WO1998026872A1 - Procede pour la mise en oeuvre d'analyses et d'extractions de composants d'interet dans des echantillons de fluides - Google Patents

Procede pour la mise en oeuvre d'analyses et d'extractions de composants d'interet dans des echantillons de fluides Download PDF

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Publication number
WO1998026872A1
WO1998026872A1 PCT/US1997/022654 US9722654W WO9826872A1 WO 1998026872 A1 WO1998026872 A1 WO 1998026872A1 US 9722654 W US9722654 W US 9722654W WO 9826872 A1 WO9826872 A1 WO 9826872A1
Authority
WO
WIPO (PCT)
Prior art keywords
pipettes
array
fluid samples
collection
compartments
Prior art date
Application number
PCT/US1997/022654
Other languages
English (en)
Inventor
Dennis D. Blevins
Original Assignee
Ansys, Inc.
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 Ansys, Inc. filed Critical Ansys, Inc.
Priority to AU56939/98A priority Critical patent/AU5693998A/en
Publication of WO1998026872A1 publication Critical patent/WO1998026872A1/fr

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Classifications

    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • B01L3/508—Containers for the purpose of retaining a material to be analysed, e.g. test tubes rigid containers not provided for above
    • B01L3/5085—Containers for the purpose of retaining a material to be analysed, e.g. test tubes rigid containers not provided for above for multiple samples, e.g. microtitration plates
    • 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
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N1/00—Sampling; Preparing specimens for investigation
    • G01N1/28—Preparing specimens for investigation including physical details of (bio-)chemical methods covered elsewhere, e.g. G01N33/50, C12Q
    • G01N1/40—Concentrating samples
    • G01N1/405—Concentrating samples by adsorption or absorption
    • 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
    • G01N2030/009—Extraction
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • G01N35/10—Devices for transferring samples or any liquids to, in, or from, the analysis apparatus, e.g. suction devices, injection devices
    • G01N2035/1027—General features of the devices
    • G01N2035/1048—General features of the devices using the transfer device for another function
    • G01N2035/1055—General features of the devices using the transfer device for another function for immobilising reagents, e.g. dried reagents

