Chromatography Columns

Abstract

The present invention relates to a chromatography column (100, 100') comprising a tubular side wall (110) having an inner wall (112), an adapter assembly (120), and a base assembly (125). A closed bed space (130) is defined between the adapter assembly (120), the base assembly (125), and the inner wall (112) of the tubular side wall (110). The adapter assembly (120) is axially movable within the tubular side wall (110) relative to the base assembly (125). The inner wall (112) comprises at least one groove (180, 180', 180'', 180''') disposed within the lower half of the tubular side wall (110) of the chromatography column (100), allowing air and other fluids to pass through the adapter assembly (120) via the groove (180, 180', 180'', 180''') when the adapter assembly is disposed in a priming position where the adapter assembly intersects with at least a portion of the at least one groove (180, 180', 180'', 180''').

Description

[Technical Field]

[0001] The present invention relates to a chromatography column, a method for priming a chromatography column, and a method for unpacking a chromatography column. [Background technology]

[0002] Chromatography columns provide a means for the separation, purification, and isolation of chemical or biological compounds. The size and type of column used for these operations typically depend on the scale of the process in question, with small glass- or plastic-walled columns typically used for research purposes and larger metal columns for industrial purposes. For example, chromatography columns can be used in manufacturing processes to purify process fluids and separate target substances from those fluids, typical examples of which include large-scale preparative purification of fine chemicals and pharmaceuticals, as well as biological products.

[0003] The present invention relates to both plastic-walled and larger metal-walled chromatography columns, but is particularly useful for the manufacture of industrial-scale chromatography columns. Industrial-scale chromatography columns typically comprise a hollow, axial, vertical tubular housing containing a liquid inlet at the upper end through which buffer and substances to be separated are dispensed onto a media bed disposed within the cavity of the tube, and a liquid collection system at the lower end for collecting the substances and buffer. Disposed between the liquid inlet and the collection system is a particulate chromatography media or bed through which the buffer fluid and / or substances to be separated and purified permeate.

[0004] An adapter assembly is typically attached to the upper end of the tubular housing, and a base assembly is attached to the lower end, where it is bolted to the bottom flange. Each of these assemblies typically includes a rigid backing plate and a distributor plate that further supports the bed support, which is a layer of mesh, screen, filter, sinter, or other fluid-permeable media-retaining material that retains the particulate media bed while allowing process fluid to flow into and out of the chromatography bed space or cavity. To achieve adjustability and control of bed height and bed compression, the adapter assembly is typically made in the form of a piston or sliding adapter inside the column tube. After the column is filled with bed media, typically through a valve or nozzle, the adapter can be forced toward the bottom of the tube to compress or pressurize the media bed. Generally, the base assembly is a fixed structure bolted to the bottom flange of the column tube, but in some instances it may be in the form of a movable, sliding piston or adapter.

[0005] The backing plate of the base assembly generally serves to support the column and is itself supported on legs or some other stand device that allows clearance for the outlet piping that protrudes below the base assembly.

[0006] Liquid chromatography is a technique for separating individual compounds present in a sample. Using this technique, the sample is dissolved and carried in a liquid called the mobile phase. The sample-carrying mobile phase is then moved through a bed of particulate media, sometimes called the stationary phase. Different compounds will have different migration rates through the media, resulting in the separation of the compounds in the sample. The bed of particulate media is formed by gravity-flowing the mobile phase and / or by compression using an adapter or piston. Before a column can be used to separate compounds by liquid chromatography and before it is packed with chromatography resin, trapped air within the column must be removed from the bed space; otherwise, the air may interfere with the separation process. Air may be naturally present within the bed space itself or may enter the bed space from associated column components such as tubing, pumps, or bed supports. Problems are often encountered when attempting to remove air from a column before performing liquid chromatography. Trapped air can create air pockets within the stationary phase, where chemical interaction between the sample and the media cannot occur. These air pockets therefore adversely affect the separation of the various components in the sample.

[0007] Patent document 1 discloses a chromatography column specially designed to allow removal of air trapped in the bed space: an elongated groove is provided in the inner wall of the tubular side wall of the chromatography column housing.

