Patent Document

CROSS-REFERENCE RELATED APPLICATIONS  
       [0001]     This application is a Divisional application of U.S. application Ser. No. 10/373,293, filed on Feb. 24, 2003, which claims the benefit of U.S. Provisional Application No. 60/361,483, filed on Mar. 4, 2002. The entire contents of the related application are incorporated in their entirety. 
     
    
     BACKGROUND OF THE INVENTION  
       [0002]     Chromatography columns have been used for years for the separation and/or purification of different materials such as proteins.  
         [0003]     These columns are formed of three basic components; a column tube, a bottom fixed end and a top, movable end. See U.S. Pat. No. 4,350,595 and U.S. Pat. No. 6,139,732. The top end moves relative to the tube so as to be capable of removal for introduction and removal of chromatography media in the tube and to be capable of longitudinal travel into the tube to compress the media for use.  
         [0004]     This top end however needs to be fixed at some point to the column in order to move relative to the column.  
         [0005]     A first means for accomplishing this is to form a tube of high strength materials, including metals such as stainless steel or rigid structural plastics, such as acrylics or polymethylpentenes such as TPX® plastic available from Mitsui Petrochemical Industries Ltd Corporation of Japan. The tube has a flange at the upper end to which a top plate is attached to the column and a flange at the lower end to which a fixed bottom end is attached. The top, movable end is then attached to this top plate and travels relative to it in and out of the tube.  
         [0006]     An example of this type of structure is shown in  FIG. 1 . The tube  2  has a bottom plate  4  fixed in place by bolts  6  attached to a flange  8  of the tube  2 . A top plate  10  is fixed to a top flange  12  of the tube  2  by setscrews  13 . A movable end  14  is centrally located in the top plate  10  and is capable, by movement of rod  16 , of moving into or out of the tube  2 .  
         [0007]     As the end  14  moves into the tube  2  to compress the media bed  18  for use, longitudinal forces are carried from the end  14  to the rod  16  to the top plate  10  and then to the tube  2  itself.  
         [0008]     The other alternative is shown in  FIG. 2 . It uses a series of rods  20  or screws closely aligned around the outside of the tube  24  to carry the longitudinal forces rather than the wall of the tube itself. This allows one to use less structurally rigid materials, such as glass or plastics, preferably acrylic or styrene, and to also use thinner walled tubes. All of this reduces the weight and cost of the device.  
         [0009]     Most of the elements of that tube  24  of  FIG. 2  are similar to those of  FIG. 1 . One has a movable top end plate  22 , a bottom plate  26 , attached to a fixed bottom end  27 , flanges  28 , either as part of the tube  24  or in this example as separate pieces to secure the fixed top plate  30  and bottom plate  26  to the tube  22 . A rod  32  extends through the plate  30  and is connected to the movable end  22  by a handle  34 . A bed of chromatography media  36  is compressed by the movement of the end  22 . Also shown in  FIG. 2  are a series of guide rods  36 , which are used, in larger columns to keep the end  22  horizontal during movement. Plate  30  is normally affixed on flange  33  and attached by numerous mechanical fasteners  31 .  
         [0010]     Both of these designs have their limitations. The need to use rigid structural materials for the tube in the embodiment of  FIG. 1  limits one&#39;s choices of materials and often is more expensive. Also, the materials used are not translucent so that one cannot view the interior of the column. Removing the movable end from the column, such as to add or remove media is a cumbersome task requiring the removal of the top plate and bolts in order to do so. Also, once removed, one must find a place to position these pieces (top plate  10 , rod  16  and end  14 ) where they will not be damaged or contaminated.  