Definitions

  • the present invention is generally related to a method for conducting assays for components of interest in fluid samples. More particularly the present invention is directed to a method for the testing and/or analysis of fluid samples usually of a chemical, biochemical or biological nature.
  • Fluid samples for example, a solution, colloidal dispersion, or suspension may be separated into individual components through the use of extraction media.
  • a typical device is set forth in U.S. Patent No. 5,264,184 describing devices for separating liquid samples into components which include a container and a separation layer abutting a bottom wall of the container with an outlet opening formed therein.
  • a vacuum is utilized to pass fluids through the separation layer which are caught drop-by-drop in a collecting container.
  • sample containers and collection containers may be arranged closely adjacent to one another so that a simultaneous separation of a plurality of liquid samples is made possible.
  • the sample containers may be arranged, for example, side-by-side in a single row and interconnected, or they can be arranged in rows and columns in a two-dimensional matrix and interconnected with the columns being orthogonal to the rows.
  • U.S. Patent 5,417,923 teaches an assay tray assembly which includes a plastic molded test tray removably mounted in an overlying relationship in engagement with a plastic molded collection tray.
  • the test tray has a spaced array of discrete identical chambers to accommodate a predetermined volume of liquid for analysis with each chamber being formed with a top opening and a bottom opening for flow of liquid or air through the separation media.
  • the bottom opening is located in a downward projecting tubular spigot for the respective chamber and each chamber carries a separation medium to which the liquid is to be subjected. After passing through the assay tray assembly, the liquid passes into the individual chambers formed in the collection tray.
  • U.S. 5,417,923 teaches the use of the separate assay tray assembly along with a corresponding collection tray.
  • the assay trays typically have a plurality of wells, for example, ninety-six (96), arranged in rows and columns into which the particulate solid phase is placed and treated sequentially with the liquid reagents and washes involved in the assay of interest.
  • 96 ninety-six
  • the object of the present invention is to eliminate the need for the assay tray in conducting multiple simultaneous assays.
  • An assay or liquid separation method in accordance with the present invention for components of interest in fluid samples generally includes the steps providing a plurality of pipettes disposed in an array for the transfer of fluid samples along with disposing a solid phase extraction medium in each of the pipettes.
  • the method in accordance with the present invention also provides for preparing samples for subsequent analysis by separating liquid samples into their individual components.
  • a collection tray having a plurality of collection compartments disposed in an array for receiving fluid samples.
  • the method further includes a step of positioning the pipette array over the collection tray and directly transferring fluid samples through the pipettes and extraction medium therein into the collection compartment.
  • the method in accordance with the present invention may include the step of withdrawing fluid sample directly from the collection compartments and through the pipette and extraction medium therein.
  • transferring fluids through the extraction medium may be effected by both passing fluid from the pipettes into the compartments and by passing fluid from the compartments into the pipette.
  • this bidirectional fluid sequence through the pipette and extraction medium may be iterated any number of times with various fluids to enable a great number of procedures to be conducted, if desired, during an assay or liquid separation preparation for a subsequent assay.
  • the method of the present invention may also include the step of providing a second collection tray having a plurality of collection compartments disposed in an array, each with a second fluid sample therein, and directly transferring the second fluid samples through the pipettes and extraction medium therein.
  • the method in accordance with the present invention may further comprise a step of providing a second plurality of pipettes disposed in an array, disposing a solid phase extraction medium in each of the pipettes in the second array and directly transferring the second fluid samples through the pipettes in the second array and extraction medium therein.
  • the method in accordance with the present invention also includes the step of providing a collection tray with an array of compartments of equal number to the number of pipettes in the pipette array.
  • the compartments and pipettes have identical arrays.
  • a method for performing an assay for components of interest in a fluid sample may include providing a plurality of pipettes disposed in an array for transfer of fluid samples and disposing a solid phase extraction medium in each of the pipettes.
  • a collection tray is provided with a plurality of collection departments disposed in an array and a fluid sample disposed in each of the compartments.
  • the method then includes positioning the pipette over the collection tray and directly transferring the fluid samples from the compartments into the pipettes through the extraction medium.
  • This particular embodiment of the method of the present invention provides for initial movement of fluid samples from the compartments into the pipettes and through the extraction medium, as opposed to the initial transfer of fluid samples from the pipette through the extraction medium and into the compartments.
  • Figure 1 shows a perspective view of an array of pipettes and a collection tray having a corresponding array of compartments therein;
  • Figure 2 is a cross-section of a portion of pipette suitable for use in the method of the present invention showing a solid phase extraction medium therein.
  • the technology of solid phase extraction is well-explained in the literature and has been the topic of numerous patents. Although specific terms are used to describe the invention, techniques that operate equivalently are included.
  • the solid phase extraction experiment involves the selective sorption of components from a mixture by, most commonly, passing the mixture through the extraction media. If desired, the sorbed analytes are removed from the extraction media by passing another solvent, having select different properties compared to the sample, through the extraction media.
  • an array 12 which includes a plurality of pipettes 14 held in the array 12 by a fixture (not shown) which also provides a means for forcing a fluid sample (not shown) out of tips 16 of the pipettes 14 and through a solid phase extraction disc, or medium, 20 disposed within each pipette 14.
