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GB2456050A - Analysis of a chromatographic stationary phase in situ by determining capacitance - Google Patents

Analysis of a chromatographic stationary phase in situ by determining capacitance Download PDF

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Publication number
GB2456050A
GB2456050A GB0724148A GB0724148A GB2456050A GB 2456050 A GB2456050 A GB 2456050A GB 0724148 A GB0724148 A GB 0724148A GB 0724148 A GB0724148 A GB 0724148A GB 2456050 A GB2456050 A GB 2456050A
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United Kingdom
Prior art keywords
chromatography column
electrodes
chromatographic apparatus
permittivity
chromatographic
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
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Application number
GB0724148A
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GB0724148D0 (en
Inventor
Michael Anthony Conboy
Christopher Mark Conboy
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MACONTROLS Ltd
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MACONTROLS Ltd
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Publication date
Application filed by MACONTROLS Ltd filed Critical MACONTROLS Ltd
Priority to GB0724148A priority Critical patent/GB2456050A/en
Publication of GB0724148D0 publication Critical patent/GB0724148D0/en
Publication of GB2456050A publication Critical patent/GB2456050A/en
Withdrawn legal-status Critical Current

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Classifications

    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
    • G01N30/02—Column chromatography
    • G01N30/50—Conditioning of the sorbent material or stationary liquid
    • G01N30/56—Packing methods or coating methods
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N27/00—Investigating or analysing materials by the use of electric, electrochemical, or magnetic means
    • G01N27/02—Investigating or analysing materials by the use of electric, electrochemical, or magnetic means by investigating impedance
    • G01N27/22—Investigating or analysing materials by the use of electric, electrochemical, or magnetic means by investigating impedance by investigating capacitance
    • G01N27/226—Construction of measuring vessels; Electrodes therefor
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
    • G01N30/02—Column chromatography
    • G01N30/60—Construction of the column
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
    • G01N30/02—Column chromatography
    • G01N30/62—Detectors specially adapted therefor
    • G01N30/64—Electrical detectors
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
    • G01N30/02—Column chromatography
    • G01N30/50—Conditioning of the sorbent material or stationary liquid
    • G01N30/56—Packing methods or coating methods
    • G01N2030/562—Packing methods or coating methods packing
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
    • G01N30/02—Column chromatography
    • G01N30/50—Conditioning of the sorbent material or stationary liquid
    • G01N30/56—Packing methods or coating methods
    • G01N2030/562—Packing methods or coating methods packing
    • G01N2030/565—Packing methods or coating methods packing slurry packing
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
    • G01N30/02—Column chromatography
    • G01N30/60—Construction of the column
    • G01N30/6004—Construction of the column end pieces
    • G01N2030/6013—Construction of the column end pieces interfaces to detectors

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  • Chemical & Material Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Analytical Chemistry (AREA)
  • Biochemistry (AREA)
  • Physics & Mathematics (AREA)
  • General Physics & Mathematics (AREA)
  • Immunology (AREA)
  • Pathology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Electrochemistry (AREA)
  • Treatment Of Liquids With Adsorbents In General (AREA)

Abstract

Chromatographic apparatus is disclosed, which comprises a chromatography column (10) adapted to contain a chromatographic bed (14). The chromatography column (10) includes a fluid inlet (42) and a fluid outlet (22), and the apparatus includes a pair of electrodes (128,148, 262, 264, 310, 362, 462, 464) that are electrically insulated from each other. The apparatus is arranged such that at least part of the interior of the chromatography column (10) is disposed between the electrodes and that the electrodes are adapted to be connected to a circuit (50) for measuring the capacitance of the electrodes.

Description

I
Title -Improvements relating to Column Chromatography This invention relates to a column chromatography, and in particular to sensing the state of material within a chromatography column.
Chromatography is a separation method in which different components of a mixture migrate through a chromatographic bed at different rates. In particular, chromatography uses a mobile phase to move a mixture of substances through a stationary phase of a chromatographic bed. The different components of the mixture have different affinities for the mobile and stationary phases, and emerge from the chromatographic bed at different times. In particular, chromatographic systems may fractionate the components of a mixture based upon physical criteria, such as molecular weight, or chemical criteria, such as ionic charge, hydrophobicity, and the presence of certain chemical moieties such as antigenic determinants or lectin-binding sites on the components.
Column chromatography is a type of chromatography in which the stationary bed is situated within a vertically-orientated tube. Chromatography columns of various sizes are used in both laboratory analysis operations, and also for industrial scale production operations to purify liquids and separate substances of interest from process liquids.