[0008] A problem with the chromatography column described in US Pat. No. 6,229,633 is that the entire column needs to be filled with pure water during the priming process to remove any trapped air, a process that is not only time consuming but also requires large amounts of pure water. [Prior art documents] [Patent documents]

[0009] [Patent Document 1] U.S. Patent No. 7,820,042 Summary of the Invention [Problem to be solved by the invention]

[0010] An object of the present invention is to improve and facilitate the priming of chromatography columns.

[0011] A further object of the present invention is to improve the feasibility of removing all of the slurry from the column during unpacking. [Means for solving the problem]

[0012] These objects are achieved by a chromatography column, a method for priming a chromatography column and a method for unpacking a chromatography column according to the independent claims.

[0013] According to one aspect of the present invention, there is provided a chromatography column comprising: a tubular sidewall having an inner wall; an adapter assembly; and a base assembly, wherein a closed bed space is defined between the adapter assembly, the base assembly, and the inner wall of the tubular sidewall; the adapter assembly is axially movable within the tubular sidewall relative to the base assembly; the inner wall comprises at least one groove disposed within a lower half of the tubular sidewall of the chromatography column; and air and other fluids are capable of passing through the adapter assembly via the groove when the adapter assembly is disposed in a priming position where the adapter assembly intersects at least a portion of the at least one groove.

[0014] According to another aspect of the invention, there is provided a method of priming a chromatography column according to the invention, said method comprising the steps of lowering an adapter assembly within the tubular side wall to a priming position such that the adapter assembly intersects at least a portion of at least one groove in the interior wall thereby allowing air and other fluids to pass through the adapter assembly via said at least one groove, providing a priming liquid to fill the enclosed bed space with the priming liquid, and removing air by supplying more priming liquid to the enclosed bed space so that air can pass through the adapter assembly via said at least one groove and / or by axially lowering the adapter assembly within the tubular side wall so that air can be forced out through the at least one groove.

[0015] According to another aspect of the present invention, there is provided a method of unpacking a chromatography column according to the present invention, comprising the steps of resuspending a packed bed of chromatography medium provided in the chromatography column by providing a fluid to the bed space; removing the resuspended chromatography medium through a chromatography medium outlet of the chromatography column; lowering the adapter assembly to a position within the tubular side wall such that the adapter assembly intersects / fluidly couples with at least a portion of at least one groove; flowing the fluid through at least one priming fluid passage provided through the adapter assembly such that the fluid exits a first end opening of each of the at least one priming fluid passage and flows into the bed space via the groove for resuspension of any remaining chromatography medium in the bed space; and removing the resuspended chromatography medium through the chromatography medium outlet.

[0016] Thus, a chromatography column is provided in which trapped air can be removed by lowering the adapter to a priming position in the lower half of the column, where a groove is located on the inner wall. When the adapter is positioned in the priming position in line with the groove, i.e., aligned so that the adapter intersects with at least a portion of the groove, priming liquid is introduced into a relatively small compartment located between the adapter and the base assembly. The priming liquid is introduced until any potential air passes through the at least one groove into the adapter assembly. Alternatively, when the bed space between the adapter assembly and the base assembly is filled with priming liquid, the adapter is lowered a short distance, thereby forcing some of the priming liquid, along with any potential air, through the at least one groove into the adapter assembly. The presence of at least one groove relatively low in the chromatography column wall near the base assembly requires only a small amount of priming liquid compared to conventional methods in which the entire column must be filled to perform priming. This saves time and money. An additional advantage of having the groove located in the lower half of the column is that the groove can be used to channel fluid from outlets located around the circumference of the adapter assembly. In this case, such fluid flow can pass through the adapter assembly via at least one groove and into the bed space. This can be used during unpacking of the chromatography column. Any remaining chromatography material can be flushed out by this flow. When the groove is provided near the base assembly, this is even more useful than in the prior art, where the groove was provided at the top of the column.

[0017] In one embodiment of the invention, the at least one groove is provided within a distance from the base assembly that is less than 20 cm or less than 10 cm.

[0018] In one embodiment of the invention, the at least one groove is a continuous groove around the circumference of the inner wall.

[0019] In one embodiment of the invention, there are several separate grooves distributed around the circumference of the inner wall.

[0020] In one embodiment of the invention, the at least one groove is provided as a continuous spiral groove around the circumference of the inner wall beginning less than 20 cm from the base assembly and ending less than 15 cm from the base assembly.

