Patent Publication Number: US-2022226751-A1

Title: Components that Facilitate Maintenance of Chromatography and Synthesis Columns

Description:
FIELD OF THE DISCLOSURE 
     The present disclosure generally relates 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 
     Preparative liquid chromatography is widely used in different forms for purifying chemical and biological substances. 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 liquid mobile phase through the bed and is removed via an outlet. Separation of substances takes place between the mobile phase carrying the product through the column and the stationary phase of the porous media. Typically, the porous media is compressed in the column as a packed bed, generally formed by consolidating a suspension of discrete particles, known as slurry, that is pumped or poured into the column and consolidated by compression with a movable piston. 
     Routine maintenance of the chromatography column may include packing and unpacking the bed using ports in the main tube called slurry ports. Slurry ports may be in the main tube near the top, the bottom, or both. Slurry ports near the top of the main tube are typically used to fill the interior of the column with the slurry. Slurry can be poured or pumped into the upper slurry port to fill the column. The line used to dispense the slurry may be rinsed into the upper slurry port to chase every drop of media into the interior of the column. The upper slurry port can be closed, and the slurry consolidated into a bed by moving a piston within the column to squeeze the liquid out of the slurry. The bed thus formed may be solid or a semi-solid depending on the media of the slurry and the pressure of the piston. Slurry ports near the bottom of the main tube are typically used to unpack a semi-solid bed. A semi-solid bed can be unpacked by releasing pressure on the piston, flowing to disrupt the bed, opening the lower slurry port(s) and flushing out the bed or recirculating the media. Slurry ports provide access to the inside of the column and it is advantageous to clean them out after use. 
     However, known slurry ports present several different problems. First, traditional slurry ports are spaced apart from one another along the circumference of the main tube, which is inefficient for flushing out the bed because eddies form inside the column, thereby impeding uniform cleanout of the column. Second, slurry ports in general tend to create blemishes in the cylindricity of the internal wall of the column, which in turn has a negative influence on chromatography. 
     SUMMARY 
     In accordance with a first aspect, a chromatography column includes: a main tube with an internal radial groove; a top plate removably connected to a first end of the main tube; a bottom plate removably connected to a second end of the main tube, which bottom plate is movable within the main tube and has slurry ports on the underside; a piston assembly movable within the main tube; a piston rod connected to the piston assembly, which piston rod is arranged to extend through an opening in the top plate; and a frame supporting the column on the floor, which frame is connected to the main tube and capable of lifting the main tube relative to the immobile bottom plate. Actuating means are arranged on the three legs of the frame so that an internal 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 slurry ports arranged in the bottom plate. In a second position relative to the bottom plate, the internal radial groove in the main tube is exposed to the slurry ports so they may be cleaned while the second position also provides 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. 
     In accordance with a second aspect, a chromatography column includes: a main tube with an internal radial groove; a top plate removably connected to a first end of the main tube; a bottom plate removably connected to a second end of the main tube, which bottom plate is movable within the main tube and has slurry ports on the underside; a piston assembly movable within the main tube; and a piston rod connected to the piston assembly, which piston rod is arranged to extend through an opening in the top plate. 
     In accordance with 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 an internal groove formed in an interior surface of the main tube, wherein the internal groove interacts with the bottom plate and selectively provides an internal flow path between each of the lower media ports. 
     In accordance with a fourth aspect, a chromatography column includes: a main tube comprising an interior chamber that is adapted to contain a bed of media; a bottom plate coupled to 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, wherein the interior chamber is selectively accessible via the internal groove, and wherein the internal groove provides an internal flow path between each of the lower media ports. 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
       The features of this disclosure which are believed to be novel are set forth with particularity in the appended claims. The present disclosure may be best understood by reference to the following description taken in conjunction with the accompanying drawings, in which like reference numerals identify like elements in the several figures, in which: 
         FIG. 1  is a perspective view of a chromatography and synthesis column and base assembly in accordance with various embodiments; 
         FIG. 2  is a side cross-sectional view of a leg assembly for a base assembly showing a hydraulic cylinder in accordance with various embodiments; 
         FIG. 3  is a side cross-sectional view of a leg assembly for a base assembly showing a hydraulic cylinder and swing arm in accordance with various embodiments; 
         FIG. 4  is a side cross-sectional view of a leg assembly for a base assembly showing a guide block in accordance with various embodiments; 
         FIG. 5  is a side elevational view of the chromatography and synthesis column and base assembly of  FIG. 10  with the removable leg mounted thereto in accordance with various embodiments; 
         FIG. 6  is a side cross-sectional schematic view of a hydraulic cylinder system in accordance with various embodiments; 
