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WO2000000259A1 - Chromatographic column - Google Patents

Chromatographic column Download PDF

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Publication number
WO2000000259A1
WO2000000259A1 PCT/GB1999/001284 GB9901284W WO0000259A1 WO 2000000259 A1 WO2000000259 A1 WO 2000000259A1 GB 9901284 W GB9901284 W GB 9901284W WO 0000259 A1 WO0000259 A1 WO 0000259A1
Authority
WO
WIPO (PCT)
Prior art keywords
housing
chromatography column
adjustable
rod
cell assembly
Prior art date
Application number
PCT/GB1999/001284
Other languages
French (fr)
Inventor
Neil Francis Frazer
Original Assignee
Millipore Corporation
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Application filed by Millipore Corporation filed Critical Millipore Corporation
Priority to JP2000556843A priority Critical patent/JP2002519167A/en
Priority to EP99919371A priority patent/EP1098687A1/en
Publication of WO2000000259A1 publication Critical patent/WO2000000259A1/en

Links

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
    • G01N30/60—Construction of the column
    • G01N30/6004—Construction of the column end pieces
    • G01N30/6021—Adjustable pistons
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01D—SEPARATION
    • B01D15/00—Separating processes involving the treatment of liquids with solid sorbents; Apparatus therefor
    • B01D15/08—Selective adsorption, e.g. chromatography
    • B01D15/10—Selective adsorption, e.g. chromatography characterised by constructional or operational features
    • B01D15/22—Selective adsorption, e.g. chromatography characterised by constructional or operational features relating to the 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
    • G01N30/50—Conditioning of the sorbent material or stationary liquid
    • G01N30/52—Physical parameters
    • G01N2030/522—Physical parameters pressure
    • 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
    • G01N30/6047—Construction of the column with supporting means; Holders

