Patent Abstract:
The present invention relates to methods for conducting maintenance on chromatography columns used in industrial-scale chromatography. In particular, the invention is concerned with safer methods for performing maintenance on such columns, such as cleaning and replacing bed supports, distributors, nozzles, O-rings and other column components, by the use of a handling device to support, lift, carry and manipulate such column components.

Full Description:
CROSS-REFERENCE TO RELATED APPLICATIONS 
     This application is a divisional of U.S. patent application Ser. No. 11/834,864 filed Aug. 7, 2007, now U.S. Pat. No. 7,780,853, which is a continuation-in-part of U.S. patent application Ser. No. 11/763,477, now U.S. Pat. No. 7,708,891; the entire disclosure of which is incorporated herein by reference in its entirety. 
    
    
     FIELD OF THE INVENTION 
     The present invention relates to methods for conducting maintenance on chromatography columns used in industrial-scale chromatography. In particular, the invention is concerned with safer methods for performing maintenance on such columns, such as cleaning and replacing bed supports, distributors, O-rings and other column components, by the use of a handling device to support, lift, carry and manipulate such column components. 
     BACKGROUND OF THE INVENTION 
     Chromatography columns may be used in industrial processes to purify process liquids and separate substances of interest from process liquids; typical examples include large-scale preparative purification of fine chemicals and pharmaceuticals, together with biological products. 
     Industrial-scale chromatography columns typically comprise a hollow, axially vertical tubular housing including a liquid inlet at the upper end and through which the buffer and substances to be separated are dispensed to the media bed located within the cavity of the tube, and a liquid collecting system at the lower end for collecting substances and buffer. The particulate chromatographic media or bed through which the buffer fluid and/or substances to be separated and purified percolates is located between the liquid inlet and collecting system. 
     An adapter assembly is typically affixed to the upper end of the tubular housing and a base assembly to the lower end where it is bolted to the bottom flanges. Each of these assemblies typically comprises a strong backing plate and a distributor plate which further supports a bed support; a bed support is a layer of mesh, screen, filter, sinter or other fluid-permeable media-retaining material which permits process liquid flow into and out of the chromatography bed space or cavity while retaining the bed of particulate medium. To provide adjustability and control of the bed height and bed compression, the adapter assembly is typically made in the form of a piston or sliding adapter in the column tube interior. After the column is charged with bed media, typically through a nozzle, the adapter may be forced toward the bottom of the tube to compress or pressurize the media bed. Generally the base assembly is a fixed structure which is bolted against the bottom flange of the column tube but, in some instances, may also be in the form of a movably slidable piston or adapter. 
     The backing plate of the base assembly generally acts as a support for the column, being itself supported on legs or some other stand arrangement which allows clearance for outlet pipework projecting beneath the base assembly. 
     When such a column requires maintenance to, or cleaning of, internal components, such as the valves, seals, meshes/screens, distribution systems etc., heavy lifting gear such as a crane or hoist is necessary to lift the upper end/adapter assembly away from the column tube and the column tube away from the lower end/base assembly as these assemblies can weigh in excess of three tons. Lifting of these assemblies then provides access to the internal column components, but often it is necessary to remove some of these components prior to maintenance. As these components can be very heavy (bed supports, for example, may weigh in excess of 100 kg), their manual removal and re-introduction poses a potential safety risk to operators who must physically support and manipulate them. 
     The use of heavy overhead lifting equipment to disassemble the column in order to carry out internal maintenance is, in itself, highly undesirable. Operator safety is obviously a concern when heavy equipment is lifted overhead and technicians exposed below. Furthermore, alignment structures are required to keep the column and its base/adapter assemblies axially aligned as they are separated from each other, to avoid damage to the precision components. Moreover, the requirement to use heavy lifting equipment imposes constraints on housing such columns, sufficient overhead space and support being required to accommodate hoists or cranes. Further, the presence of such hoists or cranes in GMP facilities used for biopharmaceutical manufacturing (such facilities also being known as “clean rooms”) is highly undesirable due to the shedding of particulate matter such as dirt during their operation and maintenance. 
     U.S. Pat. No. 6,736,974 addresses some of the above problems by providing a column which is capable of lifting the adapter assembly above the column tube and/or raising the column tube above the base assembly by means of an hydraulic system which is integral to the column. 
     However, the system described in U.S. Pat. No. 6,736,974 has significant disadvantages associated with it by virtue of its design. As can be seen from FIGS. 4 and 5 of U.S. Pat. No. 6,736,974 and described in column 4, lines 63-66 of that document, in order to remove the distributor plate ( 31 ) and/or bed support/mesh ( 28 / 60 ) from the interior of the column, the operator must work within the centre of the drum ( 18 ) to access and remove the fixing nut ( 30 ) which secures these component parts. As industrial columns typically have diameters ranging from about 200 mm to 2000 millimeters, this means that the operator must work below a suspended or supported load to unscrew the nut. This clearly poses a significant safety risk to the operator, particularly where the operator&#39;s arm or head is exposed below the suspended or supported load. 
