Proxcys B.V. is the world's primary producer of high performance low pressure cGMP compliant radial chromatography equipment

Micro RFC

Micro RFC columns: chromatographic performance of the radial column format in analytical scale volumes. Since the Micro RFC columns are an accurate scale-down...

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Lab HP-RFC

Lab HP-RFC columns offer “Radical” Chromatographic performance on bench scale. Ultra fast processing in robust processes with any resin and easy handling. Lab columns' suitability...
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SUPR columns

Extended range Micro to Process RFC columns in a prepacked-prevalidated format "plug-and-produce". Prepacked columns can be used for extended periods, dedicated projects...
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Pilot Process Industrial RFC

Proxcys High-Performance Radial Flow Chromatography (HP-RFC) columns are applicable from Pilot to Industrial scale operations. The "work-horses"...

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Accessories & Systems

Proxcys offers a full range of cGMP compliant accessories including sanitary Bubble traps, Intelligent packing systems and miscellaneous...
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Custom Engineering

Proxcys will develop and supply ancillary equipment that support your Downstream Processing tasks and handling. Sophisticated 3D modelling will allow fast turnaround...
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Dynamic Capacity

Velocity profile: larger surface area and volume of resin at outside of column = lower velocity at outside of column = improved mass transfer at outside of column = increased dynamic capacity at outside of column.

 

The velocity profile below shows lower LV at inlet side (left) increasing proportionally to higher LV at column exit.

 

The green line would be the axial alternative column. Top X-axis shows the actual volume distribution. The intersection between axial and radial is calculated. The surface area between the blue and green line below the green line (at column entrance) is the dynamic capacity gain, the area above is dynamic capacity loss.

 

Would the RFC column express a larger dynamic capacity at breakthrough experiements? No. The capacity gain at the entrance is partially negatively compensated by the loss at the inner volume. So there is no capacity gain? Incorrect!!!  

 

Calculating the added capacity gain at given bed protrusion the transition position of 80% saturation in radial lies at lesser bed protrusion (lower bed volume).

 

Since most applications will saturate up to a calculated saturation of 80% (referring to axial column saturation profile), radial column will achieve this 80% saturation at 10-20% lower bed volume, thus at about 65-70% of the radial column packed bed volume. In other words one could increase the load or the processing speed without risk of loss of product.

 

So do we have a capacity gain at radial columns.? Yes, we can only not show this gain by breakthrough curves.

 

 

So it wouldn't be interesting to look at radial when we saturate 100%.? WRONG, Review column cost, footprint.

How to transfer Axial process to Radial

Residence time is a popular parameter in transferring processes. In fact this is only valid when the bed height of the column remains the same or very similar.

 

Since Radial columns offer a stable low bed-height bed at large bed volumes, with Radial one can combine increased productivity, resin cost saving and increased product yield. Processes often run more than proportionally faster because the pressure buildup is more than proportionally less in radial columns.

 

Therefore translate residence time into (average) LV and try running a bit faster than that.

 

This transfer is done by using the reference area value which is provided with each radial column.The reference area is a imaginary cylinder (blue) which represents the corrected average surface area between the outer (2) and inner (1) boundaries Proxcys indicates the reference area in the type number of Pilot and Process HP-RFC columns e.g. CA 602 = 6cm bed height with a reference surface area of 0,2m2. Hence this column will have a flow of 200L/hr at 100cm/hr.

 

Axial:

Processing velocity expressed in LV

  • Residence time / surface area
  • Normalize to cm/hr

Radial:

Axial LV projected on Radial reference area

  • Correct for reduced pressure drop
  • Correct for increased loading efficacy

Fig. 6: From axial to radial

 

Differences in favour of Radial processing (optimizing to lower bed height)

  • Pressure drop 20-50% reduced
  • Loading efficacy improved
  • Complex feed handling improved
  • Binding kinetics (dynamic capacity)
  • Process robustness (larger process tolerance window)
  • Higher Throughput

Radial Compressed© packing results in homogenous packing

Annular Port packing demonstrated in the animation below clearly demonstrates the controlled (vertical) buildup of the resin layering it gently but firmly as a perfect cylinder against the outer frit.

 

 

Annular port Radial Compressed© packing packs the radial columns with unique precision and reproducibility. This packing technique allows accurate and reproducible packing of extremely short bed heights (< 3cm !!) and tall columns (130 cm !!). Flow rate during packing is optimized for each resin.