         FIG. 7  is a top schematic view of a chromatography and synthesis column and base assembly with a swing arm configured to guide pivoting of a bottom plate in accordance with various embodiments; 
         FIG. 8  is a top schematic view of an alternative chromatography and synthesis column and base assembly with a swing arm configured to guide pivoting of a bottom plate in accordance with various embodiments; 
         FIG. 9  is a side elevational view of a chromatography and synthesis column and base assembly with a telescoping leg in accordance with various embodiments; 
         FIG. 10  is a top cross-sectional view of the telescoping leg of  FIG. 7  in accordance with various embodiments; 
         FIG. 11  is a side cross-sectional view of the telescoping leg of  FIG. 7  in accordance with various embodiments; 
         FIG. 12  is a side elevational view of a chromatography and synthesis column and base assembly with a removable leg being mounted thereto in accordance with various embodiments; 
         FIG. 13  is a diagrammatic view of an air driven hydraulic control circuit in accordance with various embodiments; 
         FIG. 14  is a top plan view of a bottom plate for a chromatography and synthesis column with radially opening slots in accordance with various embodiments; 
         FIG. 15  is a side plan view of a chromatography and synthesis column including the bottom plate of  FIG. 14  and a main tube showing pendulum members to secure the bottom plate to the main tube in accordance with various embodiments; 
         FIG. 16  is a sectional side view of the chromatography and synthesis column of  FIG. 15  in accordance with various embodiments; 
         FIG. 17  is a sectional side view of the chromatography and synthesis column of  FIG. 15  in accordance with various embodiments; 
         FIG. 18  is a side cross-sectional view of a chromatography and synthesis column with a bottom plate inserted to cover a slurry port in accordance with various embodiments; 
         FIG. 19  is a side cross-sectional view of the chromatography and synthesis column of  FIG. 18  in accordance with various embodiments; 
         FIG. 20  is a cross-sectional view of a portion of a chromatography and synthesis column with an internal groove and lower media ports in accordance with various embodiments, showing a bottom plate in a first position relative to a main tube; 
         FIG. 21  is similar to  FIG. 20 , but shows the bottom plate in a second position relative to the main tube; 
         FIG. 22  is a side view of the bottom plate and the lower media ports of the chromatography and synthesis column of  FIG. 20 ; 
         FIG. 23  is a bottom view of the bottom plate and the lower media ports of the chromatography and synthesis column of  FIG. 20 , with a first portion of the lower media ports hidden; and 
         FIG. 24  is a bottom view of the bottom plate and the lower media ports of the chromatography and synthesis column of  FIG. 20 , with a second portion of the lower media ports hidden. 
     
    
    
     Skilled artisans will appreciate 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 to improve understanding of various embodiments of the present invention. Also, common but well-understood elements that are useful or necessary in a commercially feasible embodiment are often not depicted in order to facilitate a less obstructed view of these various embodiments. It will further be appreciated that certain actions and/or steps may be described or depicted in a particular order of occurrence while those skilled in the art will understand that such specificity with respect to sequence is not actually required. It will also be understood that the terms and expressions used herein have the ordinary technical meaning as is accorded to such terms and expressions by persons skilled in the technical field as set forth above except where different specific meanings have otherwise been set forth herein. 
     DETAILED DESCRIPTION 
     The present disclosure is generally directed to chromatography and synthesis columns, assemblies, components, and methods of assembly and disassembly. The chromatography and synthesis columns as provided herein can be easily assembled and disassembled for maintenance saving time and potential damage to the columns. The chromatography and synthesis columns can further be provided with a stable base for securely moving the columns. The chromatography and synthesis columns can alternatively or additionally be provided with components (e.g., internal grooves, media ports) that facilitate efficient maintenance of the columns. 
     An exemplary support assembly  10  for a chromatography and synthesis column  12  that includes a generally annular main tube  14  and a bottom plate  16  is described with reference to  FIGS. 1-12 . As shown in  FIG. 2 , in one form, the support assembly  10  includes a rigid frame  18  that has a house-shaped pentagon configuration with cross-members  19  extending around a rear rectangular portion  20  and a forward triangular portion  22 . In the illustrated form, the frame  18  is sized to extend around the column  12  such that the column  12  is disposed both within the rectangular and triangular portions  20 ,  22 . 
     The support assembly  10  further includes two rear legs  24  that are mounted to the frame  18  at rear corners  26  of the rectangular portion  20  and a front leg  28  mounted to the frame  18  at a forward corner  30  of the triangular portion  22 . As shown, the frame  18  is configured so that the forward corner  30  and front leg  28  align with a midpoint of the frame cross-member  19  extending between the rear corners  26 . Further, in one form, the front leg  28  is set a distance from the column  12  generally equal to the closest perpendicular spacing of the column  12  to the three cross-members  19  of the frame  18  in the rectangular portion  20 . 
     In some embodiments, the support assembly  10  can be configured to lift the column  12  to thereby ease removal of the bottom plate  16  and other maintenance actions. 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 lower leg assemblies  46 ,  48  for the rear legs  24  and front leg  28 , respectively, cooperate to lift the frame  18  and the column  12  secured thereto. 
