CHROMATOGRAPHY COLUMNS AND THEIR OPERATION

Abstract

A chromatography column comprises a 2-axis inclinometer for determining or monitoring the orientation the axial verticality of the column tube or of a column component such as a piston. A column inclinometer may be mounted on the column. A piston inclinometer may be mounted on the piston. Outputs from the inclinometer may be fed to a programmable logic controller and used to control the operation of the column, e.g. by adjusting a support stand of the column, or controlling a piston drive mechanism.

Claims

1. A chromatography apparatus comprising: a chromatography column, said column comprising additionally at least one inclinometer for measuring the orientation of the column, or of one or more components thereof, relative to the horizontal and/or vertical.

2. The chromatography apparatus of claim 1 in which: a said inclinometer is a two-axis inclinometer, operable and positioned to measure the orientation or inclination of the column or component thereof in respective mutually transverse or perpendicular axes.

3. The chromatography apparatus of claim 1 in which the apparatus comprises first and second inclinometers, operable and positioned to measure the orientation or inclination of the column or component thereof in respective mutually transverse or perpendicular axes.

4. The chromatography apparatus of claim 1 in which the inclinometer is an electronic or electric device operable to produce an electrical output signal.

5. The chromatography apparatus of claim 1 in which the inclinometer is fixedly mounted to a flat reference surface of the column, the reference surface being normal to an axial direction of the column.

6. The chromatography apparatus of claim 1 which further comprises a display to show the inclination or orientation of said column or component from the inclinometer output.

7. The chromatography apparatus of claim 6 in which said display: is on a said inclinometer; is carried on the column; is carried on a support structure of the column; or is mounted on a separate skid comprised in the apparatus.

8. The chromatography apparatus of claim 1 in which a said inclinometer is: on a sidewall or end flange of a column tube component of the chromatography column, or on a fixed top closure or bottom closure end member component of the chromatography column.

9. The chromatography apparatus of claim 1 in which the chromatography column comprises an end cell piston component or column piston component and a column tube component in which said piston component is slidable, and said inclinometer is on the end cell piston component or column piston component.

10. The chromatography apparatus of claim 1 which further comrpises a control processor connected to the output from the inclinometer.

11. The chromatography apparatus of claim 10 in which the control processor comprises a programmable logic controller (PLC).

12. The chromatography apparatus of claim 10 in which the control processor is programmed to perform one or more selected from the following procedures: operate an adjustable support structure for the column, or a support drive structure for a mobile column component to adjust its orientation in dependence on the output signal from the inclinometer; indicate a levelling adjustment for levelling the column/component; give an alarm or warning in the event of a change of a detected inclination; give an alarm or warning in the event that a detected inclination exceeds a predetermined deviation from the horizontal or other desired orientation; and/or record or log the orientation over a period.

13. The chromatography apparatus of claim 10 which further comprises an adjustable support structure for the column and wherein the control processor is programmed to operate the adjustable support structure to adjust its orientation in dependence on the output signal from the inclinometer.

14. The chromatography apparatus of claim 13 in which the support structure for the column is a stand having a set of support feet to make respective support contacts distributed around the column to support it stably on a support surface, and comprises levelling adjustment mechanism for adjusting the relative axial positions of the respective support contacts.

15. The chromatography apparatus of claim 14 in which the levelling adjustment mechanism comprises a power drive for the adjusting mechanism.

16. The chromatography apparatus of claim 1 having one or more selected from the following features: the chromatography column components include an end cell piston or column piston slidable in a column tube, and a said inclinometer is on the end cell piston; the apparatus comprises a support and/or drive mechanism for the piston comprising a set of power-driven supports distributed around the piston and operable to drive the piston axially relative to the column; the apparatus comprises a control processor connected to the output from the inclinometer on the end cell piston; and the control processor is programmed to operate the support and/or drive mechanism for the piston, in dependence on the output from the inclinometer to keep the piston level as it is moved.