Chromatography columns typically comprise a column wall in the form of a vertically-orientated hollow tube, which is connected to an upper end unit and a lower end unit. The upper end unit is provided with a fluid inlet, typically comprisIng an inlet conduit and an inlet valve, and the lower end unIt is provided with a fluid outlet, typically comprising an outlet conduit and an outlet valve. The Internal diameters of chromatography columns for laboratory analysis are usually 1-7 mm. By contrast, the internal diameters of production scale chromatography columns can range from a few centimeters up to two meters.
At the large sizes of production scale columns, it can be difficult to ensure uniform packing of the chromatographic bed. A homogeneous packed bed is critical for maximum efficiency, high product yield, and purity. Irregularities in packing may cause uneven flow within the bed, which may result in fraction broadening, fraction mixing, changes in flow rate, and subsequent loss of product yield and quality. Furthermore, monitoring of the chromatographic process within the chromatographic bed is typically achieved using visual indicators, which may be unreliable and/or inaccurate, or else only the output of the chromatographic process is monitored.
There has now been devised improved chromatography apparatus and an improved method of sensing the state of material within a chromatography column which overcome or substantially mitigate the above-mentioned and/or
other disadvantages associated with the prior art.
According to a first aspect of the Invention, there Is provided chromatographic apparatus comprising a chromatography column adapted to contain a chromatographic bed, the chromatography column induding a fluid Inlet and a fluid outlet, wherein the apparatus includes a pair of electrodes that are electrically insulated from each other, at least part of the Interior of the chromatography column being disposed between the electrodes, and the electrodes being adapted to be connected to a circuit for measuring the capacitance of the electrodes.
According to a further aspect of the invention, there is provided a method of sensing the state of material within a chromatography column, which method comprises the following steps: (a) providing chromatographic apparatus as described above; (b) providing a circuit for measuring the capacitance of the electrodes; and (c) measuring the capacitance of the electrodes.
The chromatographic apparatus and method according to the invention are advantageous principally because the capacitance measurement of measurement circuit enables the permittivity of the part of the interior of the chromatography column that is disposed between the electrodes to be determined. Since this perrniUivity will be dependent upon the state of the material contained within the chromatography column, the apparatus according to the invention may enable the state of that material to be determined. The present Invention therefore offers an accurate and unobtrusive method of sensing the state of material within a chromatography column.
The chromatography column will typically comprise components including a hollow tube, which Is generally orientated with Its longitudinal axis substantially vertical. The chromatography column will typically comprise a lower end unit and an upper end unit, wherein the space bounded by these components is adapted to contain the chromatographic bed. Furthermore, the upper end unit will generally Include the fluid inlet and also a fluid distribution cell for distributing fluid into an upper part of the chromatography column, and the lower end unit will generally include the fluid outlet and also a fluid distribution cell for collecting the distributed fluid from within a lower part of the chromatography column.
The material within the chromatography column, ie the chromatographic bed and any added substances, will typically be a complex mixture of different substances. in particular, the added substances will typically be a fluid, and will typically be a mobile phase of a chromatographic process including a mixture of substances to be separated.
In presently preferred embodiments, at least one electrode, and preferably both of the electrodes, Is disposed externally of the chromatographic bed.
Furthermore, In order to ensure insulation of each electrode from any surrounding conductors, at least one electrode, and preferably both of the electrodes, may indude a coating of electrically-insulating material, such as a plastics material or a metal oxide. The electrodes are preferably substantially planar, but may also be curved along one or more axes.
The electrodes may be arranged at the upper and lower ends of the chromatography column, and hence may conveniently be incorporated into the upper and lower end units. Alternatively, where the hollow tube of the chromatography column is formed of an electrically-conductive material, this hollow tube may be adapted to define one of the electrodes. The other electrode may then be incorporated into one of the end units.
Where an electrode is incorporated into an end unit, the electrode may be mounted to an exterior surface of the end unit, or alternatively mounted within the end unit. The electrode may therefore include one or more apertures through which one or more fluid conduits extend. In these arrangements, the remainder of the end units, save for electrical connections to the electrodes, are preferably formed of an electrically-insulating material.
A particularly convenient arrangement of the invention comprises a chromatography column including an electrically-conductive fitter for the fluid inlet and/or the fluid outlet, wherein the filter includes an electrically-insulating coating and is adapted to define an electrode of the chromatographic apparatus. in particular, the filter preferably extends across substantially the entire cross-section of the chromatography tube, and forms part of a fluid distribution cell as discussed in more detail below.
