WO2000033050A1 - Procede et dispositifs jetables permettant d'effectuer une microextraction - Google Patents

Procede et dispositifs jetables permettant d'effectuer une microextraction Download PDF

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Publication number
WO2000033050A1
WO2000033050A1 PCT/NO1999/000359 NO9900359W WO0033050A1 WO 2000033050 A1 WO2000033050 A1 WO 2000033050A1 NO 9900359 W NO9900359 W NO 9900359W WO 0033050 A1 WO0033050 A1 WO 0033050A1
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Prior art keywords
liquid
container
solution
acceptor
analyte
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PCT/NO1999/000359
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English (en)
Inventor
Knut E. Rasmussen
Mette Krogh
Stig Pedersen-Bjergaard
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Rasmussen Knut E
Mette Krogh
Pedersen Bjergaard Stig
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Application filed by Rasmussen Knut E, Mette Krogh, Pedersen Bjergaard Stig filed Critical Rasmussen Knut E
Priority to AU16986/00A priority Critical patent/AU766012B2/en
Priority to JP2000585638A priority patent/JP2002531823A/ja
Priority to CA002353130A priority patent/CA2353130C/fr
Priority to EP99960040A priority patent/EP1137924A1/fr
Publication of WO2000033050A1 publication Critical patent/WO2000033050A1/fr
Priority to AU2004200049A priority patent/AU2004200049B2/en

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    • 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
    • G01N1/4005—Concentrating samples by transferring a selected component through a membrane
    • 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
    • G01N1/4005—Concentrating samples by transferring a selected component through a membrane
    • G01N2001/4016—Concentrating samples by transferring a selected component through a membrane being a selective membrane, e.g. dialysis or osmosis
    • 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
    • G01N1/4055—Concentrating samples by solubility techniques
    • G01N2001/4061—Solvent extraction

