Abstract:
A chromatography column, or other type of processing column, including a column tube having a top end cap having an opening there through and an open bottom end. A bottom end cap covers and is removably attached to the open bottom end of the column tube and a piston is slidably positioned within the column tube. A rod is attached to the piston and passes through the top end cap opening. The length of the rod may be extended so that the piston may be lowered partially through the open bottom end of the column tube when the bottom end cap is removed. An arrangement for raising the piston includes a hydraulic pump that communicates with a portion of an interior of the column tube above the piston via a port formed in the top end cap.

Description:
CLAIM OF PRIORITY  
       [0001]     This application claims priority from U.S. Provisional Patent Application Ser. No. 60/607,557, filed Sep. 7, 2004. 
     
    
     BACKGROUND OF THE INVENTION  
       [0002]     The present invention relates generally to processing columns such as dynamic axial compression chromatography columns and, in particular, to a specially designed column innovation that eliminates the need for overhead hoists during maintenance and operation procedures and a method for retrofitting industrial chromatography columns with the innovation to improve column handling and operation.  
         [0003]     Liquid chromatography (LC) columns are used in many industrial processes at various pressure ratings from low pressure (LPLC) to medium pressure (MPLC) and high pressure (HPLC). The use of large scale chromatography to purify raw materials, intermediates and end products is common in many industrial segments including pharmaceutical products, biopharmaceutical products, nutraceutical products, food and beverage products, household products, personal care products, petroleum products, chemical products and other specialty products. In addition, certain industries such as the Biopharmaceutical Industry require the use of multiple chromatographic purification steps for every product made.  
         [0004]     The state of the art in large-scale column chromatography utilizes a technology referred to as “dynamic axial compression” in which an adjustable position piston head is used. This approach requires an outer column tube within which an internally located piston head is dynamically compressed by means of pneumatic or hydraulic pressure that permits both the formation and maintenance of homogenously packed beds of particulate chromatography matrices (e.g. polymeric or silica gel based chromatography medias). The force on the piston may be either externally applied to the piston via a rod or internally applied (i.e. within the column) to the piston itself with the rod providing guidance for the piston movement.  
         [0005]     These columns also need to include mesh frits at the interface with the media, which then retains the chromatography media in place during column bed formation and subsequent processing operation. The frits are friction fitted within the column, or may be welded or bolted into place, and a typical column has two frits with one of the frits positioned on the inlet side of the media and the other frit positioned on the outlet side of the media.  
         [0006]     After use, the columns are emptied and the frits, seals that may be present to hold the frits in position and piston head seals that prevent liquid transfer around the edges of the piston head need to be easily inspected, cleaned and removed for external cleaning procedures or replacement. Normally this is accomplished through the use of industrial multi-ton capable overhead hoists that remove the piston head by lifting it out from the top of the column tube. The removed piston head has to be carefully stabilized and protected from scratches, dents, deformations or other catastrophic damage while it is out of the column during maintenance or operation procedures. In addition to the operational difficulties there is the risk of operator injury during handling of the heavy piston components.  
         [0007]      FIG. 1  illustrates a prior art approach to removing a piston head from a large-scale dynamic axial compression chromatography column  10 . The system of  FIG. 1  requires an externally powered and operated winch or hoist trolley system  14  of significant size and capacity to remove the internal piston head  12  and column end plate through which the column piston rod extends, as illustrated by arrow  11 . In addition, the location of the hoist  14  must be such that the piston head can be removed in exact alignment because any skewing of the piston head during removal can cause the head to become seized in place and both the tube and piston head damaged. As illustrated in  FIG. 2 , the removed piston head is lowered onto a platform  13  or the like and must be very carefully handled, transported and protected during maintenance. There is also the need to secure the base of the column securely to make sure the entire column assembly is not picked up off the floor during hoisting. To this end, column legs  15  must be bolted or otherwise secured to floor  17 , as illustrated in  FIG. 3 .  
