CLEANING CHROMATOGRAPHY PACKED BED MATERIAL WITH THE AID OF A PROCESSING VESSEL, AND SAID VESSEL

Abstract

Packed bed gel material cleaning vessel, has an internal processing volume, to contain the gel, delimited by a circumferential, axially extending, upright vessel wall at both axial ends sealed by a top vessel wall and an opposite bottom vessel wall, the internal processing volume is above 10 litre; sensors of the vessel monitor the filling level of the vessel. A bottom filter completely covers the vessel bottom wall A circumferential, axially extending, cylindrical vertical filter is provided a short radial distance, e.g. between 1 and 20 millimetre internally from, parallel and concentrically with, the upright vessel wall, providing a torus like flow gap concentrical with the upright vessel wall.

Claims

1-12. (canceled)

13. Packed bed gel material cleaning vessel, wherein the vessel has an internal processing volume, to contain the gel, which volume is delimited by a circumferential, axially extending, upright vessel wall (during normal operation of the vessel) at both axial ends sealed by a top vessel wall and an opposite bottom vessel wall, wherein the internal processing volume is more than 10 litre and wherein sensors of the vessel monitor the filling level of the vessel; and wherein the vessel is “sanitary” and all surfaces delimiting the spaces that contain gel or liquid flowing to or from the gel are mirror polished in stainless steel.

14. The vessel according to claim 13 has the following features: a bottom filter extends closely above the vessel bottom wall, such that liquid internal of the vessel can only enter the space internal of the vessel at the opposite side of the bottom filter by passing through the bottom filter; a lower vessel volume under the bottom filter, in which the liquid that has downwardly passed through the bottom filter is collected internally of the vessel above the bottom vessel wall and below the bottom filter; a separate bottom particle draining port in the axial centre of said bottom filter, for draining of the upper vessel volume (above the bottom filter and containing the gel) from the vessel to the outside through the vessel bottom wall; this bottom particle draining port is sealed from the lower vessel volume below the bottom filter and is in fluid communication with the upper vessel volume above the bottom filter, via a draining pipe sealingly penetrating the bottom filter and the vessel bottom wall; the external access to and from the lower vessel volume below the bottom filter is provided by a bottom draining port and is sealed from the external access to and from the upper vessel volume via the bottom particle draining port; thus liquid free of gel particles and thus able to pass the bottom filter can be extracted from or added to the upper vessel volume, into respectively from the lower vessel volume via the bottom filter and the bottom draining port (arrow D) while independent or simultaneously gel can be extracted from or added to the upper vessel volume via the bottom particle draining port (arrow B); a circumferential, axially extending, cylindrical vertical filter is provided a short radial distance from, parallel and concentrically with, the upright vessel wall, providing a torus like flow gap concentrical with the upright vessel wall; the top edge of this vertical filter is above the maximum fill level (for the gel) of the vessel; a vertical filter-draining port in the external wall of the vessel, at the lowest point of the vertical filter acts as liquid access to the flow gap (arrow C); a mixer axially of the vessel, equipped with vessel internal blades near and above the vessel bottom filter, to stir the content of the upper vessel volume.

15. The vessel according to claim 13, wherein the top vessel wall is equipped with a vessel inlet tube and a handway; wherein the vessel inlet tube is designed to deliver its liquid from above against the vertical shaft of the mixer at an angle of 45 degrees relative to the vessel axial direction, debouching just above the maximum fill level and wherein the mixer shaft acts as a guide for the liquid further down into the gel.

16. The vessel according to claim 13, wherein the vessel bottom wall is provided with grooves at its upper face, wherein the grooves are straight and designed to collect and distribute the liquid over the complete surface of the vessel bottom wall, wherein there are provided long grooves and short grooves branching from the long grooves, wherein each long groove debouches at the central outlet port and extends radially outward to the outer circumference of the upright vessel wall and a short groove branches from each long groove at a location between the opposite longitudinal ends of the long groove, and wherein the pattern of grooves resembles a leaf grain.

17. The vessel according to claim 13, wherein the suspension of the mixer stirrer shaft is provided with a washing system mounted on top of the vessel, providing a gap around the shaft that is in fluid connection with an inlet channel and an outlet channel, such that the gap can be flown through by a liquid, flowing from the inlet channel to the outlet channel wherein the gap, completely filled with liquid, provides a liquid sleeve circumferentially and axially around the drive shaft, wetting and/or washing it.

18. The vessel according to claim 17, wherein the suspension of the mixer stirrer shaft is provided with a means that provides an expandable housing for the drive shaft part that is displaced between above and below the top plate while changing between the high and low position.

19. The vessel according to claim 13, wherein a filter comprises at least two layers of woven wires of stainless steel, directly laid on top of each other providing a united assembly, each layer has a pore size at least 20% different from the immediately adjacent layer, wherein a layer is directly exposed to the gel in the vessel.