         [0011]     The embodiment of  FIG. 2  provides one with the ability to use translucent materials such as glass or acrylic; however, the rods (which typically number between 8 and 12 per column) obscure one&#39;s view. Moreover, it is even more cumbersome to disassemble. One must disconnect all of the mechanical fasteners  31  from the ends of the rods  20  before removing the top plate  30  and end assembly ( 22 ,  32 ,  34 ). It too suffers from having to find a place to put these pieces where they will not be damages or contaminated. Further, reassembly is difficult, as one needs to align each of the mechanical fasteners  31  into their respective hole in the top plate  30  and flange  33 .  
         [0012]     What is needed is a simpler and easier mechanism for handling the longitudinal load of a column and which allows one to easily assemble and disassemble the column as needed.  
         [0013]     The present invention provides such a device.  
       SUMMARY OF THE INVENTION  
       [0014]     The present invention relates to a chromatography column. More particularly, it relates to a chromatography column that utilizes an external structure to support any longitudinal loads imposed on the column.  
         [0015]     The present invention removes the longitudinal load from the column tube altogether and transfers it to a yoke and stanchion arrangement situated around but external to the column tube. By using the yoke/stanchion system, the central adjuster can be used to move the top end into and out of the housing. Thus, when internal pressure is applied to the column, the tube experiences no longitudinal load. Additionally, the yoke and stanchion design allows for complete removal of the end from the tube without cumbersome disassembly. Moreover, the yoke provides a place to retain the end while the tube is being filled, emptied, cleaned or repaired.  
         [0016]     It is an object of the present invention to provide a chromatography column comprising a base plate, a column tube attached to the base plate in a liquid tight arrangement, a movable top plate capable of moving into and out of the tube and a support structure external of the tube and free of support on the tube to support longitudinal loads imposed on the column.  
         [0017]     It is another object of the present invention to provide a chromatography column comprising a base plate, column tube, a bottom edge of the tube being attached in a liquid tight sealing arrangement to the base plate, the base plate having diameter greater than that of the tube, two or more stanchions, each having a lower end and an upper end, the lower ends being attached to the base plate external of the tube, a yoke connected to the two or more stanchions such that it spans the width and centerline of the tube, a central adjuster is formed on the yoke over the centerline of the tube, the adjuster being movably connected to a top surface of a column top end plate so that the top end plate may move into and out of the tube interior.  
         [0018]     It is a further object of the present invention to provide a chromatography column using an external set of stanchions and a yoke connected to the stanchions to carry any longitudinal load imposed on the tube of the column and to provide a yoke that is capable of pivoting vertically, horizontally or both about the centerline of the column tube so as to provide free and easy access to the column tube&#39;s interior.  
         [0019]     It is an additional object of the present invention to provide a chromatography column using an external set of stanchions and a yoke connected to the stanchions to carry any longitudinal load imposed on the tube of the column and to provide a column that allows for the removal or repair of the top plate, tube or bottom plate of the column without complete disassembly of the column.  
         [0020]     It is another object of the present invention to provide a modular chromatography column having a base plate capable of holding column tubes of varying sizes and heights, using an external set of stanchions connected to the base plate and a yoke connected to the stanchions wherein the stanchions are formed of two or more pieces and are capable of being adjusted in height by the addition or subtraction of one or more pieces of the stanchions. 
     
    
       [0021]     In the Drawings  
         [0022]      FIG. 1  shows a first embodiment of a prior art column in cross sectional view.  
         [0023]      FIG. 2  shows a second embodiment of a prior art column in cross sectional view.  
         [0024]      FIG. 3  shows a first embodiment of the present invention in planar view.  
         [0025]      FIG. 4  shows the embodiment of  FIG. 3  in a retracted/pivoted position.  
         [0026]      FIG. 5  shows the embodiment of  FIG. 3  in cross sectional view. 
     
    
     DETAILED DESCRIPTION OF THE INVENTION  
       [0027]      FIG. 3  shows a first embodiment of the present invention. The chromatography column consists of a base plate  50  to which the bottom edge of the tube  52  is attached. One can form a flange (not shown) on the bottom edge of the tube, if desired, either as a part of the tube or separately. Unlike in the prior art, as the tube does not bear any longitudinal load, the flange does not need to have significant structural strength, thus one can easily make a flange on an acrylic or glass column.  