  • fluid sample may be drawn through the tip 16 and the extraction medium 20 into a frusta conical tip 22 of the pipette with sufficient force to prevent dislodging thereof when fluid flow is from outside of the pipette 14 into a body 24 thereof.
  • the extraction medium 20 is preferably press fit.
  • any suitable fixture for holding the pipettes in an array and providing fluid samples thereto may be utilized.
  • the fluid samples may be predisposed into the pipettes before assembly into the array 12, then supported by the fixture (not shown) which may provide air pressure for movement of fluid samples through the pipette in the directions hereinabove described.
  • a collection tray 26 which includes a plurality of compartments 28 therein. Any number of pipettes 14 and compartments 28 may be provided, for example, ninety-six (96), disposed in an array of 8 x 12.
  • the array 12 includes the pipettes 14 disposed in a matching array with the compartments 28 of the collection tray 26. However, it should be appreciated that unequal numbers of pipettes 14 and compartments 28 may be utilized.
  • the pipette array 12 is positioned over the collection tray 26 and fluid samples are passed through the pipettes and the extraction medium into the collection compartment 28.
  • the pipette array 12 is lowered until proximate the collection tray 26 as indicated by the arrow 30 which also shows movement of the pipette array 12 away from the collection tray 12 to facilitate handling of the collection tray which may be subsequently moved to another site for further analysis.
  • pipette array (not shown) which may be identical to the pipette array 12 shown in Figure 1 may be used to further transfer fluids to and from the compartments and through solid extraction media disposed in the pipettes 14.
  • a second collection tray (not shown), which may be identical to the collection tray 26 shown in Figure 1, may be utilized and positioned under the pipette array 12 for transfer of fluids from the pipettes 14 into the compartments 28 or vice versa.
  • any combination of steps which may be necessary for a particular assay that includes the use of multiple fluids and multiple extraction media may be formed with the method in accordance with the present invention.
  • Example 1 This example illustrates the sorption of a colored dye component from a mixture to allow visualization of the technique. The use of such compounds helps those skilled in the art to understand the retention of specific analytes under defined conditions.
  • Solid phase extraction is a sample preparation technique that employs disposable devices to quickly extract desired analytes from a given sample.
  • SPEC® non-polar extraction media such as C18
  • SPEC® extraction media contain silica particles bonded with hydrophobic groups.
  • the extraction process begins with a conditioning sequence of methanol followed by an aqueous solution in order to prepare the SPEC® extraction media for use.
  • an aqueous wash solution is passed through the SPEC® media to remove sample matrix interference.
  • the analyte is eluted using an organic solvent, such as methanol.
  • a disc 20 of SPEC® Cl 8 SPE extraction media was inserted and pressed into the disposable pipette tip 22 towards the bottom. The media was held in place by the press fit on the sides of the frusta conical chamber.
  • One tenth (0.1) mL methanol was added to the disc through the opening at the top and pushed through the disc using the pipettor. Then 0.1 mL water was added to the disc in a similar fashion to displace excess methanol.
  • a pipettor (not shown) was attached to the pipette 14 containing the SPEC® disc 20 and the plunger depressed.
  • the tip 22 was then inserted into a compartment 28 containing 0.5 mL of an aqueous solution containing dilute green food coloring (a mixture of the blue and yellow compounds described above).
  • the plunger of the pipettor was slowly released, drawing the colored solution through the disc 20. Whilst the liquid was flowing through the disc 20, the blue component was sorbed on the surface of the disc 20, and the yellow solution was in the pipette tip 22 above the disc 20.
  • the pipette tip 22 was then moved to a clean compartment and the pipettor plunger was depressed, expelling the liquid, reversing the direction of sample flow through the disc 20. The blue compound remained adsorbed on the extraction disc 20 and the yellow component was in the compartment.
  • the pipettor was removed from the pipette 14 containing the extraction media, disc 20, and 0.25 mL methanol was added to the pipette 14 above the disc 20. The pipettor was re- attached, and the tip 22 was placed into a clean compartment. Depressing the plunger on the pipettor caused the methanol to flow through the disc 20, eluting the blue component into the compartment.
  • Example 2 This example shows an application extracting morphine and codeine from an authentic urine specimen using the SPEC® pipette tip extraction device format.
  • Urine specimens were spiked with morphine and codeine at three different levels; negative, the SAMHSA cutoff level of 300 ng/mL, and a higher concentration of 750 ng/mL.
  • the experiments were run in triplicate for specimens containing the analytes. The quantitation was based on a relative recovery experiment with the deuterated internal standards added to the urine specimen.
  • the method used was a modification of the published SPEC® extraction procedure for the extraction of morphine and codeine from urine specimens.
  • the pipette tips were constructed in a similar fashion to the device outlined in Example 1, except using the SPEC® MP1 (mixed phase 1) extraction media instead of the C18 media.
  • the MP1 extraction media contains both hydrophobic and cation exchange moieties.
  • the procedural steps for processing the specimens follow.
  • the columns were conditioned with 0.1 mL methanol.
  • the excess solvent was pushed through the extraction media using the pipettor.
  • the pipette tip containing the conditioned media was lowered into a test tube containing the urine sample.
  • the plunger was released drawing the urine through the extraction media in the pipette tip.
  • the plunger was depressed pushing the urine back through the disc into the original test tube.
  • a wash step for the disc inside the pipette tip consisted of the sequential addition of 0.25 mL water, 0.1 M acetic acid, and methanol, ensuring displacement of each solvent before the addition of the next solvent.
  • the analytes of interest were eluted from the disc by the addition of 0.25 mL mixture of ethyl acetate, methanol, and ammonium hydroxide and collecting the solvent into a clean vial. The elution step was repeated one time. The collected solvent was processed in the appropriate manner, including a derivatization step and the final extracts were analyzed using gas chromatography mass spectrometry (GC/MS).
  • GC/MS gas chromatography mass spectrometry
  • Table I The quantitative results are given in Table I.
  • the data in Table I demonstrate that the pipette tip SPE device and method employing the device performed according to the present invention. In all cases, the expected results were obtained for the morphine and codeine levels spiked.