[0021] In some embodiments of the present invention, the adapter assembly comprises at least one priming fluid passageway extending therethrough, wherein each priming fluid passageway has a first end opening disposed at a position around the circumference of the adapter assembly, whereby, when more than one priming fluid passageway is provided, the respective first end openings of the priming fluid passageways are distributed around the circumference of the adapter assembly, whereby the at least one priming fluid passageway is configured for the transfer of fluid between the exterior of the chromatography column and the circumference of the adapter assembly.

[0022] In some embodiments of the present invention, the at least one first end opening of each of the at least one priming fluid passages is located between two scrapers of the adapter assembly, and the scrapers seal against the inner wall of the tubular side wall of the chromatography column.

[0023] In some embodiments, the method for priming a chromatography column includes a further step d) performed after step c), wherein step d) includes axially raising the adapter assembly within the tubular side wall and away from the base assembly such that the adapter assembly is cleared from at least one groove such that air or other fluids cannot further pass through the adapter assembly.

[0024] In some embodiments of the method for unpacking a chromatography column, the step of flowing fluid through the at least one priming fluid passage further includes simultaneously moving the adapter assembly axially within the tubular side wall such that the adapter assembly passes through a grooved distance, wherein the groove is configured as a spiral groove, whereby the fluid flow exiting through the at least one first end opening is transported through the spiral groove into the bed space from different directions depending on the position of the adapter assembly. [Brief explanation of the drawings]

[0025] [Figure 1a] 1 is a cross-sectional view of a chromatography column according to one embodiment of the present invention. [Figure 1b] 1 is a cross-sectional view of a portion of a chromatography column according to one embodiment of the present invention. [Figure 2a] 1 is a schematic diagram of a portion of a tubular side wall of a chromatography column according to one embodiment of the present invention. [Figure 2b] FIG. 2 is a schematic diagram of a portion of a tubular side wall of a chromatography column according to another embodiment of the present invention. [Figure 2c] FIG. 2 is a schematic diagram of a portion of a tubular side wall of a chromatography column according to another embodiment of the present invention. [Figure 3a] 1 is a cross-sectional view of a chromatography column according to one embodiment of the present invention. [Figure 3b] FIG. 3b is a cross-sectional view of the same chromatography column as shown in FIG. 3a with the adapter assembly in the lowered position. [Figure 4] 1 is a schematic diagram of a movable flow path around a floor support surface depending on the height of an adapter assembly according to one embodiment of the present invention. FIG. [Figure 5] FIG. 1 is a perspective view of an adapter assembly according to one embodiment of the present invention. [Figure 6] 1 is a flow diagram of a method according to one embodiment of the present invention. [Figure 7] 4 is a flow diagram of a method according to another embodiment of the present invention. DETAILED DESCRIPTION OF THE INVENTION

[0026] 1a is a cross-sectional view of a chromatography column 100 according to one embodiment of the present invention. The chromatography column 100 comprises an elongated tubular sidewall 110 having an inner wall 112, an adapter assembly 120, and a base assembly 125. A closed bed space 130 is defined between the adapter assembly 120, the base assembly 125, and the inner wall 112 of the tubular sidewall 110. The adapter assembly 120 comprises an upper inlet 108 and is axially movable relative to the base assembly 125 within the tubular sidewall 110. A chromatography media inlet / outlet 225 is provided centrally in the base assembly 125.

[0027] The adapter assembly 120 is a cylindrical, disk-like structure that operates by moving axially within the central interior of the tubular side wall 110 in the direction of arrow A. The circumference of the disk is adapted to fit approximately flush with the surface of the interior wall 112. The bed space 130 is designed to contain a bed of particulate media suspended in a liquid carrier. The adapter assembly 120 is used to stabilize the bed of particulate media, initially in the form of a slurry, by forcing it down onto it. The adapter assembly 120 can then be used to compress and pack the particulate media to achieve a packed bed suitable for chromatographic separations. As the adapter 120 is pressed down, the volume of the media bed reduces the column 100 (i.e., in the direction of arrow A in FIG. 1a), thereby forcing the liquid carrier through the particulate media and out of the column through a port in the base assembly 125 or adapter assembly 120.

