WO2012074452A1

WO2012074452A1 - Chromatography column assembly comprising a sealing device

Info

Publication number: WO2012074452A1
Application number: PCT/SE2011/051294
Authority: WO
Inventors: Robert Charles Towill
Original assignee: Biotage Ab
Priority date: 2010-11-30
Filing date: 2011-10-28
Publication date: 2012-06-07
Also published as: FR2967916A3; FR2967916B3; AU2011101524A4; JP3187642U; ITMI20110345U1

Abstract

The present invention relates to a chromatography column assembly comprising a chromatography column (13) and a chromatography column sealing device (5), wherein the chromatography column (13) comprises a tubular body (17) having an open end (18) and an inner surface (12), and wherein the chromatography column sealing device (5) comprises a cylindrical body (6) comprising an upper end (7) and a lower end (8), having a main axis A extending along the body (6), and having a height H along the axis A between the upper and lower ends (7, 8). The chromatography column sealing device (5) further comprises a connection port (9), for connecting the chromatography column sealing device (5) to a source of fluid for chromatography analysis. The connection port (9) is a canal (10) extending along the axis A from the upper end (7) to the lower end (8) of the cylindrical body (6), and the cylindrical body (6) is provided with a circumferential outer surface (11) adapted to abut against an inner surface (12) of the chromatography column (13). The cylindrical body (6) is further provided with a circumferential outer surface (11) adapted to abut against the inner surface (12) of the chromatography column (13) along substantially the entire height H, and wherein the circumferential outer surface (11) is adapted to be fixed in relation to the inner surface (12) of the chromatography column (13).

Description

Title

Chromatography column assembly comprising a sealing device

Field of the invention

The present invention relates to a chromatography column assembly, and a method of producing said chromatography column assembly according to the preambles of the independent claims. Background of the invention

In order to purify individual chemical compounds from mixtures of compounds a chromatography column may be used. A classical chromatography column is a metal, glass or plastic tube with a diameter from 5 mm to 50 mm and a height of 50 cm to 1 m with a tap at the bottom.

An example of a chromatography column according to the prior art is disclosed in US 20080217250 Al .

In US 20050082213 Al a further example of a chromatography column is disclosed. The chromatography column is provided with a plug which is adapted to be received within an open end of the chromatography column.

US 20070175809 Al discloses a chromatography column consisting of three parts, a column body with an integral outlet port molded on one end, a sealing insert with an inlet port, and a perforated cap providing downward force to compress the sealing insert into the column body.

Chromatography columns are generally provided with a cap for sealing the top of the column. The caps used today are often provided with threads located on the cap adapted to threadingly engage threads being provided on the chromatography column. A problem with such known chromatography columns and caps is that it may be difficult to seal the column sufficiently. In addition, using a cap provided with threads is also a relatively time-consuming way of closing the chromatography column.

Thus, there is a need for a chromatography column and an associated sealing device which provides for an improved seal between the column and the sealing device, and which ensures that the sealing device is thoroughly attached to the chromatography column.

Thus, an object of the present invention is to provide a chromatography column assembly which provides a sufficient seal of the chromatography column, and which ensures that the assembly does not leak.

Still a further object of the present invention is to provide a chromatography column assembly with an improved attachment of the sealing device. A further object of the present invention is to provide a disposable sealing device and chromatography column, which furthermore are inexpensive to manufacture and easy to use.

Summary of the invention

The above-mentioned objects are achieved by the present invention according to the independent claims.

Preferred embodiments are set forth in the dependent claims. The chromatography column assembly in accordance with the present invention comprises a chromatography column and a chromatography column sealing device, wherein said chromatography column comprises a tubular body having an open end and an inner surface, and wherein the chromatography column sealing device comprises a cylindrical body having an upper end and a lower end, having a main axis A extending along said body, and having a height H along said axis A between said upper and lower ends. The chromatography column sealing device further comprises a connection port, for connecting said chromatography column sealing device to a source of fluid for chromatography analysis. The connection port is a canal extending along said axis A from said upper end to said lower end of said cylindrical body, and said cylindrical body is provided with a circumferential outer surface adapted to abut against the inner surface of the chromatography column along substantially the entire height H. The circumferential outer surface is adapted to be fixed in relation to said inner surface of said

chromatography column. According to one aspect, the circumferential outer surface is fixed in relation to said inner surface by means of friction. According to another aspect, the circumferential outer surface is fixed in relation to said inner surface by means of a weld. According to a further aspect, the circumferential outer surface is fixed in relation to said inner surface by means of friction and by means of a weld.