17. A method of operating a chromatography apparatus according to claim 1, comprising the step of determining the orientation or alignment of the column or a component thereof using the respective inclinometer.

18. The method according to claim 17 comprising levelling the column or component thereof in dependence on output from the inclinometer, by means of automatic control using a programmed controller to operate a support adjustment mechanism for the column or for the component thereof.

19. The method according to claim 17 comprising one or more selected from the following procedures: operating an adjustable support structure for the column, or a support/drive structure for a mobile component such as a column end piston, to adjust its orientation in dependence on the output signal from the inclinometer; indicating a levelling adjustment needed for levelling the column/component or how to make such adjustment; giving an alarm or warning in the event of a change of the detected inclination; giving an alarm or warning in the event that the detected inclination exceeds a predetermined deviation from the horizontal or other desired orientation; and/or recording or logging the orientation over a period.

Description

BRIEF DESCRIPTION OF THE DRAWINGS

[0041] Examples of chromatography columns and processes embodying our proposals are now described, with reference to the accompanying drawings in which:

[0042] FIG. 1 is a schematic perspective view showing a packed-bed industrial chromatography column.

[0043] FIG. 2 is an axial cross section of an industrial expanded bed adsorption (EBA) colum.

[0044] FIG. 3 is a fragmentary detail of FIG. 2.

DESCRIPTION OF THE SELECTED EMBODIMENTS

[0045] For the purpose of promoting an understanding of the principles of the invention, reference will now be made to the embodiments illustrated in the drawings and specific language will be used to describe the same. It will nevertheless be understood that no limitation of the scope of the invention is thereby intended. Any alterations and further modifications in the described embodiments, and any further applications of the principles of the invention as described herein are contemplated as would normally occur to one skilled in the art to which the invention relates. One embodiment of the invention is shown in great detail, although it will be apparent to those skilled in the relevant art that some features that are not relevant to the present invention may not be shown for the sake of clarity.

[0046] With reference to FIG. 1, a large-scale packed bed chromatography column has a steel column tube 1 mounted axially vertically on a support structure 4 which supports a base 2 of the column on which the column tube 1 rests at its lower end. Other column materials e.g. glass or plastics such as acrylic, may be used. The top of the column tube is closed by a movable top piston 3 suspended by support rods 33 from a support ring 32 spaced above the column tube 1. A piston drive mechanism indicated generally at 34 is provided in this embodiment by a set of three vertically-acting hydraulic drive cylinders 35 mounted equidistantly around the column, fixed to the base 2, and having respective drive rods 36 which reach up to the piston support ring 32. Together, these elements constitute a piston support structure 31. For simplicity, some guide structures for the drive rods and piston support have been omitted.

[0047] The stand 4 consists of a set of upright legs 41 each with a respective foot 43 connected to the fixed leg 41 through a driveable adjuster mechanism 44, indicated schematically. The drivable adjuster mechanisms incorporate for example servo motors driving a screw-threaded connection to adjust the axial projection of each foot 43 relative to its fixed leg 41. Cross braces 42 between the legs 41 provide rigidity of the support structure 4.

[0048] Again, for simplicity the power supplies to the drivable foot adjusters 44 and the power and hydraulic supplies for the piston drive cylinders 35 are omitted from the figure but are provided in accordance with normal practice. By a conventional communications protocol, the foot adjusters 44 and the piston drive cylinders 35 are automatically controllable from a control processor such as a programmable logic controller (PLC) 10 indicated schematically in FIG. 1, connected to a suitable user interface such as a PC 11 with video display 12 (e.g. LED, LCD or standard monitor) also shown schematically in FIG. 1. An optional connection 13 to a distributed control system is indicated schematically.

[0049] In practice the controller 10 and interface 11,12 are preferably mounted on a separate mobile skid. Skids are conventionally used with industrial chromatography columns so the details are not critical and the skid 14 is indicated here only schematically.