[0028] To completely confine the carrier liquid and particulate medium, it is necessary to ensure that the solution cannot pass through the adapter assembly 120. A sealing assembly 160, located around the circumference of the adapter assembly 120, is used to form a dynamic seal between the adapter assembly 120 and the inner wall 112. An example of the sealing assembly 160 can be seen more clearly in FIG. 1b, which shows a cross section of the same portion of the chromatography column 100 shown in FIG. 1a, with the adapter assembly 120 in a lowered position within the tubular side wall 110. In this embodiment, the sealing assembly 160 comprises two sealing devices 160a, 160b: an upper sealing device 160a including an upper O-ring 161a and an upper scraper 163a, and a lower sealing device 160b including a lower O-ring 161b and a lower scraper 163b. Upper O-ring 161a is disposed within an upper recess 162a in the circumference of adapter assembly 120, and lower O-ring 161b is disposed within a lower recess 162b in the circumference of adapter assembly 120. Additionally, scrapers 163a, 163b act as brushes to remove particulate media from the surface of inner wall 112. Scrapers 163a, 163b are circular hook-like structures attached to the outer edges of O-rings 161a, 161b and are supported by O-rings 161a, 161b and adapter assembly 120 in a manner that allows radial freedom. The compressed O-rings 161a, 161b act on scrapers 163a, 163b to press them outward against tubular side wall 110 to form a fluid-tight seal. In other embodiments, the two sealing devices 160a, 160b may comprise a single sealing member, such as an O-ring or an integrated scraper seal, i.e., separate O-rings and scrapers are not required. In yet other embodiments, the sealing assembly 160 may comprise only one sealing device, i.e., only one of the upper and lower sealing devices, but not both.

[0029] 1a and 1b, some further details will now be provided. The adapter assembly 120 comprises an upper floor support 121a, an upper distributor 122a, and an adapter backing plate 123a. The base assembly 125 comprises a bottom floor support 121b, a bottom distributor 122b, and a bottom backing plate 123b.

[0030] The adapter assembly 120 includes one or more priming fluid passages 171. One such priming fluid passage 171 is visible in FIG. 1b. The priming fluid passage 171 has a first end opening 172 located at a position around the circumference of the adapter assembly 120. If more than one priming fluid passage 171 is provided in the adapter assembly 120, the different first end openings 172 for the different priming fluid passages 171 are distributed around the circumference of the adapter assembly 120. The priming fluid passages 171 are configured for the transfer of fluid between the exterior of the chromatography column 100 and the circumference of the adapter assembly 120. Thus, the priming fluid passage 171 can be connected to a liquid source located outside the chromatography column 100 via tubing 401, seen in FIG. 5 . 1a and 1b, the first end opening 172 is located between the upper scraper 163a of the upper sealing device 160a and the lower scraper 163b of the lower sealing device 160b of the adapter assembly 120. In some embodiments, the first end opening 172 may be located closer to the upper sealing device 160a than to the lower sealing device 160b to better flush the area between the two sealing devices 160a, 160b.