Thus, by providing a chromatography column assembly according to the present invention an improved seal between the chromatography column and the chromatography column sealing device is achieved. According to one aspect, the chromatography column is sealed by means of friction without the need for threads on the column sealing device and on the column body, and the weld ensures that the chromatography column sealing device is thoroughly attached to the chromatography column.

According to a further aspect, the present invention relates to a method of producing a chromatography column assembly. The method includes:

- providing a chromatography column;

- arranging the chromatography column sealing device such that an circumferential outer surface abuts against an inner surface of the chromatography column.

According to another aspect, the method further includes providing a weld in the area where the circumferential outer surface abuts against the inner surface.

Short description of the appended drawings

Figure 1 shows a prior art disposable syringe barrel.

Figure 2 shows the chromatography column assembly according to the present invention. Figure 3 shows a side view of a chromatography column sealing device of the

chromatography column assembly according to the present invention.

Figure 4 shows a cross section A-A of the chromatography column sealing device shown in Figure 3

Figure 5a shows a top view of a chromatography column sealing device of the

chromatography column assembly according to one embodiment of the present invention. Figure 5b shows an elevated view a chromatography column sealing device of the chromatography column assembly according to another embodiment of the present invention.

Figure 6 shows a chromatography column assembly, according to the present invention, in an opened state.

Figure 7 shows the chromatography column assembly according to one embodiment of the present invention. Detailed description of preferred embodiments of the invention

The present invention will now be described in detail with references to the appended drawings.

In Fig. 1, a disposable syringe 1 of a conventional design is illustrated. The disposable syringe barrel 1 shown in Fig. 1 comprises tube 2 being provided with an upper opening 3 and a lower opening 4. This type of disposable syringe barrels is used as a

chromatography column in the present invention.

Fig. 2 illustrates a chromatography column assembly, comprising a chromatography column 13 and a chromatography column sealing device 5, according to the present invention. The chromatography column 13 comprises a tubular body 17 having an open end 18 and an inner surface 12. The cylindrical body 6 of the chromatography column sealing device 5 is provided with a circumferential outer surface 1 1 adapted to abut against the inner surface 12 of the chromatography column 13 along substantially the entire height H. The circumferential outer surface 1 1 is adapted to be fixed in relation to the inner surface 12 of the chromatography column 13. In one embodiment the circumferential outer surface 11 is adapted to be fixed in relation to the inner surface 12 by means of friction. In another embodiment, the circumferential outer surface 11 is adapted to be fixed in relation to the inner surface 12 by means of a weld 22. According to another embodiment, the circumferential outer surface 1 1 is adapted to be fixed in relation to the inner surface 12 by means of friction and by means of a weld 22.

In Fig. 2, a weld 22 is provided adjacent to an upper edge 23 of the chromatography column 13, and extends circumferentially around the cylindrical body 6, such that the cylindrical body 6 is joined to the chromatography column 13. However, the weld 22 may be provided at any other suitable place at the circumferential outer surface 11. It may be provided in the vicinity or adjacent to the upper end 7 of the cylindrical body 6. According to another embodiment, the weld 22 covers substantially the entire height H of the cylindrical body 6 and extends circumferentially around the cylindrical body 6 such that the circumferential outer surface 1 1 is attached to the inner surface 12 of the

chromatography column 13. In another embodiment the weld 22 comprises a plurality of welds extending circumferentially next to each other around the cylindrical body 6 and spaced apart along the height H.

