WO2003020394A1

WO2003020394A1 - Chromatography vessel

Info

Publication number: WO2003020394A1
Application number: PCT/GB2002/003933
Authority: WO
Inventors: John Davis
Original assignee: Amersham Bioscience AB
Current assignee: Cytiva Sweden AB
Priority date: 2001-08-29
Filing date: 2002-08-29
Publication date: 2003-03-13
Anticipated expiration: 2004-02-29
Also published as: GB0120805D0

Abstract

The present invention relates to a chromatography vessel in which the surface of the first end section (3) inside the vessel is convex and the surface of the second end section (5) that is inside the vessel is concave. The end sections (3, 5) are arranged concentrically and with both narrow ends pointing in the same direction and preferably with the end sections (3, 5) arranged with their interior surfaces equidistant from each other.

Description

CHROMATOGRAPHY VESSEL

Field of the Invention

The present invention relates to chromatography vessels and components for such vessels of the type mentioned in the preambles of the independent claims.

Prior Art

Broadly speaking, liquid chromatography is a method of separating compounds out of a liquid by passing a liquid containing a dissolved or suspended compound though a matrix in a liquid chromatography column. The matrices used in liquid chromatography are usually comprised of particles that are packed together in a column tube to form a bed. The bed is usually held in the tubular column by two flat end plates, each of which covers an end of the bed. One of the end plates will usually have an inlet for elution agent which prior to penetrating the matrix bed is passed through a porous plate or machined element which distributes the flow uniformly over the surface area of the end of the column. The other end plate usually has an outlet for elution agent which prior to entering the outlet passes through a porous plate which collects the flow uniformly over the end area of the bed prior to the elution agent exiting through the outlet. Additionally a fine net is often placed between each porous plate or machined element and the matrix bed in order to prevent the matrix material from leaving the confinement of the column. A problem with such prior art devices is that the column is a pressure vessel and as the flat plates at either end of a cylinder are part of the pressure containing envelope they need to be thick enough to withstand said pressure. Additionally deflection of said end plates needs to be kept to a practical minimum so as not to affect the separation process. This results in the end plates having to be made even thicker. As end plates are typically made out of metal, e.g. stainless steel, this results in them being heavy. This makes then unwieldy and expensive to machine and to handle. Additionally, as they are heavy then the column walls and end plate supports have to be made strong enough, and provided with heavy flanges or the like, to support them and this leads to the columns becoming very heavy and expensive to construct. A further problem with prior art chromatography columns is that the diameter of the columns is increasing due to market demand. This increase in diameter is resulting in columns that are extremely heavy and cumbersome. These large columns also need more floor space and strong flooring capable of supporting them.

Summary of the Invention

According to the present invention, at least some of the problems with the prior art are solved by means of a chromatography vessel having the features present in the characterising part of claim 1 and a chromatography vessel end section having the features of the characterising part of claim 14.

Brief Description of the Figures

Figure 1 shows schematically a section through a first embodiment of a chromatography vessel in accordance with the present invention,

Figure 2 shows a plan view of the vessel of figure 1,

Fig 3 shows schematically a section through a second embodiment of a chromatography vessel in accordance with the present invention,

Figure 4 shows a plan view of the vessel of figure 3;

Figure 5 shows schematically a section through a third embodiment of a chromatography vessel in accordance with the present invention and,

Figure 6a-6c) shows schematically further embodiments of a chromatography vessel in accordance with the present invention.

Detailed Description of Embodiments Illustrating the Invention Figure 1 shows schematically a vertical section though a first embodiment of a chromatography vessel 1 in accordance with the present invention. Vessel 1 comprises a first, upper conical end section 3 of diameter DI and a second, lower truncated conical end section 5 of diameter D2. In this embodiment DI is less than D2. End sections 3 and 5 are arranged so that they are substantially concentric and are joined together by a truncated conical vessel wall 7 of width d (where the width of the vessel wall is defined as the distance between the mutually facing inner surfaces 9 resp.l 1 of the upper and lower conical end sections at their circumferences) which connects the outer circumference of end section 3 with the outer circumference of end section 5. The internal angle of end section 3 is α degrees and the internal angle of end section 5 is β degrees. In this embodiment angles α and β are the same, and vessel wall 7 is attached at a nominal angle of 90 degrees to the planes of the surfaces of the end sections 3, 5 so that the perpendicular distance between inner surface 9 and inner surface 11 is substantially equal over the whole of the inner surface 9. The tip of end section 3 and the narrow end of end section 5 both point in the same direction, namely, in this embodiment, downwards.