     As shown in  FIGS. 2-4 , the lower leg assemblies  46 ,  48  of the rear legs  24  and front leg  28  include a base  50 , a caster  52  mounted to an 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 the main tube  14 . So configured, the lower leg assemblies  46 ,  48  control upward and downward movement of the frame  18  by raising and lowering the piston rod  57  of the hydraulic cylinder  54 . In the illustrated form, the hydraulic cylinders  54  are inverted with the barrel  55  coupled to the frame  18 . This advantageously avoids movement of hydraulic hoses and other components relative to the frame  18 . 
     In order to orient and couple the lower leg assembly  46  to the frame  18 , the frame  18  includes downwardly depending tubular leg portions  58  disposed at the corners  26 ,  30  that have a vertical sidewall  59  extending around an interior  60  thereof. The leg portions  58  are sized so that the support  56  and the hydraulic cylinder  54  can extend upwardly into the interior  60  thereof. Bearings  61  are disposed along the height of and coupled to the support  56  to contact the leg portion sidewall  59  to orient the lower leg assembly  46  within the frame leg portion  58  as the hydraulic cylinder  54  moves the frame  18  upwardly and downwardly. 
     To further ensure that the frame leg portion  58  is aligned with the base  50 , the base  50  can include a block  62  having a vertical slot  64  extending through a portion thereof. The block  62  is positioned on the base  50  so that the sidewall  59  of the leg portion  58  shifts therein during lifting and lowering operations. Further, the block  62  can be configured to prevent the lower leg assembly  46 ,  48  from rotating relative to the frame  18 . 
     In order to shield the moving components of the support assembly  10  during lifting and lowering operations, the base  50  can include an upstanding wall  66  that extends around a perimeter thereof. As shown, the wall  66  is spaced outwardly of the sidewall  59  of the leg portions  58  and has a height to project above a lower edge  68  of the leg portions  58  with the hydraulic cylinder  54  in a raised configuration. So configured, the leg portion  58  and the wall  66  telescope with respect to one another during lifting and lower operations, which effectively prevents a user from inadvertently putting a hand or other object underneath the frame  18 . 
     By 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 raised portions  71  that project upwardly towards the frame  18 . The raised portions  71  are configured so that when the leg portion  58  is lowered, the lower edge  68  abuts a top surface  72  of the raised portion  71  resulting in the frame  18  being disposed at a height suitable for operation. For storage, a user can slide the height guide member  70  so that the raised portions  71  are misaligned with respect to the sidewall  59  and a lowering operation causes the edge  68  to abut a lower surface  73  of the guide member  70 . As shown in  FIG. 4 , the upstanding wall  66  of the base  50  can include openings  74  extending therethrough to allow the guide member  70  to be slid to a desired position on the base  50 . Further, to keep the guide member  70  disposed on the base  50 , the guide member  50  can include end stops  75  that are configured to abut the upstanding wall  66  or base  50  when the guide member  50  is slid from one end to the other. By one approach, the end stops  75  can be utilized to position the guide member  70  in the raised or lowered configurations, allow a user to simply shift the guide member  70  until the desired end stop  75  prevents further movement. 
     Due to the high precision required to insert and remove the bottom plate  16 , by one approach, the hydraulic cylinders  54  can be configured to operate in lockstep, providing synchronized up and down movement of the frame  18  and, therefore, the main tube  14 . The asymmetrical 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. 
     To accomplish a coordinated lift, as shown in  FIG. 5 , the hydraulic cylinders  54  can be double acting cylinders. The double rod configuration makes the area of the exposed piston  100  equal in each chamber  102 ,  104  of the double acting cylinder  54 . This allows one pump  106  ( FIG. 6 ) to synchronize multiple cylinders  54  and provide the coordinated descent of the cylinders  54  when there is an uneven load distributed across the cylinders  54 . As illustrated in  FIG. 5 , the cylinders  54  are connected in series. A first closed system  108 , which is filled with a hydraulic fluid as understood, is established between the top chamber  102  of the first cylinder  54   a  and the bottom chamber  104  of the second cylinder  54   b . A second closed system  110  is established between the top chamber  102  of the second cylinder  54   b  and the bottom chamber  104  of the third cylinder  54   c . As the bottom chamber  104  of the first cylinder  54   a  is being filled by hydraulic fluid, the top chamber  102  of the first cylinder  54   a  will fill the bottom chamber  104  of the second cylinder  54   b . As the bottom chamber  104  of the second cylinder  54   b  is being filled, the top chamber  102  of the second cylinder  54   b  will fill the bottom chamber  104  of the third cylinder  54   c . As the bottom chamber  104  of the third cylinder  54   c  is being filled, the top chamber  102  will express hydraulic fluid into a reservoir  112  supplying the pump  106  for the first cylinder  54   a . While this hydraulic configuration of the system  108  is inefficient relative to traditional hydraulic cylinders, the double rod configuration of the cylinders  54  reduces the area of exposed piston  100  and the cylinders  54  in series adds the load on all of the cylinders  54  together and applies the total load to the reduced area of the piston  100  of the first cylinder  54   a . This disadvantage can be tolerated because while the columns  12  are large, the hydraulic cylinders  54  are more than sufficient to handle the load, and operating the cylinders  54  in sync provides a significant advantage of perfectly synchronized cylinders  54  moving the frame  18 , and the column  12  secured thereto, upwardly and downwardly. 
