Disposable radial flow chromatographic column

Abstract

A liquid chromatography column, utilizing a horizontal or radial flow of sample material passing through it, preferably in an inward direction, comprising: a housing defining a chamber therein and including at least one removable end section, for example, a screw cap; first and second longitudinally extending porous frits located within said chamber of said housing; a bed or packing of chromatographic separation material, preferably particulate, located within said chamber of said housing and between said porous frits, the first of said porous frits being adjacent to said housing and an inlet channel, the second of said porous frits being located adjacent to a central element and an outlet channel; distribution means operatively connected to said inlet channel;collecting means operatively connected to said outlet channel, said distribution means and said inlet channel being constructed to direct the associated material to be separated in said bed uniformly along a longitudinal length of said bed in a substantially horizontal direction.;

Description

[0001] The present invention relates to a column for liquid chromatography, which includes a column tube intended to be filled with a separation medium, and inlet and outlet means.BACKGROUND

[0002] It is often necessary or desirable to fractionate a fluid mixture to separate out / Isolate useful or desired components. This can be achieved by using liquid chromatography systems.

[0003] With the need for high performance chromatography, horizontal or radial flow type chromatographic columns were developed.

[0004] As used herein, the terms "horizontal or radial flow mode", which are used interchangeably, are defined as flow of the sample or eluant fluid through the chromatographic column in a direction that is perpendicular to the longitudinal axis of the column, regardless of the position of the column relative to the work bench or support stands or other equipment used to support or stack the columns.

[0005] This chromatographic separation in a radial, in other words horizontal, mode may be accomplished by means of a chromatographic column constructed so as to have an inner and outer annuli, with the matrix material being packed there between. The bed height is thus computed as the distance between the inner and outer annuli. Chromatography consequently takes place radially in the column. Furthermore, radial flow may also be achieved in a cubic arrangement where the flow takes place between two vertically held end plates.

[0006] Chromatography columns utilizing radial flow of sample material passing therethrough are disclosed in patent documents US 4 676 898 and US 4 708 782 and in article "Evaluation of radial chromatography versus axial chromatography, practical approach" (CABANNE, JOURNAL OF CHROMATOGRAPHY B: BIOMEDICAL SCIENCES & APPLICATIONS, vol. 845, no. 2, 12 January 2007).DISCLOSURE OF THE INVENTION

[0007] The object of the invention is to provide a radial flow high performance chromatography column which is improved over the prior art column of this type by substantially lowering fabrication costs, providing small footprint and high throughput.

[0008] The invention relates to a liquid chromatography column according to claim 1. The removable axial / longitudinal end section is, preferably a screw lid (such that preferably by turning / rotating the section itself it can be mounted / dismounted relative to the column).

[0009] Preferably, one or more of the following further features apply to the inventive column: the exhaust channel is coaxial with the first or second frit; the supply channel is radially spaced from the housing centre and / or the exhaust channel; the housing has a substantially cylindrical wall; the exhaust channel extends substantially the complete height of the chamber; the supply channel extends at an angle of at least 10 degrees relative to the exhaust channel; the cartridge, in the operative position within the chamber, extends from the end section opposite the removable lid beyond the axially extending housing wall; the exhaust channel extends inside, preferably lengthwise of, the core member and / or debouches at the axial / longitudinal end of the core member within the chamber; the core member extends substantially the complete height of the chamber; the core member penetrates the lid; the core member projects from the lid; the lid has a circumferential flange or depending skirt that carries internal, preferably repeatedly disconnectable and connectable, mounting means, e.g. screw thread, engaging external, preferably repeatedly disconnectable and connectable, mounting means, e.g. screw thread, at the axially extending housing wall; the lid has a central bore penetrated by the core member; the central bore of the lid has a circumferential, axially extending flange tightly engaging a circumferential recess in the top face of the top end wall connecting the first and second frit for positive locating of the packing within the housing; the core member is a separate part that preferably carries external, preferably repeatedly disconnectable and connectable, mounting means, e.g. screw thread, preferably engaging internal, preferably repeatedly disconnectable and connectable, mounting means, e.g. screw thread, of the closure; the core member keeps with its axial / longitudinal end a gap with the end section preferably opposite the removable lid and / or tapers towards the end section preferably opposite the removable lid; the distribution means comprise a radially narrowing, preferably the core member circumventing distribution space, preferably between the end section, preferably lid, and the space containing the packing and the supply channel preferably connects to, more preferably debouches into, said distribution space; the cross sectional area of the outlet channel increases, preferably continuously, along the axial direction, preferably due to the taper of the core member; one of the end sections, preferably the one opposite the lid, contains a means, such as a closable fill port, to supply the space between the frits with packing material for column packing purposes, while the column is completely assembled (e.g. a fill system according to WO2007136247 (Raedts); between the core member and at least one of the lid and the cartridge or the end wall connecting the first and second frit a seal is present; the device has a handy outer dimension in the order of one litre contents.NON-LIMITING EXAMPLES