     Furthermore, once the column tube/cylinder or adapter assembly has been raised from the base assembly or tube, respectively, removal of the heavy bed support or distributor from the column can only be accomplished by tilting the bed support or distributor at an angle to negotiate the hydraulic drive pistons or safety rods. This can clearly be seen from, for example,  FIGS. 3 ,  4  and  5  in which the distance between any two safety rods ( 69 ) or between any two hydraulic pistons ( 36 ) is less than the diameter of the bed support/mesh ( 28 / 60 ) or distributor plate ( 31 ). The same problem would exist for the base or adapter bed support (not shown). Removal of these internal components, which could weigh in excess of 100 kg, requires considerable manhandling by the operator and necessitates their being exposed below the suspended column or adapter assembly. Once again, this represents a significant safety risk for the operator. 
     The task of physically removing the heavy bed support or distributor, as described in U.S. Pat. No. 6,736,974, must be carried out by an operator, there being no disclosure of the use of any lifting aid to assist in this task. The configuration of the hydraulic pistons and the safety rods, and the need to tilt the bed support and/or distributor in order to avoid the supporting structures in withdrawing these components from the column, makes their manual withdrawal and re-introduction a difficult and potentially dangerous task. 
     WO 2005/056156 (Euroflow (UK) Limited) also discloses a column which can be accessed for maintenance without the need for a crane or hoist. The column is designed such that the tube and the base assembly can be separated by means of hydraulic drive cylinders to provide an access space between them to conduct maintenance or service on the base assembly. The piston of the adapter assembly can be advanced through the column tube to expose it at the open end of the column tube, i.e. in the space between the tube and the base assembly, for maintenance. 
     However, as is evident from this document (for example, FIGS. 19 and 20 and related description on page 23) access to release the fastening screws retaining the bed support/mesh in place is provided by the space between the tube and the base assembly. Removal of the bed support/mesh necessitates the operator being exposed to a suspended load while retaining screws are removed. Furthermore, the distance between any two drive cylinders for maintenance access is less than the diameter of the bed support (see, for example,  FIG. 7 ), which requires the operator to manhandle and tilt the mesh or bed support when removing or replacing it. Once again, there is no mention of the use of a handling device in the removal or re-introduction of column components. Maintenance of the column thus imposes a potential safety risk for the operator in physically supporting and manipulating the heavy column components. 
     U.S. Pat. No. 7,708,891, entitled “Chromatography Column and Method of Maintenance”, filed by the same applicants and hereby incorporated by reference in its entirety, describes a chromatography column which addresses some of the above problems. 
     Accordingly, a need exists to improve the maintenance methods available for chromatography columns by providing devices which facilitate the handling, manipulation and transportation of heavy column components without the need to work under suspended loads and thereby reduce the risk of operator error and injury. 
     SUMMARY OF THE INVENTION 
     The present invention recognizes and addresses these needs and others. In a first aspect of the present invention, there is provided a method for conducting maintenance on a chromatography column comprising the steps of:
         a) providing a chromatography column comprising;
           a dispersion system comprising a nozzle including a mobile phase pathway connected to a liquid inlet;   a tube with an adaptor assembly, said adapter assembly moveable within a cavity of said tube in an operational mode;   the adapter assembly comprising, a distributor and a bed support fastened to each other by releasable fixing means,   a collection system opposing the dispersion system; and one or more seals;   
           b) disconnecting the adapter assembly from the tube;   c) lifting the adapter assembly above the tube to provide a gap for access therebetween;   d) unfastening the bed support from the distributor by releasing the fixing means;   e) removing the bed support from the column with a handling device;   f) conducting maintenance on the column and/or the bed support and/or said one or more seals;   g) returning the bed support to the column with said handling device and fastening the bed support to the distributor; and   h) lowering the adapter assembly to an operational position within the tube and reconnecting the adapter assembly to the tube.       

     In one aspect, the method further comprises the step of removing the distributor from the column with the handling device and conducting maintenance on the column and/or said distributor. 
     In one aspect, the method further comprises the steps of removing said nozzle from the column with the handling device prior to step d) and returning the nozzle to the column with the handling device following step g). 
     Preferably, the handling device is in the form of a cart having a pillar and comprising one or more arms projecting from said pillar for supporting the bed support or the distributor or the nozzle thereon. Preferably, the arms are extendable from the pillar. More preferably, the arms are vertically movable on the pillar. 
     In one aspect, lifting the adapter assembly in step c) and/or lowering the adapter assembly in step h) is carried out by means of an overhead hoist or crane. 
     In another aspect, lifting the adapter assembly in step c) and/or lowering the adapter assembly in step h) is carried out by means of a drive system comprising one or more cylinders which are mounted to or are integral with the column. 
     Optionally, the method additionally comprises the step of removing said one or more cylinders from the column with the handling device. 
