Abstract:
A chromatography column is normally filled with a slurry of media for operation. A piston normally compacts the slurry in the column. The piston moves through a cavity in communication with both a slurry inlet and slurry ports which are in communication with the interior of the chromatography column. A controller is configured to automatically adjust piston speeds along elevation zones of operation. Furthermore, presetting specific speeds less the maximum speed can be accomplished with the controller. A pressure sensor may also be employed to assist in switching speed of operation of the piston under particular pressure events.

Description:
BACKGROUND OF THE INVENTION 
       [0001]    1. Field of the Invention 
         [0002]    The present invention relates an apparatus and method of operating a chromatography column and, more particularly, to such a chromatography column and a method for effectively packing media and/or automatically moving the top flow adapter at at least one predetermined speed less than a maximum speed and/or providing at least one programmably set bottom limit stop. 
         [0003]    2. Description of Related Art 
         [0004]    Chromatography is a process of separating components of a mixture of chemical substances through the percolation of fluid through a body or bed of comminuted or porous rigid material, known as media. In the process, the various component are often resolved, or separated, by their selective retardation as they are transported through the bed by a moving fluid or buffer. A solution of the substances to be separated becomes the moving phase of the system passing through the interstices in the stationary or continuous phase which are finely divided particles, possibly in the form of a gel slurry. 
         [0005]    The substances in the moving phase are normally poured into the top of a chromatography column filled with the finely divided material, i.e., the media, that can absorb differentially the substances to be separated. The particular material used for the media varies widely with the substances to be separated. As the solution percolates down the column the components are separated from the buffer fluid which may be pumped back into the top of the column so as to again pass down through the bed as a carrier. The different substances as they travel down the column at different rates form bands of the different substances which are individually collected at the outlet. 
         [0006]    A chromatography column typically comprises a hollow vertically disposed cylindrical housing including a liquid dispensing section, also referred to as a top flow adapter or plunger in many embodiments, at the upper end and through which the buffer and substances to be separated are dispensed to the media bed, and a liquid collecting section at the lower end for collecting the substances and buffer individually. The media or bed through which the buffer fluid and mixture to be separated and purified percolates is located between these sections. The liquid dispensing section and liquid collecting section may each include a respective distribution plate and at least one of the plates may be connected in an assembly with an axially movable plunger-like body positioned within the housing. After the column is charged with the bed media, the plunger body is often forced toward the bottom to compress or pressurize the media bed which has been poured into the column. 
         [0007]    Prior art designs have allowed for the plunger to be moved with hydraulics manually controlled by an operator such as those shown and described in Applicant&#39;s U.S. Pat. No. 6,736,974, incorporated herein by reference. When the operator manually actuated the hydraulic controls of the prior art design, he or she would cause valves to open and shut to move the plunger up or down at a single, or maximum speed. In order to change the speed of operation of the plunger, in a prior art device, air pressure provided to a hydraulic pump could be varied manually with a regulator on the air supply. However, this process was completely operator dependent and not particularly precise. If left to normal operation with the controller, the only speed of operation was the maximum speed. 
         [0008]    The prior art packing technique involved an operator lowering a plunger until it stopped. When lowering the plunger at its single fastest speed, when the liquid in the column was first encountered, the plunger could continue downward at this speed thereby likely continuing to pack the bed. This could lead to an undesirable pack in at least some situations. 
         [0009]    Accordingly, a need exists to improve the operational methods by providing an improved chromatography column. 
       SUMMARY OF THE INVENTION 
       [0010]    The present invention recognizes and addresses these needs and others. 
         [0011]    Consequently, it is an object of at least one embodiment of the present invention to provide an improved chromatography column and method of its operation. 
         [0012]    It is another object of at least one embodiment of the present invention to provide a chromatography column capable of automatically changing plunger speeds according to predetermined settings. 
         [0013]    It is another object of at least one embodiment of the present invention to provide a chromatography column with a controller which can move the top flow adapter at least two programmably selected and/or predetermined speeds. 
         [0014]    Accordingly, the present invention provides a chromatography column having a cylinder defining a cavity for containing media therein. A top flow adapter or plunger is operatively coupled to a hydraulic piston moveable through at least a portion of the cavity within the cylinder during operation. A base is normally connected to the cylinder. The plunger may be operatively coupled to the hydraulic piston to adjust the height of the plunger above the base to provide a desired resin height between the plunger and the base for operation. The plunger may also be utilized to exert a force on the resin to “pack” the resin in the column. 