     The reverse operations happen when lowering the frame  18 . The load of the column  12  and frame  18  is used to drive the cylinders  54  downwardly and, as shown in  FIG. 9 , a metering valve  114  on the first cylinder  54   a  defines the rate of descent of all the cylinders  54 . The load pushing down on the third cylinder  54   c  causes the bottom chamber  104  to fill the top chamber  102  of the second cylinder  54   b . At the same time, the top chamber  102  of the third cylinder  54   a  is filling by suction of the fluid in the reservoir  112  supplying the pump  106 . The top chamber  102  of the second cylinder  54   b  being filled by the third cylinder  54   c  and the load on the second and third cylinders  54   b ,  54   c  causes the bottom chamber  104  of the second cylinder  54   b  to fill the top chamber  102  of the first cylinder  54   a . The top chamber  102  of the first cylinder  54   a  being filled by the second cylinder  54   b  and the load on the first, second and third cylinders  54  causes the bottom chamber  104  of the first cylinder  54   a  to express fluid. The metering valve  114  put on the fluid flow from the bottom chamber  104  of the first cylinder  54   a  defines 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  upwardly and downwardly. 
       FIG. 9  is a process and instrument diagram for an example air-driven hydraulic control circuit  116 . As shown, the control circuit  116  is provided for driving movement of the cylinders  54  by controlling operation of the pump  106 . In the illustrated form, the pump  106  is an air-over-hydraulic pump and the control circuit  116  is air driven. It will be understood that other circuits, including electrical, could alternatively be utilized to accomplish the hydraulic pump and control circuit. By one approach, a user can provide input to the control circuit  116  using a pendent  118  having pushbutton vents  120  to provide convenience for the operator and to facilitate one-man operation. It will be understood that the valve components of the pendent  118  can be located elsewhere and/or alternative embodiments for the circuit can perform the same or similar functions. 
     The control circuit  116  includes an inlet  122  from an air supply  123  suitable to drive the pump  106  to the pressure required by the cylinders  54  to lift the frame  18  and column  12  and an outlet  124  connected to the cylinders  54 . As shown, the control circuit  116  can further utilize a 3-way manual valve  126  as an on/off control, a pressure regulator  128 , various pressure gauges  130 , a manual shut-off service valve  132 , pneumatic valves  134 , and a pressure relief valve  136 . 
     With the control circuit  116  shown in  FIG. 9 , movement of the cylinders  54  can be locked out by the on/off valve  126  which simultaneously vents the pneumatics whether the cylinders  54  are moving or sitting idle. A first pressure gauge  130  is included so the inlet air pressure can be confirmed when the on/off valve  126  is in the on position and that the pneumatic pressure is vented when the on/off valve  126  is in the off position. The pendent  118  has two pneumatic valves  120  that are normally closed. To lower the frame  18  and column  12 , the “down” valve  120  is in communication with the on/off valve  126  and the actuator of the down shutoff valve  134 . To raise the frame  12  and column  12 , the “up” valve  120  is in communication with the on/off valve  126  and the actuator of the up-shutoff valve  134 . The pressure regulator  128  is in communication with the on/off valve  126  and the air side of the air driven 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 fluid in the hydraulic fluid reservoir  112  and the up-shutoff valve  134 . The pressure relief valve  136  is in communication with the hydraulic fluid reservoir  112 , the up-shutoff valve  134 , the metering valve  114 , and the output  124  to the hydraulic cylinders  54 . A third pressure gauge  130  is in communication with the up-shutoff valve  134 , the pressure relief valve  136 , the metering valve  114 , and the output  124  to the hydraulic cylinders  54 . 
     As discussed above, the bottom plate  16  of the column  12  is removed for many maintenance actions. In order to easily and repeatably move the bottom plate  16  from underneath the main tube  14  and realign the bottom plate  16  with the main tube  14 , a swing arm  32  is provided that pivotably couples the bottom plate  16  to the support assembly  10  at the front support leg  28  via a bearing  29  ( FIG. 3 ). The swing arm  32  is rigid so that the bottom plate  16  can be pivoted 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 legs  24  so that the bottom plate  16  can easily pass therebetween. 