End section 3 is provided with at least one fluid inlet 13, preferably three or more. In this embodiment of the present invention there are four equally spaced fluid inlets in the form of hollow tubes 13 that pass though end section 3 and communicate with the cavity 15 formed between the end sections 3, 5 and vessel wall 7. Cavity 15 contains the chromatography matrix 17 when the vessel is being used.

h this embodiment of the present invention the downward facing, convex surface 9 of end section 3 that faces toward the inside of the vessel is provided with a fluid distribution system 19 which distributes, preferably equally over the inner surface 9, any fluid entering the vessel though fluid inlets 13. Fluid distribution system 19 can be any suitable system, such as appropriately shaped (e.g. conical) removable or fixed plates with fluid distributing channels, a coarse mesh or the like mounted on inner surface 9 or channels formed in the surface 9 itself, etc. The surface area of conical surface 9 (which has a maximum diameter of DI) is greater than the surface area of a circular flat surface of diameter D 1. Therefore the vessel in accordance with the present invention can achieve the performance of a larger column with conventional flat end plate, and can do so with a smaller diameter and footprint. Additionally, as the non-flat end section is inherently more rigid that a flat end plate of the same material thickness it can be made thinner that a flat end plate for a prior art column of comparable size or pressure containment requirements. For example, if angles α and β are both 90°, if the vessel wall height is 200 mm, the wall thickness is 12.5 mm, DI is 1.4 m then the diameter of the foot print of the vessel i.e. D2 would be about 1.7 m (needing a floor space of 2.27 square metres), and the surface area of conical surface 7 would be 3.73 square metres which is equivalent to the end plate surface area of a 2.17 m circular column. Thus with the present invention the performance of a prior art column needing 3.73 square metres of floor space can be achieved by a vessel in accordance with the present invention which only needs 2.27 square metres of floor space.

A conical mesh or the like 21 for preventing the vessel matrix 17 from entering the fluid distribution system is attached to end section 3. Mesh 21 preferably has a shape which is complementary with that of the inner surface 9 and is preferably mounted so that it is substantially equidistant from inner surface 9. As mesh 21 is conical, its shape imparts it with a natural rigidity which may allow it to be simply fastened at its circumference to end section 3 or vessel wall 7, for example by a continuous seam weld if it and end section 3 or vessel wall 7 are made of suitable materials, instead of requiring a number of intermediate fixings.

In a similar manner, end section 5 is provided with at least one fluid outlet 23, preferably three or more. In this embodiment of the present invention there are four equally spaced fluid outlets 23 in the form of hollow tubes 23 that pass though end section 5 and communicate with the cavity 15. The upwards facing, concave surface 11 of end section 5 inside the vessel is provided with a fluid collecting system 25 which collects equally over the inner surface 11 fluid that has passed though the matrix 17 and transports the fluid to the outlets 23. Fluid distribution system 25 can be any suitable system, such as removable or fixed appropriately shaped (e.g. shaped as a truncated cone) plates with fluid distributing channels or a coarse mesh or the like mounted on inner surface 11 or channels formed in the surface 11 itself.

A truncated conical mesh 27 for preventing the matrix 17 from entering the fluid system is attached to end section 3. Mesh 27 preferably has a shape which is complementary with that of the inner surface 11 and is preferably mounted so that it is substantially equidistant from inner surface 11. As with mesh 21, the shape of mesh 27 imparts it with a natural rigidity which allows it to be simply fastened at its outer circumference to end section 5 or vessel wall 7 and, if desired by its inner circumference to end section 5 or a valve body 29 described below.

The skilled person understands that the position and number of inlet and outlet tubes will vary dependant on the diameter/cross sectional area of the end sections. It is also possible to reverse the direction of flow, i.e. hollow tubes 13 could be outlets and hollow tubes 23 could be inlets.