         [0008]     As  FIG. 3  demonstrates, the final major challenge occurs during replacement of the removed piston unit  12  back into the chromatography column  10 , as indicated by arrow  19 . If any slight mishandling occurs, critical seals can be compromised which will cause column malfunction during operation. In addition, if any skewing occurs during repositioning, the head can become lodged in place or easily damaged resulting in shut down of critical manufacturing processes at an extremely high cost.  
         [0009]     In the past, large-scale chromatographic purification work was conducted in industrial manufacturing environments with easy access to ancillary equipment such as overhead trolley hoist systems. The recent expansion of the Biotech Industry, which is heavily reliant on LC processes, as well as the need to perform this purification work in controlled areas such as certified clean rooms or purification suites, has created an operational problem where access to overhead hoists is no longer available. In addition, “lean” manufacturing approaches throughout the industries mentioned above has led to the establishment of multiple-use smaller scale manufacturing areas that do not have the same capabilites as traditional large single space areas. Large chromatography columns (typically up to 2 meters internal diameter) can weigh multiple tons and are no longer portable. The difficulties and costs associated with using hoists in controlled areas to perform operations and maintenance has become unacceptable for many facilities. Thus, a chromatograhy column that does not require external hoists is of great necessity and value.  
         [0010]     In addition, ease of use is critical for large operations where multiple process operators need to be trained in the safe and reproducible use of processing equipment. An uncomplicated and robust solution to large chromatographic column operation is required.  
         [0011]     Accordingly, it is an object of the present invention to provide a hoist-free method and apparatus that are capable of providing easy access to key piston head components and frits of a chromatography column, or other type of processing column, for maintenance and operational procedures. This provides a significant advantage even in areas where hoists are available, as discussed above  
         [0012]     It is another object of the present invention to provide hoist-free capability that may be applied to existing industrial chromatography columns, or other processing columns, of various designs or manufacturers as an upgrade.  
       SUMMARY OF THE INVENTION  
       [0013]     The present invention is directed to a chromatography column, or other type of processing column, including a column tube having a top end cap having an opening there through and an open bottom end. A bottom end cap covers and is removably attached to the open bottom end of the column tube and a piston is slidably positioned within the column tube. A rod is attached to the piston and passes through the top end cap opening. The length of the rod may be extended so that the piston may be lowered partially through the open bottom end of the column tube when the bottom end cap is removed. The rod features a threaded bore and the removable extension piece features a threaded stud that engages the threaded bore of the rod. Alternatively, a second rod having a longer length may replace the first rod.  
         [0014]     The column features an arrangement for raising the piston including a hydraulic pump that communicates with a portion of an interior of the column tube above the piston via a port formed in the top end cap. Alternatively, a jack may be used for raising the piston. As another alternative, a vacuum pump that communicates with the portion of the interior of the column tube above the piston may be used to raise the piston. As another alternative, a port formed in the bottom end plate may be engaged by a pump that pumps liquid into the column tube below the piston.  
         [0015]     The following detailed description of embodiments of the invention, taken in conjunction with the appended claims and accompanying drawings, provide a more complete understanding of the nature and scope of the invention. 
     
    
     BRIEF DESCRIPTION OF THE DRAWINGS  
       [0016]      FIG. 1  is a side elevational view of a prior art chromatography column and an overhead winch or hoist being used to remove a compression piston from the chromatography column in accordance with the prior art;  
         [0017]      FIG. 2  is a side elevational view showing the removed piston of  FIG. 1  being lowered onto a platform using the overhead winch or hoist in accordance with the prior art;  
         [0018]      FIG. 3  is a side elevational view showing the piston of  FIGS. 1 and 2  being inserted back into the column using the overhead winch or hoist in accordance with the prior art;  
         [0019]      FIG. 4  is a cross sectional view of a chromatography column constructed in accordance with the present invention with the piston lowered partially through the open bottom of the column in accordance with an embodiment of the method of the present invention;  
         [0020]      FIG. 5  is an enlarged cross sectional view of the piston rod and piston rod extension of  FIG. 4 ;  
         [0021]      FIG. 6  is cross sectional view of the column of  FIG. 4  showing the piston being raised within the column;  
         [0022]      FIG. 7  is a schematic view of the hydraulic system of an embodiment of the chromatography column of the present invention;  
         [0023]      FIG. 8  is a side elevational view of the column of  FIG. 4  and a jack being used to raise the piston in accordance with an embodiment of the method of the present invention. 
