WO2000010676A1 - Module and method for introducing a sample into a chromatography column - Google Patents

Module and method for introducing a sample into a chromatography column Download PDF

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Publication number
WO2000010676A1
WO2000010676A1 PCT/US1999/016010 US9916010W WO0010676A1 WO 2000010676 A1 WO2000010676 A1 WO 2000010676A1 US 9916010 W US9916010 W US 9916010W WO 0010676 A1 WO0010676 A1 WO 0010676A1
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WO
WIPO (PCT)
Prior art keywords
sample
module
chromatography
media
flow
Prior art date
Application number
PCT/US1999/016010
Other languages
French (fr)
Inventor
Ivan Hargro
Jeffrey A. Horsman
Peter C. Rahn
Peter C. Vandavelaar
Original Assignee
Dyax 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
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Application filed by Dyax Corporation filed Critical Dyax Corporation
Priority to DE69939479T priority Critical patent/DE69939479D1/en
Priority to JP2000565989A priority patent/JP4328898B2/en
Priority to AU49973/99A priority patent/AU4997399A/en
Priority to EP99934054A priority patent/EP1113849B1/en
Publication of WO2000010676A1 publication Critical patent/WO2000010676A1/en

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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
    • G01N30/60—Construction of the column
    • G01N30/6004—Construction of the column end pieces
    • G01N30/6026—Fluid seals
    • 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
    • B01D15/14—Selective adsorption, e.g. chromatography characterised by constructional or operational features relating to the introduction of the feed to the apparatus
    • 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
    • G01N30/60—Construction of the column
    • G01N30/6004—Construction of the column end pieces
    • G01N30/6017—Fluid distributors
    • 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
    • G01N30/6091—Cartridges
    • 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
    • G01N30/04—Preparation or injection of sample to be analysed
    • G01N30/06—Preparation
    • G01N30/08—Preparation using an enricher
    • G01N2030/085—Preparation using an enricher using absorbing precolumn
    • 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
    • G01N30/04—Preparation or injection of sample to be analysed
    • G01N30/16—Injection
    • G01N2030/167—Injection on-column injection
    • 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
    • G01N30/6004—Construction of the column end pieces
    • G01N30/6021—Adjustable pistons
    • 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
    • G01N30/6052—Construction of the column body
    • G01N30/6069—Construction of the column body with compartments or bed substructure