[0031] According to the present invention, the inner wall 112 includes at least one groove 180 through which air and other fluids can pass through the adapter assembly 120 when the adapter assembly is in the priming position, a position in which the adapter assembly is aligned with the groove 180 to allow fluid passage. The at least one groove 180 is formed in the inner wall 112 such that, when the lower sealing device 160b is aligned with the at least one groove 180, at least one fluid passageway is formed between the volume of the chromatography column 100 below the adapter assembly 120, i.e., the closed bed space 130, and the first end opening 172 of the fluid passageway 171 in the adapter assembly 120. The at least one groove is located within a distance from the base assembly 125 to limit the amount of priming liquid required to prime the column. By providing the at least one groove 180 within the lower half of the column, only a portion of the column needs to be filled with priming liquid during priming. The at least one groove 180 can be located in the lower half of the tubular sidewall 110 of the chromatography column 100, where lower refers toward the base assembly 125, i.e., the at least one groove 180 is located closer to the base assembly 125 than to the upper portion 110a of the tubular sidewall 110. In one embodiment, the at least one groove 180 is located in the lower third or lower quarter of the tubular sidewall. In some embodiments, the at least one groove is located closer to the base assembly 125, but a location is provided in the lower portion of the adapter to accommodate the at least one groove 180. In some embodiments of the present invention, the at least one groove 180 is positioned within a distance of less than 20 cm (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 cm), preferably within a few centimeters (e.g., about 3-5, about 3-10 cm) from the base assembly 125. The at least one groove 180 can be substantially circumferential. The at least one groove 180 can have an axial dimension. For example, the at least one groove 180 can extend within the tubular sidewall over a range of axial distances.For example, such axial distance range can be from about 2, 3, 4, or 5 to about 20 cm, from about 2, 3, 4, or 5 to about 10 cm, from about 2, 3, 4, or 5 to about 15 cm, from about 10 to about 20 cm, from about 10 to about 15 cm, from about 15 to about 20 cm, etc., from the base assembly 125 within the chromatography column 100. The distance between the at least one groove 180 and the base assembly 125 can be measured between the bottom 181 of the at least one groove 180 and the bottom floor support 121b of the base assembly 125, and can be less than 20 cm, or in other embodiments of the invention, less than 10 cm or even less than 5 cm. The lower the at least one groove 180 is positioned within the column, the less priming liquid is required for priming, and the shorter the priming time. Furthermore, during column unpacking, the media bed can be effectively flushed by providing flow through at least one groove, with lower grooves being more effective. When the adapter assembly 120 is positioned low, i.e., in the priming position aligned with at least one groove 180, the fluid flow provided through the fluid passage 171 can be effectively used to flush the remaining portion of the media bed. Therefore, this fluid flow comes from a short distance, providing a high flow rate, thereby effectively flushing the media. In conventional systems, removing the entire chromatography media during unpacking can be problematic. Furthermore, providing more than one fluid passage 171 within the adapter assembly 120 can increase the fluid flow to more effectively unpack and flush the media bed. However, for unpacking some types of chromatography media, it may be preferable to position the at least one groove slightly higher for optimal effectiveness. In some embodiments, a groove height of 10 cm or even 15 cm or 20 cm may be an appropriate position. In FIG. 1b, it can be seen that the adapter assembly 120 is aligned with the groove 180, providing a passage between the inner wall 112 of the tubular side wall 110 and the lower part of the adapter assembly 120.Air and other fluids can pass through groove 180, past lower scraper 163b, and into first end opening 172 of priming fluid passageway 171. This occurs during priming of the chromatography column.

[0032] There is also provided a method according to the present invention for priming a chromatography column as described above. The method steps are shown in the flow diagram of Figure 6. The method comprises the following steps: S1: Lowering the adapter assembly 120 within the tubular side wall 110 to a priming position, where the adapter assembly 120 is aligned with at least one groove 180 in the inner wall 112 so that air and other fluids can pass through the adapter assembly 120 through said at least one groove 180. S2: Providing a priming liquid to fill the closed bed space 130 with the priming liquid. The priming liquid can be water, e.g., purified water, or a buffer. The priming liquid is provided through the inlet / outlet 225 at the bottom of the column or through the bottom mobile phase (not visible in these drawings). S3: Removing air by bringing more priming liquid into the closed floor space 130 so that the air can pass through the adapter assembly 120 through at least one groove 180 and through one or more priming fluid passages 171, and / or by axially lowering the adapter assembly 120 within the tubular side wall 110 so that the air can be pushed out through at least one groove 180 and through one or more priming fluid passages 171.

[0033] Optionally, the method further comprises the following steps: S4: Axially raising the adapter assembly 120 from the base assembly 125 within the tubular side wall 110 so that the adapter assembly 120 is cleared from at least one groove 180, thereby preventing air or other fluids from passing through the adapter assembly 120. This prevents air from reaching the sealed bed space 130. During this step, the flow rate of the priming fluid into the enclosed bed space 130 is kept higher than the corresponding adapter displacement rate, i.e., the fluid flow rate cm / h measured at the column height (i.e., depending on the column cross-sectional area) is kept higher than the adapter displacement cm / h measured along the column tubing height. This ensures that no air enters the sealed bed space. S5: After priming the column, a step of introducing a slurry into the column is typically performed to pack the media bed from the slurry within the column. The slurry is introduced through the chromatography media inlet / outlet 225.

[0034] FIG. 2a schematically illustrates a portion of a tubular sidewall 110 of a chromatography column according to one embodiment of the present invention. In this embodiment, a single continuous groove 180 is provided around the circumference of the inner wall 112 of the tubular sidewall 110. The groove 180 is provided in the lower portion of the tubular sidewall 110, i.e., in a portion of the sidewall 110 that is closer to the base assembly 125 of the chromatography column 100 than the upper portion of the tubular sidewall 110. The width of the groove 180, i.e., its extension along the height of the inner wall 112 of the tubular sidewall 110, should not be greater than the distance between the upper and lower sealing devices 160a, 160b. The width and depth of the groove 180 should be sufficient to allow fluid to pass through when the upper or lower sealing device 160a, 160b is aligned in line with the groove 180. In one embodiment of the present invention, the width of the groove 180 can be, for example, between 5 and 60 mm.