The measurement circuit may be supplied as part of the chromatographic apparatus. In particular, the measurement circuit may be housed within a component of the chromatography column, such as within one of the end units, or the measurement circuit may be provided within a separate housing. Where the measurement circuit is provided within a separate housing to the components of the chromatography column, the measurement circuit is preferably either permanently or removably connected to the electrodes by appropriate electrical connections, such as wired connections.
Alternatively, the measurement circuit may be supplied separately from the remainder of the chromatographic apparatus. In this case, the chromatographic apparatus is preferably adapted to be removably connected to the measurement circuit, Indeed, in the simplest aspect of this invention, the measurement circuit may be a conventional capacitance meter.
Where the wired connections between the measurement circuit and the electrodes are removable connections, each electrode is preferably connected to an electrical connector, such as an electrical socket, that is adapted to be engaged by a corresponding electrical connector, such as an electrical plug, of a wired connection to the measurement circuit. In this arrangement, the electrical connectors of the electrodes are preferably mounted to an exterior surface of a component of the chromatography column.
The measurement circuit is adapted to measure the capacitance of the electrodes, and hence enable determination of the permittivity of the material contained within the part of the interior of the chromatography column that is disposed between the electrodes. In presently preferred embodiments, the entire interior of the chromatography column that is suitable for containing the chromatographic bed is disposed between the electrodes, such that the capacitance measurement of the measurement circuit enables determination of the permittivity of the material within the chromatography column. In particular, the determined permittivity of the material within the chromatography column will be an average permittivity for the entire body of material that is disposed between the electrodes.
The capacitance measurement of the measurement circuit may be indicated directly to the user, for instance by means of an appropriate display. The user may then be able to utilise the capacitance measurements to determIne the permittivity of the material within the chromatography column, and hence obtain information concerning the state of that material. In particular, the chromatography apparatus may be supplied with information for the user, such as one or more tables, that enables determination of the permittivity of the material within the chromatography column on the basis of the capacitance measurement, and/or provides information of the state of the material within the chromatography column on the basis of the capacitance measurement. Alternatively, the measurement circuit itself may determine the permittivity of the material within the chromatography column. The determined permittivity may be indicated directly to the user, for instance by means of a display, or may form the basis of indications to the user regarding the state of the material within the chromatography column, such as volume, concentration, homogeneity, stage of separation process, etc. In order to determine an accurate value for the permittivity of the material within the chromatography column, the measurement circuit is preferably calibrated on the basis of a capacitance measurement when the chromatography column is charged with air only, or some other material of known permittivity.
The permittivity of a homogeneous material is usually given relative to that of vacuum, as a relative permittivity Er (also called the dielectric constant). In particular, where two electrodes in the form of simple conductive plates are Insulated from each other, a capacitance Is generated between them based on the interaction of their electromagnetic fields within the intervening dielectric medium. This is given by the formula: C = ErEO(A/l) (1) where C is capacitance In farads (F), A Is the area of the plates In meters squared (m2) and I Is the separation of the plates in meters (m). Er is the relative permlttivity of the Intervening dielectric medium (Fm1) and t Is the permittlvlty of a vacuum (Fm1), which Is a constant and equals 8.85x1 012 Fm. Hence, where the electrodes have the form of conductIve plates, the measurement cIrcuit may calculate the average relative permittivity of the material within the chromatography column using data from Its calibration and the theory outlined above. Where the conditions do not conform to this simple model, for example where the electrodes do not have the form of simple conductive plates, the measurement circuit is preferably adapted to take into account these conditions using appropriate theory and/or further calibration measurements.
In order to measure the capacitance of the electrodes, it will generally be necessary to incorporate the electrodes within an electrical circuit, such that one of the electrodes has a positive electrical charge, whilst the other electrode has a negative charge. Most preferably, a DC current is applied to the electrodes, such that the electric field generated by the electrodes Is a static electric field. In this case, the measurement circuit is preferably adapted to calculate the static relative permittivity, also known as the static dielectric constant, of the material within the chromatography column between the electrodes.
However, it is feasible that an AC current could be applied to the electrodes, in which case the measurement circuit is preferably adapted to determine the relative permittivity of the material within the chromatography column as a functIon of frequency. In particular, the measurement circuit may be adapted to measure the capacitance of the electrodes for a plurality of frequencies of the applied electric current. This technique may enable a more complex analysis of the material within the chromatography column.