[0050] The structure of the column, base, piston and supports is generally primarily of stainless steel and may be of great size, e.g. up to two metres or more in diameter, and weight. As is well known, in practice a packed bed of particulate chromatography medium is established in the internal volume of the column beneath the piston 3 and process liquid is passed through from an inlet structure 39typically in the centre of the top piston 3 as indicated generallyto an outlet typically in the base (not shown). During establishment of the packed bed it is necessary to move the piston 3 axially relative to the column tube, with peripheral seals thereof making sliding contact, using the hydraulic drive cylinders 35 to control and guide the movement. For this, it is important that the cylinders work accurately in concert to ensure that the piston 3 remains accurately perpendicular to the column tube axis. Even slight non-perpendicularity can cause a spoiled pack of the column, leading to great waste of time and sometimes even damage to the piston seals or other problems.

[0051] For operation of the column, it also is of critical importance that it is axially vertical so that fluid flow (influenced by gravity) is accurately axial, and that the column tube 1 is accurately perpendicular to the base 2 and piston 3 as mentioned.

[0052] Thus, as a skilled person knows, packing normally includes a stage of filling a slurry into the bed space, flow packing to expel all air and compact the bed at the bottom of the space by flowing liquid down through it with the piston in a raised position, and then lowering the piston gradually onto the top of the bed. Especially in this latter stage piston alignment is critical.

[0053] A column inclinometer 8, that is to say, an inclinometer for determining the orientation of the column tube 1 relative to the vertical, is mounted on a reference surface of the column tube which is machined to be precisely perpendicular to the column tube axis. In the illustrated embodiment this reference surface is an upward surface 161 of a bottom flange 16 of the column tube 1. Additionally or alternatively, a column inclinometer could be positioned on the top flange, or mounted on a separate formation projecting from the column wall, and/or on a formation integral with the base plate or indeed the support structure 4. For example 8 indicates schematically an alternative inclinometer position on the underside of the base plate 2. The inclinometer is a 2-axis electronic inclinometer able to detect and signal variations relative to the vertical down to 0.01. It has a signal output line 81, such as an ethernet cable, connecting to the controller 10.

[0054] A piston inclinometer 9, that is to say an inclinometer mounted to determine the orientation of the piston axis relative to the vertical, is mounted on a reference surface on top of the piston, being a surface portion of the piston machined to be precisely perpendicular to the piston axis. As for the column, a 2-axis inclinometer is used and has a signal output line 91 to the programmed controller 10. The controller 10 is connected to control operation of the piston support and drive mechanism 34 through piston control signal lines 92 (indicated schematically) and operation of the drivable foot adjusters 44 individually by support control signal lines 82, also indicated schematically. These control lines 82,92 are installed in accordance with the relevant communication protocol, and may be for example cables using 4-20 mA signals for controlling the relevant servo motors, stepper motors, hydraulic or pneumatic pumps or whichever other drive and control mechanisms are used in the system.

[0055] The controller 10 is programmed to maintain perpendicularity/horizontality of the column tube 1 and piston 3 by means of a control program which in itself may use known program elements. Thus for example, the column inclinometer 8 continuously reports to the controller 10 and any non-perpendicularity is processed by a levelling algorithm to determine appropriate movements of one or more of the feet 43 to level the column. Corresponding signals are then sent by the control lines 82 to trigger appropriate driving of the relevant foot/feet 43. Preferably a closed loop or servo feedback is applied, in which the ongoing signals from the inclinometer are used to confirm that perpendicularity/horizontality is achieved or restored by the adjustment.

[0056] A similar control scheme may be used in relation to control of the movement of the piston 3, at least when it is being moved, using signals from the piston inclinometer 9 which, processed by the relevant levelling control algorithm in the controller 10, are used to control the three hydraulic cylinders 35 with appropriate feedback to keep the piston level as it moves.