     Preferably, the step of removing the bed support from the column and/or the step of returning the bed support to the column with the handling device is carried out without substantially tilting the bed support. This reduces operator exposure beneath the suspended load and facilitates mechanical handling of the bed support. The term ‘without substantially tilting’ as used herein means ‘tilting at an angle of no more than 5° to the horizontal’. 
     Optionally, the step of removing the bed support from the column and/or the step of returning the bed support to the column with the handling device is carried out by tilting the bed support at an angle of more than 5° to the horizontal. This may be necessary where the distance between any two drive cylinders is less than the diameter of the bed support. 
     In a second aspect of the present invention, there is provided a method for conducting maintenance on a chromatography column comprising the steps of:
         a) providing a chromatography column comprising;
           a dispersion system comprising a nozzle including a mobile phase pathway connected to a liquid inlet;   a tube with an adapter assembly and a base assembly, said adapter assembly moveable within a cavity of said tube in an operational mode;   the base assembly comprising a distributor and a bed support fastened to each other by releasable fixing means;   a collection system opposing the dispersion system; and one or more seals;   
           b) releasing the tube from the base assembly;   c) lifting the tube and the adapter assembly above the base assembly to provide a gap for access therebetween;   d) unfastening the bed support from the distributor by releasing the fixing means;   e) removing the bed support from the column with a handling device;   f) conducting maintenance on the column and/or the bed support and/or said one or more seals;   g) returning the bed support to the column with said handling device and fastening the bed support to the distributor; and   h) lowering the tube and the adapter assembly and reconnecting the tube to the base assembly.       

     In one aspect, the method further comprises the steps of removing the distributor from the column with the handling device and conducting maintenance on the column and/or said distributor. 
     Preferably, the handling device is in the form of a cart having a pillar and comprising one or more arms projecting from said pillar for suspending the bed assembly or distributor thereon. Preferably, the arms are extendable from the pillar. More preferably, the arms are vertically movable on the pillar. 
     In one aspect, lifting the tube and the adapter assembly in step c) and/or lowering the tube and the adapter assembly in step h) is carried out by means of an overhead hoist or crane. 
     In another aspect, lifting the tube and the adapter assembly in step c) and/or lowering the tube and the adapter assembly in step h) is carried out by means of a drive system comprising one or more cylinders which are mounted to or are integral with the column. 
     Optionally, the method additionally comprises the step of removing said one or more cylinders from the column with the handling device. 
     Preferably, the step of removing the bed support from the column and/or the step of returning the bed support to the column with the handling device is carried out without substantially tilting the bed support. This reduces operator exposure beneath the suspended load and facilitates mechanical handling of the bed support. The term ‘without substantially tilting’ as used herein means ‘tilting at an angle of no more than 5° to the horizontal’. 
     Optionally, the step of removing the bed support from the column and/or the step of returning the bed support to the column with the handling device is carried out by tilting the bed support at an angle of more than 5° to the horizontal. This may be necessary where the column has drive cylinders and the distance between any two drive cylinders is less than the diameter of the bed support. 
     In a third aspect of the present invention, there is provided a handling device for use in a method of conducting maintenance on a chromatography column as hereinbefore described, said device comprising a frame with wheels and a pillar, one or more arms projecting from said pillar for supporting or suspending a chromatography column component therefrom, said one or more arms being movable vertically along the axis of the pillar by mechanical means, wherein the one or more arms has an attachment means for securing said column component thereto. Optionally, the device may additionally comprise a handle to facilitate steering. 
     In one aspect, the chromatography column component is selected from the group consisting of bed support, distributor, nozzle and drive cylinder. 
     In another aspect, the attachment means is a raised element on the surface of the one or more arms for receipt of a fixing means in said column component. Preferably, the raised element is located centrally on one or more arms or at the intersection of the one or more arms. More preferably, the raised element is conically shaped to facilitate attachment of the column component to the arm. 
     In another aspect, the attachment means comprises a fixture for receipt of fixing means in the column component. 
     In a further aspect, the one or more arms additionally comprise a pad for resting the column component thereon. This prevents damage to the column component. Preferably, the one or more arms are extendable. 
     In a further aspect, the one or more arms are removable and replaceable with different arms to allow attachment of different column components. 
     In one aspect, the mechanical means for moving the one or more arms vertically along the axis of the pillar comprises a pulley or jack. Preferably, the mechanical means for moving the one or more arms vertically along the axis of the pillar is powered by electrical, pneumatic or hydraulic means. 
     In another aspect, the wheels are independently rotatable to improve the maneuverability of the handling device. Preferably, the wheels are independently lockable. Preferably, the wheels are independently levelable; for example, by means of jacking devices attached to each wheel. Levelable wheels provide easier and smoother operation of the handling device on surfaces which are uneven such as clean rooms with sloping floors. More preferably, the wheels are powered by electrical means. 
     In a particularly preferred aspect, the one or more arms can rotate or pivot about the axis of the pillar to facilitate removal of the bed support or distributor where the column has drive cylinders and the distance between any two cylinders is less than the diameter of the bed support or distributor. 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
       The features and advantages of the invention will become apparent from the following description taken in connection with the accompanying drawings in which: 
         FIG. 1  shows an embodiment of a column known in the art in a first maintenance position in cross sectional view. 