Definitions

  • the present invention relates to a chromatography column.
  • liquid chromatography may briefly be described as the fractionation of components of a mixture based on differences in the physical or chemical characteristics of the components.
  • the various liquid chromatographic systems fractionate the components with a fractionation matrix.
  • Some liquid chromatographic matrix systems fractionate the components of a mixture based upon such physical parameters as molecular weight.
  • Still other liquid chromatographic systems will fractionate the components of a mixture based upon such chemical criteria as ionic charge, hydrophobicity, and the presence of certain chemical moieties such as antigenic determinants or lectin-binding sites on the components.
  • Chromatography systems of various sized are used in both laboratory analysis operations and for industrial scale production operations in which separation steps such as separating out a fraction from human blood or separating out impurities from a pharmaceutical can be carried out on a large scale in a batch process.
  • FIG. 1 A typical known construction of chromatography column is shown in Figure 1 in which a column tube 2 for holding a chromatography medium is defined laterally by a cylindrical housing 4, a fixed cell assembly 6 fixed at one end of the cylindrical housing 4 (in this case the lower end of the housing 4) and an adjustable cell assembly 8 towards the other end of the housing 4 (in this case the upper end of the housing 4) .
  • Upper and lower valve assembly 10 and 12 provide access to the column tube 2 from outside the column tube 2.
  • the adjustable cell assembly 6 is relatively movable within, and sealable to, the cylindrical housing 4. It is held in place beneath a support plate 14 by a number of threaded rods 16, which plate 14 is in turn, supported by a flange 18 on the housing 4 by a number of rods 20 between the plate 14 and flange 18. Each rod 18 is fixed to the support plate 14 but passes through a respective through- hole in the flange 18 and fixed relative to it by a pair of bolts 22,24 mounted on each rod above and below the flange 18.
  • Adjustments of the position of the adjustable cell assembly 6 within the housing 4 is a very time consuming process. If the adjustable cell assembly 8 is to be moved upwards, the nut 22 of one rod must be loosened, by a quarter turn say, and the nut 24 moved upwards by that amount. This is repeated until all the nut positions on the rods 20 have been adjusted by the same small amount. The sequence is then repeated, possibly many times, until the adjustable cell assembly 8 is in the desired new position.
  • the lower nut 24 on rod is loosened by a quarter turn and upper nut 22 tightened downwards to force the adjustable cell assembly downwards.
  • the sequence is repeated until the adjustable cell assembly 6 exerts the required pressure on the chromatography medium.
  • the present invention which is as claimed in the claims, provides a chromatography column which is more readily adjustable than such prior art chromatography columns .
  • Figure 1 is a side sectional view of a prior art chromatography column
  • Figure 2 is a side sectional view of a chromatography column according to the present invention.
  • Figure 3 is a detailed side sectional view of a part of the chromatography column of Figure 2 ;
  • Figure 4 is an end view of Figure 3 viewed in the direction IV of Figure 3.
  • a chromatography column 40 includes a column tube 42 partially defined by a cylindrical housing 44 with an outwardly extending flange 46 at its lower end to which is bolted, in sealing relationship, a fixed cell assembly 48.
  • the upper end of the column tube 42 is defined by an adjustable cell assembly 50 mounted for movement relative to the housing 44.
  • the housing 44 is, in this case, mounted on a pair of I-beams 52 by bolts 54 joining the I-beams to an annular collar 56 fixed to surrounding the housing 44.
  • valve assemblies 60 and 58 Access to the interior of the column tube is provided by upper and lower valve assemblies 60 and 58.
  • the specific arrangements of these valve assemblies and associated controls are not part of the present invention. They may be any suitable system for the processes to be carried out by the chromatography column 40 and so will not be described in any further detail .
  • the housing 44 has at its upper extremity an outwardly extending annular flange 60.
  • the adjustable cell assembly 50 is secured to an annular plate 62.
  • the flange 60 and plate 62 have a series of three, circumferentially spaced apart aligned bores, such as 64, for receiving a respective threaded support rod 66 (one of which is fully shown in Figures 2 and 3) .
  • Each rod 64 is rotatable but fixed longitudinally with respect to the plate 62 by a flange mounted bearing 68 and a keyed spur gear 70.
  • a handwheel 72 is fixed to the upper end of one rod 66 so the rod 66 can be rotated manually.
  • Each rod 66 is located in a bore 64 of the flange 60 by a retaining housing 74 secured to the flange 60 by a clamp nut 76.
  • a ball nut assembly 78 is located on each rod 66 above the retaining housing 74 and secured to the housing 44 as shown in Figure 2.
  • An annular ring gear 80 is mounted for rotation on the base plate 62 within a two-part annular mounting 82 comprising a lower ring with an L-shaped cross-section 84 and an annular top-plate 86.
  • the ring 84 and top-plate 86 are secured together to hold the ring gear 80 in place, and to the base plate 62, by a number of bolts 88.
  • the ring gear 80 engages each of the spur gars 70 keyed to respective rods 66 which rods 66 are therefore all constrained to rotate together and so be simultaneously adjusted on manual rotation of the handwheel 72.
  • a non-rotatable locking cog (not shown) is movable into and onto of engagement with one of the spur gears 70 locks one rod 66 against rotation, and so all of the rods 66, when the adjustable cell assembly 50 has been moved to the desired position within the housing 44.
  • the rods 66 may be sufficiently long to allow the adjustable cell assembly 50 to be fully retracted from within the portion of the housing 44 used to define the column tube 42 to allow full access to the interior of the housing 44 by an operator.
  • the diameter of the handwheel 72 is chosen to allow manual application of the maximum pressure to be applied to compress the chromatography column medium to the required degree .
  • the support assembly of the embodiment of Figures 2 to 4 provides a compact and efficient means of providing simultaneous adjustment of the adjustable supports (rods 66) mounting the adjustable cell assembly 50 to the housing 44 but other designs of support assemblies may be employed to put the present invention into effect.
  • the drive means for adjusting the adjustable supports may be an electric motor, for example, which would allow a degree of automation to the adjustment of the position of the adjustable cell assembly 50.

Landscapes

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

Abstract

A chromatography column (40) in which an adjustable cell assembly (50) is movable within a housing (44) by a support assembly including three ball-threaded rods (66) interlinking the adjustable cell assembly (50) and housing (44). Each rod (66) is rotatable but longitudinally fixed in a base plate (64) fixed to the adjustable cell assembly (50). A ball nut (78) is mounted on each rod (66) and fixed to a flange (60) fixed to the housing (44). Fixed to each rod (64) is a spur gear (70), all the gears (70) being interconnected by a ring gear (80). A handwheel fixed to one rod (66) allows manual adjustment of all the rods (66) simultaneously to provide rapid adjustment of the position of the adjustable cell assembly (50) relative to the housing (44).