[0057] The skilled person will appreciate that the sensing of horizontality by the inclinometers 8,9 is significant not only at the time of adjustment, but also during operation of the column if for example there is any possible disturbance to the apparatus such as by an impact or an earthquake. For this case the system may be programmed to signal a warning or alarm. In any event, the system is preferably programmed to record the alignment/orientation history of the column 1 and/or the piston 3 during set-up and/or during of the chromatography process.

[0058] According to normal practice, use of a PLC is preferred for direct control, being simple and highly reliable. The PC 11 is out of the direct line of control and used for adjustment, program modification, input and monitoring. The skilled person is aware of other available programmable control arrangements which may be used.

[0059] FIG. 2 illustrates an inclinometer on an EBA column which in this embodiment is of a kind described in our recently-filed EP16161264.3 and equivalents in other countries, claiming the priority of GB1504695.6, the entire contents of which are incorporated herein by reference. However many of the features relevant for the present purpose are common to other EBA columns. The column comprises a column tube 100, e.g. of acrylic, mounted vertically between top and bottom clamping rings 102,103 which seal respectively to a top cover 300 and a base plate 200. A set of circumferentially-spaced tie rods 101 clamps these components together axially. The base 200 is mounted fixedly on a stand 140 comprising four rigid legs 141 each with a roller foot 143 at its bottom end. Each roller 143 is connected to the respective leg 141 by an adjustable screw thread mechanism 144 which is adjustable manually for levelling the column.

[0060] FIG. 2 also shows an inlet structure 202 at the base 200 and an outlet structure 309 in the top cover 300. These are not particularly relevant to the operation of the inclinometer, and so are not discussed further. The top cover 300 has a central conical portion 301 and a peripheral flange 302. A 2-axis inclinometer 108 is mounted on a top surface 303 of the peripheral flange which is very accurately perpendicular to the top cover axis. The whole top surface 303 may be accurately perpendicular, or, if preferred, a portion thereof may be machined for this purpose. As an alternative, a perpendicular platform for the inclinometer may be provided (e.g. machined integrally with the top cover 300 or welded thereto) closer to the centre.

[0061] As known, EBA columns generally have an open top or top piston rather than a fixed top, in which case the top

[0062] The inclinometer 108 has a signal output line 181 shown schematically, and communicating to a display 112, conveniently mounted to one of the tie rods 101 of the column tube. The display may alternatively be mounted to the top ring 102 or cover 300 of the column, to be nearer (standing) eye level, or to the stand 140 to be nearer eye level for a person adjusting the stand. The inclinometer 108 is also connected to a programmable logic controller 110 and as in the first embodiment this can conveniently be mounted on an associated skid 114 indicated schematically, and carrying a display 1122, PC 111 and DCS connection 113. Further connections to external devices may be provided if wished.

[0063] Vertical orientation of the column tube is of great importance in expanded bed adsorption to ensure uniform flow through the expanded particle bed. By provision of the inclinometer 108, this verticality can be assured when setting up the column, and monitored during operation of the column. In this embodiment the adjustment of the support structure 140 is manual, but can be assisted by the logic controller 110 on the skid 114. The display 112 may simply indicate the detected inclinations in the x and y directions of the column. These readily indicate to the user whether the column is level or not. The controller may be programmed with a control or levelling algorithm to indicate to a user which feet 143 need to be adjusted to level the column while maintaining stability: this is notoriously difficult when done by trial and error. Incidentally, it may be noted that the conical top of the column in this special example, advantageous for separate reasons, would make the conventional use of a spirit level difficult.

[0064] While the invention has been illustrated and described in detail in the drawings and foregoing description, the same is to be considered as illustrative and not restrictive in character, it being understood that only the preferred embodiment has been shown and described and that all changes, equivalents, and modifications that come within the spirit of the inventions defined by following claims are desired to be protected. All publications, patents, and patent applications cited in this specification are herein incorporated by reference as if each individual publication, patent, or patent application were specifically and individually indicated to be incorporated by reference and set forth in its entirety herein.