         FIG. 2  is a cross sectional view showing the same embodiment of the column of  FIG. 1  in a second maintenance position. 
         FIG. 3  is a schematic exploded front view of a column described in applicant&#39;s U.S. Pat. No. 7,708,891. 
         FIG. 4   a  is a schematic front view of a column described in U.S. Pat. No. 7,708,891;  FIG. 4   b  is a side sectional view of the column of  FIG. 4   a ; and  FIG. 4   c  is a top plan view of the column of  FIG. 4   a.    
         FIG. 5   a  is a front perspective view showing the adapter assembly raised and secured into position to provide a gap for access;  FIG. 5   b  shows removal of the fastening means securing the backing plate to the distributor and bed support. 
         FIG. 6  is a perspective view of a handling device used to remove/insert a distributor or a bed support from/into a column in accordance with the method of the invention. 
         FIG. 7   a  and  FIG. 7   b  are perspective views of the column of  FIG. 5  showing the removal of securing rods which fasten the bed support to the distributor and backing plate. 
         FIG. 8   a  and  FIG. 8   b  are perspective views showing the removal of the bed support from the column. 
         FIG. 9   a  is a perspective view of a column with an inset showing a locking system;  FIG. 9   b  shows the column tube raised above the base and in the process of being locked into position. 
         FIG. 10  is a perspective view of a column with the column tube raised and locked into position in readiness for maintenance. 
         FIG. 11   a  and  FIG. 11   b  illustrate the process of removing the bed support from the column using a handling device. 
         FIG. 12  shows the bed support having been removed from the column in readiness for maintenance. 
         FIG. 13  is a perspective view of the column of  FIGS. 10 and 11  with the column tube lowered awaiting bolting to the base. 
         FIG. 14  is a perspective view showing a handling device tilting a bed support to remove it from the gap in a column where the distance between each of the drive cylinders is less than the diameter of the bed support. 
         FIG. 15  depicts a handling device carrying a drive cylinder. 
         FIG. 16  shows a handling device supporting a nozzle which has been removed from a column. 
     
    
    
     DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS 
     The present invention is concerned with a method and apparatus for conducting maintenance on a chromatography column. The invention is described by reference to chromatography columns which utilise drive systems to lift and/or lower the adapter assembly, and lift and/or lower the tube and adapter assembly. It will be understood that the invention could equally be described by reference to chromatography columns wherein these components are raised and/or lowered by an overhead hoist or crane.  FIG. 1  shows a column  10  known in the art and described in U.S. Pat. No. 6,736,974 which permits maintenance within a chromatography column without the need for a hoist or crane. The column  10  comprises an elongated hollow cylindrical housing  12 , or tube, having a dispersion system  14  at the top and a collection system  16  at the bottom. The dispersion system  14  includes a cylindrical drum  18  having an upper cylindrical plunger head or adapter  20  formed at the lower or interior end (i.e. interior to the column). The adapter  20  is normally disposed within the upper portion of tube  12  such as is illustrated in the first operational position of  FIG. 1 . The adapter  20  may be moved by a drive system  34  such as the hydraulic arrangement shown in  FIG. 1 . The movement of the adapter  20  allows for the compression of chromatography media in order to produce a packed media bed of the optimum height within the column; a cavity  22  is formed between the dispersion and collection systems  14 ,  16  and/or between the adapter  20  and the base  64 . 
     The dispersion system  14  may include a mobile phase pathway connected to a liquid inlet  24  together with an inlet manifold  26  to distribute incoming liquid throughout a top portion of a media bed contained within the cavity  22 . A bed support or inlet screen  28  is attached to the adapter  20  by connectors and/or by an inner clamp nut  30  which is accessible from the cavity  22 . The bed support  28  may be removed manually for maintenance purposes by release of the clamp nut  30 ; the distributor plate  31  may also be manually removable (see U.S. Pat. No. 6,190,560 for a description of a distributor plate design). 
     A drive system is used to move the adapter  20  in an operational mode. The drive system is comprised of at least one and preferably three or more, drive cylinders  34 . The drive cylinders  34  move drive pistons  36  which are coupled to the drum  18 . A portion of the drive pistons  36  may by threaded  38  to allow for the drive piston  36  to connect or couple to connection arms  40  at specific locations relative to the drive piston  36  such as with nuts  42 ,  44 . 
       FIG. 1  shows a first maintenance position of the adapter  20  wherein the adapter  20  is raised a predetermined distance from a top  54  of the cavity  22  within the cylinder by means of the drive system  34  and piston  36 . The operator is thereby provided access with a hand to the centre of the drum  18  to release or affix nut  30  which retains the distributor plate  31  and bed support  28  to the adapter  20 . The distributor plate  31  and or/bed support  28  may then be removed manually, without the use of a handling device, for maintenance. Once maintenance has been carried out, these components are then replaced by manual means, affixed to the adapter  20  and the adapter  20  lowered to return to an operational mode, nuts  42 ,  44  being reset to a proper operational configuration, if necessary. 