Description

CHROMATOGRAPHY COLUMN
The present invention relates to a chromatography column.
Frequently it is desirable to separate out one or more useful components from a fluid mixture that contains other components which may not be useful or are less valuable. To accomplish this it is often necessary or desirable to fractionate such a fluid mixture to separate out the useful or desired components. This can be carried out by using liquid chromatography systems. Liquid chromatography may briefly be described as the fractionation of components of a mixture based on differences in the physical or chemical characteristics of the components. The various liquid chromatographic systems fractionate the components with a fractionation matrix. Some liquid chromatographic matrix systems fractionate the components of a mixture based upon such physical parameters as molecular weight. Still other liquid chromatographic systems will fractionate the components of a mixture based upon such chemical criteria as ionic charge, hydrophobicity, and the presence of certain chemical moieties such as antigenic determinants or lectin-binding sites on the components.
Chromatography systems of various sized are used in both laboratory analysis operations and for industrial scale production operations in which separation steps such as separating out a fraction from human blood or separating out impurities from a pharmaceutical can be carried out on a large scale in a batch process.
A typical known construction of chromatography column is shown in Figure 1 in which a column tube 2 for holding a chromatography medium is defined laterally by a cylindrical housing 4, a fixed cell assembly 6 fixed at one end of the cylindrical housing 4 (in this case the lower end of the housing 4) and an adjustable cell assembly 8 towards the other end of the housing 4 (in this case the upper end of the housing 4) . Upper and lower valve assembly 10 and 12 provide access to the column tube 2 from outside the column tube 2.
The adjustable cell assembly 6 is relatively movable within, and sealable to, the cylindrical housing 4. It is held in place beneath a support plate 14 by a number of threaded rods 16, which plate 14 is in turn, supported by a flange 18 on the housing 4 by a number of rods 20 between the plate 14 and flange 18. Each rod 18 is fixed to the support plate 14 but passes through a respective through- hole in the flange 18 and fixed relative to it by a pair of bolts 22,24 mounted on each rod above and below the flange 18.
Adjustments of the position of the adjustable cell assembly 6 within the housing 4 is a very time consuming process. If the adjustable cell assembly 8 is to be moved upwards, the nut 22 of one rod must be loosened, by a quarter turn say, and the nut 24 moved upwards by that amount. This is repeated until all the nut positions on the rods 20 have been adjusted by the same small amount. The sequence is then repeated, possibly many times, until the adjustable cell assembly 8 is in the desired new position.
Similarly if the adjustable cell assembly is to be forced downwards, to compact a chromatography medium in the column tube for example, the lower nut 24 on rod is loosened by a quarter turn and upper nut 22 tightened downwards to force the adjustable cell assembly downwards. When all the nuts 22, 24 on the rods 20 have been so adjusted the sequence is repeated until the adjustable cell assembly 6 exerts the required pressure on the chromatography medium.
The adjustment of the position of such adjustable cell assemblies is very time consuming, especially with large industrial columns, and the resultant down-time results is lost productivity as the column is idle while it is being adjusted.
The present invention, which is as claimed in the claims, provides a chromatography column which is more readily adjustable than such prior art chromatography columns .
An embodiment of the present invention will now be described, by way of example only, with reference to the accompanying drawings, of which:
Figure 1 is a side sectional view of a prior art chromatography column;
Figure 2 is a side sectional view of a chromatography column according to the present invention;
Figure 3 is a detailed side sectional view of a part of the chromatography column of Figure 2 ; and
Figure 4 is an end view of Figure 3 viewed in the direction IV of Figure 3.
Referring to Figure 2, a chromatography column 40 includes a column tube 42 partially defined by a cylindrical housing 44 with an outwardly extending flange 46 at its lower end to which is bolted, in sealing relationship, a fixed cell assembly 48. The upper end of the column tube 42 is defined by an adjustable cell assembly 50 mounted for movement relative to the housing 44.
The housing 44 is, in this case, mounted on a pair of I-beams 52 by bolts 54 joining the I-beams to an annular collar 56 fixed to surrounding the housing 44.
Access to the interior of the column tube is provided by upper and lower valve assemblies 60 and 58. The specific arrangements of these valve assemblies and associated controls are not part of the present invention. They may be any suitable system for the processes to be carried out by the chromatography column 40 and so will not be described in any further detail .
Referring now also to Figures 3 and 4, the housing 44 has at its upper extremity an outwardly extending annular flange 60. The adjustable cell assembly 50 is secured to an annular plate 62. The flange 60 and plate 62 have a series of three, circumferentially spaced apart aligned bores, such as 64, for receiving a respective threaded support rod 66 (one of which is fully shown in Figures 2 and 3) .
Each rod 64 is rotatable but fixed longitudinally with respect to the plate 62 by a flange mounted bearing 68 and a keyed spur gear 70. A handwheel 72 is fixed to the upper end of one rod 66 so the rod 66 can be rotated manually.
Each rod 66 is located in a bore 64 of the flange 60 by a retaining housing 74 secured to the flange 60 by a clamp nut 76. A ball nut assembly 78 is located on each rod 66 above the retaining housing 74 and secured to the housing 44 as shown in Figure 2.
An annular ring gear 80 is mounted for rotation on the base plate 62 within a two-part annular mounting 82 comprising a lower ring with an L-shaped cross-section 84 and an annular top-plate 86.
The ring 84 and top-plate 86 are secured together to hold the ring gear 80 in place, and to the base plate 62, by a number of bolts 88. The ring gear 80 engages each of the spur gars 70 keyed to respective rods 66 which rods 66 are therefore all constrained to rotate together and so be simultaneously adjusted on manual rotation of the handwheel 72. A non-rotatable locking cog (not shown) is movable into and onto of engagement with one of the spur gears 70 locks one rod 66 against rotation, and so all of the rods 66, when the adjustable cell assembly 50 has been moved to the desired position within the housing 44.
The rods 66 may be sufficiently long to allow the adjustable cell assembly 50 to be fully retracted from within the portion of the housing 44 used to define the column tube 42 to allow full access to the interior of the housing 44 by an operator.
The diameter of the handwheel 72 is chosen to allow manual application of the maximum pressure to be applied to compress the chromatography column medium to the required degree .
The support assembly of the embodiment of Figures 2 to 4 provides a compact and efficient means of providing simultaneous adjustment of the adjustable supports (rods 66) mounting the adjustable cell assembly 50 to the housing 44 but other designs of support assemblies may be employed to put the present invention into effect. The drive means for adjusting the adjustable supports may be an electric motor, for example, which would allow a degree of automation to the adjustment of the position of the adjustable cell assembly 50.