According to one embodiment, the weld 22 is made by means of laser welding. However, any other suitable welding technique may be used in order to achieve the weld, such as any type of fusion or friction welding. The weld 22 may be a continuous circumferential weld which extends substantially around the entire cylindrical body 6, it may extend partly around the cylindrical body 6, or it may be spot-welded. In the spot-welded embodiment, the number of spots at the circumferential outer surface 11 the assembly is welded in, may be approximately between 2-100.

In Fig. 3, the chromatography column sealing device 5 of the chromatography column assembly according to the present invention, is shown. The chromatography column sealing device 5 comprises a cylindrical body 6 comprising an upper end 7 and a lower end 8, having a main axis A extending along the body 6, and having a height H along the axis A between the upper and lower ends 7, 8. The chromatography column sealing device 5 further comprises a connection port 9, for connecting the chromatography column sealing device 5 to a source of fluid for chromatography analysis (not shown). In one embodiment, shown in Fig. 3, the cylindrical body 6 is provided with guiding means 14 for guiding the cylindrical body 6 when being inserted into the chromatography column 13. As shown in Fig. 3, the guiding means 14 is a chamfering provided at the lower end 8 of the cylindrical body. The chamfering facilitates the insertion of the chromatography column sealing device 5 into the chromatography column 13.

According to a preferred embodiment, the connection port 9 is arranged in a cylindrical connecting part 15 protruding from the upper end 7 of the cylindrical body 6 along the axis A, as illustrated in Fig. 4. The connection port 9 preferably comprises a "luer lock" connection 16, for connecting the chromatography column device 5 to a chromatography equipment.

Fig. 4 further illustrates that the connection port 9 is a canal 10 extending along the axis A from the upper end 7 to the lower end 8 of the cylindrical body 6. Furthermore, the cylindrical body 6 is provided with a circumferential outer surface 1 1 adapted to abut against an inner surface 12 of the chromatography column 13, as shown in Figs. 2 and 6. The circumferential outer surface 1 1 of the cylindrical body 6 is adapted to engage the inner surface 12 of the chromatography column 13 by means of friction and by means of a weld 22.

In one embodiment the circumferential outer surface 1 1 of the cylindrical body 6 is adapted to engage the inner surface 12 of the chromatography column 13 by means of friction along substantially the entire height H of the cylindrical body 6 and by means of a weld 22.

As disclosed in the Figures, the chromatography column sealing device 5 does not comprise threads for achieving a threaded connection to the chromatography column 13, i.e. it is adapted for a threadless connection to the chromatography column 13.

According to a preferred embodiment of the present invention, shown in Fig. 5a, the cylindrical body 6 has a circular cross-section. However, the cylindrical body 6 may have other cross-sections that correspond to the cross-section of the chromatography column 13, such as an oval, a triangular, or a square cross-section. As further illustrated in Fig 5a, the cylindrical body 6 of the chromatography column device 5 is partly hollow, wherein the circumferential outer surface 1 1 is arranged at an outer side of a circumferential wall 20. Furthermore, the cylindrical connecting part 15 is provided with a plurality of supporting means 19 extending between a lower part of the cylindrical connecting part 15 and an inner side 21 of the circumferential wall 20. In Figure 5a, the chromatography column device 5 is provided with four supporting means 19, but the number of supporting means 19 may be different depending on the size of the chromatography column device 5. Figure 5b, illustrates another embodiment of the chromatography column device 5, wherein the number of supporting means 19 is twelve.

According to a preferred embodiment of the present invention, an outer diameter D of the cylindrical body 5 is adapted to an inner diameter d of the chromatography column 13, as illustrated in Fig. 6.

The cylindrical body 6 is preferably made from a resilient material, such as plastic. In a preferred embodiment the cylindrical body 6 is made from polypropylene. However, other suitable materials may be used, such as rubber, or other flexible materials. According to one embodiment, the materials of the chromatography column 13 and the cylindrical body 6 should be "weldable", i.e. the materials should be chosen such that they are suitable to be joined by means of welding.