         [0028]     Alternatives to the flange can be used to secure the bottom of the tube to the base plate  50 .  
         [0029]     The base plate  50  has diameter greater than that of the tube  52 . Arranged around the base plate  50 , external to the tube  52  are two or more stanchions  54 . The stanchions are structurally strong and typically formed of engineered materials that provide such strength such as metals, including stainless steel and aluminum, composites such as graphite or carbon composites and engineered plastics or composite plastics.  
         [0030]     The stanchions  54  have a height equal to or greater than that of the tube  52 . Preferably, they have a height that is greater than the tube  52 .  
         [0031]     A yoke  56  is connected to the two or more stanchions and it spans the width and centerline of the tube  50 . The yoke  56  is retained to the stanchions  54  by means such as slot  58  (as shown), a ring or other device that can affirmatively hold the yoke in place. A central adjuster  60  is formed in the yoke  56  over the centerline of the tube  52 . The adjuster  60 , as shown, uses a screw-threaded rod  62  connected to the top surface  64  of the movable end  66 . This central adjuster  60  is used to change the height of the movable end  66  within the tube  52 .  
         [0032]     The yoke  56  may be permanently attached to the two or more stanchions  54  or if one wishes, it may be removably connected to the stanchions  54  by bolts, clevis pins, cotter pins, clamps and the like. In one preferred embodiment, the yoke  56  is attached to one stanchion  54  by a bolt and the other stanchion by a clevis pin so that when the end  66  is withdrawn from the column by retracting the central adjuster  60  to its uppermost position, the yoke  56  can be pivoted vertically about the stanchion  54  containing the bolt and moved up and out of the way of the tube  50  so as to allow easy access to the column interior.  FIG. 4  shows that embodiment in the retracted/pivoted position.  
         [0033]     Alternatively, one can form hooks, eyelets or openings (not shown) in or on the yoke  56  such that one may use a crane, come along winch or other such whincing device to vertically lift the yoke  56 , central adjuster  60  and end  66  off of the system in order to provide access to the column interior.  
         [0034]     In another embodiment, the yoke  56  can also rotate in a horizontal circular motion away from the mouth of the column.  
         [0035]     In a further embodiment, the yoke  56  can be detachable from all but one stanchion  54 . That stanchion  54  is of a height that the end  66  is out of the tube  52  when the central adjuster  60  is fully retracted. The yoke  56  does not pivot vertically. The stanchion  54  however is capable of horizontal, circular motion away from the tube.  
         [0036]     If desired, one may form a stop (not shown) on the yoke  56  or stanchion  54  about which it rotates vertically so as to limit the yoke&#39;s  56  range of motion so that it does not pivot to a position where the yoke  56  or end  66  can be damaged.  
         [0037]     In a further embodiment, the yoke  56  remains fixed to the one or more stanchions  54 . The stanchions  54  have a height that is greater than the height of the tube  52  so that the end may be fully removed from the tube  52  and provide adequate space for one to enter the tube.  
         [0038]     The central adjuster  60  may be manually, pneumatically, electrically or hydraulically adjustable between positions or a combination of actuation methods maybe used. Non-manual actuation maybe preferable when additional force, speed or convenience is required.  
         [0039]     As the tube wall of the column does not bear any of the longitudinal forces, the materials selected for the tube do not have to be structurally supportive. Glass and various plastics can be used. Suitable plastics are preferably translucent to allow for the viewing of the interior of the column tube. Such plastics include but are not limited to acrylics, styrene, polycarbonate and TPX® polymethylpentene® resin. If desired, metals, such as stainless steel, and other materials typically used in chromatography columns may also be used.  