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Analytical Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Hematology (AREA)
  • Clinical Laboratory Science (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Physics & Mathematics (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Biochemistry (AREA)
  • General Physics & Mathematics (AREA)
  • Immunology (AREA)
  • Pathology (AREA)
  • Sampling And Sample Adjustment (AREA)

Abstract

Cette invention concerne un procédé de mise en oeuvre d'analyses et d'extractions de composants d'intérêt dans des échantillons de fluides, qui consiste à utiliser une pluralité de pipettes disposées au sein d'une matrice, en vue du transfert des échantillons de fluides, et à disposer un milieu d'extraction en phase solide dans chacune des pipettes. Un plateau de récupération (26) comportant une pluralité de compartiments de récupération (28) disposés au sein d'une matrice (12), sert à recevoir les échantillons de fluides. La matrice de pipettes (12) est disposée au dessus du plateau de récupération (26) et ceci permet d'effectuer un transfert bidirectionnel d'échantillons de fluides, avec les compartiments de récupération (28), par l'intermédiaire des pipettes et du milieu d'extraction.
PCT/US1997/022654 1996-12-18 1997-12-11 Procede pour la mise en oeuvre d'analyses et d'extractions de composants d'interet dans des echantillons de fluides WO1998026872A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
AU56939/98A AU5693998A (en) 1996-12-18 1997-12-11 Method for conducting assays and separations for components of interest in fluid samples

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US76865696A 1996-12-18 1996-12-18
US08/768,656 1996-12-18

Publications (1)

Publication Number Publication Date
WO1998026872A1 true WO1998026872A1 (fr) 1998-06-25

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Application Number Title Priority Date Filing Date
PCT/US1997/022654 WO1998026872A1 (fr) 1996-12-18 1997-12-11 Procede pour la mise en oeuvre d'analyses et d'extractions de composants d'interet dans des echantillons de fluides

Country Status (2)

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AU (1) AU5693998A (fr)
WO (1) WO1998026872A1 (fr)

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2000075623A1 (fr) * 1999-06-08 2000-12-14 Dna Research Innovations Limited Dispositif de traitement d'echantillons
WO2000079238A1 (fr) * 1999-06-18 2000-12-28 Proteome Systems Ltd Appareil et procedes de separation et d'analyse de composes a haute resolution
US7163660B2 (en) 2000-05-31 2007-01-16 Infineon Technologies Ag Arrangement for taking up liquid analytes

Citations (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3807235A (en) * 1971-10-13 1974-04-30 Hoffmann La Roche Micropipetting apparatus
US3982438A (en) * 1975-06-23 1976-09-28 The Salk Institute For Biological Studies Multiple sample pipetting apparatus
US4158035A (en) * 1978-03-15 1979-06-12 Byrd William J Multiple sample micropipette
US5092184A (en) * 1989-12-22 1992-03-03 Medical Research Institute Of The Mary Imogene Bassett Hospital Cell staining system for flow cytometry
US5156811A (en) * 1990-11-07 1992-10-20 Continental Laboratory Products, Inc. Pipette device
US5264184A (en) * 1991-03-19 1993-11-23 Minnesota Mining And Manufacturing Company Device and a method for separating liquid samples
US5403489A (en) * 1993-06-24 1995-04-04 Minnesota Mining And Manufacturing Company Solid phase extraction method and apparatus
US5417923A (en) * 1991-04-24 1995-05-23 Pfizer Inc. Assay tray assembly
US5456879A (en) * 1990-05-04 1995-10-10 Biohit Oy Pipette
US5496523A (en) * 1994-05-06 1996-03-05 Sorenson Bioscience Filtered micropipette tip for high/low volume pipettors

Patent Citations (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3807235A (en) * 1971-10-13 1974-04-30 Hoffmann La Roche Micropipetting apparatus
US3982438A (en) * 1975-06-23 1976-09-28 The Salk Institute For Biological Studies Multiple sample pipetting apparatus
US4158035A (en) * 1978-03-15 1979-06-12 Byrd William J Multiple sample micropipette
US5092184A (en) * 1989-12-22 1992-03-03 Medical Research Institute Of The Mary Imogene Bassett Hospital Cell staining system for flow cytometry
US5456879A (en) * 1990-05-04 1995-10-10 Biohit Oy Pipette
US5156811A (en) * 1990-11-07 1992-10-20 Continental Laboratory Products, Inc. Pipette device
US5264184A (en) * 1991-03-19 1993-11-23 Minnesota Mining And Manufacturing Company Device and a method for separating liquid samples
US5417923A (en) * 1991-04-24 1995-05-23 Pfizer Inc. Assay tray assembly
US5403489A (en) * 1993-06-24 1995-04-04 Minnesota Mining And Manufacturing Company Solid phase extraction method and apparatus
US5496523A (en) * 1994-05-06 1996-03-05 Sorenson Bioscience Filtered micropipette tip for high/low volume pipettors

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2000075623A1 (fr) * 1999-06-08 2000-12-14 Dna Research Innovations Limited Dispositif de traitement d'echantillons
AU778440B2 (en) * 1999-06-08 2004-12-02 Invitrogen Corporation Sample processing device
WO2000079238A1 (fr) * 1999-06-18 2000-12-28 Proteome Systems Ltd Appareil et procedes de separation et d'analyse de composes a haute resolution
US7163660B2 (en) 2000-05-31 2007-01-16 Infineon Technologies Ag Arrangement for taking up liquid analytes

Also Published As

Publication number Publication date
AU5693998A (en) 1998-07-15

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