Claims

CLAIMS :
1. A chromatography column including a column tube for holding a chromatography medium defined in part by a housing and an adjustable cell assembly movable relative to and within the housing, the adjustable cell assembly being mounted on the housing and movable relative to it by a support assembly which includes a plurality of adjustable supports, the adjustable supports being interconnected such that they are adjustable simultaneously and a drive means for effecting the simultaneous adjustment of the adjustable supports .
2. A chromatography column as claimed in claim 1 in which each adjustable support comprises a ball screw assembly which includes a rotatable, ball-threaded rod which is longitudinally fixed to a support on which the adjustable cell assembly is mounted and a ball nut mounted on the rod and secured to the housing.
3. A chromatography column as claimed in claim 2 in which each rod has fixed to it a gear wheel, the gear wheels of all the rods being interconnected by a ring gear.
4. A chromatography column as claimed in claim 3 in which the gear wheels are disposed at the outside of the ring gear.
5. A chromatography column as claimed in any one of claims 2 to 4 including a handwheel fixed to a rod.
6. A chromatography column as claimed in any preceding claim including a brake for releasably holding the support assembly against adjustment by the drive means.
7. A chromatography column as claimed in claim 7 as dependent on any claim 3 in which the brake is a non- rotatable gear wheel movable into and out of engagement with a gear wheel of one of the rods .
8. A chromatography column having a support assembly substantially as hereinbefore described, or as shown in, Figures 2 to 4 of the accompanying drawings .
PCT/GB1999/001284 1998-06-30 1999-04-26 Chromatographic column WO2000000259A1 (en)