In a further embodiment of the present invention, the outer diameter D of the cylindrical body 6 is adapted to be slightly larger than the inner diameter d of the chromatography column 13. According to this embodiment, when the chromatography column sealing device 5 is inserted into the chromatography column 13, the cylindrical body 6 is slightly squeezed together. According to the present invention the chromatography column sealing device 5 is able to withstand pressures up to approximately 14 bar or higher, depending of the

chromatography column wall thickness. In one embodiment, the chromatography column 13 is a plastic tube, preferably a disposable syringe. However, the chromatography column 13 may be made from other suitable material.

Fig. 6 illustrates an opened state of the chromatography column assembly before the chromatography column sealing device 5 has been introduced into the chromatography column 13 and the chromatography column sealing device 5 has been attached to the chromatography column by means of friction, by means of welding, or by means of friction and by means of a weld.

In order to make the chromatography column assembly ready for use, the chromatography column 13 is filled with chromatography medium, and the chromatography column sealing device 5 is inserted through the open end 18 of the tubular body 17 and arranged in an upper part of the chromatography column 13. Thereafter, according to one

embodiment, the chromatography column sealing device 5 is fixed in relation to the chromatography column 13 by means of welding. As discussed above, the

chromatography column 13 and the chromatography column sealing device 5 may be joined by means of laser welding, the weld 22 is then achieved by focusing a laser beam towards the area where the circumferential outer surface 11 abuts against the inner surface 12 of said chromatography column 13, such that the beam causes the materials the change from solid to liquid, and then when the laser beam is removed, back to solid again.

Thus, according to a further aspect, the present invention relates to a method of producing a chromatography column assembly. The method includes:

- providing a chromatography column 13;

- arranging the chromatography column sealing device 5 such that an circumferential outer surface 11 abuts against an inner surface 12 of the chromatography column 13;

In one embodiment, the method further includes filling the chromatography column 13 with a chromatography medium. The filling is performed prior to arranging said chromatography column sealing device 5 such that an circumferential outer surface 11 abuts against an inner surface 12 of said chromatography column 13.

According to another embodiment, the method further includes providing a weld 22 in the area where the circumferential outer surface 1 1 abuts against the inner surface 12.

Preferably, the chromatography column assembly is pre-filled with the chromatography medium. In use, a source of chromatography medium is connected to the connection port 9. A frit may be introduced into the chromatography column 13 and positioned at the bottom end of the column in order to prevent chromatography medium to exit the column through the lower opening 4. A frit may also be introduced between the chromatography medium and the chromatography column sealing device 5. The chromatography is then performed according to a predetermined protocol, and thereafter the chromatography column 13 may be discarded.

According to a preferred embodiment of the present invention the outer diameter D of the cylindrical body 6 is approximately 20-22 mm, and preferably 20,8 mm. However, diameters in the range 5-400 mm are possible. The length L of the chromatography column 13 may be in the range of 20-500 mm. However, other lengths L of the chromatography column 13 is possible. The wall thicloiess of the chromatography column 13 may be approximately 0,1-10 mm, preferably 2.5 mm.

In one embodiment, as illustrated in Fig. 7, the outer diameter D of the cylindrical body 6 is approximately 47.5 mm and the length L of the chromatography column 13 is approximately 215 mm. In another embodiment, the outer diameter D of the cylindrical body 6 is approximately 38.2 mm and the length L of the chromatography column 13 is approximately 151 mm. According to yet another embodiment, the outer diameter D of the cylindrical body 6 is approximately 32.4 mm and the length L of the chromatography column 13 is approximately 99 mm. In a further embodiment, the outer diameter D of the cylindrical body 6 is approximately 27.25 mm and the length L of the chromatography column 13 is approximately 90 mm. The present invention is not limited to the above-described preferred embodiments. Various alternatives, modifications and equivalents may be used. Therefore, the above embodiments should not be taken as limiting the scope of the invention, which is defined by the appending claims.