Chromatography columns typically comprise a column wall in the form of a hollow tube, which is connected at one end to an upper end unit including an upper fluid distribution cell, and which is connected at the other end to a lower end unit IncludIng a lower fluId distribution cell. The upper end unit Is preferably provided with a fluid Inlet, typically comprising an Inlet conduit and an inlet valve, and the lower end unIt is preferably provided wIth a fluid outlet, typically comprising an outlet conduit and an outlet valve. The upper and lower end units may be substantially identical, such that either end can be used as the inlet end while the other end is used as the outlet end.
The chromatography column is preferably adapted to contain a chromatographic bed that includes a stationary phase of a chromatographic process. The stationary phase may comprise solid particles or a support coated with a liquid stationary phase. Furthermore, the stationary phase may occupy the entire cross-section of the tube (packed column), or may be concentrated on or along the interior surface of the tube wall, thereby defining an open, unrestricted path for the mobile phase in a central part of the tube (open tubular column).
The fluid inlet is preferably adapted to introduce the mobile phase of the chromatographic process, including a mixture of substances to be separated and a generally also a suitable solvent, such as a weak buffer, into an upper part of the chromatography column, and the fluid outlet is preferably adapted to remove the mobile phase from a lower part, and most preferably the base, of the chromatography column once it has travelled through the stationary phase.
Typically, the stationary phase comprises beads of a suitable substrate, such as silica (Sb2) or alumina (A1203), which is mixed with the solvent being used for the mobile phase to yield a viscous slurry. The solvent of the mobile phase is typically a liquid that Is chosen to maximise the separation of the mixture during the chromatographic process. This may be water or any organic solvent.
The fluid distribution cell of the upper end unit is preferably adapted to distribute the mobile phase substantially uniformly across the cross-section of the chromatography column, and hence the chromatographic bed. Typically, this fluid distribution cell comprises an inlet conduit Including an Inlet valve, and an inlet screen over which the mobile phase Is distributed before it permeates the screen and hence enters the Interior of the chromatography column. Similarly, the fluid distribution cell of the lower end unit is preferably adapted to collect the mobile phase substantially uniformly across the cross-section of the chromatography column, and hence the chromatographic bed. Typically, this fluid distribution cell comprises an outlet screen that supports the chromatographic bed, and allows the mobile phase to exit the chromatographic column through an outlet valve and an outlet conduit.
The inlet and outlet screens are preferably sufficiently porous in order to allow the mobile phase to move through them into, or out of, the chromatography column at a sufficient rate for the chromatographic process. Additionally, the outlet screen is preferably sufficiently rigid to support the weight of the chromatographic bed and any pressured applied to the system. In particular, the Inlet and outlet screens commonly have the form of a metal or plastics filter, for instance in the form of a woven mesh of plastics or metal fibres, a monolayer or multilayer sintered metal filter, or a perforated plate with a hole diameter less than the lower particle diameter of the stationary phase.
The end units typically hermetically seal the ends of the chromatography column, save for the fluid inlet and outlet. Hence, the end units preferably include one or more seals, which are typically 0-rings, wiper seals or Inflatable seals, for hermetically sealing the end units to the ends of the chromatography column.
The end units are typically fastened to end flanges of the chromatography column, or the end units are held in place by extemal longitudinal threaded tie bars with tensioning nuts.
The permittivity readings of the measurement circuit may be utilised by a user during preparation of the chromatography column, and/or during the chromatography process Itself, to sense and/or monitor the state of the material within the chromatography column. In particular, during preparation of the chromatography column, the permlttlvlty readings of the measurement circuit may be utilised to indicate the volume, uniformity and other parameters of the chromatographlc bed, which are critical to the chromatography process.
Furthermore, during the chromatography process itself, the permittlvity readings of the measurement circuit may be utlllsed to monitor the separation of materials within the mobile phase, ion exchange between the mobile and stationary phases, and any other changes In the state of the material within the chromatography column.
Presently preferred embodiments of the invention will now be described in greater detail, by way of illustration only, with reference to the accompanying drawings, in which Figure 1 is a schematic diagram of a first embodiment of chromatographic apparatus according to the invention, in which a pair of electrodes are defined by external metal plates of the apparatus; Figure 2 is a schematic diagram of a first embodiment of chromatographic apparatus according to the invention, in which a pair of electrodes are defined by metal filters of the apparatus; Figure 3 is a schematic diagram of a second embodiment of chromatographic apparatus according to the invention, In which a pair of electrodes are defined by embedded metal plates; Figure 4 is a schematic diagram of a third embodiment of chromatographic apparatus according to the invention, in which a first electrode is defined by an embedded metal plate and a second electrode is defined by a metal wall of a chromatography column; and Figure 5 is a schematic diagram of a fourth embodiment of chromatographic apparatus according to the invention, in which a pair of electrodes are mounted externally of a chromatography column.