20. A method of cleaning used gel for a packed bed chromatography column by using the cleaning vessel according to claim 14, wherein the gel comprises beads having a diameter between 10 and 1100 micrometre (0.01-1.1 millimetre), wherein after use in the liquid chromatography separation column, the gel is taken from said column and introduced into the upper vessel volume to make it ready for re-use, wherein process liquid is added to the gel inside the vessel and the mixture of gel and process liquid in a mixed state inside the upper vessel volume is, stirred by the vessel mixer; during the processing of the gel, liquid is supplied to the upper vessel volume via the bottom particle draining port (arrow B), thus above the bottom filter, and via the vessel inlet tube (arrow A), and filtered liquid is, after having passed through the relevant filter, withdrawn from the lower vessel volume via the bottom draining port (arrow D) and from the flow gap between the vertical filter and the upright vessel wall via the vertical filter-draining port (arrow C).

21. Method according to claim 20, at the end of processing of the gel, the liquid supply via the bottom particle draining port (arrow B) and the vessel inlet tube (arrow A) is stopped and the gel content inside the upper vessel volume is concentrated by continuing removing filtered liquid via the bottom draining port (arrow D) and the vertical filter-draining port (arrow C).

22. Method according to claim 20, wherein “floating bed” draining is applied, wherein liquid is supplied to the upper vessel volume via the bottom filter and the bottom draining port, so flowing from the bottom draining port in the bottom wall upward through the bottom filter into the upper vessel volume (opposite arrow D); this results in a local dilution of the mixture just above the bottom filter, creating a floating bed onto which the gel mixture floats.

23. Method according to claim 22, wherein during “floating bed” draining the supplied liquid flows from the bottom draining port into and along the grooves such that the liquid is evenly distributed across the top surface of the bottom plate and subsequently passes the bottom filter, evenly distributed across the top surface of the bottom filter and thus creating a “floating bed” evenly distributed across the top surface of the bottom filter; and during “floating bed” draining the bottom particle draining port is opened and the “floating bed” created causes the gel to easily flow into the bottom particle draining port by gravity action, avoiding leaving particulate residue behind on the upper surface of the bottom filter facing the top vessel wall.

24. Method according to claim 20, wherein the filter surface facing the internal of the vessel is such that the gel cannot enter the cavities of the filter; this provides that the beads of the gel will always stay on top of the filter surface.

Description

NON-LIMITING EXAMPLES

[0067] The accompanying drawings, which are incorporated and form a part of the specification, illustrate an embodiment of the invention and, together with the description, serve to explain the principles of the invention. Shown is in:

[0068] FIG. 1 an example of a chromatography column of radial type in sectional side view;

[0069] FIG. 2 the column of FIG. 1 in top view;

[0070] FIG. 3 a perspective view of a torus shaped filter bed;

[0071] FIG. 4 a sectional side view of an example of the preparation vessel;

[0072] FIG. 5-6 a detail of FIG. 4 at a larger scale;

[0073] FIG. 7 an alternative to the FIG. 4 vessel;

[0074] FIG. 8 a possible application of the vessel;

[0075] FIG. 9-10 the vessel bottom plate in top and perspective view, respectively;

[0076] FIG. 11 the top part of the vessel in perspective view;

[0077] FIG. 12 a picture of the top part of the vessel during operation; and

[0078] FIG. 13 a detail in sectional side view of a component at the top part of the vessel.

[0079] The following reference numbers are used: column 1; cylindrical housing wall 2; axial housing end plate 3; seal 4; liquid inlet 5; liquid outlet 6; packed bed 7; inner flow channel 8; outer flow channel 14; core 15; inner frit 16; outer frit 17; axial bed end plate 18; distribution space 19; collector space 20; outflow channel 21; liquid outlet 22; bed height H; outer frit radius R1; inner frit radius R2; axial direction arrow A; vessel top plate 31; inlet tube 32; drive shaft 33 of the mixing vanes 24. The radial direction is perpendicular to the axial direction.

[0080] The liquid chromatography column shown in FIG. 1 comprises: a housing, of cylindrical shape, defining a chamber therein and including a removable axial end plate 3 of circular shape; a first (outer) and second (inner) porous frits 16, 17 or membranes of cylindrical shape; a bed 7 or packing of particulate chromatographic separation material positioned intermediate said porous frits; optionally an axially extending core 15. The axially extending cylindrical external housing wall 2, first 17 and second 16 frit and core 15 are coaxial.

[0081] The torus shaped packed bed 7 allows the radial flow (viz. the arrows in FIG. 2) of process liquid through the column.