 

Recycling packing is the most flexible packing mode, suitable for medium- to rigid resins (sepharose, polymeric). Recycling packing procedure allows a starting slurry concentrations between 50% and 80% therewith reducing the packing vessel volume to a suitable size.

 

During the recycling packing procedure the packing liquid is fed back into the packing vessel (see scheme below), causing the slurry to be diluted during packing. The compression of the resin during Radial Compressed packing is a function of Packing velocity (energy) and packing duration (compacting). Proper balance of the hydrodynamics cause the packing to be firm and homogenous. The main recycling packing control parameters are:

  • Slurry concentration
  • Packing velocity
  • Amount of settleled resin: suplus or insufficient
  • Viscosity (density) of the packing buffer

 

Effect of resin quantity and packing velocity

Graphs below show the mechanism behind recycling packing. Diluted starting slurry will increase the durstion of packing, hence allowing the resin to compact stronger. A number of protocol variants are available to make a robust reproducible S.O.P. for the packing of any column.  

 

Fig. 5: Packing process modulation

 

The Picture shows a column being packed. ~85% of the resin is packed. The arrows point to the direction the packed bed is growing (outside-in). The clear cylinder in the middle clearly shows the accuracy of the packed bed cylinder.

 

Radial Compressed© Packing Summary

  • Easy handling and set-up
  • Fast packing
  • Reproducible
  • Compatible with all resins
  • Optimized compression
  • No loss of valuable resin
  • Packing with zero excess possible

Linear Scaling Radial Columns

Within a bed height range HP-RFC columns scale up by increase of the body height (fig. 1).

Constant

  • Bed height
  • Footprint
  • Hydrodynamics
  • Packing duration
  • Packing performance

 

Fig. 1: Linear upscaling of a radial column

Principle of Operation

The Annular packing of the HP-RFC columns results in a uniform packed bed. In the packed bed the resistance of the resin is the only parameter to determine ΔP over the length (height) of the bed.Principle_of_operation2

 

The bed length (height) is identical in A-B-C-D-E. Hence the resistance by the resin is identical in A-B-C-D-E, thus the ΔP is identical. Absolute P (top to bottom) is influenced by the height of the the column. However the water column exists on outer and inner space (communicating vessels) and therefore ΔP is still only determined by the resistance of the resin.

 

The dead-space outside the outer frit and inside the inner frit are similar the vertical liquid velocity in the dead-spaces “Vo” and “Vi” are identical Vo=V. The sloped line is a dramatized representation of the product-front. It indicates the saturation of the column will start from the top down. The "head-start" that the product in "lane-A" has over "lane-E" is lost again on the inside of the column since Vo=Vand the vertical speed is identical. Hence the height (= volume !) of the column does not influence the performance of the radial column.

 

Why would the liquid not take a diagonal through the column? The diagonal is a longer distance through the bed = more resistance. Since liquid will always take the path of least resistance. All flow will automatically align horizontal.

 

(A=B=C=D=E)

 

  • Identical Pressure drop

(ΔP1 = ΔP2 = ΔP3)

 

  • Identical velocity

(Vo = Vi)   (RV0 = RVI)

 

Suitability of radial columns for compressible media is explained in fig. 2 and 3. The forces on the media are partially radial and partially tangential causing less deformation and therefore resulting in less resistance = less operating pressure = higher flow. Even Metacrylate and polystyrene are compressed. Apart from the obvious suitability of agaroses sepharoses and celluloses, polymeric resins are extremely well suited for radial columns.

 

Pressure_and_bed_stability_axial

 

      

Pressure_and_bed_stability_radial

 

 

Fig 2: Radial Forces

  

Fig 3: Axial Forces

 

Radial:

Normal (radial) forces partially absorbed tangentially (sideways)

  • Reduced directional compression
  • Reduced deformation (soft gel)
  • Reduced flow resistance

 

Axial:

Compression forces are in-line to the direction of the flow

  • Increased directional compression
  • Increased deformation (soft gel)
  • increased flow resistance

Proxcys B.V. is the world's primary producer of high performance low pressure cGMP compliant radial chromatography equipment.

Contact

Proxcys BV

Bedrijvenweg 4

NL-7833 JH Nieuw-Amsterdam

The Netherlands

Phone: +31 591 677 447

Fax: +31 591 677 448

Email: info@proxcys.com