         [0015]    A controller is also provided which preferably at least assists in providing one of a number of operational capabilities not provided in the prior art. The controller receives an input relative to at least one of three of the hydraulic cylinders utilized in the preferred embodiment relating to at least one of position and/or pressure. These inputs can be utilized to move the top flow adapter relative to the column of at least two predetermined speed settings such as could be set to occur at a particular plunger elevation, to switch to a slower speed upon encountering a predetermined pressure or pressure differential pressure at each of at least some of the pistons, and/or to prevent the top flow adapter from contracting a manual step in such an embodiment. 
         [0016]    The hydraulic system preferably includes at least one piston which is driven by at least one hydraulic cylinder. In the preferred embodiment, a plurality of hydraulic cylinders are utilized which are driven from a common hydraulic pressure source which is coupled to a controller through a proportional servo valve. The controller receives feedback related to each of the cylinders for increased performance capabilities. Upon receipt of a signal from a controller, the hydraulic cylinder(s) drive the hydraulic piston(s) at a programmable speed at maximum speed or slower. Depending upon the configuration of the column, the piston(s) drive the plunger and/or the cylinder upwardly or downwardly. 
     
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
         [0017]    The particular features and advantages of the invention as well as other objects will become apparent from the following description taken in connection with the accompanying drawings in which: 
           [0018]      FIG. 1  is a side plan view of a chromatography column according to the present invention in a first operational position; and 
           [0019]      FIG. 2  is a side plan view of the chromatography column illustrated in  FIG. 1  in a second operational position. 
       
    
    
     DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS 
       [0020]    The present invention is concerned with a method and apparatus for permitting maintenance within a chromatography column which houses a slurry and/or media during operation.  FIGS. 1-2  depict one such chromatography column  10  with the slurry removed. The column  10  comprises an elongated hollow cylindrical housing  12 , or cylinder, having a dispersion section  14  at the top and a collecting section  16  at the bottom. The dispersion section  14  includes a cylindrical drum  18  having an upper cylindrical plunger head  20  formed at the lower end. The plunger  20  or top flow adapter is normally disposed within the upper portion of the housing  12  such as illustrated in the first operational position of  FIG. 1 . The plunger  20  may also be moved, such as with a drive system similar to the hydraulic arrangement illustrated to the second operational position of  FIG. 2 . The movement of the head  20  allows for the compression of media to “pack” resin and/or for the use of a particularly sized media column with the cavity  22  formed between the dispersion and collection sections  14 , 16  and/or between the plunger  20  and the base  64 . 
         [0021]    The dispersion section  14  may also include a product inlet  24  along with an inlet manifold  26  to distribute incoming fluid throughout a top portion of a resin column contained within the cavity  22 . An inlet screen  28  may be connected to the plunger head  20  by connectors such as TEFLON™ snaps (not illustrated) and/or an inner clamp nut  30 . The distributor plate  31  may be removable as well. A discussion of a distributor plate  31  design may be found in U.S. Pat. No. 6,190,560. A slurry fill valve  32  such as the valve taught in co-owned U.S. Pat. No. 6,190,560 may also be connected to the plunger head  20  and/or dispersion section  14 . The slurry fill valve  32  provides a way to fill the cavity  22  with resin without the need to lift the plunger  28  out of the cavity  22  within the cylinder  12 . Although a preferred dispersion section  14  is described, other dispersion sections designs could be utilized as well. 
         [0022]    In order to move the plunger head  20  in an operational mode from the first operational position shown in  FIG. 1  to the second operational position of  FIG. 2 , a drive system, illustrated as a hydraulic system is preferably utilized. Other systems, such as electric or pneumatic may be appropriate drive systems in other embodiments. 
         [0023]    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 . In the preferred embodiment, a portion of the drive pistons is a threaded portion  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 . Guide rods  46  may be utilized in addition to the drive system to ensure linear movement of the drum  18  and plunger  20  within the cavity  22  of the cylinder  12 . 
         [0024]    The drive system also includes a control unit  48  which may be operated to control movement of the plunger  20 . The control unit preferably has a hydraulic engine which provides fluid under pressure to operate the drive cylinders  34  or may be connected to a hydraulic supply. Controls  50  allow an operator to direct the movement of the plunger  20  within the cylinder  12 . Controls  50  may allow for operation of the hydraulic engine, or pump, a float switch, direction of movement selection and/or controlling valves. Gauges  52  allow for the operating parameters to be monitored. Gauges  52  may monitor air pressure, column pressure and/or drive system pressure, such as hydraulic pressure. 
         [0025]    The control unit  48  is also preferably equipped with a controller which is a hydraulic control unit (HCU)  54 . The HCU  54  is preferably equipped with a touch screen  56  for operation of at least certain functions of the HCU  54 . As discussed below, some of the operations which can be performed and or assisted by the HCU  54  include the movement of the top flow adapter through the movement of the plunger  20  down and possibly up at a plurality of predetermined speeds including first and second speeds, stopping movement of the plunger at a bottom limit, and/or movement of the plunger at programmed speeds such as in a pack process as will be discussed in further detail below. It will be understood to one of ordinary skill in the art that as the plunger  20  moves, so does the top flow adapter in the preferred embodiment. 
