Components for easy maintenance of chromatography and synthesis columns

Abstract

A chromatography and synthesis column including a main tube, a plurality of lower media ports 300, and an internal groove 304. The internal groove 304 is formed in the interior surface of the main tube 324 and selectively provides an internal flow path between each of the internal lower media ports 300. This facilitates quick and easy maintenance of the internal lower media ports, as well as other components of the chromatography and synthesis column.

Description

[Technical Field]

[0001] The present disclosure relates generally to chromatography and synthesis columns, and more particularly to components (e.g., internal grooves, media ports) that facilitate maintenance of chromatography and synthesis columns. [Background technology]

[0002] Preparative liquid chromatography is widely used in different forms to purify chemical and biological materials. A typical liquid chromatography apparatus has an upright housing in which a bed of porous media rests against a permeable bed support. A liquid mobile phase enters a distributor plate, which distributes the fluid mobile phase through the bed and is removed via an outlet. Separation of materials occurs between the mobile phase, which carries the product through the column, and the stationary phase of the porous media. Typically, the porous media is compressed within the column as a packed bed, commonly formed by consolidating a suspension of discrete particles, known as a slurry, which is pumped or injected into the column and consolidated by compression with a moving piston.

[0003] Routine maintenance of a chromatography column can include packing and discharging the bed using ports in the main tube called slurry ports. Slurry ports can be located in the main tube near the top, bottom, or both. The slurry port near the top of the main tube is typically used to fill the interior of the column with slurry. The slurry can be injected or pumped into the upper slurry port to fill the column. The line used to dispense the slurry can be rinsed into the upper slurry port to drive all drops of media into the interior of the column. The slurry can be consolidated into a bed by closing the upper slurry port and squeezing the liquid out of the slurry by moving a piston within the column. The bed thus formed can be solid or semi-solid, depending on the slurry media and the piston pressure. The slurry port near the bottom of the main tube is typically used to discharge semi-solid beds. Semi-solid beds can be discharged by releasing the pressure on the piston, allowing it to break up, opening the lower slurry port(s), and either flushing the bed or recirculating the media. Slurry ports provide access to the inside of the column and are advantageous for cleaning them after use.

[0004] However, known slurry ports present several different problems. First, traditional slurry ports are spaced far apart around the circumference of the main tube, which is inefficient at flushing the bed because vortices form inside the column, thereby preventing uniform cleaning of the column. Second, slurry ports generally tend to create imperfections in the cylindricity of the inner wall of the column, which adversely affects chromatography. Summary of the Invention

[0005] According to a first aspect, a chromatography column includes a main tube having an inner radial groove, a top plate detachably connected to a first end of the main tube, a bottom plate detachably connected to a second end of the main tube, the bottom plate being movable within the main tube and having a slurry port on its underside, a piston assembly movable within the main tube, a piston rod connected to the piston assembly and arranged to extend through an opening in the top plate, and a frame supporting the column on a floor, the frame being connected to the main tube and capable of lifting the main tube relative to the stationary bottom plate. The actuating means is disposed on three legs of the frame such that the inner radial groove in the main tube can be moved to a first position relative to the bottom plate to expose the inside of the main tube to the slurry port disposed in the bottom plate. In a second position relative to the bottom plate, the inner radial groove in the main tube is exposed to the slurry port, thereby allowing the slurry port to be washed, while the second position is provided for operating and packing the chromatography column. In a third position relative to the bottom plate, the main tube is completely removed from the bottom plate.

[0006] According to a second aspect, a chromatography column includes a main tube having an internal radial groove, a top plate detachably connected to a first end of the main tube, a bottom plate detachably connected to a second end of the main tube, the bottom plate being movable within the main tube and having a slurry port on an underside thereof, a piston assembly movable within the main tube, and a piston rod connected to the piston assembly, the piston rod being positioned such that the piston rod extends through an opening in the top plate.

[0007] According to a third aspect, a chromatography column includes a main tube, a bottom plate coupled to the main tube, a plurality of lower media ports carried by the bottom plate, and internal grooves formed in the interior surface of the main tube, the internal grooves interacting with the bottom plate and selectively providing internal flow paths between each of the lower media ports.

[0008] According to a fourth aspect, a chromatography column includes a main tube with an internal chamber adapted to accommodate a bed of media, a bottom plate coupled to the main tube, a plurality of lower media ports carried by the bottom plate, and internal grooves formed in the internal surface of the main tube, the internal chamber being selectively accessible via the internal grooves, and the internal grooves providing internal flow paths between each of the lower media ports.

[0009] The features of the present disclosure that are believed to be novel are set forth with particularity in the appended claims. The present disclosure can be best understood by referring to the following description taken in conjunction with the accompanying drawings, in which like reference numerals identify like elements in the several views. [Brief explanation of the drawings]