     In order to perform a second maintenance operation, such as removal of the lower bed support or screen  160  which is typically positioned so that its outer edge  162  is between the tube  112  and the collection system  116 , the tube  112  may be raised by the drive system as illustrated in  FIG. 2 . The bolts which normally secure the tube  112  to the base  164  are removed, and the nuts  142 ,  144  may be coupled to the piston  136  to drive the tube  112  along with the drum  118  upwards as shown. A gap is thus provided which allows access for an operator to loosen nut  132 , which affixes the lower bed support/screen  160  to the base  164 , and remove the bed support  160  manually for maintenance. Once maintenance has been completed, the bed support  160  is manually replaced, affixed by nut  132  to the base  164  by the operator, and the process reversed to lower tube  112  and the drum  118  into an operational position. 
     Although not described below, it will be understood that the maintenance of the column described in  FIGS. 1 and 2  could be carried out in accordance with the present invention. 
     The present invention will now be described with reference to  FIGS. 3 to 16 ;  FIGS. 3 to 8  relate to providing access to the upper adapter assembly,  FIGS. 9 to 14  to providing access to the base assembly for maintenance and  FIGS. 15 and 16  to the use of the handling device of the invention in carrying/lifting other column components not described in the preceding figures. 
       FIG. 3  is a schematic exploded front view of a column described in applicant&#39;s U.S. Pat. No. 7,708,891. The column is made of strong, inert materials such as stainless steel and other materials which are suitable for use in a GMP environment typical of the pharmaceutical industry. The column  210  is supported on legs  204  having feet  206  which are adjustable in order to modify the height and/or the level of the column. The legs  204  support the column  210  which comprises a cylindrical housing or tube  212  separating a base assembly  263  at one end from an adapter assembly  215  at the other. The tube  212  may typically be made from stainless steel, or other strong, inert materials. Adjacent to the adapter assembly  215  is a dispersion system comprising a nozzle  211  which includes a mobile phase pathway, for the introduction of buffer or other suitable mobile phase liquids or chemicals/materials to be separated, and a liquid inlet  209 . The tube  212  may be connected to the adapter assembly  215  and base assembly  263  by a drive system having one or more cylinders  234 . The drive system may be a hydraulic system, as shown, or may be powered by other suitable means, such as pneumatic or electrical means. The adapter assembly  215  is moveable within a cavity  222  of the tube  212  in an operational mode, for example, to pack or compress the bed of chromatographic media used to effect chromatographic separation of chemicals within the column. The adapter assembly  215  comprises an adapter flange  217 , one or more distance pillars  219 , a backing plate  220  made typically of stainless steel, a distributor  231  which may take the form of a plate having many channels to effect the even distribution of liquids, and a bed support  228  comprising a screen or mesh or filter and optionally a sealing ring (e.g.  229 ). The bed support may be made of an inert plastic or metal material such as stainless steel. The distributor  231  and bed support  228  are fastened to each other by releasable fixing means (not shown). Typical releasable fixing means include, but are not limited to, a screw, a nut or a clamp. The fixing means  230  may only be accessed and thus released from the exterior face of the backing plate  220 , that is the face of the plate furthest away from the cavity  222 . In the present example, the nozzle  211  must first be removed to provide access to the fixing means  230 . Additional releasable fixing means, accessible from the exterior face of the backing plate, may optionally be employed to fasten the backing plate, distributor and bed support together. These fixing means can take the form of bolts inserted through corresponding holes around the perimeter of the components. Access from the exterior face of the backing plate avoids unnecessary exposure of the operator to a suspended or supported load within the column. 
     The base assembly  263  comprises a backing plate  264  together with a distributor  266  and a bed support  268  fastened to each other by releasable fixing means  269 . The bed support  268  comprises a screen or mesh or filter and optionally a sealing ring (e.g.  274 ). The bed support may be made of an inert plastic or metal material such as stainless steel. Releasable fixing means  269  are, for example, a screw, a nut, a bolt or a clamp; it will be appreciated that other releasable fixing means are also possible. As can be seen from the figure, the fixing means  269  secures bed support  268  and the distributor  266  through a central hole in each component. The fixing means  269  is only accessible and may therefore only be released from the exterior face of the backing plate  264 . In  FIG. 3 , nozzle  272  must first be removed to provide access to release fixing means  269 . Additional releasable fixing means, accessible from the exterior face of the backing plate, may optionally be employed to fasten the distributor and bed support together. These fixing means can take the form of bolts inserted through corresponding holes around the perimeter of the components. Access from the exterior face of the backing plate  264  avoids operator exposure beneath a suspended load, were access only to be available from within the interior of the column. 