     In an alternative embodiment as shown in  FIG. 8 , a frame  18 ′ can have a rectangular configuration where the legs  24  are spaced a sufficient distance from one another for the bottom plate  16  to be pivoted between two adjacent legs by a rigid swing arm  32 ′. While this configuration may be suitable for many purposes, the footprint of the frame  18 ′ is larger in comparison to the size of the column  12  as with the above embodiment. 
     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 fork lift. With this configuration, a user can easily maneuver the carriage  34  on the casters  38 , which avoids the precarious movements of a lift device. Moreover, the carriage  34 , along with the swing arm  32 , ensures that movement of the bottom plate  16  is precisely controlled along the radius of the swing arm  32  so that contact, and any resulting damage, between the bottom plate  16  and the support assembly  10  is prevented. 
     As discussed above, moving the bottom plate  16  back underneath the main  14  to insert a plug portion  25  thereof into the main tube  14  requires that the bottom plate  16  be aligned translationally, rotationally, and horizontally with the main tube  14 . The swing arm  32  advantageously provides easy, repeatable alignment because the bottom plate  16  can be fixedly mounted to the swing arm  32  so that the plate  16  cannot rotate relative to the swing arm  32  and the swing arm  32 , and carriage  34 , can maintain the bottom plate  16  in an horizontal orientation. Further, a stop  39  can be mounted to the support assembly  10  and/or the main tube  14  so 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, a user can simply push the bottom plate  16  on the carriage  34  and the swing arm  32  will direct movement along the radius thereof until the bottom plate  16  contacts the stop  39 . 
     A lifting mechanism, such as the hydraulics  54  discussed above, can further be utilized to reliably remove the bottom plate  16  from the main tube  14 . As discussed above, the bottom plate  16  includes a plug portion  25  that projects into and seals against an 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 an anchor  78 , such as a ring as illustrated, and the bottom plate  16  can include a corresponding anchor  80 . A removable or releasable coupling  81  can then be installed between the anchors  78 ,  80  to couple the bottom plate  16  to the lower leg assemblies  46 ,  48  when the frame  18  is in the lowered position holding the bottom plate  16  in a fixed position. In the illustrated form, the three couplings  81  to the rear and front legs  24 ,  28  hold the bottom plate  16 , so that, when the hydraulic cylinders  54  raise the frame  18 , the bottom plate  16  and carriage  34  remain stationary. As the main tube  14  is raised, 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 . Thereafter, the couplings  81  can be removed or released and the bottom plate  16  can be pivoted on the swing arm  32  to a position exterior of the frame  18  through the spacing between the front and rear legs  28 ,  24  as discussed above. It will be understood that the anchors  78 ,  80  and couplings  81  can take any suitable form, such as hooks, straps, fasteners, and so forth. Further, in another form, the carriage  34  can include one or more of the anchors  78  rather than the bottom plate  16 . 
     Referring back to  FIG. 3 , due to the swing arm  32 , the lower leg assembly  48  of the front leg  28  can be modified relative to the rear legs  24  to include structure in addition to the components described above. More specifically, the lower leg assembly  48  includes a lower support  51  and base  53 , with the caster  52  mounted to the lower base  53 . The lower support  51  has a cylindrical configuration and is sized so that the bearing  29  of the swing arm  32  coupled thereto can freely rotate and has room to move upwardly and downwardly as the hydraulic cylinders  54  move the frame  18 . 
     As is understood, support assemblies  10  having three legs may result in less stable movement for the column  12 , especially where the weight of the column  12  has asymmetrical loading as with the frame  18  discussed above. To provide additional support, as shown in  FIGS. 9-11 , the support assembly  10  can include telescoping legs  82  at intermediate corners  31  of the frame  18  between the rear corners  26  and the front corner  30 . By having a telescoping functionality, the legs  82  can be moved out of the path of the bottom plate  16  as the bottom plate is moved out from beneath the main tube  14 , such as by using the swing arm  32  described above. 
     As shown in  FIGS. 10 and 11 , each telescoping leg  82  includes an elongate shaft  83  with a cross bar  84  extending outwardly from an intermediate portion thereof and a caster  85  mounted on a distal end thereof. A telescoping housing  86  is mounted to the frame  18  at the corner  31 . The housing  86  includes openings  87  extending through the top and bottom thereof so that the leg  82  can extend therethrough. If desired, the housing  86  can include bearings  88  disposed around the openings  87  to align and aid in movement of the leg  82 . 
