chromatographic column

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). An enclosed 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 relative to the base assembly (125) inside the tubular side wall (110). The inner wall (112) comprises at least one recess (180; 180'; 180''; 180''') positioned in a lower half of the tubular side wall (110) of the chromatography column (100), through which recess (180; 180'; 180''; 180''') air and other fluids can pass the adapter assembly (120) when the adapter assembly is positioned in a packing position in which the adapter assembly intersects at least part of the at least one recess (180; 180'; 180''; 180''').

Description

Technical Field

[0001] This invention relates to a chromatographic column, a method for packing a chromatographic column, and a method for unpacking a chromatographic column. Background Technology

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

[0003] While this invention relates to both plastic-walled and larger metal-walled chromatographic columns, it is particularly useful for manufacturing and industrial-scale chromatographic columns. Industrial-scale chromatographic columns typically comprise a hollow, axially vertical tubular shell including a liquid inlet at the upper end and a liquid collection system at the lower end for collecting substances and buffer solutions. The buffer solutions and substances to be separated are dispensed through the liquid inlet into a media bed located within the cavity of the tube. The buffer fluids and / or substances to be separated and purified percolated through a particulate chromatographic medium or bed located between the liquid inlet and the collection system.

[0004] The adapter assembly is typically attached to the upper end of the tubular housing, and the base assembly is attached to the lower end, wherein the base assembly is bolted to the bottom flange. Each of these assemblies typically includes a robust backing plate and a distributor plate that further supports the bed support; the bed support is a layer of mesh, screen, filter, sinter, or other fluid-permeable media-holding material that allows process liquids to flow in and out of the chromatographic bed space or cavity while holding the bed of particulate media. To provide adjustability and control over bed height and bed compression, the adapter assembly is typically manufactured in the form of a piston or sliding adapter inside the column tube. After the column is typically filled with bed media 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 against the bottom flange of the column tube, but in some cases, it may also take the form of a piston or adapter capable of movable sliding.

[0005] The backing plate of the base assembly generally serves as a support for the column, and is itself supported on the leg or some other support structure, which allows for clearance for the outlet piping system protruding below the base assembly.

[0006] Liquid chromatography (LC) is a technique used to separate individual compounds present in a sample. In this technique, the sample is dissolved and carried in a liquid called the mobile phase. The mobile phase carrying the sample is forced to migrate through a bed of particulate media, sometimes called the stationary phase. Different compounds will have different rates of migration through the medium, which achieves the separation of components in the sample. The particulate media bed is formed under gravity, washed with the mobile phase, and / or compressed by an adapter or piston. Before the column can be used to separate compounds by LC, and before the column is packed with chromatographic resin, it is necessary to remove air that has become trapped in the column, otherwise the air will interfere with the separation process. Air may be initially present in the bed space itself or may have moved into the bed space from associated piping, pumps, or column components (such as bed supports). Problems are often encountered when attempting to remove air from the column before performing LC. Trapped air can create cavitation in the stationary phase, where chemical interactions between the sample and the medium cannot occur. Therefore, these cavitations negatively affect the separation of different components in the sample.

[0007] US7820042 discloses a chromatographic column specifically designed to allow the removal of air trapped within the bed space. Elongated grooves are provided in the inner wall of the tubular sidewall of the column housing.

[0008] The problem with the chromatographic columns described in US7820042 is that the entire column needs to be filled with pure water during the packing process to remove any trapped air. This process is both time-consuming and requires a large amount of pure water. Summary of the Invention

[0009] The purpose of this invention is to improve and facilitate the packing of chromatographic columns.

[0010] Another objective of the present invention is to increase the possibility of removing all slurry from the column during unloading.

[0011] These objectives are achieved by the chromatographic column according to the independent claims, the method for packing the chromatographic column, and the method for unloading the chromatographic column.