FIgure 1 shows a first embodiment of chromatographlc apparatus according to the invention. The chromatographic apparatus comprises a chromatography column 10, a lower end unit 20, a support 30, an upper end unit 40 and a monitoring device 50.
The chromatography column 10 has the form of a hollow cylinder, and Is formed of transparent acrylic. The lower end unit 20 forms a base for the chromatography column 10, but also extends radially beyond the wall of the chromatography column 10. Two diametrically-opposed tie bars 32 extend upwardly from a peripheral potion of the lower end unit 20, externally of the chromatography column 10. These tie bars 32 pass through apertures in a flange 12 provided at the upper end of the chromatography column 10, and are fastened at their upper ends to the support 30.
The support 30 extends diametrically over the upper end of the chromatography column 10, and includes a central aperture through which a vertically-orientated threaded rod 34 extends. The threaded rod 34 is fixed at its lower end to an upper surface of the upper end unit 40, and a rotatable adjustment wheel 36 is mounted about the threaded rod 34, immediately above the support 30, in order to enable the upper end unit 40 to be raised and lowered during use.
The lower end unit 20 includes a sealing arrangement that hermetically seals the lower end unit 20 to the wall of the chromatography column 10. In addition, the upper end unit 40 includes a sealing arrangement that enables it to slidable along the longitudinal axis of the chromatography column 10, whilst being hermetically sealed to the interior surface of the chromatography column 10. The space bounded by the chromatography column 10, and the upper and lower end units 20,40, defines a container adapted to contain a chromatographic bed 14.
The upper end unit 40 Includes a fluid Inlet 42 with an Inlet valve. The fluid Inlet 42 is adapted for connection to a supply of a mobile phase for a chromatographic process, and the inlet valve enables a user to control flow of the mobile phase Into the chromatographic column 10 during use. Furthermore, the upper end unit is provided with a plurality of channels (not visible in Figure 1) and an Inlet screen (not visible in Figure 1) that are adapted to distribute the mobile phase substantially uniformly across the cross-section of the chromatography column 10, and hence the upper surface of the chromatographic bed 14. In particular, the plurality of channels and the inlet screen are adapted such that the mobile phase is distributed across the upper surface of the inlet screen before the mobile phase permeates the inlet screen and hence enters the Interior of the chromatography column 10.
The lower end unit 20 includes an outlet screen (not visible in Figure 1) that supports the chromatographic bed 14. The outlet screen also enables the mobile phase to move from the chromatographic bed 14 into the lower end unit 20, substantially uniformly across the cross-section of the chromatography column 10. Furthermore, the lower end unit 20 includes a plurality of channels (not visible In Figure 1), which lead to a fluid outlet 22 adapted for connection to apparatus for product collection and/or analysis.
The upper end unit 40 and the lower end unit 20 are both formed substantially from plastics material. However, the upper end unit 40 includes a metal backing plate 44 that is fixed to its upper surface by electrically-insulating fastenings, and the lower end unit 20 includes a metal backing plate 24 that Is fixed to its lower surface by electrically-insulating fastenings. These metal backing plates 2444 define an upper electrode 44 and a lower electrode 24. In particular, these metal backing plates 24,44 are electrically-insulated from any surrounding conductors, save for a connection to an electrical connector 26,46 mounted to each of the backing plates 24,44.
in this embodiment, the monitoring circuit 50 is housed separately from the remainder of the chromatography apparatus. A first wired connection 52 is provided that connects the monitoring circuIt 50 to the electrical connector 26 for the lower electrode 24, and a second wired connection 54 Is provided that connects the monitoring circuit 50 to the electrical connector 46 for the upper electrode 44. These wired connections 52,54 extend from the housing of the monitoring circuit 50, and each include an appropriate electrical plug for engagement with the corresponding electrical connector 26,46.
The monitoring circuit 50 Is a bridge circuit that measures the capacitance of the upper and lower electrodes 44,24. The monitoring circuit 50 includes a calibration function that measures the capacitance of the upper and lower electrodes 44,24 when the chromatography column is charged with a medium, such as air, of known perrnlttlvity. A calculation function of the monitoring circuit is able to determine the average permithvity of the material within the chromatography column, based upon the calibration measurement, and a display is provided that communicates the determined permittivity to the user.