Definitions

  • the invention relates to introducing a sample into a chromatography column.
  • Liquid chromatography is a technique for separating the individual compounds that exist in a subject sample.
  • the subject sample is carried in a liquid, called a mobile phase.
  • the mobile phase carrying the subject sample is caused to migrate through a media, called a stationary phase.
  • Different compounds will have differing rates of migration through the media, which effects the separation of the components in the subject sample.
  • Liquid chromatography is commonly performed with reusable columns or with disposable cartridges, both of which are usually cylindrical, in which the media bed is bounded axially by porous plates, or plates containing defined flow paths, through which the mobile phase will flow. (See U.S. Pat. No. 4,250,035 to McDonald et al . and U.S. Pat. No. 5,601,708 to Leavesley)
  • chemists When chemists optimize liquid chromatographic separations conditions, they may need to dissolve the sample mixture in a dissolution solvent which may be nonideal for elution. This can result in poor separation and poor recovery of desired components.
  • One solution to this problem is to pre-absorb the sample onto a media prior to chromatography. This involves dissolving the sample mixture in a suitable solvent and adding an amount of a dry media (usually similar to the media being used for the separation) to this solution. The dissolution solvent is then evaporated off, usually using a rotary evaporator, leaving the sample mixture dry, and absorbed to the media. The pre-absorbed media is then placed at the head of a pre-packed glass, metal or plastic chromatography column, and the optimized chromatographic solvent would flow through the pre-absorbed media and then through the column of separation media. This method has the potential hazard of the operator coming into contact with the dry powdery media both before and after the addition of the sample. This method also can lead to poor separations and recovery. Summary of the Invention
  • the invention features, in general, a chromatography sample module including a flow-through member having an inlet and an outlet and chromatography media within the flow-through member. A sample is added to the media, and the module, with the sample carried therein, can then be connected to a separation column.
  • the chromatography sample module is a tubular member that is sized to fit within the end of a chromatography column that is used for separation of the sample contained on the media in the module.
  • the module can be connected to the chromatography separation column by a flow line.
  • the sample in the dissolution solvent can be added to the sample module, and then the dissolution solvent can be evaporated.
  • the sample in the dissolution solvent can be added to the sample module as a liquid without evaporation.
  • the invention features a rack of sample modules arranged in an array.
  • Embodiments of the invention may include one or more of the following advantages.
  • the samples can be easily introduced into separation columns.
  • Various solvents can be used for separation and dissolution of the sample, permitting optimization of the separation procedure.
  • Samples are easily preprocessed, and the operator is not exposed to the media before or after adding the sample.
  • a large number of samples can be prepared for processing at one time, facilitating the carrying out of multiple separations at one time.
  • Fig. 2 is a vertical sectional view of a chromatography sample module used in the Fig. 1 system.
  • Fig. 3 is a plan view of a rack containing a plurality of the Fig. 2 sample modules in an array.
  • Fig. 4 is an elevation of the Fig. 3 rack and modules .
  • Fig. 5 is a vertical sectional view showing the Fig. 2 sample module in position between a sealing head and a chromatography column used in the Fig. 1 system prior to assembly.
  • Fig. 6 is a vertical sectional view showing the Fig. 5 components in an assembled and sealed state.
  • chromatography system 10 which includes a source of solvent 12, pump 14, sample module 16, liquid chromatography column 18, and sample collection vessel 20.
  • the sample to be analyzed is preabsorbed onto media in sample module 16 prior to pumping solvent into module 16 and into chromatography column 18 to perform the separation procedure .
  • sample module 16 includes cylindrical plastic tube 22, porous plates 24, 26 (made of inert plastic porous frits), and chromatography media 28 (only partially shown in the figures) between porous plates 24, 26.
  • sample module 16 is designed to fit within chromatography column 18 at the entrance thereof and to be sealably connected to the sealing head.
  • Tube 22 is designed to fit within column 18 with minimal space between the two; in particular, there is 0.000" to 0.010" of radial clearance.
  • Sample module 16 can be filled with media that is the same as or is different from the media of chromatography column 18.