[0010] [Figure 1] 1A-1D are perspective views of chromatography and synthesis columns and base assemblies according to various embodiments. [Figure 2] FIG. 10 is a side cross-sectional view of a leg assembly for a base assembly showing a hydraulic cylinder according to various embodiments. [Figure 3] FIG. 10 is a side cross-sectional view of a leg assembly for a base assembly showing a hydraulic cylinder and a swing arm according to various embodiments. [Figure 4] 12A-12C are side cross-sectional views of a leg assembly for a base assembly showing a guide block according to various embodiments. [Figure 5] FIG. 11 is a side elevation view of the chromatography and synthesis column and base assembly of FIG. 10 with detachable legs implemented, according to various embodiments. [Figure 6] FIG. 1 is a side cross-sectional schematic view of a hydraulic cylinder system, according to various embodiments. [Figure 7] 1A-1C are top schematic views of a chromatography and synthesis column and base assembly having a swing arm configured to guide pivoting of the bottom plate, according to various embodiments. [Figure 8] FIG. 10 is a top schematic view of an alternative chromatography and synthesis column and base assembly having a swing arm configured to guide pivoting of the bottom plate, according to various embodiments. [Figure 9] FIG. 1 is a side elevation view of a chromatography and synthesis column and base assembly with telescoping legs, according to various embodiments. [Figure 10] 8A-8C are top cross-sectional views of the telescoping legs of FIG. 7 according to various embodiments. [Figure 11] 8 is a side cross-sectional view of the telescoping leg of FIG. 7 according to various embodiments. [Figure 12] FIG. 1 is a side elevation view of a chromatography and synthesis column and base assembly with removable legs implemented according to various embodiments. [Figure 13] FIG. 1 is a diagrammatic view of an air-driven hydraulic control circuit, according to various embodiments. [Figure 14] 1A-1C are top plan views of bottom plates for chromatography and synthesis columns with radially opening slots, according to various embodiments. [Figure 15] 15A-15C are side plan views of chromatography and synthesis columns including the bottom plate of FIG. 14 and a main tube showing a pendulum member for securing the bottom plate to the main tube, according to various embodiments. [Figure 16] 16A-16C are cross-sectional side views of the chromatography and synthesis column of FIG. 15, according to various embodiments. [Figure 17] 16A-16C are cross-sectional side views of the chromatography and synthesis column of FIG. 15, according to various embodiments. [Figure 18]FIG. 1 is a side cross-sectional view of a chromatography and synthesis column with a bottom plate inserted over a slurry port, according to various embodiments. [Figure 19] 19 is a cross-sectional side view of the chromatography and synthesis column of FIG. 18, according to various embodiments. [Figure 20] FIG. 1 is a cross-sectional view of a portion of a chromatography and synthesis column having an internal groove and a lower media port, according to various embodiments, showing the bottom plate in a first position relative to the main tube. [Figure 21] 21 is similar to FIG. 20, but showing the bottom plate in a second position relative to the main tube. [Figure 22] FIG. 21 is a side view of the bottom plate and lower media port of the chromatography and synthesis column of FIG. 20. [Figure 23] 21 is a bottom view of the bottom plate and lower media port of the chromatography and synthesis column of FIG. 20, with a first portion of the lower media port hidden. FIG. [Figure 24] 21 is a bottom view of the bottom plate and lower media port of the chromatography and synthesis column of FIG. 20, with the second portion of the lower media port hidden. FIG. DETAILED DESCRIPTION OF THE INVENTION

[0011] Those skilled in the art will understand that elements in the figures are illustrated for simplicity and clarity and have not necessarily been drawn to scale. For example, the dimensions and / or relative positioning of some of the elements in the figures may be exaggerated relative to other elements to help improve understanding of various embodiments of the present invention. Also, common and well-understood elements that are useful or necessary in commercially feasible embodiments are often not shown to facilitate an unobstructed view of these various embodiments. It will be further understood that while certain operations and / or steps may be described or shown in a particular chronological order, those skilled in the art will understand that such specificity with respect to order is not actually required. It will also be understood that the terms and phrases used herein have the ordinary technical meanings as assigned to such terms and phrases by those skilled in the art as described above, unless a different specific meaning is otherwise set forth herein.

[0012] The present disclosure is generally directed to chromatography and synthesis columns, assemblies, components, and methods of assembly and disassembly. Chromatography and synthesis columns as provided herein can be easily assembled and disassembled for maintenance, reducing time and potential damage to the column. Chromatography and synthesis columns can further be provided with a stable base for reliable column movement. Chromatography and synthesis columns can alternatively or additionally be provided with components (e.g., internal grooves, media ports) that facilitate efficient column maintenance.

[0013] Generally, an exemplary support assembly 10 for a chromatography and synthesis column 12, including an annular main tube 14 and a bottom plate 16, is described with reference to Figures 1-12. As shown in Figure 2, in one configuration, the support assembly 10 includes a rigid frame 18 having a house-shaped, pentagonal configuration with cross members 19 extending around a rear rectangular portion 20 and a front triangular portion 22. In the illustrated configuration, the frame 18 is sized to extend around the column 12 so that the column 12 is disposed in both the rectangular portion 20 and the triangular portion 22.

[0014] The support assembly 10 further includes two rear legs 24 mounted to the frame 18 at rear corners 26 of the rectangular portion 20, and front legs 28 mounted to the frame 18 at forward corners 30 of the triangular portion 22. As shown, the frame 18 is configured such that the forward corners 30 and the front legs 28 are aligned with the midpoints of the frame cross members 19 extending between the rear corners 26. Furthermore, in one form, the front legs 28 are set at a distance from the columns 12 to the three cross members 19 of the frame 18 within the rectangular portion 20 that is approximately equal to the nearest vertical spacing of the columns 12.

[0015] In some embodiments, the support assembly 10 is configured to elevate the column 12, thereby simplifying removal of the bottom plate 16 and other maintenance procedures. To accomplish this, as shown in FIGS. 1-6 , the frame 18 is secured to the main tube 14 using brackets 44 or other suitable methods, such as welding, and the lower leg assemblies 46, 48 for the rear legs 24 and front legs 28, respectively, cooperate to elevate the frame 18 and the column 12 secured thereto.

[0016] As shown in FIGS. 2-4 , the lower leg assemblies 46, 48 of the rear legs 24 and front legs 28 include a base 50, a caster 52 mounted on the underside of the base 50, a hydraulic cylinder 54 including a barrel 55 and a piston rod 57, and a support 56 disposed between the base 50 and the hydraulic cylinder 54. The base 50 and support 56 are sized to position the hydraulic cylinder 54 so that movement of the piston rod 57 results in a desired amount of upward or downward movement of the frame 18 and main tube 14. So configured, the lower leg assemblies 46, 48 control the upward and downward movement of the frame 18 by raising and lowering the piston rod 57 of the hydraulic cylinder 54. In the illustrated configuration, the hydraulic cylinder 54 is inverted with the frame 18 coupled to the barrel 55. This advantageously avoids movement of hydraulic hoses and other components relative to the frame 18.