[0082] FIG. 4-13 elaborate the preparation vessel. Above the top wall 31 a drive motor 40 is present from which a drive shaft 33 extends vertically downward towards mixing vanes 24 at the bottom of the vessel 23, to mix the vessel contents. Below the mixing vanes 24 the bottom filter plate 26 is present just above the vessel bottom wall 10. FIG. 4 shows: liquid is supplied from the top (arrow A) and bottom (arrow B). Liquid from the vessel upper internal storage space is drained as follows: after downward passage through the bottom filter (arrow D) or after sideways passage through the vertical filter (arrow C). An alternative for the vessel upper internal storage space: extraction of processed gel (opposite arrow B) and liquid supply through the bottom filter (opposite arrow D), e.g. for “floating bed” draining.

[0083] FIG. 7 slightly differs from FIG. 4 and illustrates the mutual location of the vertical filter 29, bottom filter 26, bottom particle draining port (arrow B), vessel lower internal storage space 9, vessel upper internal storage space 21, vessel bottom wall 10, vessel circumferential (in this case cylindrical) wall 2, vertical draining port (arrow C), bottom draining port (arrow D), mixing blades 24, seal 11, vertical collection space 35.

[0084] FIG. 5-6 illustrate the flow sideways through the vertical filter 29 and into the flow gap 35, subsequently within the flow gap 35 downwards towards and into the collection channel 34 at the lower edge of the vertical filter 29 and subsequently from the collection channel sideways through the outlet (arrow C).

[0085] FIG. 8 shows the vessel 23 of FIG. 7 during cleaning of gel. The gel is supplied from container L2, cleaning liquid is supplied from container L1. Liquid is recirculated (lines C+D) and finally dispensed with by switching the valves in a different position.

[0086] FIG. 9-10 show the vessel bottom wall 10, in the shape of a funnel or reversed dome, having its lowest point at the axial centre of the vessel (or: the centre of the vessel bottom wall, seen in top view) and the central outlet port is located at the axial centre and crosses the bottom plate 10.

[0087] FIG. 9-10 show the inventive pattern of grooves in the top face (i.e. the to the inner space of the vessel facing face) of the vessel bottom wall (also called: bottom plate) to drain liquid to the central outlet port. Each long straight groove 12 debouching at the central outlet port extends radially outward from the central outlet port to the outer circumference of the vessel circumferential wall and a short straight groove 13 branches from each long groove at a location between the opposite longitudinal ends of the long groove, extends towards and makes a sharp angle of at least 10 degrees with the long groove and ends at its distal end at a radial distance from the location where the radial outer end ends and also is spaced from an adjacent long or short groove. Thus, each long groove is branched once. It could be said that the pattern of grooves resembles a leaf grain. Adjacent long grooves make a mutual angle. The number of long grooves is 16. A short groove branches from the long groove at 50% the long groove length. A short groove and corresponding long groove make a mutual angle of 22.5 degrees. A short groove has its distal end at equal distance to its associated long groove and the adjacent long groove. In the space between two adjacent long grooves only a single short groove extends. All long grooves have their short groove at the same side, as viewed in tangential direction (in other words: clockwise). The pattern of long and short grooves has a symmetry, e.g. a rotational symmetry of order 16.

[0088] FIG. 11 shows the top plate 31 that carries the inlet tube 32. The nozzle of the inlet tube 32 has an inclination of 40 degrees relative to the vertical and faces and is located 10 millimetre from the drive shaft 33 such that it ejects the liquid against the vertically oriented drive shaft 33.

[0089] FIG. 12 shows the top plate 31 that carries the drive motor and associated stirrer shaft 33 and mixing vanes 24 of the mixer. By lifting means of the vessel 23, the complete mixer can take a low position (vanes at short distance above the bottom sieve 29) and a high position (as shown; vanes 24 above the maximum vessel fill level). The bellows 41 provides an expandable housing for the drive shaft part that is displaced between above and below the top plate 31 while changing between the high and low position.

[0090] FIG. 13 shows the inventive suspension showing that the length part of the drive shaft inside the suspension 45 is embedded by a sleeve of wash liquid contained within a gap 44 between the suspension and the drive shaft 33. The flow of wash liquid from the inlet 42 to the outlet 43 is such that the wash liquid is forced by axial and radial internal grooves at the surfaces of the mixer suspension 45 facing the drive shaft, to flow in radial and axial direction across the drive shaft surface. In this manner the drive shaft surface of a length part of the drive shaft, accommodated inside the suspension, is thoroughly wetted and flooded all around by the advancing wash liquid. There are spaces around the drive shaft inside the suspension 45 that become filled with wash liquid.

[0091] The measures disclosed herein can be taken together individually in any other conceivable combination and permutation to provide an alternative to the invention. Included are also technical equivalents and genuses or generalizations of the revealed measures. A measure of an example is also generally applicable within the scope of the invention. A measure disclosed herein, for example of an example, can be readily generalized for inclusion in a general definition of the invention, for example to be found in a patent claim.