[0012] According to one aspect of the invention, a chromatographic column is provided, comprising a tubular sidewall having an inner wall, an adapter assembly, and a base assembly, wherein an encapsulation bed space is defined between the adapter assembly, the base assembly, and the inner wall of the tubular sidewall, and wherein the adapter assembly is axially movable relative to the base assembly inside the tubular sidewall, wherein the inner wall includes at least one groove positioned in the lower half of the tubular sidewall of the chromatographic column, through which air and other fluids are permissible when the adapter assembly is positioned in a filling position, wherein the adapter assembly intersects at least a portion of the at least one groove.

[0013] According to another aspect of the invention, a method for packing a chromatographic column according to the invention is provided. The method includes the steps of: lowering an adapter assembly to a packing position within a tubular sidewall such that the adapter assembly intersects at least a portion of at least one groove in the inner wall, allowing air and other fluids to pass through the adapter assembly via the at least one groove; providing packing liquid to fill the encapsulated bed space with packing liquid; allowing air to pass through the adapter assembly via the at least one groove by providing more packing liquid to the encapsulated bed space; and / or removing air by axially lowering the adapter assembly within the tubular sidewall to force air out via the at least one groove.

[0014] According to another aspect of the invention, a method for removing a chromatographic column according to the invention is provided, wherein the method comprises the steps of: resuspending a packed bed of chromatographic media disposed in the chromatographic column by supplying fluid to the bed space; removing the resuspended chromatographic media via a chromatographic media outlet of the chromatographic column; lowering an adapter assembly to a position within a tubular sidewall such that the adapter assembly intersects / fluidically engages with at least a portion of at least one groove; allowing fluid to flow through at least one filling fluid channel disposed through the adapter assembly, whereby the fluid will exit through a first end opening of each of the at least one filling fluid channel and flow via the groove into the bed space for resuspending any remaining chromatographic media in the bed space; and removing the resuspended chromatographic media via a chromatographic media outlet.

[0015] Therefore, a chromatographic column is provided in which trapped air can be removed by lowering an adapter to a loading position in the lower half of the column, wherein a groove is positioned in the inner wall. When the adapter is positioned in a loading position in line with the groove, i.e., the adapter is aligned to intersect at least a portion of the groove, packing liquid is supplied to a relatively small compartment disposed between the adapter and the base assembly. Packing liquid is supplied until any possible air has passed through the adapter assembly via at least one groove. Alternatively, when the bed space between the adapter assembly and the base assembly is filled with packing liquid, the adapter can be pushed down a small distance, thereby forcing some of the packing liquid, along with any possible air, through the adapter assembly via at least one groove. Due to the relatively low position of the at least one groove in the column wall near the base assembly, a very small amount of packing liquid is required compared to the previous method, in which the entire column had to be filled for packing. This saves both time and cost. Another advantage of the groove positioned in the lower half of the column is that the groove can be used to allow fluid to flow from an outlet disposed circumferentially around the adapter assembly. Such a fluid flow can then pass through at least one groove into the adapter assembly and thus into the bed space. This can be used during column unloading. Any remaining chromatographic material can be flushed out by this flow. This is far more useful when the groove is positioned closer to the base assembly compared to prior art where the groove is located in the upper portion of the column.

[0016] In one embodiment of the invention, at least one groove is provided at a distance from the base assembly, the distance being less than 20 cm or less than 10 cm.

[0017] In one embodiment of the invention, at least one groove is a continuous groove surrounding the circumference of the inner wall.

[0018] In one embodiment of the invention, there are multiple individual grooves circumferentially distributed around the inner wall.

[0019] In one embodiment of the invention, at least one groove is configured as a continuous spiral groove arranged around the circumference of the inner wall, the continuous spiral groove starting less than 20 cm from the base assembly and ending less than 15 cm from the base assembly.

[0020] In some embodiments of the invention, the adapter assembly includes at least one filling fluid channel passing through the adapter assembly, wherein each filling fluid channel has a first end opening disposed at a position surrounding the circumference of the adapter assembly, such that if more than one filling fluid channel is provided, the first end openings for each of the filling fluid channels are distributed around the circumference of the adapter assembly, thereby the at least one filling fluid channel is configured to transfer fluid between the outside of the chromatographic column and the circumference of the adapter assembly.