[0010] 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. Fig. 1 shows the column in perspective view; Fig. 2 shows the column of fig. 1 in sectional side view; Fig. 3 and 4 show the column of fig. 1 in sectional perspective view from two different angles; Fig. 5 shows a detail of fig. 2 at larger scale; Fig. 6 shows a further detail of fig. 2 at larger scale; Fig. 7 shows a perspective view of the cartridge; Fig. 8 shows the cartridge of fig. 7 in sectional view; Fig. 9 shows the core member in sectional side view and in perspective view; and Fig. 10 and 11 show the main elements in exploded view, the cartridge located aside the housing, wherein in fig. 10 the main elements are shown in section.

[0011] The liquid chromatography column shown in fig. 1-11 comprises: a housing defining a chamber therein and including a removable screw lid such that this lid can be mounted and dismounted by turning around the lid; a first (outer) and second (inner) porous frits or membranes; a bed or packing of particulate chromatographic separation material positioned intermediate said porous frits; an axially extending core. The axially extending cylindrical external housing wall, first and second frit and core are coaxial.

[0012] The first frit is adjacent the axially extending cylindrical external housing wall and defines with said wall a cylindrical shaped ring type inlet channel. The second frit is adjacent the core member and defines with said core member a cylindrical shaped ring type outlet channel.

[0013] The lid is penetrated by both a supply and exhaust channel. The exhaust channel is coaxial with the core and extends through the core to debouch just above the bottom end wall of the housing. The supply channel is radially spaced from the core and the exhaust channel. The exhaust channel extends substantially the complete height of the chamber. The supply channel extends at an angle of 15 degrees relative to the exhaust channel. This allows for optimised supply flow characteristics.

[0014] The first and second frit are part of a cartridge removably contained in the housing. At both axial ends the first and second frit are connected by a radial extending end wall closing the space between the first and second frit to capture the doughnut shaped packing. The bottom end wall of the cartridge simultaneously provides the bottom wall of the housing and is releasable mounted to the axial housing wall through a circumferential shoulder at said wall.

[0015] The lid has a radially outer depending skirt that carries internal screw thread, engaging external screw thread at the axially extending housing wall. Viewed in the axial direction from the housing bottom end, the cartridge extends beyond the axially extending housing wall. The top part of the cartridge thus co extends with the depening skirt of the lid. This allows for ease of fine tuning of the merge of the distribution space and the inlet channel.

[0016] The cartridge plus the core almost completely fill the housing. Between the top face of the cartridge and the bottom face of the lid there is a distribution space into which the supply channel debouches. This distribution space tapers in the radial outward direction and merges at the radial outer circumference with the circumferential extending inlet channel. The circumferential outlet channel, surrounding the core, tapers towards the lid along the core and merges at the lower end of the core with a collector space delimited between the lower core end and the bottom end of the housing. This tapered shape of the outlet channel is due to the opposite taper of the core. The taper of the inlet and outlet channel optimises flow characteristics.