[0017] To orient and couple the lower leg assembly 46 to the frame 18, the frame 18 includes downwardly depending tubular leg sections 58 disposed at the corners 26, 30 having vertical sidewalls 59 extending around an interior 60 thereof. The leg sections 58 are sized to allow the supports 56 and hydraulic cylinders 54 to extend upwardly into the interior 60 thereof. Bearings 61 are disposed along the height of the supports 56 and coupled to the supports 56 so as to contact the leg section sidewalls 59 and orient the lower leg assembly 46 within the frame leg sections 58 as the hydraulic cylinders 54 move the frame 18 upward and downward.

[0018] To further ensure that the frame leg portions 58 are aligned with the base 50, the base 50 may include a block 62 having a vertical slot 64 extending through a portion thereof. The block 62 is positioned on the base 50 such that the side walls 59 of the leg portions 58 transition therein during lifting and lowering movements. Additionally, the block 62 may be configured to prevent the lower leg assemblies 46, 48 from rotating relative to the frame 18.

[0019] To shield the moving components of the support assembly 10 during lifting and lowering operations, the base 50 may include an upright wall 66 extending around its periphery. As shown, the wall 66 is spaced outwardly from the sidewalls 59 of the leg portions 58 and has a height that projects above the lower edges 68 of the leg portions 58 that have the hydraulic cylinders 54 in the raised configuration. So configured, the leg portions 58 and the wall 66 telescope relative to one another during lifting and lowering operations, thereby effectively preventing a user from inadvertently placing hands or other objects under the frame 18.

[0020] In a further approach, as shown in FIG. 4 , the leg assemblies 46, 48 can include a height guide member 70 that is slidable along the base 50. The guide member 70 includes a raised portion 71 that projects upward toward the frame 18. The raised portion 71 is configured so that when the leg portion 58 is lowered, the lower edge 68 abuts against a top surface 72 of the raised portion 71, disposing the frame 18 at a suitable height for operation. For storage, a user can slide the height guide member 70 so that the raised portion 71 is not properly aligned with the side wall 59 and the lowering action causes the edge 68 to abut against a lower surface 73 of the guide member 70. As shown in FIG. 4 , the upright wall 66 of the base 50 can include an opening 74 extending therethrough to allow the guide member 70 to be slid to a desired position on the base 50. Additionally, to maintain guide member 70 disposed on base 50, guide member 50 may include end stops 75 configured to abut upright wall 66 or base 50 as guide member 50 is slid from one end to the other. By one approach, end stops 75 may be utilized to position guide member 70 in a raised or lowered configuration, allowing a user to simply transition guide member 70 until the desired end stop 75 prevents further movement.

[0021] Due to the high precision required to insert and remove the bottom plate 16, by one approach, the hydraulic cylinders 54 may be configured to operate in lockstep to provide synchronized up and down movement of the frame 18, and therefore the main tube 14. Asymmetric loading on the three lifting leg assemblies 46, 48 due to the offset positioning of the column 12 within the frame 18 makes synchronized movement more difficult.

[0022] As shown in FIG. 5, the hydraulic cylinders 54 can be double-acting cylinders to achieve coordinated lifting. The dual-rod configuration equalizes the exposed piston 100 area within each chamber 102, 104 of the double-acting cylinder 54. This allows a single pump 106 (FIG. 6) to synchronize multiple cylinders 54 and provide coordinated lowering of the cylinders 54 when there is an uneven load distributed across the cylinders 54. As shown in FIG. 5, the cylinders 54 are connected in series. A first closed system 108, filled with hydraulic fluid as will be understood, is established between the top chamber 102 of the first cylinder 54a and the bottom chamber 104 of the second cylinder 54b. A second closed system 110 is established between the top chamber 102 of the second cylinder 54b and the bottom chamber 104 of the third cylinder 54c. When the bottom chamber 104 of the first cylinder 54a is filled with hydraulic fluid, the top chamber 102 of the first cylinder 54a will fill the bottom chamber 104 of the second cylinder 54b. When the bottom chamber 104 of the second cylinder 54b is filled, the top chamber 102 of the second cylinder 54b will fill the bottom chamber 104 of the third cylinder 54c. When the bottom chamber 104 of the third cylinder 54c is filled, the top chamber 102 will pump hydraulic fluid into a reservoir 112 that supplies a pump 106 for the first cylinder 54a. While this hydraulic configuration of the system 108 is inefficient compared to traditional hydraulic cylinders, the dual-rod configuration of the cylinders 54 reduces the exposed piston 100 area, and the series cylinders 54 add load to all of the cylinders 54 together, applying the total load to the reduced area of ​​the piston 100 of the first cylinder 54a. While the column 12 is large, this drawback can be tolerated because the hydraulic cylinders 54 are more than adequate to handle the load and synchronous operation of the cylinders 54 provides the important advantage of perfectly synchronized cylinders 54 moving the frame 18 and the column 12 fixed thereto upward and downward.

[0023] The reverse action occurs when the frame 18 is lowered. The load on the column 12 and frame 18 is used to drive the cylinders 54 downward, and the metering valve 114 on the first cylinder 54a determines the rate of descent of all cylinders 54, as shown in FIG. 9. The load pushing down on the third cylinder 54c causes the bottom chamber 104 to fill the top chamber 102 of the second cylinder 54b. Simultaneously, the top chamber 102 of the third cylinder 54a is filled by the suction of fluid in the reservoir 112 supplying the pump 106. The top chamber 102 of the second cylinder 54b being filled by the third cylinder 54c, and the load on the second and third cylinders 54b, 54c, causes the bottom chamber 104 of the second cylinder 54b to fill the top chamber 102 of the first cylinder 54a. The top chamber 102 of the first cylinder 54a being filled by the second cylinder 54b, and the loads of the first, second, and third cylinders 54, cause the bottom chamber 104 of the first cylinder 54a to pump fluid. A metering valve 114 placed in the fluid flow from the bottom chamber 104 of the first cylinder 54a determines the rate of descent of all three cylinders 54. So configured, the three cylinders 54 work in lockstep to move the frame 18 and column 12 upward and downward.