         [0026]    The column  10 , like that disclosed in co-owned U.S. Pat. No. 7,402,251, incorporated herein by reference, preferably utilizes sensors which provide input to the HCU  54  which can then vary signals to control operation of certain procedures in an improved manner as will be discussed below. The cylinders  34  may have sensors  58  in communication therewith which can sense a pressure relative to column pressure. Sensors  58  provide an output which is received by the HCU  56  in the preferred embodiment. Sensors  60  which sense position of the plunger  20  either directly or indirectly are also employed which provide a position relative to each of the pistons  36 . Output from sensors  60  is also provided to the HCU  54 . 
         [0027]    Position sensors  60  in cooperation with the HCU  54  provide various capabilities which have not been achievable with prior art designs. First, height ranges of the plunger  20  can have preset speeds of operation. The height ranges and settings related to speeds may be programmed by the operator. 
         [0028]    In an operational mode, the operator may utilize a touch screen  56 , or other input device, to input a predetermined or programmed speed of the plunger  20  at or less than a maximum speed setting, and thus the top flow adapter, should be moved. The HCU  54  preferably then directs selective opening of valves  62  to each of the cylinders  36  to provide for the desired piston movement with the hydraulic system while also providing signal to proportional valve  66 . Predetermined speed setting could be relative settings such as 100% of voltage or maximum voltage to the valve  66 , 25% voltage to the valve, and/or a specific speed setting such as 2 cm/min, etc. 
         [0029]    A speed less than maximum speed of plunger  20  can be inputted in the HCU  54  and the HCU receives position information from sensor(s)  60  from which speed can be calculated. The proportional valve  66  can be employed either in the air and/or hydraulic system to selectively vary the flow of hydraulics which moves plunger  20  through movement of pistons  36  at a predetermined speed. By receiving updated information from sensors  60 , a feedback loop may be established. 
         [0030]    For instance, if a maximum speed of 3 cm/min could be achieved for a given drive system, the controller could provide for the selection of a speed of 3 or less, such as 2 cm/min. The HCU  54  would receive signal input from signals  60  and output a control signal to proportional valve  66 . The proportional valve  66  may open or close until the 2 cm/min set point is reached and then possibly continue to hunt. 
         [0031]    In addition to pre-setting a speed, speed zones for given elevation ranges could be provided through use of a presently preferred embodiment. For instance, if a column has an operational height of 78 inches, fluid filled to 74 inches, and a resin bed starting at 20 inches, it may be desirable to select 100% speed above 75 inches, then 75% speed to 74 inches, 25% speed to 22 inches and 10% speed to 19 inches. At 19 inches, a bottom limit stop may be reached which could be set at any value at or above a mechanical stop. Accordingly, it may be possible to start downward movement at the first speed and automatically change speeds, in this instance to slower speed at 75 inches and then again automatically change speeds at 74 inches, etc. In this example, the height or elevation at an end of a speed zone is a preset condition identified by the controller  34  with signals provided to the proportional valve  66  to change the speeds. Any of the numbers in this paragraph including speeds and distances could be set at any value desired by the user and may be expressed differently. Percentages have been found effective as they can represent voltage provided to the proportional valve and may not equate directly to a percentage of maximum speed, but to valve parameters. 
         [0032]    Alternatively, predetermined speed settings could be provided for in each of the zones in a more direct approach such as by inputting distance/time. The height of specific zones can be selected by the operator in the preferred embodiment. 100% speed may allow for movement when the operator knows the plunger  20  is not in contact with fluid. A slower speed may be desirable as the plunger approaches the fluid. Contacting the fluid and continuing to push at full speed may undesirably pack resin for some applications. Accordingly, slowing to 75% as the fluid is approached is helpful, especially since most columns  10  are stainless steel and thus not transparent to see when contact is made visually. When the operator thinks the fluid will be contacted, a speed of 50% may be desirable. This may continue until the resin bed itself is approached at which time another speed could be selected, such as 25%. 
         [0033]    After slowly going through a specific portion of the resin bed, the HCU  54  may stop further compression with a programmably set bottom limit stop. 
         [0034]    Since each of the pistons  36  which control movement of the plunger  20  are equipped with position sensors  60 , the output from these sensors  60  received by the HCU  54  can be utilized. The elevation of each of the pistons  36  or other elevation corresponding to each of the lifting units connected to the plunger can be monitored. 