     It will be understood that separation of chemical or biological materials on the column, when the tube  212  is full of chromatographic media, can be carried out in either a downward or upward flow. Thus, in a downward flow, liquid containing chemical or biological materials to be separated is introduced through nozzle  211  and moves in a downward direction through the bed of media, to be collected in the collection system at the base of the column via an outlet port (not shown). In upward flow mode, liquid containing materials to be separated is introduced via the bottom nozzle  272  and flows upwards through the media bed to be collected at the top of the column via an outlet port (not shown). In the interests of clarity, the maintenance or servicing of the column will be described in downward flow mode. 
     In order to conduct maintenance on the adapter assembly  215  or distributor  231 , the adapter assembly  215  is disconnected from the column tube  212  by unscrewing the nuts which join the adapter flange  217  to the upper column flange  213   a . The drive system then raises the adapter assembly  215  by means of cylinders  234  to allow for access to the interior of the column for maintenance or service. The adapter assembly  215  is locked into position by means of locking rods  225  which are aligned with and screwed into threaded holes in the locking system  270 . In this secured position, the adapter bed support and/or the distributor may be removed from the column with a handling device (not shown) for maintenance once the fixing means are released, release being effected by removal from the exterior face of the column following removal of the nozzle  211  as described above. Once maintenance has been carried out on the column (e.g. the bed support  228  has been replaced by means of the handling device), the column  210  is made operational again by reversing the above procedure: the adapter assembly  215  is released from the locking rod  225  and lowered by use of cylinders  234 , and then reconnected to the column tube  212  by replacing the nuts which join the adapter flange  217  to the upper column flange  213   a.    
     Maintenance or service is carried out on the bottom distributor  266  or base assembly  263  by releasing the tube  212  from the base assembly  263  and lifting the tube  212  and adapter assembly  215  with the aid of the drive system. The bolts on the lower flange  213   b  of the column tube  212  which join it to the bottom backing plate  264  are removed. The column tube  212  and adapter assembly  215  are then lifted by means of the drive cylinders  234 . The tube  212  and upper adapter assembly is secured in position above the base with the cylinder brackets  236  by screwing locking bolts through holes aligned in the locking pin  270 , bracket  236  and cylinder  234 . 
     The bottom nozzle  270  is then disconnected from the back plate  264  and distributor  266 . The nozzle  270  is removed together with the distance ring  235 , to allow access to release the fixing means  269  which may be in the form of a nut. The nut  269  is removed from the exterior face of the backing plate  264 , i.e. the face distant from the cavity  222 , and thus eliminates operator exposure to a suspended or supported load. If additional releasable fixing means, such as bolts inserted through the backing plate, distributor and bed support as described above are present, these must be removed from the exterior face of the backing plate. The interior of the column may now be accessed for maintenance or service, such as the replacement or cleaning of the bed support  268  and/or O-rings, the bed support being removed with the aid of a handling device (not shown). To return the column to an operational mode, the above procedure is reversed. 
       FIG. 4   a  is a schematic front view of a column of  FIG. 3 . The column  310  is supported on legs  304  and has a base assembly  363  separated from an adapter assembly  315  by a tube  312 . These components are made of strong, inert materials which are approved for GMP within the pharmaceutical industries, such as stainless steel. In the figure, the base assembly  363  and adapter assembly are connected to a drive system which takes the form of three hydraulic cylinders  334 . It will be understood that in other embodiments, different drive systems may be used to raise and lower the column, such as those powered by compressed air or electricity. Furthermore, it is not essential that three cylinders are used, in some cases one being sufficient. The column  310  has a top nozzle  311  and a bottom nozzle for the introduction of liquids into the column. An electrical unit  378  for controlling the drive system is also shown. 
       FIG. 4   b  is a side sectional view of the column of  FIG. 4   a  showing one of the hydraulic cylinders  334  in cross section. The cavity  322  for containing the bed of chromatographic media can be seen in cross section. The liquid inlet  305 ,  375  and outlet  306 ,  376  of the top  311  and bottom  372  nozzle are shown, for the introduction and removal of liquids from the column  310 . The cylinder  334  is connected to the base assembly (comprising backing plate  364 , distributor  366  and bed support  368 ) and the adapter assembly  315  (comprising backing plate  320 , distributor  331  and bed support  328 ). 
       FIG. 4   c  is a top plan view of the column of  FIG. 4   a  which shows the three hydraulic cylinders  334  and nozzle  311  with liquid inlet  305  and outlet  306 . 
     To raise the adapter assembly  315  for maintenance purposes, the nuts under the upper column flange, which join the adapter  315  and column flange  313   a , are loosened and removed. The drive system then lifts the adapter assembly  315  by means of the hydraulic cylinders  334 . The adapter assembly  315  is raised until the locking bolts are opposite the threaded holes in the hydraulic cylinders  334  and the bolts screwed in to secure the assembly in the service or maintenance position (see  FIG. 3 ). 