[0024] 9 is a process and instrumentation diagram for an exemplary air-driven hydraulic control circuit 116. As shown, the control circuit 116 is provided to drive the movement of the cylinder 54 by controlling the operation of the pump 106. In the illustrated form, the pump 106 is a pneumatic hydraulic pump, and the control circuit 116 is air-driven. It will be appreciated that other circuits, including electrical, can alternatively be utilized to implement the hydraulic pump and control circuit. By one approach, a user can provide input to the control circuit 116 using a pendant 118 having a push-button outlet 120 to provide operator convenience and facilitate one-person operation. It will be appreciated that the valve components of the pendant 118 can be located elsewhere and / or alternative embodiments of the circuit can perform the same or similar functions.

[0025] The control circuit 116 includes an inlet 122 from an air supply 123 suitable for driving the pump 106 to the pressure required by the cylinder 54 to lift the frame 18 and column 12, and an outlet 124 connected to the cylinder 54. As shown, the control circuit 116 may further utilize a three-way manual valve 126 as an on / off control, a pressure regulator 128, various pressure gauges 130, a manual shut-off service valve 132, a pneumatic valve 134, and a pressure relief valve 136.

[0026] The control circuit 116, shown in FIG. 9, allows the movement of the cylinder 54 to be locked out by an on / off valve 126, which simultaneously releases air pressure, whether the cylinder 54 is moving or idle. A first pressure gauge 130 is included to verify the inlet air pressure when the on / off valve 126 is in the on position and release the air pressure when the on / off valve 126 is in the off position. The pendant 118 has two air pressure valves 120, which are normally closed. To lower the frame 18 and column 12, the "down" valve 120 communicates with the actuators of the on / off valve 126 and the down shutoff valve 134. To raise the frame 18 and column 12, the "up" valve 120 communicates with the actuators of the on / off valve 126 and the up shutoff valve 134. A pressure regulator 128 communicates with the on / off valve 126 and the air side of the air-powered pump 106. A second gauge 130 is in communication with the pressure regulator 128 and the air side of the air driven pump 106. The liquid side of the air driven pump 106 is in communication with the hydraulic fluid reservoir 112 and the fluid in the up shut-off valve 134. A pressure relief valve 136 is in communication with the hydraulic fluid reservoir 112, the up shut-off valve 134, the metering valve 114, and the output 124 to the hydraulic cylinder 54. A third pressure gauge 130 is in communication with the up shut-off valve 134, the pressure relief valve 136, the metering valve 114, and the output 124 to the hydraulic cylinder 54.

[0027] As mentioned above, the bottom plate 16 of the column 12 is removed for many maintenance procedures. To easily and repeatedly move the bottom plate 16 from beneath the main tube 14 and realign the bottom plate 16 with the main tube 14, a swing arm 32 is provided that pivotally couples the bottom plate 16 to the support assembly 10 at the front support leg 28 via bearings 29 (FIG. 3). The swing arm 32 is rigid so that the bottom plate 16 can pivot along a set radius from the front support leg 28. Advantageously, as shown in FIG. 7, the three-legged configuration of the support assembly 10 provides sufficient clearance between the front leg 28 and the rear leg 24 so that the bottom plate 16 can easily pass between them.

[0028] 8, the frame 18' may have a rectangular configuration in which the legs 24 are spaced a sufficient distance from each other so that the bottom plate 16 pivots between two adjacent legs by means of a rigid swing arm 32'. This configuration may be suitable for many purposes, although the footprint of the frame 18' is larger compared to the size of the column 12, as in the above embodiment.

[0029] By one approach, as shown in FIG. 9 , to aid in moving the bottom plate 16, the bottom plate 16 can be mounted to a carriage 34 having a housing 36 or other supporting framework and casters 38. The carriage 34 allows the weight of the bottom plate 16 to be supported on the casters 38 rather than a separate lifting device such as a forklift. This configuration allows a user to easily maneuver the carriage 34 on the casters 38, thereby avoiding unstable movement of the lifting device. Furthermore, the carriage 34, together with the swing arm 32, ensures that the movement of the bottom plate 16 is precisely controlled along the radius of the swing arm 32 to prevent contact between the bottom plate 16 and the support assembly 10 and any resulting damage.

[0030] As mentioned above, moving the bottom plate 16 back under the main tube 14 and inserting its plug portion 25 into the main tube 14 requires that the bottom plate 16 be translationally, rotationally, and horizontally aligned with the main tube 14. The swing arm 32 advantageously provides easy and repeatable alignment because the bottom plate 16 can be fixedly mounted to the swing arm 32 so that it cannot rotate relative to the swing arm 32, and the swing arm 32 and carriage 34 can maintain the bottom plate 16 in a horizontal orientation. Furthermore, the stop 39 can be mounted to the support assembly 10 and / or the main tube 14 such that an inwardly facing surface 40 of the stop 39 positions the bottom plate 16 in translational alignment with the main tube 14 when the bottom plate 16 abuts the surface 40. So configured, the user simply pushes the bottom plate 16 onto the carriage 34 and the swing arm 32 directs movement along that radius until the bottom plate 16 contacts the stop 39.

[0031] A lifting mechanism, such as the hydraulic cylinder 54 described above, can further be utilized to securely remove the bottom plate 16 from the main tube 14. As described above, the bottom plate 16 includes a plug portion 25 that protrudes into and seals against the interior surface 76 of the main tube 14 with one or more seals 77. As shown in FIG. 9 , the lower leg assemblies 46, 48 can include anchors 78, such as rings as shown, and the bottom plate 16 can include corresponding anchors 80. The bottom plate 16 can then be coupled to the lower leg assemblies 46, 48 when the frame 18 is in a lowered position, with removable or releasable couplings 81 installed between the anchors 78, 80 to hold the bottom plate 16 in a fixed position. In the illustrated configuration, three couplings 81 to the rear legs 24 and front legs 28 hold the bottom plate 16 so that the bottom plate 16 and carriage 34 remain stationary when the hydraulic cylinder 54 raises the frame 18. As the main tube 14 rises, the plug portion 25 is pulled from within the main tube 14 until the plug portion 25 has sufficient clearance from the main tube 14. The couplings 81 can then be removed or released, and the bottom plate 16 can be pivoted on the swing arms 32 to a position exterior to the frame 18, through the space between the front legs 28 and rear legs 24, as described above. It will be appreciated that the anchors 78, 80 and the couplings 81 can take any suitable form, such as hooks, straps, fasteners, etc. Furthermore, in another form, the carriage 34 can include one or more of the anchors 78 rather than the bottom plate 16.