         [0035]    The HCU  54  can direct the selective opening and closing of at least some of the valves  62  which are in communication with respective cylinders  34  or other appropriate driver to ensure that the top flow adapter and the plunger  20  remain level within the chromatography cylinder  12 . By level, it will be understand that being within a predetermined tolerance range of level will be sufficient, such as within a centimeter for a two meter diameter cylinder  12 , or other appropriate first tolerance. 
         [0036]    Another advantage of using the improved HCU  54  of the preferred embodiment is the ability to further automate the packing process. The output from one or more pressure sensors  60  which could relate to back pressure on the cylinders  34  and/or pressure within the cavity  22 . In the prior art, the HCU could downwardly direct the plunger  20  until reaching a predetermined backpressure as measured from the sensor, and preferably while employing the auto level feature, the HCU could secure downward movement upon reaching the set pressure and/or after a predetermined time after reaching the set pressure. However, instead of securing the downward movement which remains a possibility, slowing or otherwise adjusting the speed may be desirable under certain situations such as a pressure event which could include sensing a predetermined pressure and/or a pressure change such as a change in pressure over a given interval. 
         [0037]    Additionally, the HCU  54  can also store pressure information at regular intervals such (time intervals could be set such as every ten seconds) as the piston travels. An average of several recorded values could be stored. This average pressure valve can be a travel pressure and is somewhat created by forcing of fluid through the media at specific speeds. This average value can be compared to the actual pressure value as measured in real time. As fluid is expelled, the piston eventually comes in contact with solid media and the actual pressure can increase against the solid bed resistance. When the actual pressure exceeds the travel pressure by a particular amount, a pressure event could possibly be created thereby triggering a shift to a next speed and/or speed zone. 
         [0038]    This feature has been found to assist in preventing spring back off of the media. In some embodiments there is a tendency to have premature compression which could otherwise occur when shifting to a slow speed occurs too soon which could cause somewhat of a tendency for media to expand before restricting the spring back tendency with the piston since the fluid being compressed at a particular speed tends to act to assist in compression. This is preferably avoided with some optimum packs. If waiting to shift to a slower speed occurs too late, further compression in the media could occur prematurely with brute pressure force which could also be undesirable in certain situations. Accordingly, utilizing the controller with pressure events has been desirable at least in some applications. 
         [0039]    The HCU may also provide the ability to stop movement of the plunger  20 , such as if the operator decided to terminate the automated packing process and/or to move the top flow adapter to a preset height. 
         [0040]    The new controller  48  may now be utilized with various columns. The preferred embodiment of the controller  48  can identify the type and/or height of the column to which it is connected. This can be advantageous as different control parameters may be utilized with different sized columns. A PLC (or other computer) within the controller such as HCU, or otherwise, upon connection with a cable  64 , senses inputs which can be combined as binary numbers (such as the preset open or closed condition of two switches) to identify cylinder diameter and/or cylinder stroke and/or max bed height, etc. The switches provide inputs to the HCU  54  through cable  64  or otherwise. 
         [0041]    While the HCU  54  can provide a plurality of automated features, it is also anticipated that it can provide for manual operation including operation of separate valves  62  to respective cylinders (which was not an option in the prior art). Of course, any and potentially all of the automated features can be selected to be off through use of input such as touchscreen  56 . 
         [0042]    The HCU preferably includes a PLC which is provided with the controller  48 . The PLC used in one operational version is an Allen-Bradley (A-B) MocroLogic 1500 Processor with I/O modules. This PLC monitors and controls the operation of three cylinders that support the plunger. The touchscreen  56  is an A-B PanelView 550. Rockwell Automation Software including RSLogix 500 were utilized to develop the PLC programming, PanelBuilder32 was utilized to develop a graphics interface and RSLink was utilized to communicate downloads to the PLC as well as interface with a PC and the touchscreen  56 . Other software and hardware as known in the art could also be utilized including computers with monitors that are provided and may have such improved capabilities of improved data storage and/or other capabilities. Other data storage possibilities such as a USB port could also be provided. 
         [0043]    The component parts, such as the drum  18 , the cylinder  12 , and the base are preferably constructed from stainless steel and/or high nickel alloy and/or acrylic. The drive system may be constructed out of appropriate materials including stainless steel. Three or more legs  76 , only two of which are illustrated, are connected to the base  64 . The drive cylinders  34  are connected to the rim  70  of the base. 
         [0044]    Numerous alternations of the structure herein disclosed will suggest themselves to those skilled in the art. However, it is to be understood that the present disclosure relates to the preferred embodiment of the invention which is for purposes of illustration only and not to be construed as a limitation of the invention. All such modifications which do not depart from the spirit of the invention are intended to be included within the scope of the appended claims.