[0035] Figures 2b and 2c show schematically portions of the tubular side wall 110 of two chromatography columns according to two other embodiments of the invention. In these two embodiments, several distinct grooves 180', 180" are distributed around the circumference of the inner wall 112 of the tubular side wall 110. As shown in Figures 2b and 2c, the distinct grooves 180', 180" can be straight or inclined.

[0036] FIG. 3a is a cross-section of a chromatography column 100′ according to another embodiment of the invention. FIG. 3b is a cross-section of the same chromatography column 100′ as shown in FIG. 3a, with the adapter assembly 120 lowered so that it is aligned with the groove 180′″. The only feature that differs in this embodiment compared to the embodiment described with reference to FIGS. 1a and 1b is the design of the groove 180′″. All other features are the same, are indicated by the same reference numerals, and therefore will not be described in detail again. In this embodiment, the groove 180′″ is a spiral groove 180′″ disposed in the inner wall 112 of the tubular side wall 110 of the chromatography column 100′. The groove 180′″ is disposed as a continuous spiral groove 180′″ disposed around the circumference of the inner wall 112, starting less than 20 cm from the base assembly 125 and ending less than 15 cm from the base assembly 125. As described above, the distance between the base assembly 125 and the groove 180''' can be measured between the bottom 181 of the groove 180''' and the bottom floor support 121b of the base assembly 125. The bottom end 182a of the spiral groove 180''' can be positioned less than 15 cm, or in other embodiments less than 10 cm or less than 5 cm, from the base assembly 125 or from the bottom floor support 121b of the base assembly 125. The top end 182b of the spiral groove 180''' can be positioned less than 20 cm, or in other embodiments less than 15 cm or less than 10 cm, from the base assembly 125 or from the bottom floor support 121b of the base assembly 125. The height difference between the bottom end 182a and the top end 182b along the column can be, for example, 2 to 10 cm, depending on the distance between the two sealing devices 160a, 160b of the adapter assembly 120. The height difference between the bottom end 182a and the top end 182b must be less than the distance between the two sealing devices 160a, 160b to avoid short circuiting of fluid above the adapter assembly 120. The bottom end 182a and the top end 182b may overlap by a short distance around the circumference of the inner wall 112, as seen in Figure 3a.

[0037] An advantage of the spiral groove 180''' is that it may improve the process of unpacking chromatography media from a chromatography column. This unpacking process is described further below. Additionally, with the spiral groove, priming may be more effective because, when the spiral groove intersects with the lower sealing device 160b, which will be different for different positions on the adapter assembly 120, the fluid flow will only pass through the lower sealing device 160b, allowing for a higher flow rate over a smaller portion of the circumference of the lower sealing device 160b.

[0038] The present invention further provides a method for unpacking a chromatography column, the method steps of which are illustrated in the flow diagram of Figure 7. The method steps are described sequentially below. A1: Resuspending the packed bed of chromatography media provided in the chromatography column 100, 100′ by providing a fluid to the bed space 130. This fluid is provided from a mobile phase bottom, not visible in these drawings of the chromatography column, provided at the bottom of the column. A2: Removing the resuspended chromatography medium via the chromatography medium outlet of the chromatography column 100, 100'. A3: Lowering the adapter assembly 120 to a position within the tubular side wall 110 such that the adapter assembly 120 is aligned with at least one groove 180, 180', 180", 180'". This may be the priming position described above, where the lower sealing assembly 160b intersects with at least a portion of the at least one groove 180, 180', 180'" (depending on whether the groove is a spiral groove or not). A4: A step of flowing a fluid through at least one priming fluid passage 171 provided through the adapter assembly 120, whereby the fluid exits the first end opening 172 of each of the at least one priming fluid passage 171 and flows through the at least one groove 180, 180', 180'', 180''' into the bed space 130, thereby resuspending any remaining chromatography medium in the bed space. A5: Removing the resuspended chromatography media via the chromatography media outlet.