In use, the permittivity readings of the monitoring circuit 50 may be utilised by a user during preparation of the chromatography column 10, and also during the chromatography process itself, to sense and/or monitor the state of the material within the chromatography column. In particular, during preparation of the chromatography column 10, the permittivity readings of the monitoring circuit 50 may be utilised to indicate the volume, uniformity and other parameters of the chromatographic bed 14, which are critical to the chromatography process.
During the chromatography process itself, the permittivity readings of the monitoring circuit 50 may be utilised to monitor the separation of materials within the mobile phase, ion exchange between the mobile and stationary phases, and any other changes in the state of the material within the chromatography column 10.
Figure 2 shows a second embodiment of chromatographic apparatus according to the invention. The apparatus of this embodiment is identical to the apparatus of the first embodiment, save for the form of the electrodes.
In this embodiment, the inlet screen 148 of the upper end unit 140 and the outlet screen 128 of the lower end unit 120 are both formed of metal, and respectively define the upper electrode 148 and the lower electrode 128. In particular, the inlet and outlet screens 148,128 are sintered metal filters, with a metal oxide coating, which are sufficiently porous to enable throughflow of the mobile phase of the chromatography process. The metal oxide coating is sufficient to electrically-Insulate the Inlet and outlet screens 148,128 from the mobile phase.
In addition, the inlet and outlet screens 148,128 are each mounted within the corresponding end unit 140,120 such that the screens 148,128 are electrically-insulated from any surrounding conductors, save for internal wired connections 147,127 to the corresponding electrical connector 126,146 mounted to the exterior of the corresponding end unit 140,120.
Figure 3 shows a third embodiment of chromatographic apparatus according to the invention. The apparatus of this embodiment is identical to the apparatus of the second embodiment, save for the form of the electrodes.
In this embodiment, an upper embedded plate 264 and a lower embedded plate 262 define the upper and lower electrodes 264,262. In particular, the upper embedded plate 264 is mounted within the upper end unit 240, such that the channels that extend to the inlet screen pass through the plate 264. Similarly, the lower embedded plate 262 is mounted within the lower end unit 220, such that the channels that extend from the outlet screen pass through the plate 262. The upper and lower embedded plates 264,262 are each formed of metal, but are coated with an insulating material, such as plastics material. Internal wired connections 247,227 connect the upper and lower electrodes 264,262 to the corresponding electrical connector 226,246 mounted to the exterior of the corresponding end unit 240,220.
Figure 4 shows a fourth embodiment of chromatographic apparatus according to the Invention. The apparatus of this embodiment Is Identical to the apparatus of the third embodiment, save for the form of the chromatography column and the one of the electrodes.
In this embodiment, the chromatography column 310 is formed of a hollow metal cylInder, and defines the upper electrode 310. The fourth embodiment therefore includes a lower embedded plate 362 in an identical arrangement to that of the third embodiment, which defines the lower electrode 362, but there is no upper embedded plate. Instead, the chromatography column 310 itself defines the upper electrode 210. An electrical connector 346 is therefore provided on the exterior surface of the chromatography column 310, thereby enabling connection of the upper electrode 310 to the monitoring device.
Finally, Figure 5 shows a fifth embodiment of chromatographic apparatus according to the invention. The apparatus of this embodiment is identical to the apparatus of the fourth embodiment, save for the form of the electrodes.
In this embodiment, the electrodes 462,464 take the form of shaped sheets of metal that are mounted to the cylindrical exterior surface of the chromatography column 410. In particular, each electrode 462,464 extends across approximately 25% of the circumference of the chromatography column 410 and substantially the entire height of the chromatography column 410. In addition, the electrodes 462,464 are arranged such that they are diametrically opposed, and the electrodes 462,464 are electrically-Insulated from all surrounding conductors, save for a connection to an electrical connector 426,446. In particular, the electrodes 462,464 are coated with a layer of Insulating material.
Although the electrodes In the second, third, fourth and fifth embodIments have a different form to those of the first embodiment, and hence the calibration of the monitoring circuit 50 will be different, these embodiments may otherwise be used in an identical manner to the first embodiment.

Claims (44)

  1. Claims 1. Chromatographic apparatus comprising a chromatography column adapted to contain a chromatographic bed, the chromatography column including a fluid inlet and a fluid outlet, wherein the apparatus includes a pair of electrodes that are electrically insulated from each other, at least part of the interior of the chromatography column being disposed between the electrodes, and the electrodes being adapted to be connected to a circuit for measuring the capacitance of the electrodes.