         [0040]     The tube may range in diameter from about 70 mm inner diameter to about 450 mm inner diameter. Its height may also vary from about 500 mm to about 1200 mm.  
         [0041]     The base plate may be formed of a metal such as stainless steel, aluminum and the like, a structurally rigid plastic such as TPX plastic or a composite material such as graphite or carbon composite materials.  
         [0042]     The diameter of the base plate should be large enough so as to accommodate the column and the stanchions. Preferably, it is circular in shape, to mirror the column, but it need not be so limited. It may be a polygonal shape such as a square, rectangle, pentagon, hexagon, decagon and the like. Alternatively, it may be irregular, providing sufficient area for the column and then having two or more ears extending from it on which the stanchions are mounted.  
         [0043]     The stanchions may be formed of any material that provides the necessary strength required. Metals, such as stainless steel, epoxy-coated steel and aluminum are preferred, while engineered plastics such as TPX® plastic or graphite or carbon composites may be used.  
         [0044]     Depending upon the load to be supported by the stanchions, they may be solid or hollow. They may also be formed as one piece or if desired several pieces, which are connected together by means such as bolts, clevis pins, mating screw threads and the like. The multiple piece stanchions would allow one to vary the height of the stanchions in relation to the column and would allow one to have a modular column in which different tubes of different heights and/or diameters could be used with a single base and stanchions that are capable of being varied in height.  
         [0045]     The stanchions are secured to the base by a variety of means such as welding, bolts, and the like.  
         [0046]      FIG. 5  shows preferred chromatography system according to the present invention in cross-sectional view, as it would be used in a lab or on a production floor.  
         [0047]     The system  100  is comprised of a base  102  that is supported on three or more legs  104 . Each leg  104  has a caster wheel  106  on its lower end. The caster wheel  106  may have a lockable brake (not shown) if desired. The base  102  contains a closable opening  108 , which forms either an inlet or outlet of the column. In another embodiment, the inlet or outlet on either the central adjuster or base is a more complex valve as disclosed in U.S. Pat. No. 6,123,849. The column tube  110  is mounted on top of the base  102  and secured to it by a series of two or more bolts  112 .  
         [0048]     Surrounding the tube  100  are two or more stanchions  114 . The two or more stanchions  114  are spaced apart from the tube  110  and have a height greater than that of the tube  110 . If two stanchions  114  are used, they are diametrically opposite each other. If more than two are used, they are equally spaced about the tube  110 . In that embodiment, the yoke  116  will also be formed of several equal arms running from a stanchion  114  to the central adjuster  118 . In embodiment of  FIG. 5 , two stanchions  114  being used, the yoke  116  is a straight single piece, formed of two arms in alignment with each other end meeting at the central adjuster  118 .  
         [0049]     As shown, the central adjuster has a threaded rod  120  that mates with fixed threads of the adjuster  118 . A preferred mechanism is a threaded thrust ring  119  although other means may be used. A rotatable handle  122  is used to move the rod  120  via rotation of its threads against those fixed threads of the adjuster  118 .  
         [0050]     The lower end of the rod  118  is attached to the movable end plate  124  via a series of equally spaced arms  126  that distribute the force equally around the top of the end plate  124 . Alternatively, one could eliminate those arms  126  if they were deemed unnecessary or if other alignment mechanisms were used instead.  
         [0051]     The yoke  116  is fixed at each end to the respective stanchions  114  by a locking device  127  such as a nut and bolt, a clevis pin, a spring loaded ball and detent system and the like. As stated above, the yoke  116  may instead be permanently fixed to the stanchions  114 , such as by forming the stanchions and yoke of a single piece of material or by welding or adhering the components together. It is preferred however that the yoke  116  be capable of being removed from the stanchions  114  for versatility sake.  
         [0052]     A cap  128  may be used over the top of the stanchions  114  after the yoke  114  is in place.  