     As shown, the housing  86  includes first and second position plates  89 ,  90  that extend across the interior of the housing  86 . The first and second position plates  89 ,  90  each further include a key opening  91  that extends vertically therethrough that has a shape corresponding to the cross bar  84  of the leg  82 . The first position plate  89  is disposed at a height so that with the cross-bar  84  positioned below the first position plate  89 , as shown in  FIG. 11 , the leg  82  is aligned with the other legs  24 ,  28  of the support assembly  10 . As such, the support assembly  10  in this configuration has five legs to support the weight of the column  12  and provides stable movement. The second position plate  90  is disposed above the first position plate  89  and is configured to hold the leg  82  in an elevated position out of the way for removal of the bottom plate  16 . To move the leg  82  to the elevated position, a user can align the cross bar  84  with the key opening  91  of the first position plate  89  and, subsequently, the key opening  91  of the second position plate  90 . Thereafter, the user can rotate the leg  82  so that the cross bar  84  is not aligned with the key opening  91  and the weight of the leg  82  is supported on the second position plate  90 . If desired, each leg  82  can include a handle  92  secured thereto to help a user to move the leg  82  to the elevated position. 
     By another approach, in order to provide increased stability for the support assembly  10 , the corners  31  of the frame  18  can be utilized for the attachment of removable legs  93 . The removable legs  93  include an elongate shaft  94 , casters  95  mounted at a distal end of the shaft  94 , and a coupling portion  96  at a proximal end of the shaft  94 . The corners  31  include a corresponding coupling portion  97  so that the legs  93  can be removably secured thereto. In the illustrated form, the leg coupling portion  96  includes a threaded fastener  98  that can be inserted through a throughbore  99  extending through the frame  18  and into the proximal end of the shaft  88 . By another approach, the leg  93  can include a threaded fastener and the throughbore  99  can be threaded and/or a nut can secure the leg  93  to the frame  18 . It will be understood that other coupling methods, such as snap-fit, friction, and so forth, are within the scope of this disclosure. 
     Attaching and removing the removable legs  93  can be aided by frame lifting mechanisms, such as the hydraulics  54  discussed above. More specifically, the hydraulics  54  can lift the frame  18  to a raised position and the removable legs  93  can then easily be secured to the frame  18  as discussed above. Thereafter, the hydraulics  54  can 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  can then be lifted and the legs  93  removed so that the bottom plate  16  can be pivoted out between the front  28  and rear legs  24 , as discussed above. 
     In a further embodiment shown in  FIGS. 14-17 , the bottom plate  16  can be easily secured to the main tube  14  without the use of bolts as with the conventional method. As shown in  FIG. 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 a curved interior end  152  with a rectangular radial opening  154  in the illustrated form, but other suitable configurations can be contemplated. 
     As shown in  FIGS. 15-17 , the main tube  14  has a plurality of pendulum members  156  that are pivotably coupled to an exterior  158  of the main tube  14  at spaced radial positions. Each pendulum member  156  includes a stem portion  160 , a distal, enlarged retaining portion  162 , and a proximal end  164 . Each pendulum member  156  can be coupled to the main tube  14  by any suitable method, including brackets  166  as shown. For example, in the illustrated form, the pendulum members  102  are I-bars and the proximal end  164  is retained with the brackets  166  secured to the main tube  14  so that the pendulum members  156  can be pivoted along a vertical plane. 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 portions  162  are disposed below the bottom plate  16 , which prevents the bottom plate  16  from being removed. 
     By one approach, the stem portion  160  of each pendulum member  156  is sized so that the retaining portion  162  can clear the bottom plate  16  when the plug portion  25  thereof is fully received within the main tube  14 , i.e., the hydraulic cylinders  54  are lowered to make the main tube  14  fully seat on the bottom plate  16  and compress a compliance gap  166 . Thereafter, as a result of gravity, packing, or other operation, the plug portion  25  of the bottom plate  16  slides downwardly to expand the compliance gap  166  and abut the retaining portions  110  of the pendulum members  102 . The seal between the plug portion  25  and the main tube  14  remains hermetic through 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 for the expansion of the compliance gap  166 . As a result, the pendulum members  102  capture the bottom plate  16  and secure the bottom plate  16  to the main tube  14  without the use of bolts. By one approach, a lower outer corner  170  of the bottom plate  16  can be chamfered or rounded to reduce the arcuate path of the retaining portion  110  to pivot to a position below the bottom plate  16 . If desired, the retaining portions  162  can have a flat radially inward surface  168  to provide a larger seating 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 as the retaining portion  162 . With this configuration, the flat surface  168  can provide a distinguishing feature for a user installing the pendulum members  156 . 
     Similarly, to remove the bottom plate  16 , a user can lower the main tube  14 , or raise the bottom plate  16 , so that the plug portion  25  is inserted further therein and the compliance gap  166  is reduced. With this insertion, the retaining portions  162  will be spaced from the bottom plate  16 , which allows a user to pivot the pendulum members  156  to a storage position spaced radially from or disposed above the bottom plate  16 . By one approach, coupling brackets  172  can be mounted to the main tube  14  above the pivoting brackets  166 . The coupling brackets  172  can be configured to retain the pendulum members  156  in a generally vertical orientation by clips, snap-fit, friction-fit, or other suitable methods. 