End section 5 has a central opening 31 and may with fitted with a valve body 29 that forms part of a valve system that may be used for filing the vessel, emptying the vessel and/or cleaning the interior of the vessel.

Figure 3 shows schematically a second embodiment of the present invention. In this embodiment end section 3 is joined to vessel wall 7 to form a rigid top cover unit 35. Unit 35 is movable up and down in order to vary the volume of the vessel. This can be used to pack the media and also allows the distance between the end sections to be varied if different bed heights are desired. This is achieved by means for varying the bed height in the form of pneumatic or hydraulic actuators 37 or other lifting devices such as jacks or hoists, etc. attached at one end to unit 35 and at the other end to an extension 39 of end section 5. Sealing means (not shown) prevent leakage at the mating surfaces between vessel wall 7 and extension 39.

Figure 4 shows a plan view of the second embodiment of the present invention.

Figure 5 shows schematically a third embodiment of the present invention in which the direction of fluid flow during a chromatography process is from the larger diameter end section 5 to the smaller diameter end section 3. This appears to be the best arrangement for chromatography. Fluid enters the device though a fluid inlet 13 connected to a fluid channel 61 in valve body 29, which channel 61 leads to fluid distribution system 19 which distributes the fluid over the inner surface 11 of end section 5. Fluid is removed from the device via one or more outlets 23 provided on end section 3. Figure 5 illustrates an example of means for filling the cavity 15 with chromatographic matrix 17. A matrix inlet in the form of a tube 51 is connectable to a matrix channel 53 which leads to a central cavity 55 in valve body 29. Central cavity 55 is joined to an opening 57 in valve body 29 which opens into cavity 15. Central cavity 55 has a larger cross section than opening 57. Opening 57 may be opened and closed by a movable piston 59 with a cross section adapted to fill opening which can be raised into an upper, sealing position in which it closes opening 57, and which can be lowered to a lower, open position in which there is a through path from matrix inlet 51 through matrix channel 53, central cavity 55 and opening 57 into cavity 15. The device can be filled by lowering piston 59 into the lower position, pumping matrix into the device via matrix inlet 51, matrix channel 53, central cavity 55 and opening 57 and allowing air and/or fluid displaced by the matrix to escape via outlets 23. Preferably one or more outlet 23 is positioned at the highest part of the device in order to allow all air to leave the device. Once the matrix has been loaded into cavity 15, pumping of matrix into the device is stopped and the piston 59 is raised to the sealing position. The device can be emptied by lowering piston 59 and allowing the matrix to flow out though opening 57, central cavity 55, matrix channel 53 and matrix inlet 51. The emptying can be accelerated by providing one or more gel removal inlets 63 in wall 7 which lead directly into cavity 15. These inlets are normally closed during use of the device, but when the matrix is to be removed they can be connected to a source or high pressure liquid or gas and used to pressurise the matrix, thereby speeding up the flow of it out of the cavity 15.

Figure 6a) shows a third embodiment of the present invention in which both end sections 3', 5' have the same diameter (i.e. DI = D2) and the vessel wall is vertical. In this example, the two end sections 3', 5' have the same surface area.

Figure 6b) shows a fourth embodiment of the present invention in which end sections 3", 5" are in the shape of quadratic pyramids. It is also conceivable to use other projecting shapes such as triangular pyramids, hemispheres or other rounded sections, etc for the end sections.

Figure 6c) shows a fourth embodiment of the present invention in which end sections 3 " ', 5'" are positioned with their narrow ends pointing upwards. Angles α and β can be any desired angle as long as the end sections are not flat. Preferably they are around 90° (for example between 60° and 120°) as these angles give a good rigidity to the end sections while keeping the difference in surface areas of the two end sections relatively small - although this is of course also dependent on the distance between the end sections, i.e. the height d of the vessel wall. Smaller angles, e.g. where α and β are 59° or less, lead to smaller vessels footprints for a given end section surface area, but a given increase in bed height causes the vessel to increase in width more (or the difference between the surface areas of the end sections to increase more) than for a vessel with larger angles α and β.