         [0053]     Also as shown in  FIG. 5 , the yoke  116  has an upwardly tapered profile in cross-section. This is desired but not necessary. The use of a tapered yoke  116  provides additional strength with little material or cost. Alternatively, one could use a linear yoke  116  and make its thickness greater in order to achieve the same result. If desired, the yoke can be forged, machined from a single piece, molded to be a structural beam of regular or irregular shape, formed of a lamination of materials or formed of a series of thinner layers bolted or welded together. A structural beam or laminated beam would be lighter in weight and lower cost and provide all the force transferring properties necessary for the invention.  
         [0054]     The top lip of the tube  110  has an optional end plate guide  130  that is used to direct and align the end plate  124  as it moves into and out of the tube  110 .  
         [0055]     The end plate  124  is typical of that used in a chromatography column and contains a backer plate  132  and a distributor plate  134  and an upper frit or distributor screen  136 .  
         [0056]     The stanchions  114  are attached to the base  102  and into a threaded recess in the bottom portions of the stanchions  114 .  
         [0057]     A device as shown in  FIG. 5  is operated in the following manner. To load the column, the central adjuster  118  is retracted so that the end plate  124  is out of the tube  110 . If desired, the yoke  116  has either been pivoted out of the way or it may be removed altogether as explained above.  
         [0058]     The media is placed within the column. If the yoke  116  had been pivoted or removed, it is reattached to the stanchions  114 . The end plate  124  is then driven down into the tube  110  past the guide ring  130  by the central adjuster  118 . The end plate is adjusted to the desired height, given the type and amount of media used and the desired pressures to be applied.  
         [0059]     The chromatography process is run, the captured material eluted and the system is flushed.  
         [0060]     To open the column, for example to remove the media, the end plate  124  is retracted from the tube  114  and either left hanging from the yoke  116  above the tube or the yoke is either then pivoted away or removed altogether. The media is then removed either through the top opening of the tube or if desired, through the fixed plate which is arranged with the base plate so as to be removable without the need to disassemble the entire column. This embodiment allows one to simply push the spent media out of the bottom into a catch basin.  
         [0061]     The various alternative embodiments presented by the present device are nearly endless. The present invention allows one to use a common base for different sized columns. For example, one could select a series of base plates of varying diameters that allows one to use column tubes of different sizes with basically the same device. For example, the same base plate, yoke and top plate can be used with 70 mm, 100 mm and 140 mm tubes. The stanchions if of sufficient height would not need to be changed. If additional height is required, one can use the multiple piece stanchions discussed above. Alternatively, one can form a single base plate and have an open in its center into which the end plate fits. Various extensions or fixed end plate widths can be formed and used with the same base plate to enable one to use columns of different diameters and heights.  
         [0062]     Likewise, as discussed above, stanchions of different heights can be created by using multiple piece stanchions, allowing one to use tubes of different heights with the same equipment.  
         [0063]     Also the present invention allows one an easy means for removing or repairing one component of the column without the difficult and time consuming task of disassembling the entire column as was required in the prior art.  
         [0064]     As can be appreciated, the present invention provides a chromatography column with several advantages over the prior art.  
         [0065]     Through the use of the stanchions and yoke, one eliminates the imposition of longitudinal forces on the column itself. This allows for one to use lighter, less rigid materials for the column tube. It also eliminates the need for many rods attached to the outside of the column, thus making viewing access possible and eliminating the time consuming task of aligning the rods during assembly and removing them during disassembly.  
         [0066]     Additionally, by providing a yoke capable of being vertically pivoted and/or horizontally rotated or being capable of removal altogether, one obtains a simple means for retaining the end plate in a position where it is unlikely to be damaged or contaminated during maintenance or repairs.  
         [0067]     The system allows for a modular system where columns of different heights or diameters can be used with the same basic equipment.  
         [0068]     The system of the present invention allows one to remove or repair of the top plate, tube or bottom plate of the column without complete disassembly of the column.

Technology Category: 3