     A further embodiment for the column  12  is shown in  FIGS. 18 and 19  where the main tube  14  includes upper and lower slurry ports  200 ,  202 . In operation, the bottom plate  16  is coupled to the main tube  14  and a piston  204  is driven downwardly to pack the bed  206  between the piston  204  and the bottom plate  16 . A seal  208  of the piston  204  and the bottom plate seal  77  extend circumferentially around the piston  204  and bottom plate  16  respectively within a seal groove  210 . The piston  204  and bottom plate  16  each further include a glide ring  212  disposed within a groove  214  extending circumferentially around the piston  204  and bottom plate  16  respectively. As shown, the piston  204  and bottom plate  16  can further include a scraper seal  216 , a fritt  218 , and a distributor plate  220  with a seal  222 . 
     In this embodiment, the plug portion  25  of the bottom plate  16  has a larger depth than conventional plates so that the plug portion  25  projects further into the main tube  14 . This additional depth can be utilized so that the seal  77  is driven past the lower slurry port  202  for operation. In the illustrated form, the glide ring  212  extends across the lower slurry port  202 . The hydraulics  54  configuration described above can advantageously be utilized to drive the additional depth of the bottom plate  16  into the main tube  14 . 
     Similarly, the piston  204  is driven downwardly within the main tube  14  so 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 hidden to avoid disturbing the plug flow and to obtain better chromatography, i.e., higher plate count, HETP. 
     Advantageously, the upper and lower slurry ports  200  can be utilized to re-slurry or process soft beds in the column  12 . Additionally, the upper and lower slurry ports  200  can be utilized to transfer the bed  206  in 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 hydraulics  54  and removable couplings  81  described above. 
       FIGS. 20-24  illustrate another embodiment of the column  12  in which the column  12  generally includes the main tube  14 , the bottom plate  16 , the piston  204 , as discussed above, but is different in the manner discussed below. More particularly, the column  12  in this embodiment also includes a plurality of internal lower media ports  300  (instead of the external slurry ports  200 ,  2020 ) as well as an internal groove  304  and a glide ring  306  that is carried by the bottom plate  16  and slidably engages the main tube  14 . As best illustrated in  FIGS. 20 and 21 , the plurality of internal lower media ports  300  are carried by the bottom plate  16  (whereas the slurry ports  200 ,  202  are formed in the main tube  14 ), while the internal groove  304  is formed in the interior surface  76  of the main tube  14 . As will be discussed in greater detail below, the internal groove  304  selectively provides an internal flow path between each of the internal lower media ports  300 , which in turn facilitates maintenance (e.g., cleaning) of the components of the column  12 , but 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). Moreover, the main tube  14  includes an interior chamber  316  that is adapted to contain the bed  206  (or a different bed of media) that is selectively accessible via the internal groove  304 , as will also be discussed in greater detail below. 
     In this embodiment, the plurality of internal lower media ports  300  includes four uniform internal lower media ports (only one of which is visible in  FIGS. 20 and 21 , but all of which are depicted in  FIGS. 22-24 ). Each of the four internal 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 underneath a 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 entirely disposed radially inwardly of an exterior surface  324  of the main tube  14  opposite the interior surface  76  (and at least partially, if not entirely, disposed radially inwardly of the interior surface  76  of the main tube  14 ). Moreover, each of the four lower media ports extends downwardly and radially inwardly away from the main tube  14 . In this embodiment, each of the four internal lower media ports has a first portion that is oriented at an angle of 45 degrees relative to a bottom surface of the main tube  14  and to the bottom surface  320  of the bottom plate  16 , and a second portion that is oriented at an angle of 45 degrees 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 . Additionally, as illustrated in  FIG. 22 , two of the four lower media ports  300  (in this case, lower media ports opposite one another) 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 opposite one another) are disposed at a second height (i.e., a second distance from the bottom surface  320  that is greater than the first distance). Further, as best illustrated in  FIGS. 23 and 24 , the four internal lower media ports  300  are circumferentially arranged about the bottom plate  16 , such that the four internal lower media ports  300  are staggered or offset from one another. The four internal lower media ports  300  are evenly spaced apart from one another in this embodiment, though in other embodiments, the four internal lower media ports  300  can be different distances from one another. Finally, as best illustrated in  FIGS. 23 and 24 , two of the four lower media ports  300  (e.g., the lower media ports  300  disposed at the first height) are fluidly coupled to one another via a first manifold  308 , and the remaining two of the four lower media ports  300  (e.g., the lower media ports  300  disposed at the second height) are fluidly coupled to one another via a second manifold  312 . 