Claims

1. Chromatography column assembly comprising a chromatography column (13) and a chromatography column sealing device (5), wherein said chromatography column (13) comprises a tubular body (17) having an open end (18) and an inner surface (12), and wherein said chromatography column sealing device (5) comprises a cylindrical body (6) having an upper end (7) and a lower end (8), having a main axis A extending along said body (6), and having a height H along said axis A between said upper and lower ends (7, 8), wherein said chromatography column sealing device (5) further comprises a connection port (9), for connecting said chromatography column sealing device (5) to a source of fluid for chromatography analysis, and wherein said connection port (9) is a canal (10) extending along said axis A from said upper end (7) to said lower end (8) of said cylindrical body (6), characterized in that said cylindrical body (6) is provided with a circumferential outer surface (1 1) adapted to abut against the inner surface (12) of said chromatography column (13) along substantially the entire height H, and wherein said circumferential outer surface (1 1) is adapted to be fixed in relation to said inner surface (12) of said chromatography column (13).

2. Chromatography column assembly according to claim 1, wherein said circumferential outer surface (11) is adapted to be fixed in relation to said inner surface (12) by means of friction.

3. Chromatography column assembly according to claim 1, wherein said circumferential outer surface (11) is adapted to be fixed in relation to said inner surface (12) by means of a weld (22).

4. Chromatography column assembly according to claim 1, wherein said circumferential outer surface (11) is adapted to be fixed in relation to said inner surface (12) by means of friction and by means of a weld (22).

5. Chromatography column assembly according to any of claims 3-4, wherein said weld (22) is made by means of fusion welding, preferably by means of laser welding.

6. Chromatography column assembly according to any of claims 3-5, wherein said weld (22) extends circumferentially substantially around the entire cylindrical body (6).

7. Chromatography column assembly according to any of claims 3-6, wherein said weld (22) is spot-welded.

8. Chromatography column assembly according to any of claims 1-7, wherein said chromatography column sealing device (5) is adapted for threadless engagement with a chromatography column 13.

9. Chromatography column assembly according to any of claims 1-8, wherein an outer diameter D of said cylindrical body (6) is adapted to an inner diameter d of said chromatography column (13).

10. Chromatography column assembly according to any of claims 1-9, wherein said cylindrical body (6) is made from a resilient material.

1 1. Chromatography column assembly according to claim 9, wherein said outer diameter D of said cylindrical body (6) is slightly larger than said inner diameter d of said chromatography column (13).

12. Chromatography column assembly according to any of claims 1-11, wherein said cylindrical body (6) is provided with guiding means (14) for guiding said cylindrical body (6) when being inserted.

13. Chromatography column assembly according to claim 12, wherein said guiding means (14) is a chamfering provided at said lower end (8) of said cylindrical body (6).

14. Chromatography column assembly according to any of claims 1-13, wherein said cylindrical body (6) is made from plastic, such as polypropylene.

15. Chromatography column assembly according to any of claims 9-14, wherein said outer diameter D of said cylindrical body (6) is approximately 20-22 mm, and preferably 20,8 mm.

16. Chromatography column assembly according to any of claims 1-15, wherein said connection port (9) is arranged in a cylindrical connecting part (15) protruding from said upper end (7) of said cylindrical body (6) along said axis A.

17. Chromatography column assembly according to any of claims 1-16, wherein said connection port (9) comprises a "luer lock" connection. 18. Method of producing a chromatography column assembly according to any of claims 1-17, wherein the method includes:

- providing a chromatography column (13);

- arranging said chromatography column sealing device (5) such that an circumferential outer surface (11) abuts against an inner surface (12) of said chromatography column (13).

19. Method of producing a chromatography column assembly according to claim

18. wherein the method further includes:

- filling said chromatography column (13) with a chromatography medium, wherein the filling is performed prior to arranging said chromatography column sealing device (5) such that an circumferential outer surface (11) abuts against an inner surface (12) of said chromatography column (13).

20. Method of producing a chromatography column assembly according to any of claims 18-19, wherein the method further includes:

- providing a weld (22) in the area where the circumferential outer surface (1 1) abuts against said inner surface (12).