  • the sample is dissolved in the required solvent and added to the top of sample module 16, where it is drawn into the media by capillary action. This dissolution solvent is then removed by placing sample module 16 in a vacuum chamber. Heat may also be applied.
  • sample module 16 After sample module 16 has dried, it can be placed directly inside separation column 18 so that the lower porous plate 26 is an in intimate contact with the surface of the separation media or with a porous plate within the separation column on top of the separation media .
  • sample module 16 can be placed in a remote tube connected by a solvent line.
  • the sample can be dissolved in a separation solvent (or a weaker solvent), and added to module 16.
  • the wet module can then be loaded into the column or into a remote tube .
  • Examples of the types of complex samples where this technique has particularly advantageous use include synthetic organic reaction mixtures and natural product extracts, (e.g., from fermentation broths or plants). These samples often need to be dissolved in a solvent not compatible with the optimized separation solvent. Solvents are organized according to their "solvent strength, " where hexanes have a value close to zero, and methanol has a value of 0.95. Optimized separation eluents often have a lower solvent strength; e.g., hexane :ethylacetate 1:1 has a solvent strength of 0.295.
  • the sample needs to be dissolved in a strong solvent such as methanol, there will be a solvent strength difference of 0.655 seen initially after loading the sample onto the column, and this will impair the separation of the sample. If the sample dissolved in methanol is instead preadsorbed to the media in the sample module and dried, the sample will not face this impairment during separation.
  • a strong solvent such as methanol
  • sample modules 16 can be supplied in racks 32, and a whole rack of sample modules 16 can be efficiently prepared at one time rather than one at a time.
  • Figs. 5 and 6 show the placement of a module 16 in a column 18 and the sealing of the module 16 and column 18 to a sealing head used to deliver solvent.
  • Sealing head 110 has first head piece 112, second head piece 124, intermediate head piece 128, and first and second annular elastomeric sealing members 134, 136.
  • First head piece 112 has body 114 with longitudinal axis 116. First head piece 112 has outwardly extending shoulder 118, and contact face 120. Part of contact face 120 has a slightly conical shape or other concavity. First head piece 112 defines flow path 122 along axis 116.
  • Body 114 of first head piece 112- fits slidably through central openings in second head piece 124, intermediate head piece 128, and first and second elastomeric sealing members 134, 136.
  • Second head piece 124 has outwardly extending compression member 146.
  • Intermediate head piece 128 has narrow portion 148 distal from second head piece 124.
  • First elastomeric sealing member 134 is adjacent to both shoulder 118 and narrow portion 148 of intermediate head piece 128.
  • Second elastomeric sealing member 136 is adjacent to both intermediate head piece 128 and second head piece 124.
  • the outer diameter of tube 22 of sample module 16 is sized so that tube 22 fits into column 18.
  • the inner diameter of tube 22 is sized so that it may slidably receive shoulder 118, first elastomeric sealing member 134, and narrow portion 148 of intermediate head piece 128.
  • Intermediate head piece 128, second elastomeric sealing member 136, and second head piece 124 are sized to fit slidably into column 18, having chamfered edges 140, filled with chromatography separation media 142, which is bounded axially by porous plates 144.
  • seals are formed with the apparatus by inserting sample module 16 into column 18 so that second porous plate 26 abuts first porous plate 144.
  • sealing head 110 is then inserted into column 18 and tube 22 of sample module 16, so that shoulder 118, first elastomeric sealing member 134, and narrow portion 148 are within tube 22, and contact face 120 abuts porous plate 24. Sealing head 110 extends far enough into column 18 so that second elastomeric sealing member 136 opposes the inner surface of column 18.
  • Downward compressive force applied to outwardly extending compression member 146 causes second head piece 124 to slide relative to first head piece 112 and transmits compressive force to second elastomeric sealing member 136, intermediate head piece 128, first elastomeric sealing member 134, shoulder 118, porous plate 24, sample module media 28, porous plate 26, porous plate 144, and separation media bed 142.
  • the compressive force causes first and second elastomeric sealing members 134, 136 to expand radially so that first elastomeric sealing member 134 forms a seal with tube 22, and second elastomeric sealing member 136 forms a seal with column 18.
  • tube 22 and column 18 are made of high-density polyethylene.
  • the columns may be constructed of other materials, including glass or stainless steel.
  • elastomeric sealing members are made of a fluorocarbon polymer, such as that sold under the trade name CHEMRAZ.