Preferably DI is chosen so that the diameter (or some other dimension related to the width for non-circular end sections) of first end section 3, 3', 3", 3'" is between 50% and 95% of the diameter of second end section 5, 5', 5", 5'", more preferably between 60% and 90% and most preferably between 65% and 85% of second end section 5. The relative dimensions of DI and D2 can be varied depending on the degree of chromatographic efficiency required. For given angles α and β, increasing the difference between DI and D2 implies an increase in the bed height at the same time as the amount of chromatographic tailing increases. If the increase in bed height is advantageous and the increased tailing of little or no disadvantage then it may be preferable to have DI much smaller than D2. If, on the other hand, it were necessary to reduce tailing, then a smaller bed height and consequently a DI nearer to D2 would be preferable.

Larger angles α and β, e.g. where α and β are 121° or greater, give wider vessels for a given end section surface area and have reduced end section rigidity, but a given increase in bed height has a smaller effect on the width of the vessel.

An advantage of a chromatography device in accordance with the present invention is that it weighs less than a conventional column of equivalent performance because the rigidity of the end sections imparted by their non-planar shape permits the use of thinner material. This is particularly advantageous for high pressure and/or high throughput columns which have to resist deformations caused by high pressures and/or the height weight of the column contents. Thus a 1.2 m chromatography device in accordance with the present invention weighs approximately 750 kg while a conventional 1.2 m column weighs over 2 tonnes. While the embodiments shown have end sections with angles and β which are the same it is conceivable to have vessels in which α and β are different.

It is also conceivable to stack devices in accordance with the present invention, i.e. to place one column above another, preferably one nestled in the other, whereby capacity can be doubled while the space required is not doubled.

The above mentioned embodiments are intended to illustrate the present invention and are not intended to limit the scope of protection claimed by the following claims.

Claims

1. Chromatography vessel comprising a first end section (3, 3', 3", 3'") and a second end section (5, 5', 5", 5'") separated by a vessel wall (7) characterised in that said the inner surface (9) of said first end section (3, 3', 3", 3"') that is facing the second end section

(5, 5', 5", 5'") is convex and has an interior angle of α°, and that the inner surface (11) of said second end section (5, 5', 5", 5'") that is facing said first end section (3, 3', 3", 3'") is concave and has an interior angle of β°.

2. Chromatography vessel in accordance with claim 1 characterised in that said first end section (3, 3', 3", 3'") is conical and/or said second end section (5, 5', 5", 5'") is conical.

3. Chromatography vessel in accordance with claim 1 characterised in that said first end section (3, 3', 3", 3'") is pyramidal and/orsaid second end section (5, 5', 5", 5'") is pyramidal.

4. Chromatography vessel in accordance with any of the previous claims characterised in that and β are between 30° and 150°.

5. Chromatography vessel in accordance with any of the previous claims characterised in that and β are between 60° and 120°.

6. Chromatography vessel in accordance with any of the previous claims characterised in that α and β are nominally 90°.

7. Chromatography vessel in accordance with any of the previous claims characterised in that it is provided with means for varying the bed height (37).

8. Chromatography vessel in accordance with any of the previous claims characterised in that α and β are the same.

9. Chromatography vessel in accordance with claim 1 characterised in that said end sections (3, 3', 3", 3"', 5, 5', 5", 5'") are dished.

10. Chromatography vessel in accordance with any of the previous claims characterised in that the surface area of the inner surface (9) of first end section (3, 3', 3", 3'") is between 50% and 95% of the surface area of the inner surface (11) of second end section (5, 5', 5", 5'")

11. Chromatography vessel in accordance with any of the previous claims characterised in that the diameter DI of first end section (3, 3', 3", 3'") and is between 50% and 95% of the diameter D2 of second end section (5, 5', 5", 5"').

12. Chromatography vessel in accordance with any of the previous claims characterised in that the diameter DI of first end section (3, 3', 3", 3'") and is between 60% and 90% of the diameter D2 of second end section (5, 5', 5", 5'").

13. Chromatography vessel in accordance with any of the previous claims characterised in that the diameter DI of first end section (3, 3', 3", 3'") and is between 65% and 85% of the diameter D2 of second end section (5, 5', 5", 5'").

14. End section (3, 3', 3", 3'", 5, 5', 5", 5'") for a chromatography vessel in accordance with any of the previous claims characterised in that it is formed with a non-flat shape which provides it with a greater inherent rigidity than a flat plate made of the same material with the same thickness.