[0021] In some embodiments of the invention, the at least one first end opening of each of the at least one filling fluid channel is disposed between two scrapers of the adapter assembly, the scrapers being sealed against the inner wall of the tubular sidewall of the chromatographic column.

[0022] In some embodiments, the method for packing the chromatographic column includes an additional step d) performed after step c), wherein step d) includes axially raising the adapter assembly away from the base assembly within the tubular sidewall, such that the adapter assembly is removed from at least one recess, thereby preventing air or other fluid from passing through the adapter assembly.

[0023] In some embodiments of the method for removing a chromatographic column, the step of allowing fluid flow through at least one packed fluid channel further includes simultaneously moving an adapter assembly axially within a tubular sidewall such that the adapter assembly passes over a distance in which grooves are provided, wherein the grooves are configured as helical grooves, thereby allowing fluid flow exiting through at least one first end opening to be transmitted from different directions via the helical grooves into the bed space, depending on the position of the adapter assembly. Attached Figure Description

[0024] Figure 1a A chromatographic column according to an embodiment of the present invention is shown in cross-section.

[0025] Figure 1b A portion of a chromatographic column according to an embodiment of the present invention is shown in cross-section.

[0026] Figure 2a A portion of the tubular sidewall of a chromatographic column according to an embodiment of the present invention is shown schematically.

[0027] Figure 2b A portion of the tubular sidewall of a chromatographic column according to another embodiment of the invention is shown schematically.

[0028] Figure 2c A portion of the tubular sidewall of a chromatographic column according to another embodiment of the invention is shown schematically.

[0029] Figure 3a This is a cross-section of a chromatographic column according to an embodiment of the present invention.

[0030] Figure 3b For example Figure 3a The cross-section of the same chromatographic column is shown in the figure, where the adapter assembly has been lowered.

[0031] Figure 4 The diagram schematically illustrates a movable flow path around the bed support surface, depending on the height of the adapter assembly, according to an embodiment of the invention.

[0032] Figure 5 This is a perspective view of an adapter assembly according to an embodiment of the present invention.

[0033] Figure 6 This is a flowchart of a method according to an embodiment of the present invention.

[0034] Figure 7 This is a flowchart of a method according to another embodiment of the present invention. Detailed Implementation

[0035] Figure 1a A chromatographic column 100 according to an embodiment of the present invention is shown in cross-section. The chromatographic column 100 includes an elongated tubular sidewall 110 having an inner wall 112, an adapter assembly 120, and a base assembly 125. An encapsulated 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 includes a top inlet 108 and is axially movable relative to the base assembly 125 inside the tubular sidewall 110. A chromatographic medium inlet / outlet 225 is disposed in the middle of the base assembly 125.

[0036] The adapter assembly 120 is a cylindrical disk-shaped structure that operates by axially moving along the direction of arrow A inside the center of the tubular sidewall 110. The circumference of the disk is such that it fits almost flush with the surface of the inner wall 112. The bed space 130 is designed to accommodate a bed of particulate media suspended in a liquid carrier. The adapter assembly 120 is used to settle the particulate media bed, which is initially in slurry form, by pushing it downwards; the adapter assembly 120 can then be used to compress and fill the particulate media to achieve a packed bed suitable for chromatographic separation. The adapter 120 is pushed downwards along the column 100 (i.e., along...). Figure 1a When the direction of arrow A in the diagram is reached, the volume of the media bed decreases, thereby forcing the liquid carrier through the particulate media and out of the column via the port in the base assembly 125 or adapter assembly 120.