  2. 2. Chromatographic apparatus as claimed in Claim 1, wherein at least one electrode is disposed externally of the chromatographic bed.
    00
  3. 3. Chromatographic apparatus as claimed in Claim I or Claim 2, wherein at least one electrode includes a coating of electrically-insulating material.
  4. 4. Chromatographic apparatus as claimed in any preceding claim, wherein the electrodes are arranged at the upper and lower ends of the chromatography column.
  5. 5. Chromatographic apparatus as claimed in Claim 4, wherein the electrodes are incorporated into upper and lower end units of the chromatography column.
  6. 6. Chromatographic apparatus as claimed in any one of Claims I to 3, wherein a hollow tube of the chromatography column is formed of an electrically-conductive material, and is adapted to define one of the electrodes.
  7. 7. Chromatographic apparatus as claimed in Claim 6, wherein the other electrode is incorporated into an end unit of the chromatography column.
  8. 8. Chromatographic apparatus as claimed in any preceding claim, wherein an electrode is incorporated into an end unit of the chromatography column, and the remainder of the end unit, save for electrical connections to the electrodes, is formed of an electrically-insulating material.
  9. 9. Chromatographic apparatus as claimed in any preceding claim, wherein the apparatus comprises a chromatography column including an electrically-conductive filter for the fluid inlet and/or the fluid outlet, the filter including an electrically-insulating coating and being adapted to define an electrode of the chromatographic apparatus.
  10. 10. Chromatographic apparatus as claimed in Claim 9, wherein the filter extends across substantially the entire cross-section of the chromatography column.
    CO
  11. 11. Chromatographic apparatus as claimed in any preceding claim, wherein the apparatus includes a measurement circuit adapted to measure the capacitance of C,'J the electrodes, and enable determination of the permittivity of the material contained within the part of the interior of the chromatography column that is disposed between the electrodes.
  12. 12. Chromatographic apparatus as claimed in any preceding claim, wherein the entire intetior of the chromatography column that is suitable for containing the chromatographic bed is disposed between the electrodes, such that the capacitance measurement of the measurement circuit enables determination of the permittivity of the material within the chromatography column.
  13. 13. Chromatographic apparatus as claimed in Claim 12, wherein the determined permittivity of the material within the chromatography column is an average permittivity for the entire body of material that is disposed between the electrodes.
  14. 14. Chromatographic apparatus as claimed in any preceding claim, wherein the capacitance measurement of the measurement circuit is indicated directly to the user.
  15. 15. Chromatographic apparatus as claimed in any one of Claims Ito 13, wherein the measurement circuit itself determines the permittivity of the material within the chromatography column.
  16. 16. Chromatographic apparatus as claimed in Claim 15, wherein the determined permittivity is indicated directly to the user.
  17. 17. Chromatographic apparatus as claimed in Claim 15, wherein the determined permittivity forms the basis of indications to the user regarding the state of the material within the chromatography column.
  18. 18. Chromatographic apparatus as claimed in any preceding claim, wherein the CO measurement circuit is calibrated on the basis of a capacitance measurement when the chromatography column is charged with air only, or some other material of known permittivity.
  19. 19. Chromatographic apparatus as claimed in any preceding claim, wherein a DC current is applied to the electrodes, such that the electric field generated by
    the electrodes is a static electric field.
  20. 20. Chromatographic apparatus as claimed in Claim 19, wherein the measurement circuit is adapted to calculate the static relative permittivity of the material within the chromatography column between the electrodes.
  21. 21. Chromatographic apparatus as claimed in any one of Claims I to 18, wherein an AC current is applied to the electrodes.
  22. 22. Chromatographic apparatus as claimed in Claim 21, wherein the measurement circuit is adapted to determine the relative permittivity of the material within the chromatography column as a function of frequency.
  23. 23. Chromatographic apparatus as claimed in Claim 22, wherein the measurement circuit is adapted to measure the capacitance of the electrodes for a plurality of frequencies of the applied electric current.
  24. 24. A method of sensing the state of material within a chromatography column, which method comprises the following steps: (a) providing chrornatographic apparatus as claimed in any preceding claim; (b) providing a circuit for measuring the capacitance of the electrodes; and (c) measuring the capacitance of the electrodes.
  25. 25. A method as claimed in Claim 24, wherein the capacitance measurement of the measurement circuit is indicated directly to the user.