[0017] The core is a separate part that carries external screw thread engaging internal screw thread of a central bore in the lid. The central bore of the lid has a circumferential, axially extending flange or depending skirt tightly engaging a circumferential recess in the top face of the top end wall of the cartridge. Below the skirt, the core tightly penetrates the top wall of the cartridge. By means of this, both the lid and the core provide for positive locating of the cartridge within the housing. It could however be sufficient if only one of these positive locating means is applied.

[0018] The bottom end of the cartridge contains a centrally located closable fill port, to supply the space between the frits with packing material for column packing purposes.

[0019] O-ring type seals are applied to seal the core to the lid and the cartridge and to seal the lid to the axial extending housing wall.

[0020] The column operates as follows: Fluid is introduced through the supply channel into the distribution space and from there flows radially outward towards the inlet channel. In the inlet channel the fluid flows axially downward to be evenly distributed across the complete surface of the first frit. Then, passing the first frit, the fluid flows radially inward through the packing to arrive at the second frit. Subsequently the fluid flows evenly distributed across the complete surface of the second frit through the second frit to arrive into the outlet channel. The fluid flows axially downward through the outlet channel, along the outer face of the core to be collected in the collection space. From there the fluid flows into the exhaust channel to flow axially upward through the core.

[0021] The cartridge can be replaced by unscrewing the lid and subsequently axially extracting the core from the cartridge while axially removing the lid. The cartridge is subsequently lifted from the inward projecting shoulder at the lower end of the circumferential wall of the housing by axially extracting the cartridge. Extracting / removing the lid, core and cartridge takes place in the same direction.

[0022] Further embodiments are also covered by the attached claims.

Claims

1. A liquid chromatography column, utilizing radial flow of sample material passing therethrough, comprising: a housing defining a chamber therein and including at least one removable axial end section; a first and second longitudinally extending porous frits positioned within said chamber of said housing; a bed or packing of, chromatographic separation material positioned within said chamber of said housing and intermediate said porous frits, the first of said porous frits being adjacent said housing wall and defining with said wall a cylindrical shaped ring type inlet channel; a core member centrally located in said housing chamber, the second of said porous frits being positioned adjacent said core member and defining with said core member a cylindrical shaped ring type outlet channel; distribution means operatively connected to said inlet channel; collector means operatively connected to said outlet channel; a supply channel operatively connected to the distribution means and an exhaust channel operatively connected to the collector means; said distribution means and said inlet channel being constructed to direct associated material to be separated in said bed evenly across a longitudinal length of said bed in a substantially inward radial direction, wherein said porous frits are coaxially positioned with respect to one another, said first porous frit having a larger cross-section than said second porous frit, characterised in that the packing is contained in a removable cartridge comprising the first and second frit and an axial end wall connecting both frits and closing the packing containing space; one of the axial end sections is penetrated by both the supply and exhaust channel.

2. The apparatus according to claim 1, wherein the core member is a separate part penetrating the removable axial end section and the cartridge.

3. The apparatus according to claim 1 or 2, wherein the supply channel extends at an angle of at least 10 degrees relative to the exhaust channel.

4. The apparatus according to any of claims 1-3, wherein the supply channel is radially spaced from the housing centre and / or the exhaust channel.

5. The apparatus according to any of claims 1-4, wherein the cartridge or first and / or second frit are fixedly located by a housing wall or part of it, e.g. skirt or flange and / or the core member.

6. The apparatus according to claim 5, wherein the cartridge or first and / or second frit are located by means of a tightly fit of parts.

7. The apparatus according to any of claims 1-6, wherein the removable axial end section is a screw lid.

8. The apparatus according to any of claims 1-7, wherein the removable axial end section is penetrated by both the supply and exhaust channel.

9. The apparatus according to any of claims 1-8, wherein the chromatographic separation material is particulate.

10. The apparatus according to any of claims 1-9, wherein the radial flow of sample material passing through the liquid chromatography column is in inward direction.

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