[0037] To completely confine the carrier liquid and particulate media, it must be ensured that the solution cannot penetrate the adapter assembly 120. A sealing assembly 160 disposed around the circumference of the adapter assembly 120 forms a dynamic seal between the adapter assembly 120 and the inner wall 112. Figure 1b An example of the sealing assembly 160 can be seen more clearly in the image. Figure 1b In the middle, shown in cross-section as follows Figure 1aThe diagram shows a portion of the same chromatographic column 100, with the adapter assembly 120 positioned low within the tubular sidewall 110. In this embodiment, the sealing assembly 160 includes two sealing arrangements 160a and 160b, an upper sealing arrangement 160a including an upper O-ring 161a and an upper scraper 163a, and a lower sealing arrangement 160b including a lower O-ring 161b and a lower scraper 163b. The upper O-ring 161a is located within an upper recess 162a in the circumference of the adapter assembly 120, and the lower O-ring 161b is located within a lower recess 163b in the circumference of the adapter assembly 120. The scrapers 163a and 163b also function as brushes to remove particulate media from the surface of the inner wall 112. Scrapers 163a and 163b are circular hoop-like structures mounted on the outer edges of O-rings 161a and 161b, supported by O-rings 161a and 161b and adapter assembly 120 in a manner that allows for their radial degrees of freedom. The compressed O-rings 161a and 161b act against the scrapers 163a and 163b to push them against the tubular sidewall 110 to create a fluid-impermeable seal. In another embodiment, the two sealing arrangements 160a and 160b comprise a single sealing element, such as an O-ring or an integrated scraper seal; that is, separate O-rings and scrapers are not necessary. In yet another embodiment, the sealing assembly 160 may comprise only one sealing arrangement, i.e., not both the upper and lower sealing arrangements, but only one of them.

[0038] refer to Figure 1a and Figure 1b Both, now let's describe some additional details. Adapter assembly 120 includes a top bed support 121a, a top distributor 122a, and an adapter backing plate 123a. Base assembly 125 includes a bottom bed support 121b, a bottom distributor 122b, and a bottom backing plate 123b.

[0039] The adapter assembly 120 includes one or more filling fluid channels 171. It can be used... Figure 1b A filling fluid channel 171 is seen in the image. The filling fluid channel 171 has a first end opening 172 positioned around the circumference of the adapter assembly 120. If more than one filling fluid channel 171 is provided in the adapter assembly 120, different first end openings 172 for the different filling fluid channels 171 are distributed around the circumference of the adapter assembly 120. The filling fluid channel 171 is configured to transfer fluid between the outer side of the column 100 and the circumference of the adapter assembly 120. Therefore, the filling fluid channel 171 can be... Figure 5 The pipe 401 seen in the image connects to a liquid source located outside the chromatographic column 100. In... Figure 1a and Figure 1bIn the embodiment shown, a first end opening 172 is disposed in the adapter assembly 120 between the upper scraper 163a and the lower scraper 163b of the upper sealing arrangement 160a and the lower sealing arrangement 160b. In some embodiments, the first end opening 172 may be positioned closer to the upper sealing arrangement 160a than to the lower sealing arrangement 160b to better flush the area between the two sealing arrangements 160a, 160b.