Abstract

A chromatography sample module (16) including a flow-through member having an inlet and an outlet, chromatography media (28) within the flow-through member, and a sample carried on the media (28). The module (16) can fit within a chromatography column (18), and a plurality of modules (16) can be arranged in an array in a rack to facilitate processing of multiple samples.

Description

MODULE AND METHOD FOR INTRODUCING A SAMPLE INTO A CHROMATOGRAPHY COLUMN Background of the Invention
The invention relates to introducing a sample into a chromatography column.
Liquid chromatography is a technique for separating the individual compounds that exist in a subject sample. In employing the technique, the subject sample is carried in a liquid, called a mobile phase. The mobile phase carrying the subject sample is caused to migrate through a media, called a stationary phase. Different compounds will have differing rates of migration through the media, which effects the separation of the components in the subject sample. Liquid chromatography is commonly performed with reusable columns or with disposable cartridges, both of which are usually cylindrical, in which the media bed is bounded axially by porous plates, or plates containing defined flow paths, through which the mobile phase will flow. (See U.S. Pat. No. 4,250,035 to McDonald et al . and U.S. Pat. No. 5,601,708 to Leavesley)
When chemists optimize liquid chromatographic separations conditions, they may need to dissolve the sample mixture in a dissolution solvent which may be nonideal for elution. This can result in poor separation and poor recovery of desired components.
One solution to this problem is to pre-absorb the sample onto a media prior to chromatography. This involves dissolving the sample mixture in a suitable solvent and adding an amount of a dry media (usually similar to the media being used for the separation) to this solution. The dissolution solvent is then evaporated off, usually using a rotary evaporator, leaving the sample mixture dry, and absorbed to the media. The pre-absorbed media is then placed at the head of a pre-packed glass, metal or plastic chromatography column, and the optimized chromatographic solvent would flow through the pre-absorbed media and then through the column of separation media. This method has the potential hazard of the operator coming into contact with the dry powdery media both before and after the addition of the sample. This method also can lead to poor separations and recovery. Summary of the Invention
In one aspect, the invention features, in general, a chromatography sample module including a flow-through member having an inlet and an outlet and chromatography media within the flow-through member. A sample is added to the media, and the module, with the sample carried therein, can then be connected to a separation column.
Preferably the chromatography sample module is a tubular member that is sized to fit within the end of a chromatography column that is used for separation of the sample contained on the media in the module.
Alternatively, the module can be connected to the chromatography separation column by a flow line. The sample in the dissolution solvent can be added to the sample module, and then the dissolution solvent can be evaporated. Alternatively, the sample in the dissolution solvent can be added to the sample module as a liquid without evaporation.
In another aspect the invention features a rack of sample modules arranged in an array. Embodiments of the invention may include one or more of the following advantages. The samples can be easily introduced into separation columns. Various solvents can be used for separation and dissolution of the sample, permitting optimization of the separation procedure. Samples are easily preprocessed, and the operator is not exposed to the media before or after adding the sample. A large number of samples can be prepared for processing at one time, facilitating the carrying out of multiple separations at one time. Other features and advantages of the invention will be apparent from the following description of the preferred embodiments thereof and from the claims. Brief Description of the Drawings Fig. 1 is a schematic diagram of a chromatography system according to the invention.
Fig. 2 is a vertical sectional view of a chromatography sample module used in the Fig. 1 system.
Fig. 3 is a plan view of a rack containing a plurality of the Fig. 2 sample modules in an array. Fig. 4 is an elevation of the Fig. 3 rack and modules .
Fig. 5 is a vertical sectional view showing the Fig. 2 sample module in position between a sealing head and a chromatography column used in the Fig. 1 system prior to assembly.
Fig. 6 is a vertical sectional view showing the Fig. 5 components in an assembled and sealed state. Description of the Preferred Embodiments Referring to Fig. 1, there is shown chromatography system 10 which includes a source of solvent 12, pump 14, sample module 16, liquid chromatography column 18, and sample collection vessel 20. In this system, the sample to be analyzed is preabsorbed onto media in sample module 16 prior to pumping solvent into module 16 and into chromatography column 18 to perform the separation procedure .
Referring to Fig. 2, it is seen that sample module 16 includes cylindrical plastic tube 22, porous plates 24, 26 (made of inert plastic porous frits), and chromatography media 28 (only partially shown in the figures) between porous plates 24, 26.
As appears from Figs. 5 and 6, sample module 16 is designed to fit within chromatography column 18 at the entrance thereof and to be sealably connected to the sealing head. Tube 22 is designed to fit within column 18 with minimal space between the two; in particular, there is 0.000" to 0.010" of radial clearance.