[0032] 3 , the swing arm 32 allows the lower leg assembly 48 of the front leg 28 to be adjusted relative to the rear leg 24 to include structure in addition to the components described above. More specifically, the lower leg assembly 48 includes a lower support 51 and a base 53, with casters 52 mounted to the lower base 53. The lower support 51 has a cylindrical configuration and is sized so that the bearings 29 of the swing arm 32 coupled thereto can rotate freely and have room to move upward and downward as the hydraulic cylinder 54 moves the frame 18.

[0033] As will be appreciated, a support assembly 10 having three legs may result in less stable movement of the column 12, particularly if the weight of the column 12, like the frame 18 described above, has an asymmetrical load. To provide additional support, as shown in FIGS. 9-11, the support assembly 10 may include telescoping legs 82 at the mid-corner 31 of the frame 18 between the rear corner 26 and the front corner 30. By having a telescoping capability, the legs 82 can be moved out of the path of the bottom plate 16 when the bottom plate moves out from directly beneath the main tube 14, such as by using the swing arm 32 described above.

[0034] 10 and 11 , each telescoping leg 82 includes an elongated shaft 83 having a crossbar 84 extending outward from its midsection and a caster 85 mounted on its distal end. A telescoping housing 86 is mounted to the frame 18 at the corners 31. The housing 86 includes openings 87 extending through its top and bottom to allow the legs 82 to extend therethrough. If desired, the housing 86 can include bearings 88 disposed around the openings 87 to align the legs 82 and assist in their movement.

[0035] As shown, the housing 86 includes first and second location plates 89, 90 extending across the interior of the housing 86. Each of the first and second location plates 89, 90 further includes a main opening 91 extending vertically therethrough having a shape corresponding to the crossbar 84 of the leg 82. The first location plate 89 is disposed at a height such that, with the crossbar 84 positioned below the first location plate 89, the leg 82 is aligned with the other legs 24, 28 of the support assembly 10, as shown in FIG. 11 . Thus, the support assembly 10 in this configuration has five legs to support the weight of the column 12 and provide stable movement. The second location plate 90 is disposed above the first location plate 89 and is configured to hold the leg 82 in an elevated position so as not to interfere with removal of the bottom plate 16. To move the leg 82 to the elevated position, a user can align the crossbar 84 with the main opening 91 of the first location plate 89 and subsequently with the main opening 91 of the second location plate 90. The user can then rotate the legs 82 so that the crossbars 84 are no longer aligned with the main openings 91 and the weight of the legs 82 is supported on the second location plates 90. If desired, each leg 82 can include a handle 92 secured thereto to assist the user in moving the legs 82 to the elevated position.

[0036] Alternatively, to provide increased stability for the support assembly 10, the corners 31 of the frame 18 may be utilized for attachment of detachable legs 93. The detachable legs 93 include an elongated shaft 94, a caster 95 mounted on the distal end of the shaft 94, and a coupling portion 96 at the proximal end of the shaft 94. The corners 31 include corresponding coupling portions 97 such that the legs 93 may be removably secured thereto. In the illustrated form, the leg coupling portions 96 include threaded fasteners 98 that may be inserted through through-holes 99 extending through the frame 18 to the proximal end of the shaft 88. Alternatively, the legs 93 may include threaded fasteners that may be threaded into the through-holes 99, and / or nuts may secure the legs 93 to the frame 18. It will be understood that other coupling methods, such as snap-fit, friction, etc., are within the scope of this disclosure.

[0037] Attaching and removing the detachable legs 93 may be assisted by a frame lifting mechanism, such as the hydraulic unit 54 described above. More specifically, the hydraulic unit 54 may lift the frame 18 to a raised position, and then the detachable legs 93 may be simply secured to the frame 18, as described above. The hydraulic unit 54 may then lower the frame 18 until all of the legs 24, 28, 93 support the cylinder 12 for movement. When removal of the bottom plate 16 is desired, the frame 18 may be lifted and the legs 93 may be removed, as described above, so that the bottom plate 16 can pivot between the front legs 28 and the rear legs 24.

[0038] In a further embodiment shown in Figures 14-17, the bottom plate 16 can be simply secured to the main tube 14 without the use of bolts, as is conventional. As shown in Figure 14, the bottom plate 16 has a gear-shaped configuration with an array of radially opening slots 150 extending through the bottom plate 16. The slots 150 have curved inner ends 152 with rectangular radial openings 154 in the illustrated form, although other suitable configurations may be contemplated.

[0039] As shown in FIGS. 15-17 , the main tube 14 has a plurality of pendulum members 156 pivotally coupled to an exterior 158 of the main tube 14 at spaced radial locations. Each pendulum member 156 includes a stem portion 160, a distal enlarged retaining portion 162, and a proximal end 164. Each pendulum member 156 may be coupled to the main tube 14 by any suitable method, including a bracket 166, as shown. For example, in the illustrated form, the pendulum member 152 is an I-bar, and the proximal end 164 is retained by a bracket 166 fixed to the main tube 14 so that the pendulum member 156 can pivot along a vertical plane. When so configured, to secure the bottom plate 16 to the main tube 14, a user can pivot each of the pendulum members 156 so that the retaining portion 162 is disposed below the bottom plate 16, which prevents the bottom plate 16 from being removed.