[0040] According to the 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 positioned in the filling position, wherein the filling position is a position in which the adapter assembly is arranged in a straight line with the groove 180 to allow fluid passage. At least one groove 180 is formed in the inner wall 112 such that when the current sealing arrangement 160b is aligned to intersect with the at least one groove 180, at least one fluid passage is formed between the volume of the chromatographic column 100 disposed below the adapter assembly 120 (i.e., the encapsulation bed space 130) and the first end opening 172 of the fluid passage 171 in the adapter assembly 120. The at least one groove is disposed at a distance from the base assembly 125 such that the amount of packing liquid required for packing the column can be limited. By distributing at least one groove 180 in the lower half of the column, only a portion of the column needs to be filled with packing liquid during packing. At least one recess 180 may be located in the lower half of the tubular sidewall 110 of the chromatographic column 100, where "lower" refers to the direction toward the base assembly 125, i.e., at least one recess 180 is positioned closer to the base assembly 125 than to the top portion 110a of the tubular sidewall 110. In one embodiment, at least one recess 180 is located in the lower third or lower quarter of the tubular sidewall. In some embodiments, at least one recess is positioned close to the base assembly 125, however, allowing the lower portion of the adapter to pass through the space of at least one recess 180. In some embodiments of the invention, at least one recess 180 is located at a distance from the base assembly 125 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), and preferably within a few centimeters (e.g., about 3-5, about 3-10 cm). At least one recess 180 may be substantially circumferential. The at least one groove 180 may have an axial dimension therewith. For example, the at least one groove 180 may extend within the tubular sidewall in an axial distance range. For example, such an axial distance range may be a distance from the base assembly 125 within the column 100 from about 2, 3, 4, or 5 cm to about 20 cm, from about 2, 3, 4, or 5 cm to about 10 cm, from about 2, 3, 4, or 5 cm to about 15 cm, from about 10 cm to about 20 cm, from about 10 cm to about 15 cm, from about 15 cm to about 20 cm, etc. The distance between the at least one groove 180 and the base assembly 125 may be measured between the bottom portion 181 of the at least one groove 180 and the bottom bed support 121b of the base assembly 125, and this distance may be less than 20 cm, or in another embodiment of the invention, less than 10 cm or even less than 5 cm.The lower the position of at least one recess 180 in the column, the less packing liquid is required and the less time is needed for packing. Furthermore, during column unloading, the media bed can be effectively flushed out by providing flow via at least one recess, and a lower position of the recess is more efficient. When the adapter assembly 120 is positioned in a low position, i.e., in a packing position in line with at least one recess 180, the fluid flow provided via fluid channel 171 can be effectively used to flush out the remainder of the media bed. Therefore, a fluid flow will be provided from a short distance, and a high flow rate can be provided that is effective for flushing out the media. With the prior art, there is a problem of removing all chromatographic media during unloading. Furthermore, when more than one fluid channel 171 is provided in the adapter assembly 120, the fluid flow can be increased to unload and flush out the media bed even more effectively. However, for the unloading of some types of chromatographic media, for most efficiency, the position of at least one recess may be suitably higher. For some embodiments, 10 cm or even 15 cm or 20 cm may be a suitable position for the recess. Figure 1b In this configuration, the adapter assembly 120 is positioned in line with the groove 180, and a channel is visible between the inner wall 112 of the tubular sidewall 110 and the lower portion of the adapter assembly 120. Air and other fluids can pass through the groove 180, through the lower scraper 163b, and into the first end opening 172 of the packing fluid channel 171. This is accomplished during column packing.

[0041] According to the present invention, a method for packing a chromatographic column as described above is also provided. The method steps are as follows: Figure 6 The flowchart is shown. The method includes the following steps:

[0042] S1: Lower the adapter assembly 120 to a filling position within the tubular sidewall 110, the filling position being a position in which the adapter assembly 120 is aligned with at least one groove 180 of the inner wall 112 such that air and other fluids can pass through the adapter assembly 120 via the at least one groove 180.

[0043] S2: Provide packing liquid to fill the encapsulated bed space 130. The packing liquid can be water, such as purified water, or a buffer solution. The packing liquid is provided through the inlet / outlet 225 at the bottom of the column or through the bottom mobile phase (not visible in these figures).

[0044] S3: Air is removed by providing more filling fluid to the encapsulation bed space 130, allowing air to pass through at least one groove 180 and further through one or more filling fluid channels 171 via the adapter assembly 120, and / or by axially lowering the adapter assembly 120 within the tubular sidewall 110, allowing air to be expelled through at least one groove 180 and further through one or more filling fluid channels 171.

[0045] The method may further include the following steps:

[0046] S4: The adapter assembly 120 is axially raised within the tubular sidewall 110 away from the base assembly 125, such that the adapter assembly 120 is removed from at least one recess 180, thereby preventing air or other fluid from passing through the adapter assembly 120. This achieves an air-free sealed bed space 130. During this step, the flow rate of the filling fluid into the sealed bed space 130 remains higher than the corresponding rate of adapter movement; that is, the fluid flow rate measured in cm / h along the column height (i.e., depending on the column cross-sectional area) remains higher than the adapter movement measured in cm / h along the column height. This ensures an air-free sealed bed space.

[0047] S5: After column packing, a step is often provided to introduce slurry into the column to fill the media bed with slurry. The slurry is introduced via chromatographic media inlet / outlet 225.

