Slurry Valves

“An outsider view: The path less traveled”

One of the things that makes the VERDOT InPlace™ Chromatography Column unique is the patented slurry valve used for transferring resin slurry into and out of the column.

The VERDOT slurry valve consists of a simple spring-loaded, air-actuated piston made of polyetheretherketone (PEEK). When instrument air (6 Bar) is applied to the valve, the piston moves to the open position (see slurry valve open and close animation), and resin slurry can be gently transferred into or out of the column.

When instrument air is released, the piston moves to the closed position (see slurry valve open and close animation) so the valves and slurry manifold can be flushed with a sanitization agent (usually 1N sodium hydroxide) and rinsed with WFI. In the closed position, there is no contact with the packed bed.

What makes the VERDOT slurry valve different?

First, a little background: At laboratory scale, packing chromatography columns is fairly straightforward. Just remove the top adapter, pour your slurry in, and flow pack to consolidate the bed.

For large scale chromatography, it’s impractical to remove the top adapter to pour slurry into the column. As columns increase in diameter to accommodate process scale manufacturing, the top adaptor becomes too heavy and cumbersome to easily move in and out of the column. Furthermore, there is an unacceptable risk of contamination with open columns in a GMP area.

And so “pack-in-place” columns were introduced, where the column remains static with the headplate installed. One of the biggest challenges in the design of pack-in-place columns was how to transfer the resin slurry into a closed system. For the majority of pack-in-place process scale chromatography columns, the slurry is transferred through a centrally placed valve. That is, the valve is placed right in the middle of the flow distribution plate.

For many of these columns, the type of pack-in-place technology used is called “stall packing”, where the slurry is transferred through the central nozzle while the mobile phase (i.e., packing buffer) exits through the process valve(s). The slurry is transferred through a diaphragm pump at a high flow rate to create a compressed bed inside the column until the pump “stalls”, meaning that the backpressure is too great to add more slurry. With many types of chromatography resin, this packing technique can create a non-uniform bed where the most densely packed parts of the bed are either against the column wall, or close to the spray nozzle.

Central spray nozzles have a number of disadvantages including:

• Interference with normal process flow
• A non-uniform packed bed
• And most of all, potential shear of fragile chromatography resins.

The first iteration of the VERDOT  slurry valve in 1999 provided a solution to the shortcomings mentioned above. One of the biggest advantages with the VERDOT slurry valve is actually not in the design but in the placement –  they are located on the wall of the column (Figure 1) instead of in the center of the flow distribution, so there are no areas of delayed flow as in the case of the centrally placed nozzles (Figures 2 and 3).

To perform dye testing as shown in Figures 2 and 3, a solution is prepared with a visible marker (in this case, phenol red). The dye does not interact with the resin functional groups and flows freely through the base matrix of the bed. A small volume (1.5% CV) is injected and downward flow continues until the marker is in the middle of the bed height. Then it gets a little messy! Once flow is stopped, the top adaptor is removed and the resin is scooped out so that the marker can be evaluated. Trust me, it’s harder than it seems to make it look neat!In any event, if you look at the colored line in the middle of the bed, what you will notice is that for the InPlace Column (Figure 2), the line is straight across the middle with no disruption whereas in the traditional column, there is a gap directly over the central nozzle. This means that there is essentially no flow in that area of the bed.

Perhaps the most important aspect of the VERDOT slurry valve design is that it minimizes mechanical shear. Many types of chromatography resin (e.g., ceramic hydroxyapatite, methacrylate, etc.) are sensitive and can be easily fractured in high velocity applications. Using a spray nozzle for slurry transfer is a potential source of particle damage. With the VERDOT slurry valve, resin slurry can be gently transferred into the column to reduce mechanical shear stress.

To ensure even distribution of slurry during transfer, there are usually 2 slurry valves for columns smaller than 45cm diameter and up to 8 for columns up to 2m in diameter.

In 2007, VERDOT redesigned the slurry valve to streamline operation, improve clean-in-place (CIP) capability and simplify preventive maintenance steps. The newer sanitary design allows for cleaning of the valve and slurry manifold once the column is packed, without any disturbance to the bed.

The slurry valve design is still used in InPlace columns today, one of the distinguishing features that makes Verdot columns stand out.