       FIG. 5   a  is a front perspective view showing the adapter assembly  415  raised and secured into position to provide a gap  427  for access to the interior of the column for service or maintenance. The column  410  has a drive system comprising three hydraulic cylinders  434 . The adapter bed support  428 , the distributor  431  and the backing plate  420  are now visible; the bed support  428  can be unfastened from the distributor  431  by releasing the fixing means (not shown) without accessing the gap  427 . In order to describe this process, reference is made to  FIG. 4  in that the nozzle  311  is first removed to provide access to remove the retaining nut (not shown) which secures bed support  328  to the distributor  331  without accessing the gap  427 . The fixing nut is removed from the exterior face of the backing plate  320 . 
       FIG. 5   b  shows release of the fixing means from the backing plate  420  side of the adapter assembly using a spanner  446 . The fixing means (in the form of a retaining nut, obscured by the spanner) secures the adapter bed support to the distributor. 
     The bed support  428  is heavy and requires the use of a handling device to lift it once it has been separated from the adapter assembly. 
     An embodiment of the handling device  580  is shown in  FIG. 6 . The device  580  is in the form of a trolley or cart with a vertical pillar  581  supported on frame  582  having legs  583 . The device  580  is made of strong, inert materials; such materials include, but are not limited to, stainless steel and other materials which are suitable for use in a GMP environment typical of the pharmaceutical industry. Extendable arms  585   a, b, c  project from the pillar  581  and can be raised or lowered relative to the pillar  581  by mechanical or other means. In the embodiment shown, the arms  585   a, b, c  are raised or lowered by a manual jacking mechanism (not shown) adjacent to the handle  584  which provides the means to steer or control the device. The arms  585   a, b, c  are designed to bear the weight of the distributor or bed support and are extendable to the diameter of these components. While the embodiment shown has three arms  585   a, b, c , it will be understood that the device is not so limited and that other embodiments may have less than or more than three arms (e.g. one, two, four, five) depending on the individual design. Each arm  585   a, b, c  has attachment means for securing a column component thereto. In the embodiment shown, the attachment means comprises a fixture in the form of holes  587   a, b, c , at the extremities of the arms  585   a, b, c  for bolting or securing of the distributor and/or bed support to the arms for safety, particularly during transport, removal and/or insertion of the column component. It will be understood that other attachment means can take many different forms, such as clips, clamps, fasteners etc. Pads (not shown) may be fitted to the arms  585   a, b, c  to minimise any risk of damage to the bed support/distributor when these components come into contact with the arms. A raised, central element,  588  (typically of conical shape) for receipt of the central hole in the bed support or distributor provides a means for centralising these components on the arms  585   a, b, c  of the device  580 . This element  588  may be fitted on either, or both, the upper or under side of the point where the arms  585   a, b, c  intersect. In operation, the distributor and/or bed support is either suspended from the arms  585   a, b, c  or supported on the arms. Pivotal wheels  586  allow easy movement and manoeuvrability of the handling device  580 . In the embodiment shown, the movement of the device  580  and the raising/extension of the arms  585   a, b, c  are by manual means, but it will be understood that other embodiments are possible which incorporate powered systems (e.g. electrical, pneumatic or hydraulic systems) to drive the device  580  and lift/lower the arm  585 . It will also be understood that in other embodiments of the handling device (not shown), arm  585   a  is capable of pivoting or rotation around pillar  581  to enable the arms  585   b  and  c  to access a narrow gap between any two cylinders (e.g.  434  of  FIG. 5   a ) and remove/insert a bed support and/or distributor which have a diameter which is greater than the distance between any two cylinders in the column (e.g.  434  of  FIG. 5   a ). 
     The operation of the device  580  in removing the bed support is shown in  FIGS. 7 to 9 . 
       FIG. 7   a  and  FIG. 7   b  are perspective views of the column of  FIG. 5  showing the handling device of  FIG. 6  supporting the bed support  628  on one or more arms  685 . The arms  685  are raised into position below the bed support  628 , care being taken not to damage the mesh of the bed support by positioning the pads (not shown) on the arms  685  of the handling device  680  under the outer rim of the bed support  628 , and then gently raising the arms  685  up to the bed support. Once the arms  685  are in position, the nuts on the threaded rods  633  that go through the back plate  620  and distributor  631  into the outer perimeter of the bed support  628  are loosened and the bed support can be removed on the handling device. The rods  633  are initially loosened with a spanner and finally removed by hand. As can be seen from the figures, the removal of the rods  633  is carried out from the exterior face of the backing plate  620  without accessing the gap and thus without exposing the operator to a suspended or supported overhead weight. 
       FIG. 8   a  and  FIG. 8   b  are perspective views showing the removal of the bed support  728  on the handling device  780  from the column  710 . In  FIG. 8   a  the bed support  728 , borne on the arms  785  of the device  780 , is removed from the column  710  without substantially tilting the support  728 . The device  780  can then be moved away from the column ( FIG. 8   b ) and the arms  785  lowered in order that the bed support  728  can be cleaned or replaced. Maintenance or servicing the column may now be carried out as required. For example, the bed support  728  may be cleaned or replaced, O-rings replaced and/or the distributor  731  may also be removed for cleaning. 