[0039] Step A4 of flowing fluid through the at least one priming fluid passage 171 can simultaneously include moving the adapter assembly 120 axially within the tubular side wall 110. An advantage is provided in embodiments in which the groove is a helical groove 180''', whereby the adapter assembly 120 is moved a distance of the tubular side wall 110 in which the groove 180''' is provided, such that the fluid flow exiting the at least one first end opening 172 of the at least one priming fluid passage 171 moves through the helical groove 180''' into the bed space 130 from different directions depending on the position of the adapter assembly 120. This is shown in FIG. 4, which schematically illustrates a movable flow path around the bed support surface depending on the height of the adapter assembly 120 when the groove is a helical groove 180'''. A chromatography media outlet 225 is provided in the center of the base assembly 125, through which the chromatography media is removed. The fluid flow comes from different positions around the circumference of the column wall depending on the position of the adapter assembly. By moving the adapter assembly 120, fluid flow can be effected from all angles around the circle, thus achieving effective defilling.

[0040] 5 is a perspective view of adapter assembly 120 in accordance with one embodiment of the present invention. In this embodiment of the present invention, several priming fluid passages 171 are provided through adapter assembly 120, with first end openings 172 of each of said priming fluid passages 171 distributed around the circumference of adapter assembly 120. Fluid passages 171 may be connected to a fluid source via one or more tubings 401. Also visible in this view are upper and lower O-rings 161 a and 161 b, as well as upper and lower scrapers 163 a and 163 b. By providing several priming fluid passages 171 through the adapter assembly 120, fluid flow can be effected from first end openings 172 of the priming fluid passages 171 when the adapter assembly 120 is positioned in line with the grooves 180 within the tubular side wall 110 of the column 100, thereby directing fluid flow from different circumferential positions of the adapter assembly through the grooves 180, 180''' toward the center of the bed space, thereby effectively removing any remaining chromatography media. Furthermore, if the grooves are provided as spiral grooves 180''', axial movement of the adapter assembly within the tubular side wall 110 simultaneously with the outflow of fluid through the priming fluid passages 171 can further improve cleaning effectiveness.

[0041] The combination of providing at least one groove 180, 180', 180'', 180''' in the inner wall 112 at a low position near the base assembly 125 and providing at least one, and preferably more than one, priming fluid passage 171 including a first end opening 172 distributed around the circumference of the adapter assembly 120 is particularly advantageous for effective priming as well as effective unpacking of the chromatography column.

[0042] Various alternative embodiments can also be provided. For example, various standard conventional columns can be modified to provide a priming groove in the upper portion (e.g., top half) thereof. Such a groove may be formed as a spiral and / or include multi-channel (e.g., arcuate, linear, etc.) portions, etc. Thus, such modifications can be used to provide aspects of better chromatographic performance (e.g., packed beds). [Explanation of symbols]

[0043] 100, 100' Chromatography Column 110 Tubular sidewall 110a upper 112 Inner wall 120 Adapter assembly 121a Upper floor support 121b Bottom floor support 122a Upper distributor 122b Bottom distributor 123a Adapter receiving plate 123b Bottom catch plate 125 base assembly 130 floor space 160 Sealing assembly 160a Upper sealing device 160b Lower sealing device 161a Upper O-ring 161b Lower O-ring 162a Upper recess 162b Lower recess 163a Upper scraper 163b Lower scraper 171 Priming fluid passage 172 first end opening 180, 180', 180'', 180''' Groove 181 Bottom 182a Bottom end 182b Top end 225 Entrance / Exit 401 Tubing A arrow

Claims

1. A chromatography column (100, 100'), a tubular sidewall (110) having an inner wall (112); an adapter assembly (120); a base assembly (125); Equipped with a closed floor space (130) is defined between the adapter assembly (120), the base assembly (125), and the inner wall (112) of the tubular side wall (110); the adapter assembly (120) is axially movable within the tubular sidewall (110) relative to the base assembly (125); the inner wall (112) comprises at least one groove (180, 180', 180", 180'") located in a lower half of the tubular side wall (110) of the chromatography column (100) closer to the base assembly (125) than an upper portion (110a) of the tubular side wall (110), the groove itself being configured as continuous or discontinuous around the inner circumference of the inner wall (112) to allow air and other fluids to pass through the adapter assembly (120) via the groove (180, 180', 180", 180'") when the adapter assembly (120) is positioned in a priming position where the adapter assembly (120) intersects at least a portion of the at least one groove (180, 180', 180", 180'") in the priming position; A chromatography column (100, 100'), wherein the adapter assembly (120) has at least one priming fluid passage (171) extending therethrough, each priming fluid passage (171) having a first end opening (172) located at a position around the circumference of the adapter assembly (120), such that, if more than one priming fluid passage (171) is provided, the first end openings (172) of each of the priming fluid passages (171) are distributed around the circumference of the adapter assembly (120), such that the at least one priming fluid passage (171) is configured for the transfer of fluid between the outside of the chromatography column (100, 100') and the circumference of the adapter assembly (120).