Sample module 16 can be filled with media that is the same as or is different from the media of chromatography column 18. The sample is dissolved in the required solvent and added to the top of sample module 16, where it is drawn into the media by capillary action. This dissolution solvent is then removed by placing sample module 16 in a vacuum chamber. Heat may also be applied.
After sample module 16 has dried, it can be placed directly inside separation column 18 so that the lower porous plate 26 is an in intimate contact with the surface of the separation media or with a porous plate within the separation column on top of the separation media .
Alternatively, sample module 16 can be placed in a remote tube connected by a solvent line. Alternatively, the sample can be dissolved in a separation solvent (or a weaker solvent), and added to module 16. The wet module can then be loaded into the column or into a remote tube .
Examples of the types of complex samples where this technique has particularly advantageous use include synthetic organic reaction mixtures and natural product extracts, (e.g., from fermentation broths or plants). These samples often need to be dissolved in a solvent not compatible with the optimized separation solvent. Solvents are organized according to their "solvent strength, " where hexanes have a value close to zero, and methanol has a value of 0.95. Optimized separation eluents often have a lower solvent strength; e.g., hexane :ethylacetate 1:1 has a solvent strength of 0.295. If the sample needs to be dissolved in a strong solvent such as methanol, there will be a solvent strength difference of 0.655 seen initially after loading the sample onto the column, and this will impair the separation of the sample. If the sample dissolved in methanol is instead preadsorbed to the media in the sample module and dried, the sample will not face this impairment during separation.
Referring to Figs. 3 and 4, sample modules 16 can be supplied in racks 32, and a whole rack of sample modules 16 can be efficiently prepared at one time rather than one at a time.
Figs. 5 and 6 show the placement of a module 16 in a column 18 and the sealing of the module 16 and column 18 to a sealing head used to deliver solvent. Sealing head 110 has first head piece 112, second head piece 124, intermediate head piece 128, and first and second annular elastomeric sealing members 134, 136.
First head piece 112 has body 114 with longitudinal axis 116. First head piece 112 has outwardly extending shoulder 118, and contact face 120. Part of contact face 120 has a slightly conical shape or other concavity. First head piece 112 defines flow path 122 along axis 116.
Body 114 of first head piece 112- fits slidably through central openings in second head piece 124, intermediate head piece 128, and first and second elastomeric sealing members 134, 136.
Second head piece 124 has outwardly extending compression member 146. Intermediate head piece 128 has narrow portion 148 distal from second head piece 124. First elastomeric sealing member 134 is adjacent to both shoulder 118 and narrow portion 148 of intermediate head piece 128. Second elastomeric sealing member 136 is adjacent to both intermediate head piece 128 and second head piece 124.
The outer diameter of tube 22 of sample module 16 is sized so that tube 22 fits into column 18. The inner diameter of tube 22 is sized so that it may slidably receive shoulder 118, first elastomeric sealing member 134, and narrow portion 148 of intermediate head piece 128.
Intermediate head piece 128, second elastomeric sealing member 136, and second head piece 124 are sized to fit slidably into column 18, having chamfered edges 140, filled with chromatography separation media 142, which is bounded axially by porous plates 144.
Referring to Fig. 6 seals are formed with the apparatus by inserting sample module 16 into column 18 so that second porous plate 26 abuts first porous plate 144. Referring to Fig. 5, sealing head 110 is then inserted into column 18 and tube 22 of sample module 16, so that shoulder 118, first elastomeric sealing member 134, and narrow portion 148 are within tube 22, and contact face 120 abuts porous plate 24. Sealing head 110 extends far enough into column 18 so that second elastomeric sealing member 136 opposes the inner surface of column 18.
Downward compressive force applied to outwardly extending compression member 146 causes second head piece 124 to slide relative to first head piece 112 and transmits compressive force to second elastomeric sealing member 136, intermediate head piece 128, first elastomeric sealing member 134, shoulder 118, porous plate 24, sample module media 28, porous plate 26, porous plate 144, and separation media bed 142. The compressive force causes first and second elastomeric sealing members 134, 136 to expand radially so that first elastomeric sealing member 134 forms a seal with tube 22, and second elastomeric sealing member 136 forms a seal with column 18. The seals are released by relaxing or removing the downward force to second head piece 124, thereby reducing the compressive force on the components of sealing head 110 and reducing the radial expansion of elastomeric sealing members 134, 136. Preferably, tube 22 and column 18 are made of high-density polyethylene. However, the columns may be constructed of other materials, including glass or stainless steel. Preferably, elastomeric sealing members are made of a fluorocarbon polymer, such as that sold under the trade name CHEMRAZ.
Other embodiments of the invention are within the scope of the following claims. What is claimed is:

Claims

1. A chromatography sample module comprising a flow-through member having an inlet and an outlet, chromatography media within said flow-through member, and a sample carried on said media.
2. A chromatography sample module comprising a tubular member that is sized to fit within the end of a chromatography column, said module having an inlet and an outlet, and chromatography media within said tubular member .
3. The module of claim 2 further comprising a sample carried on said media.
4. The combination comprising a chromatography column having a module receiving region at an inlet end thereof, and a chromatography sample module located within said module receiving region, said module including a flow- through member having an inlet and an outlet, and chromatography media within said flow-through member.
5. The module of claim 4 further comprising a sample carried on said media.
6. The module of claim 1, 3 or 5 wherein said sample has been absorbed onto said media.
7. The module of claim 1, 3, or 5 wherein said sample is dissolved in a solvent that is held within said module on said media.
8. A chromatography method comprising providing a chromatography sample module including a flow-through member having an inlet, an outlet, and chromatography media within said flow-through member, dissolving a sample in a solvent resulting in a dissolved sample, adding said dissolved sample to said media, and flowing solvent into said inlet and directing the effluent from said outlet to a chromatography column.
9. The method of claim 8 further comprising evaporating said solvent from said module after said adding and prior to said flowing.
10. The method of claim 8 or 9 further comprising placing said module in said chromatography column prior to said flowing.
11. The method of claim 8 or 9 further comprising placing said module in said chromatography column prior to said flowing, and providing a seal between said module and said chromatography column prior to said flowing.
12. The method of claim 8 wherein said providing includes providing a plurality of sample modules in an array in a support structure, each said module including a flow-through member having an inlet, an outlet, and chromatography media within said flow-through member, and wherein said adding includes adding dissolved samples to said media in said plurality of sample modules
13. Chromatography sample preparation apparatus comprising a plurality of chromatography sample modules, each said module including a flow-through member having an inlet, an outlet, and chromatography media within said flow-through member, and a support structure supporting said plurality of modules.
14. The apparatus of claim 13 wherein said sample modules are adjacent to each other in said support structure .
15. The apparatus of claim 13, wherein said samples are in an array in said support structure .
PCT/US1999/016010 1998-08-20 1999-07-14 Module and method for introducing a sample into a chromatography column WO2000010676A1 (en)

Priority Applications (4)

Application Number Priority Date Filing Date Title
DE69939479T DE69939479D1 (en) 1998-08-20 1999-07-14 MODULE AND METHOD FOR INTRODUCING A SAMPLE INTO A CHROMATOGRAPHIC COLONNE
JP2000565989A JP4328898B2 (en) 1998-08-20 1999-07-14 Module and method for introducing a sample into a chromatography column
AU49973/99A AU4997399A (en) 1998-08-20 1999-07-14 Module and method for introducing a sample into a chromatography column
EP99934054A EP1113849B1 (en) 1998-08-20 1999-07-14 Module and method for introducing a sample into a chromatography column

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US09/137,278 1998-08-20
US09/137,278 US6139733A (en) 1998-08-20 1998-08-20 Module and method for introducing a sample into a chromatography column

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WO2000010676A1 true WO2000010676A1 (en) 2000-03-02

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EP (1) EP1113849B1 (en)
JP (1) JP4328898B2 (en)
AT (1) ATE406947T1 (en)
AU (1) AU4997399A (en)
DE (1) DE69939479D1 (en)
ES (1) ES2313788T3 (en)
WO (1) WO2000010676A1 (en)

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2004047948A1 (en) * 2002-11-26 2004-06-10 Prime Separations, Incorporated Chromatographic separation processes and apparatus
EP1517732A1 (en) * 2002-05-01 2005-03-30 Biotage, Inc. Processing of chemicals in flow-through device with porous media