[0048] Figure 2a A portion of the tubular sidewall 110 of a chromatographic column according to an embodiment of the present invention is schematically shown. In this embodiment, a 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, that is, in the portion of the sidewall 110 that is positioned closer to the base assembly 125 of the chromatographic column 100 than to the top of the tubular sidewall 100. The width of the groove 180 (i.e., the extension along the height of the inner wall 112 of the tubular sidewall 110) should not be greater than the distance between the upper sealing arrangement 160a and the lower sealing arrangement 160b. When the upper sealing arrangement 160a or the lower sealing arrangement 160b is positioned in a straight line with the groove 180, the width and depth of the groove 180 need to be sufficient to allow fluid to pass through. In one embodiment of the invention, the width of the groove 180 may be, for example, between 5 and 60 mm.

[0049] Figure 2b and Figure 2c The diagram schematically illustrates portions of the tubular sidewall 110 of two chromatographic columns according to two other embodiments of the invention. In both embodiments, a plurality of individual grooves 180', 180'' are circumferentially distributed around the inner wall 112 of the tubular sidewall 110. Figure 2b and Figure 2c As shown, the individual grooves 180', 180'' can be straight or angled.

[0050] Figure 3a This is a cross-section of the chromatographic column 100' according to another embodiment of the present invention. Figure 3b Is it like this? Figure 3a The cross-section of the same chromatographic column 100' is shown, wherein the adapter assembly 120 has been lowered to be aligned with the groove 180'''. (Regarding...) Figure 1a and Figure 1b The only difference in this embodiment compared to the described embodiment is the design of the groove 180'''. All other features are the same and are given the same reference numerals, and 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 sidewall 110 of the chromatographic column 100'. The groove 180''' is configured as a continuous spiral groove 180''', which is arranged 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 discussed above, the distance between the base assembly 125 and the groove 180''' can be measured between the bottom portion 181 of the groove 180''' and the bottom bed support 121b of the base assembly 125. The lowermost end 182a of the spiral groove 180''' may be positioned less than 15 cm from the base assembly 125 or the bottom bed support 121b of the base assembly 125, or in another embodiment, less than 10 cm or less than 5 cm. The uppermost end 182b of the spiral groove 180''' may be positioned less than 20 cm from the base assembly 125 or the bottom bed support 121b of the base assembly 125, or in another embodiment, less than 15 cm or less than 10 cm. Depending on the distance between the two sealing arrangements 160a, 160b of the adapter assembly 120, the height difference along the column between the lowermost end 182a and the uppermost end 182b may be, for example, between 2 and 10 cm. The height difference between the lowermost end 182a and the uppermost end 182b should be less than the distance between the two sealing arrangements 160a, 160b to avoid short-circuiting of fluid on the adapter assembly 120. The lowermost end 182a and the uppermost end 182b can overlap by a small distance around the circumference of the inner wall 112, such as in Figure 3a What I saw in the video.

[0051] The advantage of the spiral groove 180''' is that it improves the process for unloading chromatographic media from the column. This unloading process is further described below. Furthermore, the filling can be more efficient with respect to the spiral groove because of the possibility of providing a higher flow rate on a smaller portion of the outer periphery of the lower sealing arrangement 160b (since the fluid flow only passes through the lower sealing arrangement 160b at the point where the spiral groove intersects with it, which will differ for different locations of the adapter assembly 120).

[0052] According to the present invention, a method for removing a chromatographic column is also provided. The method steps are as follows: Figure 7 The flowchart is shown below. The method steps are described in sequence below:

[0053] A1: By providing fluid to the bed space 130, the packed bed of chromatographic medium disposed in the chromatographic column 100; 100' is resuspended. This fluid is provided from the bottom of the mobile phase, which is not visible in these views of the column but is disposed at the bottom of the column.

[0054] A2: The resuspended chromatographic medium is removed via the chromatographic medium outlet of column 100; 100'.

[0055] A3: Lower the adapter assembly 120 into the tubular sidewall 110 such that the adapter assembly 120 is aligned with at least one groove 180; 180'; 180''; 180'''. This position may be the filling position mentioned above, wherein the lower sealing assembly 160b intersects at least a portion of the groove 180; 180'; 180''' (depending on whether the groove is a helical groove).