     In other embodiments, however, the plurality of internal lower media ports  300  can vary from what is illustrated in  FIGS. 20-24 . As an example, the plurality of internal lower media ports  300  can instead include two, three, five, six, or a different number of internal lower media ports. As another example, the plurality of internal lower media ports  300  need not be uniformly sized or otherwise constructed. As yet another example, the plurality of internal lower media ports  300  can extend and/or be located in a different manner. In other embodiments, the first and/or second portions of each of the internal lower media ports  300  can be oriented at an angle of 30 degrees, 60 degrees, 75 degrees, or some other angle relative to the bottom surface of the main tube  14  and to the bottom surface  320  of the bottom plate  16 . Further, while not illustrated herein, it will be appreciated 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 can take the form of the upper slurry port  200 , the lower media ports, or some other port. 
     In this embodiment, the internal groove  304  is formed in the interior surface  76  of the main tube  14  and extends in a radial direction around the entire circumference of the main tube  14 . Moreover, the internal groove  304  has a length that extends in a direction that is parallel to a longitudinal axis  328  along which the piston  204  moves in the main tube  14 . Thus, the internal groove  304  can also be referred to as an internal vertical groove or an internal radial groove. Further, in this embodiment, the internal groove  304  is sized so that the area of the internal groove  304  is substantially if not entirely equal to the area of the plurality of internal lower media ports  300 , which in turn promotes a uniform and balanced fluid communication between the interior 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 the upper slurry port  200 , the internal groove  304  will be disposed between the upper slurry port  200  and the plurality of internal lower media ports  300 . In other embodiments, however, the internal groove  304  can be formed and/or be located in a different manner. As an example, the internal groove  304  can, in some embodiments, extend around only a portion of the circumference of the main tube  14 . 
     As discussed above, the bottom plate  16  is movable relative to the main tube  14  via the use of the hydraulics  54  and removable couplings  81 . More particularly, 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 seated 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 in turn allows the main tube  14  and the bottom plate  16  to be presented for maintenance. 
     As illustrated in  FIG. 20 , when the bottom plate  16  is in the first position, at least a top portion of the internal groove  304  engages a wall of the bottom plate  16 , thereby sealing the interior chamber  316 . In turn, the interior chamber  316  is not accessible (e.g., via the internal lower media ports  300  or the internal groove  304 ). Moreover, when the bottom plate  16  is in the first position, the internal groove  304  provides the internal flow path within the main tube  14  and between each of the internal lower media ports  300 . The internal flow path beneficially allows the internal lower media ports  300  (and the internal groove  304 ) to be easily cleaned (and then drained) in a closed manner. For example, two of the internal lower media ports  300  can be used as inlets that receive one or more cleaning solutions and distribute the one or more cleaning solutions into the internal flow path, with the remaining two internal media ports  300  used as outlets that receive the one or more cleaning solutions after they have passed through some or all of the internal flow path before draining or exhausting those cleaning solutions out of the internal flow path. At the same time, because the interior chamber  316  is sealed, the chromatography process can be performed, without interruption, using the column  12 . 
     Meanwhile, as illustrated in  FIG. 21 , when the bottom plate  16  is in the second position, at least the top portion of the internal groove  304  is spaced from the wall of the bottom plate  16 , which thereby unseals the interior chamber  316 , exposes the interior groove  304 , and places the interior chamber  316  in fluid communication with the internal groove  304  (and, in turn, with the plurality of internal lower media ports  300 ). Beneficially, because in this embodiment the internal lower media ports  300  are equally spaced apart from one another, the internal lower media ports  300  are placed in fluid communication with the interior chamber  316  in a substantially uniform and balanced manner. In any event, this fluid communication allows the bed  206  to be evacuated via the internal groove  304  and the plurality of internal lower media ports  300  and/or media to be recirculated. To this end, the bed  206  can be floated upward, away from the bottom plate  16 , which causes a substantially uniform collapse of the bed  206  out of the interior chamber  316  and into the internal groove  304 . Importantly, the radial nature of the internal groove  304  causes the bed  206  to collapse into the internal groove  304  (and not into the center of the main tube  14 ) without eddies. In other words, the bed  206  can be uniformly (or substantially uniformly) be unpacked. In turn, the bed  206  can in turn be evacuated out of the internal groove  304  and out of the main tube  14  via the plurality of internal lower media ports  300 . It will be appreciated that the same process can be employed to re-introduce and re-form the bed  206  in the interior chamber  316 . 
     Further, in embodiments in which the column  12  also includes one or more upper media ports, this will also place the one or more upper media ports in fluid communication with the internal groove  304  (and, in turn, with the plurality of internal lower media ports  300  as well). When this happens, one or more cleaning solutions can be recirculated throughout the column  12 , namely through the one or more upper media ports, the interior chamber  316 , the internal groove  304 , and the plurality of internal lower media ports  300 . Finally, it will be appreciated that the 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. 
     Those skilled in the art will recognize that a wide variety of modifications, alterations, and combinations can be made with respect to the above described embodiments without departing from the scope of the disclosure, and that such modifications, alterations, and combinations are to be viewed as being within the ambit of the inventive concept. Further, one or more of the above components, assemblies, and embodiments can be utilized to retrofit current columns to provide the features and advantages described herein.