Families Citing this family (40)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6436284B1 (en) * 1997-11-12 2002-08-20 Biotage, Inc. Chromatography apparatus
US20030217973A1 (en) * 1998-08-20 2003-11-27 Horsman Jeffrey A. Method for introducing a sample into a chromatography column
US6679989B2 (en) * 2001-06-01 2004-01-20 Agilent Technologies, Inc. Integral, thru-bore, direct coupled high pressure liquid chromatography guard column
US20020187557A1 (en) * 2001-06-07 2002-12-12 Hobbs Steven E. Systems and methods for introducing samples into microfluidic devices
US6880576B2 (en) 2001-06-07 2005-04-19 Nanostream, Inc. Microfluidic devices for methods development
AU2003213071A1 (en) * 2002-02-13 2003-09-04 Nanostream, Inc. Microfluidic separation column devices and fabrication methods
US7261812B1 (en) 2002-02-13 2007-08-28 Nanostream, Inc. Multi-column separation devices and methods
US6649051B1 (en) 2002-05-01 2003-11-18 Biotage, Inc. Processing of chemicals in flow-through device with porous media
KR100505361B1 (en) * 2002-06-03 2005-08-03 정원조 Stainless Steel Tubing/Frit With Sintered Inorganic Particles And A Chromathography Column Manufactured By Using The Same
AU2003249231A1 (en) * 2002-07-15 2004-02-02 Phynexus, Inc. Low dead volume extraction column devices
US20040142488A1 (en) * 2002-07-15 2004-07-22 Gierde Douglas T. Method and device for extracting an analyte
US6783673B2 (en) * 2002-08-23 2004-08-31 Biotage, Inc. Composite chromatography column
DE10393207B4 (en) 2002-09-10 2022-04-07 Waters Technologies Corp. (N.D.Ges.D. Staates Delaware) Chromatography column, method for its manufacture and method for performing a chromatographic separation
US6936167B2 (en) * 2002-10-31 2005-08-30 Nanostream, Inc. System and method for performing multiple parallel chromatographic separations
AU2003301025A1 (en) * 2002-12-17 2004-07-22 Biotage, Inc. Processing of chemicals in flow-through device porous media
WO2004071615A2 (en) * 2003-02-07 2004-08-26 Waters Investments Limited Polymeric solid supports for chromatography nanocolumns
GB2413508B (en) * 2003-02-10 2007-02-21 Waters Investments Ltd Siloxane-Immobilized particulate stationary phases for chromatographic separations and extractions
US7943393B2 (en) * 2003-07-14 2011-05-17 Phynexus, Inc. Method and device for extracting an analyte
WO2005007264A2 (en) * 2003-07-14 2005-01-27 Waters Investments Limited Separation device with integral guard column
US20050011835A1 (en) * 2003-07-17 2005-01-20 Sigma-Aldrich Co. High throughput flash purification stand and cartridge
US20050011821A1 (en) * 2003-07-17 2005-01-20 Sigma-Aldrich Co. High throughput flash purification stand and cartridge
US7028536B2 (en) * 2004-06-29 2006-04-18 Nanostream, Inc. Sealing interface for microfluidic device
US20050032238A1 (en) * 2003-08-07 2005-02-10 Nanostream, Inc. Vented microfluidic separation devices and methods
US7351332B2 (en) * 2003-10-17 2008-04-01 Varian, Inc. Chromatography cartridge and method for manufacturing a chromatography cartridge
US7404893B2 (en) * 2003-10-17 2008-07-29 Varian, Inc. Chromatography cartridge and method for manufacturing a chromatography cartridge
WO2005087339A1 (en) * 2004-03-04 2005-09-22 Sigma-Aldrich Co. A high throughput flash purification stand and cartridge
US7686959B2 (en) 2004-05-05 2010-03-30 Biotage Ab Control system and method for flash separation
US20050247625A1 (en) * 2004-05-05 2005-11-10 Jianbo Liu Determining conditions for chromatography
US7138061B2 (en) * 2004-05-10 2006-11-21 Scientific Plastic Products, Inc. Flash chromatography cartridge
WO2006023524A1 (en) * 2004-08-19 2006-03-02 Waters Investments Limited Device, method and apparatus for performing separations
US7348526B2 (en) * 2004-08-20 2008-03-25 Cem Corporation Microwave-assisted chromatography preparation
US7674383B2 (en) 2005-10-25 2010-03-09 Phenomenex, Inc. Method and apparatus for packing chromatography columns
US7670487B2 (en) * 2006-07-21 2010-03-02 Wikfors Edwin E De-pressurization scheme for chromatography columns
MX2009013107A (en) 2007-12-05 2010-01-18 Alltech Associates Inc Methods and apparatus for analyzing samples and collecting sample fractions.
CN102307665A (en) 2008-12-04 2012-01-04 全技术联合公司 Methods and apparatus for moving aliquot samples of fluid
CN102316950A (en) 2008-12-10 2012-01-11 全技术联合公司 Chromatography systems and system components
EP2204225A1 (en) * 2008-12-22 2010-07-07 SynChro GmbH Column reactor
US8305582B2 (en) 2009-09-01 2012-11-06 Alltech Associates, Inc. Methods and apparatus for analyzing samples and collecting sample fractions
WO2012074452A1 (en) * 2010-11-30 2012-06-07 Biotage Ab Chromatography column assembly comprising a sealing device
JP5879592B2 (en) * 2011-12-26 2016-03-08 東京理化器械株式会社 column

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4457846A (en) * 1982-07-08 1984-07-03 Milton Roy Company Liquid chromatography methods and devices
US4565632A (en) * 1985-01-11 1986-01-21 Beckman Instruments, Inc. Chromatographic cartridge column system