[0040] By one approach, the stem portion 160 of each pendulum member 156 is sized so that when its plug portion 25 is fully received within the main tube 14, i.e., when the hydraulic cylinder 54 moves downward to seat the main tube 14 fully onto the bottom plate 16 and compress the compliance gap 166, the retaining portion 162 can pass through the bottom plate 16. Thereafter, as a result of gravity, filling, or other operation, the plug portion 25 of the bottom plate 16 slides downward, expanding the compliance gap 166 and abutting the retaining portion 110 of the pendulum member 102. The seal between the plug portion 25 and the main tube 14 remains sealed throughout this movement because the seal is an internal seal and the seal 77 is spaced from the bottom plate 16 a sufficient distance to allow the compliance gap 166 to expand. As a result, the pendulum member 102 captures the bottom plate 16 and secures it to the main tube 14 without the use of bolts. By one approach, the lower outer corners 170 of the bottom plate 16 can be chamfered or radiused to reduce the arcuate path of the retaining portion 110 to pivot into position below the bottom plate 16. If desired, the retaining portion 162 can have a flat radially inward surface 168 to provide a larger mounting area for the bottom plate 16. As shown in FIGS. 16 and 17 , the proximal end 164 of each pendulum member 156 can have a similar configuration to the retaining portion 162. With this configuration, the flat surface 168 can provide an identification feature for a user installing the pendulum member 156.

[0041] Similarly, to remove the bottom plate 16, the user can lower the main tube 14 or raise the bottom plate 16 so that the plug portion 25 is further inserted therein, reducing the compliance gap 166. This insertion spaces the retaining portion 162 from the bottom plate 16, thereby allowing the user to pivot the pendulum member 156 to a storage position radially spaced from or disposed above the bottom plate 16. By one approach, a coupling bracket 172 can be mounted to the main tube 14 above the pivot bracket 166. The coupling bracket 172 can be configured to hold the pendulum member 156 in a generally vertical orientation by a clip, a snap fit, a friction fit, or other suitable method.

[0042] A further embodiment for the column 12 is shown in Figures 18 and 19, in which the main tube 14 includes upper and lower slurry ports 200, 202. During operation, the bottom plate 16 is coupled to the main tube 14, and the piston 204 is driven downward to fill a bed 206 between the piston 204 and the bottom plate 16. A seal 208 on the piston 204 and a bottom plate seal 77 extend circumferentially around the piston 204 and the bottom plate 16, respectively, in a seal groove 210. The piston 204 and the bottom plate 16 each further include a glide ring 212 disposed in a groove 214 that extends circumferentially around the piston 204 and the bottom plate 16, respectively. As shown, the piston 204 and the bottom plate 16 may further include a distributor plate 220 having a scraper seal 216, a frit 218, and a seal 222.

[0043] In this embodiment, the plug portion 25 of the bottom plate 16 has a greater depth than conventional plates such that the plug portion 25 protrudes further into the main tube 14. This additional depth can be utilized to allow the seal 77 to be driven through the lower slurry port 202 for operation. In the illustrated configuration, the glide ring 212 extends across the lower slurry port 202. The hydraulic device 54 configuration described above can advantageously be utilized to drive the additional depth of the bottom plate 16 into the main tube 14.

[0044] Similarly, the piston 204 is driven downwardly within the main tube 14 such that the seal 208 is disposed below the upper slurry port 200 and the glide ring 212 extends across the upper slurry port 200. So configured, the lower and upper slurry ports 200, 202 are concealed to avoid obstructing plug flow and obtain better chromatography, i.e., higher plate count, HETP.

[0045] Advantageously, the upper and lower slurry ports 200 can be utilized to reslurry or treat soft beds within the column 12. Additionally, the upper and lower slurry ports 200 can be utilized to transfer beds 206 within a closed system. To utilize these features, the piston 204 is raised to expose the upper slurry port 200 and the bottom plate 16 is lowered to expose the lower slurry port 202, such as by use of the hydraulic device 54 and detachable coupling 81 described above.

[0046] 20-24 illustrate another embodiment of column 12, in which column 12 generally includes main tube 14, bottom plate 16, and piston 204, as described above, but differs in the manner described below. More specifically, column 12 in this embodiment also includes a plurality of internal lower media ports 300 (instead of external slurry ports 200, 2020), as well as an internal groove 304 and glide ring 306 carried by bottom plate 16 and slidably engaging main tube 14. As best illustrated in FIGS. 20 and 21, the multiple internal lower media ports 300 are carried by bottom plate 16 (whereas slurry ports 200, 202 are formed in main tube 14), while internal groove 304 is formed in interior surface 76 of main tube 14. As will be described in more detail below, the internal grooves 304 optionally provide an internal flow path between each of the internal lower media ports 300, which facilitates maintenance (e.g., cleaning) of the components of the column 12, but is provided in a manner that does not affect the cylindricity of the internal wall of the column 12 (a problem with known slurry ports, as discussed above). Additionally, the main tube 14 optionally includes an internal chamber 316 adapted to accommodate the bed 206 (or a bed of a different media) that is accessible via the internal grooves 304, as will be described in further detail below.

[0047] In this embodiment, the plurality of inner lower media ports 300 includes four uniform inner lower media ports (only one of which is visible in FIGS. 20 and 21 , but all of which are shown in FIGS. 22-24 ). Each of the four inner lower media ports is generally formed in and extends through the bottom plate 16 such that at least a bottom portion of each lower media port 300 is disposed below the bottom surface 320 of the bottom plate 16. While somewhat difficult to see, it will be appreciated that each of the four lower media ports is disposed entirely radially inward of the outer surface 324 of the main tube 14 opposite the inner surface 76 (and is at least partially, if not entirely, disposed radially inward of the inner surface 76 of the main tube 14). Furthermore, each of the four lower media ports extends downward and radially inward away from the main tube 14. In this embodiment, each of the four interior lower media ports has a first portion oriented at a 45 degree angle relative to the bottom surface of the main tube 14 and to the bottom surface 320 of the bottom plate 16, and a second portion oriented at a 45 degree angle relative to the first portion, such that the second portion is parallel to the bottom surface of the main tube 14 and to the bottom surface 320 of the bottom plate 16. In addition, as shown in FIG. 22 , two of the four lower media ports 300 (in this case, the lower media ports facing each other) are disposed at a first height (i.e., a first distance from the bottom surface 320 of the bottom plate 16), and the other two lower media ports 300 (also facing each other) are disposed at a second height (i.e., a second distance from the bottom surface 320 that is greater than the first distance). 23 and 24, the four inner lower media ports 300 are circumferentially positioned about the bottom plate 16 such that the four inner lower media ports 300 are staggered or offset from one another. In this embodiment, the four inner lower media ports 300 are spaced evenly apart from one another, although in other embodiments the four inner lower media ports 300 may be different distances from one another.Finally, as best shown in Figures 23 and 24, two of the four lower media ports 300 (e.g., the lower media ports 300 disposed at a first height) are fluidly coupled to each other via a first connecting pipe 308, and the remaining two of the four lower media ports 300 (e.g., the lower media ports 300 disposed at a second height) are fluidly coupled to each other via a second connecting pipe 312.