     
    
     DESCRIPTION OF THE PREFERRED EMBODIMENTS  
       [0024]     The present invention permits hoist-free operation either as a retrofit to existing chromatography columns, or other types of processing columns, or inclusion in newly constructed columns or as a method to apply to either. While the invention is described below in terms of a chromatography column, it is to be understood that it may also be applied to other types of processing columns such as a solid phase reaction or synthesis column, a filtration column or a capture step column.  
         [0025]     An embodiment of the column of the present invention is indicated in general at  20  in  FIG. 4 . As is known in the art, the inlet of the column consists of a passage  21  (see also  FIG. 5 ) formed axially through a piston rod  16 . While not illustrated in  FIG. 4 , the column  20  also features a lower column tube or bottom end plate, such as the one illustrated at  23  in  FIG. 3 , that features an outlet port  26  that serves as the outlet of the column. Port  26  may alternatively be used as an inlet port and passage  21  used as the outlet of the column. As is known in the art, the bottom plate of the column is attached to flange  31  of  FIG. 4  by bolts or an alternative removable fastening arrangement.  
         [0026]     The column  20  both permits egress of the piston head  18  from the lower end of the column tube  22  and return of the piston into the column tube. It also provides controlled and safe access to the piston head for routine or emergency frit and seal maintenance and replacement operations.  
         [0027]     As illustrated in  FIGS. 4 and 5 , the first stage of hoist-free operation in accordance with the method of the invention is accomplished, after the bottom end plate of the column is removed, by extending the length of piston rod  16  with extension  24  to permit the lowering of the internal piston head  18  down through the column tube  22  until the key maintenance areas are exposed and accessible from the open bottom of the column. This is done without allowing the piston head to fully exit the column tube. Due to the piston head exposure permitted by the piston rod extension, external overhead hoists are no longer required.  
         [0028]     An extension  24  of an existing piston rod, or the replacement of an existing piston rod  16  with a longer piston rod, permits the movement of the piston head  18  outside the lower end  20  of the column tube  22 , as illustrated in  FIG. 4 . Using the simple approach of a longer piston rod  16 , while within the scope of this invention, presents the danger that during normal use, the piston head could accidentally be forced under pressure into contact with the lower column tube end plate. This would result in damage to frits, seals and the piston head.  
         [0029]     The use of a removable extension piece  24 , which is the preferred embodiment of this invention, allows the extension piece to be installed just prior to maintenance procedures and removed afterwards. Therefore the piston rod length used during operations would be the shorter one preventing accidental contact with the lower column tube endplate.  
         [0030]     As illustrated in  FIG. 5 , the extension piece  24  preferably is attached to the existing rod  16  by a threaded stud  25  that is attached to the center of the bottom end of the extension piece and that is received within a threaded bore  27  formed in the top end of the inlet passage  21  of rod  16 , which is concentric with the longitudinal axis of rod  16 . The top end of the extension piece  24  also features a central threaded bore  29  that receives a threaded stud  31  that is attached to the bottom surface of end stop  33 . Other arrangements known in the art for attaching the ends of adjacent rods or columns together may be used as alternative to the threaded stud and bore arrangement illustrated in  FIG. 5 .  
         [0031]     The diameter of extension  24  preferably is slightly less than the diameter of rod  16  so as to avoid a raised circumferential edge that would otherwise pass over, and thus potentially damage, the seal around the opening through the upper column end plate  34  through which the rod  16  and extension piece  24  slide.  