2. 2. The chromatography column of claim 1, wherein the at least one groove is disposed within a distance from the base assembly that is less than 20 cm or less than 10 cm.

3. 3. The chromatography column according to claim 1, wherein said at least one groove (180, 180', 180'', 180''') is a continuous groove around the circumference of said inner wall (112).

4. 3. A chromatography column according to claim 1 or 2, wherein there are several distinct grooves (180', 180'') distributed around the circumference of the inner wall (112).

5. 5. A chromatography column according to claim 1, wherein the at least one groove (180'') is provided as a spiral groove (180'') around at least a portion of the circumference of the inner wall (112).

6. 6. The chromatography column of claim 5, wherein the spiral groove (180'') begins less than 20 cm from the base assembly (125) and ends less than 15 cm from the base assembly (125).

7. 2. The chromatography column of claim 1, wherein at least one first end opening (172) of each of the at least one priming fluid passage (171) is provided between two scrapers (163a, 163b) of the adapter assembly (120), the scrapers sealing the inner wall (112) of the tubular side wall (110) of the chromatography column (100, 100').

8. A method for priming a chromatography column (100, 100') according to any one of claims 1 to 7, comprising: a) lowering the adapter assembly (120) within the tubular side wall (110) to a priming position such that the adapter assembly (120) intersects with at least a portion of at least one groove (180, 180', 180'', 180''') in the inner wall (112) thereby allowing air and other fluids to pass through the adapter assembly (120) via the at least one groove (180, 180', 180'', 180'''); b) providing a priming liquid for filling the enclosed bed space (130) with said priming liquid; c) removing the air by supplying more priming liquid to the enclosed bed space (130) so that air can pass through the adapter assembly (120) via the at least one groove (180, 180', 180'', 180''') and / or by axially lowering the adapter assembly (120) within the tubular side wall (110) so that air can be forced out through the at least one groove (180, 180', 180'', 180'''); A method comprising:

9. 9. The method of claim 8, further comprising a further step d) performed after step c), wherein step d) comprises axially raising the adapter assembly (120) within the tubular side wall (110) and away from the base assembly (125) such that the adapter assembly (120) is removed from the at least one groove (180, 180', 180'', 180''') such that air or other fluids cannot further pass through the adapter assembly (120).

10. A method for unpacking a chromatography column (100, 100') according to any one of claims 1 to 7, comprising: resuspending the packed bed of chromatography media provided in said chromatography column (100, 100') by providing a fluid in the bed space (130); removing the resuspended chromatography medium through a chromatography medium outlet (225) of the chromatography column; lowering the adapter assembly (120) into a position within the tubular sidewall (110) such that the adapter assembly (120) intersects with at least a portion of at least one groove (180, 180', 180'', 180'''); flowing fluid through at least one priming fluid passageway (171) extending through said adapter assembly (120) such that said fluid exits a first end opening (172) of each of said at least one priming fluid passageway (171) and flows into said bed space (130) via said grooves (180, 180', 180'', 180''') for resuspension of any remaining chromatography media within said bed space; removing the resuspended chromatography media via the chromatography media outlet (225); A method comprising:

11. 11. The method of claim 10, wherein the step of flowing fluid through the at least one priming fluid passage (171) further comprises simultaneously moving the adapter assembly (120) axially within the tubular side wall (110) such that the adapter assembly (120) passes through the groove (180''') a distance through which the groove is provided, the groove being provided as a spiral groove (180'''), whereby fluid flow exiting through at least one first end opening (172) is transported through the spiral groove (180''') into the bed space (130) from different directions depending on the position of the adapter assembly (120).

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