[0048] However, in other embodiments, the plurality of interior lower media ports 300 can vary from those illustrated in FIGS. 20-24 . By way of example, the plurality of interior lower media ports 300 can instead include two, three, five, six, or a different number of interior lower media ports. As another example, the plurality of interior lower media ports 300 need not be uniformly sized or otherwise constructed. As yet another example, the plurality of interior lower media ports 300 can extend and / or be positioned in different manners. In other embodiments, the first and / or second portions of each of the interior lower media ports 300 can be oriented at 30 degrees, 60 degrees, 75 degrees, or some other angle relative to the bottom surface of the main tube 14 and relative to the bottom surface 320 of the bottom plate 16. Furthermore, although not illustrated herein, it will be understood that the column 12 can also include one or more upper media ports formed in the main tube 14 (or another component of the column 12) and selectively exposed to the interior chamber 316. The one or more upper media ports may take the form of an upper slurry port 200, a lower media port, or some other port.

[0049] In this embodiment, the internal groove 304 is formed in the interior surface 76 of the main tube 14 and extends radially around the entire circumference of the main tube 14. Furthermore, the internal groove 304 has a length that extends in a direction that is parallel to the longitudinal axis 328 along which the piston 204 moves within the main tube 14. Accordingly, the internal groove 304 may also be referred to as an internal vertical groove or an internal radial groove. Furthermore, in this embodiment, the internal groove 304 is sized such that the area of ​​the internal groove 304 is substantially, if not exactly, equal to the area of ​​the plurality of internal lower media ports 300, thereby promoting uniform and balanced fluid communication between the internal chamber 316 and the plurality of internal lower media ports 300 (when these components are in fluid communication with one another). In embodiments in which the column 12 also includes one or more upper media ports, the internal groove 304 will generally be disposed between the one or more upper media ports and the plurality of internal lower media ports 300. For example, when the column 12 includes an upper slurry port 200, the internal groove 304 would be disposed between the upper slurry port 200 and the plurality of internal lower media ports 300. However, in other embodiments, the internal groove 304 may be shaped and / or positioned differently. By way of example, the internal groove 304 may extend around only a portion of the circumference of the main tube 14 in some embodiments.

[0050] As mentioned above, the bottom plate 16 is movable relative to the main tube 14 through the use of the hydraulic device 54 and the detachable coupling 81. More specifically, the bottom plate 16 is movable relative to the main tube 14 between a first position (an example of which is shown in FIG. 20 ) in which the bottom plate 16 is mounted against a portion of the main tube 14 (e.g., the interior surface 76) and a second position (an example of which is shown in FIG. 21 ) in which the bottom plate 16 is spaced from that portion of the main tube 14 (e.g., the interior surface 76). It will also be appreciated that the bottom plate 16 is movable relative to the main tube 14 to a third position by decoupling the bottom plate 16 from the bottom of the main tube 14, which allows the main tube 14 and bottom plate 16 to be exposed for maintenance.

[0051] As shown in FIG. 20 , when the bottom plate 16 is in the first position, at least the top portion of the inner groove 304 engages the wall of the bottom plate 16, thereby sealing the internal chamber 316. The internal chamber 316 is then not accessible (e.g., via the inner lower media port 300 or the inner groove 304). Furthermore, when the bottom plate 16 is in the first position, the inner groove 304 provides an inner flow path within the main tube 14 and between each of the inner lower media ports 300. The inner flow paths advantageously allow the inner lower media ports 300 (and inner groove 304) to be easily cleaned (and then drained) in a closed manner. For example, two of the inner lower media ports 300 can be used as inlets to receive and distribute one or more cleaning fluids to the inner flow paths, while the remaining two inner media ports 300 can be used as outlets to receive one or more cleaning fluids after they have passed through some or all of the inner flow paths before draining or excluding them from the inner flow paths. At the same time, the column 12 can be used to carry out an uninterrupted chromatography process because the inner chamber 316 is sealed.

[0052] 21 , when the bottom plate 16 is in the second position, at least a top portion of the inner groove 304 is spaced from the wall of the bottom plate 16, thereby unsealing the inner chamber 316, exposing the inner groove 304, and positioning the inner chamber 316 in fluid communication with the inner groove 304 (and subsequently with the plurality of inner lower media ports 300). Beneficially, in this embodiment, the inner lower media ports 300 are spaced equally far from one another, so that the inner lower media ports 300 are positioned in fluid communication with the inner chamber 316 in a substantially uniform and balanced manner. In any event, this fluid communication allows the bed 206 to be withdrawn through the inner groove 304 and the plurality of inner lower media ports 300 and / or media to be recirculated. To this end, the bed 206 can float upwardly, away from the bottom plate 16, causing a substantially uniform collapse of the bed 206 from the internal chamber 316 into the internal groove 304. Importantly, due to the radial nature of the internal groove 304, the bed 206 collapses into the internal groove 304 (rather than into the center of the main tube 14) without vortices. In other words, the bed 206 can be discharged uniformly (or substantially uniformly). The bed 206 can then be extracted from the internal groove 304 and from the main tube 14 via the multiple internal lower media ports 300. It will be appreciated that the same process can be employed to reintroduce and reform the bed 206 within the internal chamber 316.