         [0032]     In  FIG. 4 , the piston  18  has been moved down in the tube  22  using either pneumatic or hydraulic pressure provided via pump  32  and a port  35  formed in the upper column end plate  34 . In the preferred embodiment, hydraulic pressure is used to provide smooth and controlled movement, whereas pneumatic pressure can allow the piston to move jerkily or suddenly due to the compressibility of typical gases used (e.g. air, nitrogen, argon, etc.)  
         [0033]     In the second stage of hoist-free operation in accordance with the method of the invention, the piston head is returned back up into the column tube into its initial use position, indicated in phantom at  37  in  FIG. 6 .  
         [0034]      FIG. 6  shows the preferred use of hydraulics, including pump  32 , to lift the piston head  18  back into the column tube  22  via suction. This is a clean, safe and self-contained approach that eliminates the need for large handling equipment in the clean room or other process areas. This approach also provides the most control over the piston head movement so that it may be moved with a high level of precision.  
         [0035]      FIG. 7  is a schematic of the hydraulic system that permits hoist-free lowering and raising of the piston. In addition to hydraulic pump  32  (also illustrated in  FIGS. 4 and 6 ), the system includes a reservoir  42  which holds and receives hydraulic fluid as well as 3-way valves  44  and  46 . The system communicates with the portion  48  ( FIG. 6 ) of the interior of column tube  22  above piston  18  via line  52  and port  35  formed in the upper column end plate  34 .  
         [0036]     When it is desired to move the piston  18  down into the position illustrated in  FIG. 4 , valve  44  is configured to supply hydraulic fluid from reservoir  42  to branches  54  and  66  of  FIG. 7  and valve  46  is configured to direct the fluid from branches  62  and  56  to branch  52  when pump  32  is activated. When it is desired to draw piston  18  up into column tube  22  into the position indicated in phantom at  37  in  FIG. 6 , the valve  46  of  FIG. 7  is reconfigured to direct hydraulic fluid from line  52  (and from the upper portion of the interior of column tube  22  above piston  18 ) to branches  58  and  66  and valve  44  is reconfigured to direct hydraulic fluid from branches  62  and  64  to reservoir  42  when pump  32  is activated.  
         [0037]     Alternatively, as illustrated in  FIG. 8 , a mechanical approach to restore the piston head into the column can be used by means of a jacking device, indicated in general at  72 , to physically push the exposed piston head back into the tube and permit replacement of the column tube end plate. Such jacking devices are available in the prior art. Jack  72  features a base  74  which is mounted upon wheels  76   a  and  76   b.  A pair of hydraulic or mechanically-activated lifts  78   a  and  78   b  are positioned on top of base  74  and raise piston  18  in the direction of arrows  82  when handle  84  is moved in the direction of arrow  86 .  
         [0038]     Another option for raising piston  18  involves mechanical insertion of the piston head into the tube, followed by replacement of the end plate, illustrated at  23  in  FIG. 3 . This is followed by the pumping of liquid into the end plate outlet or port, indicated at  26  in  FIG. 3 , which moves the piston back up inside the tube to its starting position, indicated in phantom at  37  in  FIG. 6 . A system similar to the one illustrated in  FIG. 7  may be used where line  52  would be connected to port  26 .  
         [0039]     Still another option to pull the piston head back into the column tube includes the application of a vacuum to the upper portion of the interior of column tube  22  above piston  18  ( 48  in  FIG. 6 ), whereby the extended piston head is drawn back up into position. Such an approach could use the arrangement of  FIG. 6  where a vacuum pump is substituted for hydraulic pump  32 .  
         [0040]     The advantage of the hydraulic approach over the mechanical is the elimination of possible damage to the head from the jacks or jacking procedure. The advantage of the hydraulic approach over the vacuum approach is that hydraulics permit very smooth and controlled piston head movement while the vacuum approach may cause sudden and rapid piston head movement.  
         [0041]     While the preferred embodiments of the invention have been shown and described, it will be apparent to those skilled in the art that changes and modifications may be made therein without departing from the spirit of the invention, the scope of which is defined by the appended claims.