     To return to an operational mode, the above procedure is simply reversed. The bed support and distributor are returned to the column and affixed to the backing plate, the nozzle reattached, and the adapter assembly lowered and bolted to the column tube. 
     Access to the bottom bed support and interior of the column will now be described with reference to  FIGS. 9 to 13 . To access the bottom bed support, the tube is released from the base assembly by unscrewing the bolts that join it to the base and then lifting the tube and upper adapter assembly with the hydraulic cylinders. 
       FIG. 9   a  shows a column  810  as previously described in  FIGS. 3 to 5  and  FIGS. 7 and 8 . The bolts on the lower flange  813   b  of the column tube which fasten the tube  812  to the bottom backing plate  864  are loosened and unscrewed. The column tube  812  and adapter assembly  815  are lifted by the hydraulic cylinders  834  of the drive system until the hole indicated by ‘A’ is opposite the hole indicated by ‘B’ in the inset of  FIG. 9   a . Locking bolts  837  are then introduced into the aligned holes in the locking pin  870 , bracket  836  and cylinder  834  to secure the tube and adapter assembly in position ( FIG. 9   b ). After removal of the bolts securing the tube  812  to the bottom backing plate  864 , maintenance can now be carried out on the column in the gap  827  created by raising the tube and adapter assembly. 
       FIG. 10  shows the column  910  with the tube  912  raised and mechanically locked to the cylinders  934  in readiness for maintenance. The bottom nozzle (not shown—see  272  in  FIG. 3 ) is first removed from the back plate  964  by unscrewing the retaining bolts. The retaining nut (or fixing means) which fastens the bed support  968  to the distributor  966  is released from the backing plate  964  side of the column  910 . If additional fixing means are present, such as bolts (not shown) which fasten the bed support to the distributor and the backing plate, and are located on the perimeter of the backing plate, these are released from the backing plate face of the column. 
     The bed support  1068  can now be removed from the column by use of the handling device as shown in  FIG. 11   a  and  FIG. 11   b . The handling device (as described in  FIG. 6  above)  1080  is wheeled into position where the arms  1085  are a few centimeters above the bed support  1068 . The bed support  1068  has a number of threaded holes that correspond to the holes used to bolt the bed support to the backing plate  1064 . The arms  1085  of the handling device  1080  have holes through which bolts are screwed into the bottom bed support  1068 ; these holes are aligned to those of the bed support  1068  and bolts affixed to secure the bed support to the arms  1085 . Once attached, the bed support  1068  can be removed from the column by raising the arms  1085  a few centimeters and wheeling the handling device  1080  away from the column  1010 . The bed support  1068  can now be cleaned or new O-rings replaced as necessary. Generally the bed support will be moved away from the column, as shown in  FIG. 12 , lowered onto a surface (such as a trolley or workbench) and released from the arms  1185  of the handling device  1180  to facilitate cleaning and servicing. The distributor ( 1066  in  FIG. 11 ) can also be removed and serviced in a similar manner using the handling device. 
     Once maintenance or servicing has been completed, the column is returned to an operational mode by simply reversing the process as described above. This involves replacing the bed support/and or distributor in the column, affixing the components to the backing plate, reattaching the nozzle, lowering the tube and adapter assembly.  FIG. 13  shows the column  1210  of  FIG. 11  connected to the hydraulic control unit  1290  with the tube  1212  lowered and ready to be bolted to the backing plate  1264 . 
       FIG. 14  illustrates the removal of a bed support  1368  from gap  1327  of a column  1310  in which the distance between any two drive cylinders  1334  is less than the diameter of the bed support  1368 . This is the case for example in the column in  FIG. 14  which has four drive cylinders  1334  or in the column described in  FIGS. 1 and 2 . In order to do so, arm  1385  of handling device  1380  is designed to rotate or pivot around joint  1389  and, by so doing, substantially tilt the bed support  1368  such that it can be removed or inserted between the cylinders  1334 . 
     The handling device can also be used to remove or replace other column components from/on a column.  FIG. 15  illustrates the removal of a drive cylinder  1434  from column  1410  by affixing the cylinder to the arm  1485  of the handling device  1480 . The drive cylinder  1434  is secured to the arm  1485  of the handling device  1480  by attachment means  1487  in the form of screw holes for the receipt of the drive cylinder. 
     The nozzle  1511  can also be removed or affixed to the column by the use of the handling device  1580 , as shown in  FIG. 16 . The nozzle is secured to the arm  1585  of the handling device  1580  by attachment means  1587  and may then be transported to and/or lifted away from the column. 
     All patents, patent publications, and other published references mentioned herein are hereby incorporated by reference in their entireties as if each had been individually and specifically incorporated by reference herein. While preferred illustrative embodiments of the present invention are described, one skilled in the art will appreciate that the present invention can be practiced by other than the described embodiments, which are presented for purposes of illustration only and not by way of limitation. The present invention is limited only by the claims that follow.

Technology Classification (CPC): 1