    CO
  26. 26. A method as claimed in Claim 24, wherein the measurement circuit itself determines the permittivity of the material within the chromatography column. c\J
  27. 27. A method as claimed in Claim 26, wherein the determined permittivity is indicated directly to the user.
  28. 28. A method as claimed in Claim 26, wherein the determined permittivity forms the basis of indications to the user regarding the state of the material within the chromatography column.
  29. 29. A method as claimed in any preceding claim, wherein a DC current is applied to the electrodes, such that the electric field generated by the electrodes is
    a static electric field.
  30. 30. A method as claimed in Claim 29, wherein the method comprises the step of calculating the static relative permittivity of the material within the chromatography column between the electrodes.
  31. 31. A method as claimed in any one of Claims 24 to 28, wherein an AC current is applied to the electrodes.
  32. 32. A method as claimed in Claim 31, wherein the method comprises the step of calculating the relative permittivity of the material within the chromatography column as a function of frequency.
  33. 33. A method as claimed in Claim 32, wherein the method comprises the step of measuring the capacitance of the electrodes for a plurality of frequencies of the applied electric current.
  34. 34. A method as claimed in any one of Claims 24 to 33, wherein the capacitance/permittivity readings of the measurement circuit are utilised by a user during preparation of the chromatography column, and/or during the chromatography process itself, to sense and/or monitor the state of the material CO within the chromatography column.
    C'J
  35. 35. A method as claimed in Claim 34, wherein, during preparation of the chromatography column, the capacitance/permittivity readings of the measurement circuit are utilised to indicate the volume, uniformity and/or other parameters of the chromatographic bed.
  36. 36. A method as claimed in Claim 34 or Claim 35, wherein, during the chromatography process itself, the capacitance/permittivity readings of the measurement circuit are utilised to monitor the separation of materials within the mobile phase, ion exchange between the mobile and stationary phases, and/or any other changes in the state of the material within the chromatography column.
  37. 37. Chromatographic apparatus as hereinbefore described and as illustrated in Figures 1 and 2.
  38. 38. Chromatographic apparatus as hereinbefore described and as illustrated in Figure 3.
  39. 39. Chromatographic apparatus as hereinbefore described and as illustrated in Figure 4.
  40. 40. Chromatographic apparatus as hereinbefore described and as illustrated in Figure 5.
  41. 41. A method of sensing the state of material within a chromatography column as hereinbefore described and as illustrated in Figures 1 and 2.
  42. 42. A method of sensing the state of material within a chromatography column as hereinbefore described and as illustrated in Figure 3.
  43. 43. A method of sensing the state of material within a chromatography column 00 as hereinbefore described and as illustrated in Figure 4.
    C\I
  44. 44. A method of sensing the state of material within a chromatography column as hereinbefore described and as illustrated in Figure 5.
GB0724148A 2007-12-11 2007-12-11 Analysis of a chromatographic stationary phase in situ by determining capacitance Withdrawn GB2456050A (en)

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Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3694335A (en) * 1965-10-06 1972-09-26 Victor Pretorius Chromatographic separation
WO1989007265A1 (en) * 1988-02-03 1989-08-10 Wollongong Uniadvice Limited Chromatography using electrically conductive polymer stationary phase materials
WO1996027793A1 (en) * 1995-03-03 1996-09-12 Alltech Associates, Inc. Apparatus/method for electrochemically modifying chromatographic material
US5611904A (en) * 1995-11-09 1997-03-18 The United States Of America As Represented By The Secretary Of Commerce Electrochromatography apparatus
US20050092606A1 (en) * 2003-11-05 2005-05-05 Yeda Research And Development Co. Ltd. Method and device for monitoring and controlling fluid locomotion

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3694335A (en) * 1965-10-06 1972-09-26 Victor Pretorius Chromatographic separation
WO1989007265A1 (en) * 1988-02-03 1989-08-10 Wollongong Uniadvice Limited Chromatography using electrically conductive polymer stationary phase materials
WO1996027793A1 (en) * 1995-03-03 1996-09-12 Alltech Associates, Inc. Apparatus/method for electrochemically modifying chromatographic material
US5611904A (en) * 1995-11-09 1997-03-18 The United States Of America As Represented By The Secretary Of Commerce Electrochromatography apparatus
US20050092606A1 (en) * 2003-11-05 2005-05-05 Yeda Research And Development Co. Ltd. Method and device for monitoring and controlling fluid locomotion

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