Priority Applications (2)

Application Number Priority Date Filing Date Title
JP2000556843A JP2002519167A (en) 1998-06-30 1999-04-26 Chromatographic column
EP99919371A EP1098687A1 (en) 1998-06-30 1999-04-26 Chromatographic column

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
GB9814195.5 1998-06-30
GBGB9814195.5A GB9814195D0 (en) 1998-06-30 1998-06-30 Chromatography column

Publications (1)

Publication Number Publication Date
WO2000000259A1 true WO2000000259A1 (en) 2000-01-06

Family

ID=10834719

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/GB1999/001284 WO2000000259A1 (en) 1998-06-30 1999-04-26 Chromatographic column

Country Status (4)

Country Link
EP (1) EP1098687A1 (en)
JP (1) JP2002519167A (en)
GB (1) GB9814195D0 (en)
WO (1) WO2000000259A1 (en)

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2005056156A1 (en) * 2003-12-10 2005-06-23 Pall Euroflow Limited Chromatography columns and their operation
GB2419830A (en) * 2004-11-02 2006-05-10 Amersham Biosciences Ab Chromatography column
WO2024191548A1 (en) * 2023-03-16 2024-09-19 Amgen Inc. Pressure relief valve support system and method for a chromatography column
EP4308263A4 (en) * 2021-03-16 2024-09-25 Bio Rad Laboratories Inc Dynamic axial compression for preparative columns using external compression

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0008921A1 (en) * 1978-09-08 1980-03-19 Wright Scientific Limited Column chromatography and like processes and apparatus for the practice thereof
US4797209A (en) * 1986-07-02 1989-01-10 Amicon Wright Ltd. Adjustable distribution cell apparatus
US5213683A (en) * 1991-08-08 1993-05-25 Chromaflow, Inc. Apparatus for charging and discharging of chromatography column bed
US5324426A (en) * 1992-03-20 1994-06-28 Kontes Glass Corp. Chromatography column

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0008921A1 (en) * 1978-09-08 1980-03-19 Wright Scientific Limited Column chromatography and like processes and apparatus for the practice thereof
US4797209A (en) * 1986-07-02 1989-01-10 Amicon Wright Ltd. Adjustable distribution cell apparatus
US5213683A (en) * 1991-08-08 1993-05-25 Chromaflow, Inc. Apparatus for charging and discharging of chromatography column bed
US5324426A (en) * 1992-03-20 1994-06-28 Kontes Glass Corp. Chromatography column

Cited By (11)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2005056156A1 (en) * 2003-12-10 2005-06-23 Pall Euroflow Limited Chromatography columns and their operation
US7604747B2 (en) 2003-12-10 2009-10-20 Pall Euroflow Limited Chromatography columns and their operation
US8715499B2 (en) 2003-12-10 2014-05-06 Pall Corporation Chromatography columns and their operation
GB2419830A (en) * 2004-11-02 2006-05-10 Amersham Biosciences Ab Chromatography column
US7452464B2 (en) 2004-11-02 2008-11-18 Ge Healthcare Bio-Sciences Ab Chromatography column
GB2419830B (en) * 2004-11-02 2009-11-04 Amersham Biosciences Ab Chromatography column with rotatable sections
US8778188B2 (en) 2004-11-02 2014-07-15 Ge Healthcare Bio-Sciences Ab Chromatography column
US9302202B2 (en) 2004-11-02 2016-04-05 Ge Healthcare Bio-Sciences Ab Chromatography column
US10391422B2 (en) 2004-11-02 2019-08-27 Ge Healthcare Bio-Sciences Ab Chromatography column
EP4308263A4 (en) * 2021-03-16 2024-09-25 Bio Rad Laboratories Inc Dynamic axial compression for preparative columns using external compression
WO2024191548A1 (en) * 2023-03-16 2024-09-19 Amgen Inc. Pressure relief valve support system and method for a chromatography column

Also Published As

Publication number Publication date
GB9814195D0 (en) 1998-08-26
JP2002519167A (en) 2002-07-02
EP1098687A1 (en) 2001-05-16

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