Family Cites Families (23)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE2008354A1 (en) * 1970-02-23 1971-09-09 Boehnnger Mannheim GmbH, 6800 Mann heim Combination column
US3266554A (en) * 1963-11-29 1966-08-16 Possis Machine Corp Apparatus for preparing specimens for chromatographic analysis
US3398512A (en) * 1966-04-18 1968-08-27 Continental Oil Co Chromatography apparatus
DE1801684B2 (en) * 1967-10-09 1971-12-23 Czeskoslovenska Akademie Ved., Prag DEVICE FOR CARRYING OUT A CHEMICAL REACTION OF A SUBSTANCE PRESENT IN THE FORM OF INDIVIDUAL CONCENTRATION ZONES IN A CARRIER MEDIUM
US3682315A (en) * 1969-10-20 1972-08-08 Wolfgang Haller Cartridge type column for treatment of liquid streams and substrate enclosure therefor
US3692669A (en) * 1970-08-10 1972-09-19 California Inst Of Techn Method and apparatus for micro dry column chromatography
US3902849A (en) * 1971-08-19 1975-09-02 Medi Physics Inc Radioisotope and radiopharmaceutical generators
US4093550A (en) * 1975-06-04 1978-06-06 Riedel-De Haen Aktiengesellschaft Column for high pressure liquid chromatography
US4250035A (en) * 1978-11-13 1981-02-10 Waters Associates, Inc. Radial compression of packed beds
US4565532A (en) 1981-02-18 1986-01-21 Kaama Marine Engineering, Inc. Stern drive
DE3273546D1 (en) * 1981-06-19 1986-11-06 Ceskoslovenska Akademie Ved Column for liquid chromatography
US4483374A (en) * 1982-11-01 1984-11-20 Ethyl Corporation Chromatographic column
DE3436095A1 (en) * 1984-10-02 1986-04-10 Merck Patent Gmbh, 6100 Darmstadt CHROMATOGRAPHIC COLUMN
US4636316A (en) * 1985-01-11 1987-01-13 Beckman Instruments, Inc. Disposable column cartridge
US4719011A (en) * 1985-03-22 1988-01-12 H. T. Chemicals, Inc. High pressure liquid chromatography columns
US4876005A (en) * 1988-02-12 1989-10-24 The Perkin-Elmer Corporation High pressure column assembly for a liquid chromatograph system
US5227059A (en) * 1989-11-08 1993-07-13 Alltech Associates, Inc. Chromatography columns
US5614089A (en) * 1990-07-13 1997-03-25 Isco, Inc. Apparatus and method for supercritical fluid extraction or supercritical fluid chromatography
US5234599A (en) * 1990-10-09 1993-08-10 The Dow Chemical Company On-line multidimensional chromatographic system with large volume injection handling for supercritical fluid chromatography
EP0545843B1 (en) * 1991-12-03 1995-08-16 Tracer Analitica S.L. Fixing arrangement for chromatography columns
US5338448A (en) * 1992-10-16 1994-08-16 Sarasep, Inc. Method of preventing contamination of a chromatography column
AU2276295A (en) * 1994-04-07 1995-10-30 Biotage, Inc. Apparatus for pressurizing a removable chromatography cartridge
US5462660A (en) * 1994-04-22 1995-10-31 The United States Of America As Represented By The Secretary Of Agriculture High performance liquid chromatography injection system for the simultaneous concentration and analysis of trace components

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4457846A (en) * 1982-07-08 1984-07-03 Milton Roy Company Liquid chromatography methods and devices
US4565632A (en) * 1985-01-11 1986-01-21 Beckman Instruments, Inc. Chromatographic cartridge column system

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP1517732A1 (en) * 2002-05-01 2005-03-30 Biotage, Inc. Processing of chemicals in flow-through device with porous media
EP1517732A4 (en) * 2002-05-01 2005-10-19 Biotage Inc Processing of chemicals in flow-through device with porous media
US7063784B2 (en) 2002-05-01 2006-06-20 Biotage Ab Processing of chemicals in flow-through device with porous media
WO2004047948A1 (en) * 2002-11-26 2004-06-10 Prime Separations, Incorporated Chromatographic separation processes and apparatus

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US6221252B1 (en) 2001-04-24
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