[0056] A4: Fluid is allowed to flow through at least one filling fluid channel 171 configured to pass through the adapter assembly 120, whereby the fluid will exit through a first end opening 172 of each of the at least one filling fluid channel 171 and flow via the at least one groove 180; 180'; 180''; 180''' into the bed space 130 for resuspending any remaining chromatographic media in the bed space.

[0057] A5: The chromatographic medium that has been resuspended is removed via the chromatographic medium outlet.

[0058] Step A4, which allows fluid to flow through at least one filling fluid channel 171, may include simultaneous axial movement of the adapter assembly 120 within the tubular sidewall 110. This is advantageous in embodiments where the groove is a helical groove 180'''. Thus, the adapter assembly 120 moves at a distance from the tubular sidewall 110 in which the groove 180''' is disposed, thereby allowing fluid flow exiting through at least one first end opening 172 of the at least one filling fluid channel 171 to be transmitted from different directions via the helical groove 180''' and into the bed space 130, depending on the position of the adapter assembly 120. This is in Figure 4 The diagram in the middle shows, Figure 4 A movable flow path around the bed support surface is schematically shown, depending on the height of the adapter assembly 120, where the groove is a helical groove 180'''. A chromatographic media outlet 225 is located in the center of the base assembly 125, through which the chromatographic media is removed. Depending on the position of the adapter assembly, fluid flow is provided from different locations around the circumference of the column wall. By moving the adapter assembly 120, fluid flow can be provided from all angles around the circle, and efficient unloading can be provided.

[0059] Figure 5 This is a perspective view of an adapter assembly 120 according to an embodiment of the invention. In this embodiment, a plurality of filling fluid channels 171 are arranged through the adapter assembly 120, and a first end opening 172 of each of the filling fluid channels 171 is distributed around the circumference of the adapter assembly 120. The fluid channels 171 may be connected to a fluid source via one or more conduits 401. Upper O-rings 161a and lower O-rings 161b, as well as upper scrapers 163a and lower scrapers 163b, are also visible in this view. By arranging the plurality of filling fluid channels 171 through the adapter assembly 120, when the adapter assembly 120 is positioned inside the tubular sidewall 110 of the column 100 in a straight line with the groove 180, fluid flow can be provided outward through the first end openings 172 of the filling fluid channels 171, and thus, fluid flow can be provided inward through the groove 180''' from different positions around the circumference of the adapter assembly toward the center of the bed space. Therefore, any remaining chromatographic material can be effectively removed. If the groove is further configured as a spiral groove 180''', the flushing effectiveness can be further improved by moving the adapter assembly axially within the tubular sidewall 110 as the fluid flows out through the filling fluid channel 171.

[0060] The combination of having at least one groove 180, 180', 180'', 180''' in a low position in the inner wall 112 near the base assembly 125, and having at least one and suitably more than one filling fluid channel 171 configured with a first end opening 172 circumferentially distributed around the adapter assembly 120, is particularly advantageous for both efficient loading and efficient unloading of the chromatographic column.

[0061] Various alternative embodiments are also available. For example, many standard conventional columns can be modified to include packing recesses in their upper portions (e.g., the upper half). Such recesses can be formed in a helical shape and / or have multiple pathway sections (e.g., arcuate, linear, etc.). Thus, such modifications can be used to provide better chromatographic performance (e.g., packed beds).

Claims

1. A chromatographic column (100; 100'), comprising: Tubular sidewalls (110) having an inner wall (112); Adapter component (120); as well as Base component (125), The encapsulation bed space (130) is defined between the adapter assembly (120), the base assembly (125), and the inner wall (112) of the tubular sidewall (110), wherein the adapter assembly (120) is axially movable relative to the base assembly (125) inside the tubular sidewall (110). The inner wall (112) includes at least one groove (180; 180'; 180''; 180''') located in the lower half of the tubular sidewall (110) of the chromatographic column (100), through which air and other fluids can pass via the groove (180; 180'; 180''; 180''') to the adapter assembly (120) when the adapter assembly is positioned in the filling position, wherein the adapter assembly (120) intersects at least a portion of the at least one groove (180; 180'; 180''; 180'''). The adapter assembly (120) includes at least one filling fluid channel (171) passing through the adapter assembly (120), wherein each filling fluid channel (171) has a first end opening (172) disposed at a position around the circumference of the adapter assembly (120), thereby, if more than one filling fluid channel (171) is provided, the first end opening (172) for each of the filling fluid channels (171) is distributed around the circumference of the adapter assembly (120), thereby the at least one filling fluid channel (171) is configured to transfer fluid between the outside of the chromatographic column (100; 100') and the circumference of the adapter assembly (120).

