in-process tanks to hold the batch while it is being processed. These custom systems have large hold up volumes, are complicated and expensive, and have other limitations.

Another commercially important area for UF separations and purification is the preparation of analytical samples (e.g., sample volumes less than about 1000 ml). The application of conventional TFF processes to sample preparation at the analytical scale is generally believed to be impractical due to complications inherent in the use of pumps and recirculation loops.