[0053] Furthermore, in embodiments in which column 12 also includes one or more upper media ports, this also positions the one or more upper media ports in fluid communication with internal groove 304 (and, subsequently, with the plurality of internal lower media ports 300). When this occurs, one or more wash solutions can be recirculated throughout column 12, i.e., through one or more upper media ports, internal chamber 316, internal groove 304, and the plurality of internal lower media ports 300. Finally, it will be understood that internal groove 304 and the plurality of lower media ports 300 can be used in connection with other chromatography columns 12, including any of the chromatography columns 12 described herein and other chromatography columns not discussed herein.

[0054] Those skilled in the art will recognize that numerous modifications, variations, and combinations can be made with respect to the above-described embodiments without departing from the scope of the present disclosure, and that such modifications, variations, and combinations are considered to be within the scope of the inventive concept. Furthermore, one or more of the above-described components, assemblies, and embodiments can be utilized to improve the current column to provide the features and advantages described herein.

Claims

1. 1. A chromatography column comprising: The main tube and a bottom plate coupled to the main tube; a plurality of lower media ports carried by said bottom plate; an internal groove formed in an interior surface of the main tube, the internal groove interacting with the bottom plate and selectively providing an internal flow path between each of the lower media ports; A chromatography column, wherein the bottom plate is movable relative to the main tube between a first position in which the bottom plate is mounted against a portion of the main tube and a second position in which the bottom plate is spaced apart from the portion of the main tube.

2. 2. The chromatography column of claim 1, wherein when the bottom plate is in the first position, the plurality of lower media ports are exposed to the interior groove to provide a wash path for the plurality of lower media ports.

3. 3. The chromatography column of claim 1, wherein each of the plurality of lower media ports extends to a location below the bottom surface of the bottom plate.

4. 4. The chromatography column according to claim 1, wherein each of the plurality of lower media ports is disposed entirely radially inward on the outer surface of the main tube.

5. 5. The chromatography column of claim 1, wherein the plurality of lower media ports are arranged circumferentially around the bottom plate.

6. 6. The chromatography column of claim 1, wherein the main tube comprises an internal chamber adapted to accommodate a bed of media, the internal chamber being selectively accessible via the internal groove.

7. 7. The chromatography column of claim 1, further comprising one or more upper media ports formed in an upper portion of the main tube, wherein the internal groove is disposed between the one or more upper media ports and the plurality of lower media ports.

8. 8. The chromatography column of claim 1, further comprising a piston assembly movably disposed within the main tube along a longitudinal axis, the inner groove extending in a direction parallel to the longitudinal axis.

9. 9. The chromatography column of claim 8, comprising a top plate coupled to a first end of the main tube, the bottom plate coupled to a second end of the main tube opposite the first end, and the piston assembly comprising a piston rod extending through an opening in the top plate.

10. 1. A chromatography column comprising: a main tube having an internal chamber adapted to contain a bed of media; a bottom plate coupled to the main tube; a plurality of lower media ports carried by said bottom plate; an internal groove formed on an inner surface of the main tube; the internal chamber is selectively accessible through the internal groove; the internal grooves provide internal flow paths between each of the lower media ports; A chromatography column, wherein the bottom plate is movable relative to the main tube between a first position in which the bottom plate is mounted against a portion of the main tube and a second position in which the bottom plate is spaced apart from the portion of the main tube.

11. 11. The chromatography column of claim 10, further comprising: a piston assembly movably disposed within the main tube, the main tube comprising the interior chamber adapted to accommodate the bed of media between a piston of the piston assembly and the bottom plate, wherein when the bottom plate is in the first position, the interior chamber is sealed and the plurality of lower media ports are exposed to the interior groove to provide a wash path for the plurality of lower media ports, and when the bottom plate is in the second position, the interior chamber is exposed to the plurality of lower media ports via the interior groove.

12. 12. The chromatography column of claim 10 or 11, wherein the plurality of lower media ports are arranged circumferentially around the bottom plate.

13. 13. The chromatography column according to claim 10, wherein each of the plurality of lower media ports is disposed entirely radially inward on the outer surface of the main tube.

14. 14. The chromatography column of claim 10, wherein each of the plurality of lower media ports extends to a position below the bottom surface of the bottom plate.

15. 12. The chromatography column of claim 11, further comprising the piston movably disposed within the main tube along a longitudinal axis, the internal groove extending in a direction parallel to the longitudinal axis.

16. 16. The chromatography column of claim 10, further comprising one or more upper media ports formed in an upper portion of the main tube, the internal groove being disposed between the one or more upper media ports and the plurality of lower media ports.

17. 17. The chromatography column of claim 16, wherein the bottom plate is movable relative to the main tube between a first position in which the bottom plate is mounted against a portion of the main tube and a second position in which the bottom plate is spaced from the portion of the main tube, and when the bottom plate is in the second position, the interior chamber is exposed to the one or more upper media ports.

18. 1. A method of preparing a chromatography column having a main tube, a bottom plate coupled to the main tube, a bed of media disposed within an interior chamber of the main tube, a plurality of lower media ports carried by the bottom plate, and an internal groove formed in an interior surface of the main tube, comprising: performing a chromatography process using the chromatography column when the bottom plate is in a first position relative to the main tube, wherein in the first position, the bottom plate is seated against a portion of the main tube and the interior chamber is sealed; and cleaning the plurality of lower media ports by circulating a cleaning solution through an internal flow path provided by the internal groove between each of the lower media ports when the bottom plate is in the first position; moving the bottom plate relative to the main tube from the first position to a second position in which the bottom plate is spaced from the portion of the main tube, thereby unsealing the interior chamber; and withdrawing the bed of media through the interior groove and the plurality of lower media ports when the bottom plate is in the second position.

19. 20. The method of claim 18, wherein extracting comprises floating the bed of media upwardly off the bottom plate, thereby causing a substantially uniform collapse of the bed of media from the interior chamber into the interior groove.

20. 20. The method of claim 19, wherein the bed of media collapses into the inner groove without a vortex.

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