2. The chromatographic column according to claim 1, wherein, The at least one groove (180; 180'; 180''; 180''') is disposed at a distance from the base assembly (125) of less than 20 cm.

3. The chromatographic column according to claim 2, wherein, The distance is less than 10 cm.

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

5. The chromatographic column according to claim 1, wherein, There are multiple individual grooves (180'; 180'') circumferentially distributed around the inner wall (112).

6. The chromatographic column according to any one of claims 1 to 5, wherein, The at least one groove (180''') is configured as a spiral groove (180''') that is at least partially disposed around the circumference of the inner wall (112).

7. The chromatographic column according to claim 6, wherein, The spiral groove (180''') begins at a distance of less than 20 cm from the base assembly (125) and terminates at a distance of less than 15 cm from the base assembly (125).

8. The chromatographic column according to claim 1, wherein, The at least one first end opening (172) of each of the at least one filling fluid channel (171) is disposed between two scrapers (163a, 163b) of the adapter assembly (120), the scrapers being sealed against the inner wall (112) of the tubular sidewall (110) of the chromatographic column (100; 100').

9. A method for packing a chromatographic column (100; 100') according to any one of claims 1 to 8, the method comprising the steps of: a) Lower the adapter assembly (120) to the loading position within the tubular sidewall (110) such that the adapter assembly (120) intersects at least a portion of the at least one groove (180; 180'; 180''; 180''') of the inner wall (112), allowing air and other fluids to pass through the adapter assembly (120) via the at least one groove (180; 180'; 180''; 180'''). b) Provide filling liquid to fill the encapsulation bed space (130) with filling liquid; c) Air is removed by supplying more filling liquid to the encapsulation 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 sidewall (110) so that air can be expelled via the at least one groove (180; 180'; 180''; 180''').

10. The method according to claim 9, wherein, The method includes an additional step d) performed after step c), wherein step d) includes axially raising the adapter assembly (120) away from the base assembly (125) within the tubular sidewall (110) such that the adapter assembly (120) is removed from the at least one recess (180; 180'; 180''; 180''') so that no air or other fluid can pass through the adapter assembly (120).

11. A method for removing a chromatographic column (100; 100') according to any one of claims 1 to 8, wherein the method comprises the following steps: By supplying fluid to the bed space (130), the packed bed of chromatographic medium disposed in the chromatographic column (100; 100') is resuspended; The resuspended chromatographic medium is removed via the chromatographic medium outlet (225) of the chromatographic column; The adapter assembly (120) is lowered into the tubular sidewall (110) such that the adapter assembly (120) intersects at least a portion of the at least one groove (180; 180'; 180''; 180'''). Fluid is allowed to flow through at least one filling fluid channel (171) configured to pass through the adapter assembly (120), whereby the fluid will exit through a first end opening (172) of each of the at least one filling fluid channel (171) and flow via the groove (180; 180'; 180''; 180''') into the bed space (130) for resuspending any remaining chromatographic medium in the bed space; as well as The resuspended chromatographic medium is removed via the chromatographic medium outlet (225).

12. The method according to claim 11, wherein, The step of allowing fluid flow through the at least one filling fluid channel (171) further includes simultaneously moving the adapter assembly (120) axially within the tubular sidewall (110) such that the adapter assembly (120) passes over a distance in which the groove (180''') is provided, wherein the groove is configured as a helical groove (180'''), thereby allowing the fluid flow exiting through the at least one first end opening (172) to be transmitted from different directions via the helical groove (180''') into the bed space (130) depending on the position of the adapter assembly (120).

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