Definitions

  • the present invention relates generally to extraction technology.
  • the invention relates, in a first aspect, to an apparatus having disposable elements for carrying out liquid-liquid micro extraction and liquid-liquid- liquid micro extraction.
  • the invention further relates to methods for liquid-liquid micro extraction and liquid- liquid-liquid micro extraction whereby there is obtained a high enrichment of analyte in the acceptor solution.
  • the invention relates to a special disposable device for use in liquid-liquid micro extraction.
  • this relates especially to extraction of an analyte from an aqueous sample solution to an organic solvent where the analyte is enriched in the organic solvent.
  • an analyte is extracted from an aqueous sample solution through a water immiscible liquid to an aqueous acceptor solution.
  • sample pre- treatment is necessary when these methods are used to determine analytes in complex matrices such as biological fluids.
  • the principal objectives of sample pre-treatment involves concentration of the analytes to a concentration suitable for detection and removal of as many interfering compounds as possible.
  • concentration of the analytes is concentration suitable for detection and removal of as many interfering compounds as possible.
  • the use of an extraction technique is common in the pre-treatment of most types of samples.
  • Sample extraction is the most tedious and time consuming step in the analysis of drugs present in the pg/ml to ⁇ g/ml range of biological fluids such as blood, serum, plasma, or urine.
  • No sample preparation technique is able to trap analytes in 1 - 50 ⁇ l of solvent for direct injection into the analytical instrument.
  • the analytes should be trapped in an organic solvent for injection into a GC instrument and in an aqueous solvent for injection into a CE instrument or a micro HPLC instrument.
  • the most frequently used extraction techniques are liquid-liquid extraction (LLE) and solid-phase extraction (SPE).
  • LLE liquid-liquid extraction
  • SPE solid-phase extraction
  • the primary goal of these extraction techniques is to extract the analytes quantitatively from the analytical matrix. When these techniques are used the analytes are normally collected in 0.2 - 10 ml of extraction solvent.
  • Quantitative extraction in LLE can only be achieved by using large volumes of extraction solvent relative to the sample volume.
  • 0.5 - 10 ml of extraction solvent is used for the extraction of a 1 ml sample of a biological fluid.
  • the extract is evaporated and the analytes reconstituted in a smaller amount of solvent.
  • the final extraction volume is governed by the bed volume.
  • the bed volume is the amount of solvent required to fill all the internal pores and interstitial spaces of the particles.
  • bed volumes are in the order of 120 ⁇ l per 100 mg of sorbent.
  • a 1 ml sample of a biological fluid is normally extracted on 100 mg sorbent.
  • the minimum elution volume required is 2 bed volumes or 0.24 ml of solvent. The consequence is that a maximum of 4 times enrichment is obtainable in SPE of a 1 ml sample. In order to achieve higher enrichments the elution solvent must be evaporated and the analyte reconstituted in a smaller volume of solvent.
  • a solution to this problem is to apply a micro extraction (ME) technique, in which the analytes are extracted from a large volume of sample solution into a small volume of an acceptor phase.
  • the acceptor phase can either be a solid such as in solid-phase micro extraction (SPME), or an organic solvent such as in liquid-liquid micro extraction (LLME).
  • SPME solid-phase micro extraction
  • LLME liquid-liquid micro extraction
  • a large sample volume is used in order to collect quantifiable amounts of the analytes and enrichment is facilitated by trapping the analytes in the small volume of the acceptor phase. The extraction is carried out until equilibrium.
  • Figure 1 illustrates the difference between traditional LLE and LLME.
  • a 1 ml sample containing 1 ⁇ g/ml of the analyte is extracted into 1 ml of solvent in LLE and into 10 ⁇ l of solvent in LLME.
  • the analyte partition coefficient between the aqueous matrix and the organic solvent is 100.
  • Figure 1 shows that 0.99 ⁇ g of the analyte is extracted into the organic extract by LLE and that 0.0099 ⁇ g remains in the sample.
  • Analyte concentration in the extract is 0.99 ⁇ g/ml.
  • LLME 0.5 ⁇ g of the analyte is extracted into the organic acceptor phase while 0.5 ⁇ g remains in the sample.
  • Sample concentration in the acceptor phase is 50 ⁇ g/ml. This fact demonstrates that very high enrichments are obtainable in LLME without solvent evaporation and reconstitution.
  • SPME is a well established solvent free sample preparation technique.
  • the acceptor phase is a solid polymer coated on a fibre.
  • the polymeric acceptor phase is non-volatile and acts as a sorbent for partitioning of the analytes.
  • the volume of the polymeric acceptor phase is less than 1 ⁇ l.
  • SPME was originally developed for the analysis of organic compounds in water samples and the method is particularly useful for trace analysis of volatile organic compounds prior to GC analysis.
  • bioanalytical samples such as plasma or urine
  • drug analysis enrichment from a biological matrix is greatly reduced as compared to enrichment from a pure water sample. This is due to reduced capacity of the acceptor phase.
  • the polymeric acceptor phase is easily contaminated when SPME is applied to bioanalysis and cross contamination between samples may easily occur.
  • the concentration of analyte trapped in the acceptor phase, C a is:
  • Table 1 shows the equilibrium concentration of the analyte trapped in 0.001 ml - 1 ml of acceptor phase after extraction of a 1 ml sample solution containing 1 ⁇ g/ml of the analyte.
  • the partition coefficients are 10,100 ,1000 and oo.
  • Disposable extraction sponges are used to immobilise 10 - 50 ⁇ l of extraction solvent.
  • LLME with extraction sponges is particularly suited for sample preparation of biological fluids prior to GC analysis.
  • Solvent immobilised into extraction sponges eliminates the handling problems encountered with small solvent volumes since immobilised solvents are not emulsified and are easily collected after extraction.
  • Materials used in the manufacture of extraction sponges should be solvent resistant, porous and compressible. In addition the materials should be sufficiently hydrophobic to immobilise water immiscible solvents.
  • the pore size may range from a few micrometers up to millimeters. Expanded polymers and polymeric foams are particularly suited. Examples of solvent resistant polymers are Teflon, Tefzel, Halar, polyethylene and polypropylene. The size of the polymeric material is cut to fit immobilisation of a predetermined volume of solvent.
  • the extraction sponges are filled into a container with the solvent to be immobilised.
  • the sponges are compressed to remove air trapped in the pores and are thereafter soaked in the solvent.
  • the sponges are then ready for extraction.
  • sample solutions are filled into extraction vials. Typical volumes of sample solution are 0.5 - 5 ml. Quantitative analysis is always performed by adding an internal standard to the sample solution. The internal standard is added to the sample prior to the extraction and follows the analyte through all the analytical steps. The internal standard compensates for all fluctuations in the procedure. The chemical nature of the sample is altered prior to extraction to facilitate analyte extraction into the organic solvent. This involves optimisation of pH and addition of salt.
  • One solvent sponge with immobilised solvent is removed from the container and added to the extraction vial. Extraction is performed by stirring. Any kind of stirring, for example, a magnetic stir bar, can be used. The extraction is continued until equilibrium (10 - 30 min). The solvent sponge is then removed from the sample vial. Immobilised solvent with the enriched analyte is liberated by compression. Compression can be facilitated in any device suitable for squeezing. For example the sponge can be compressed in a disposable medical syringe equipped with a needle and the liberated solvent is filled into micro sampling vials made to fit into a GC autoinjector.
  • Sponges able to immobilise 25 ⁇ l of solvent are suitable in many applications. As shown in Table 1 enrichments of 30 are obtained for analytes having a partition coefficient of 100. A solvent volume of 25 ⁇ l is sufficiently large to allow easy handling. This solvent volume is also large enough to avoid overloading and reduced enrichment during extraction. One sponge is used for each sample and used sponges can be stored safely in a container prior to destruction. Compared to traditional methods for sample preparation, LLME with solvent sponges greatly reduces solvent consumption and hazards to workers and the environment.
  • the present invention aims to solve the problem introduced above by utilising so-called micro back extraction, referred to above and hereinafter as liquid-liquid-liquid micro extraction (LLLME), to obtain a sufficiently high concentration of the material to be analysed in the acceptor solution.
  • LDLME liquid-liquid-liquid micro extraction
  • capillary electrophoresis Separation techniques used in capillary electrophoresis such as capillary zone electrophoresis, micellar electrokinetic chromatography and capillary electrochromatography favour injection of low ionic strength aqueous samples. Due to the injection of nl volumes of samples, high enrichments are required in bioanalysis of drugs present in trace amounts in biological fluids.
  • Ionic organic substances can be enriched by LLLME.
  • LLLME The principle of LLLME for isolation of ionic organic molecules is illustrated in Figure 2. Clean-up and concentration of analytes are based on partitioning of the analytes from a large volume of the aqueous sample matrix through a membrane and into a small volume of an aqueous acceptor phase. The membrane acts as a clean-up barrier between two aqueous phases. Both basic and acid compounds can be enriched with LLLME. The pH of the matrix is adjusted so that the analytes are uncharged. This permits them to pass through the membrane into the aqueous acceptor solution on the other side.
  • the pH of the acceptor solution is adjusted to a pH where the analytes are ionised, thus preventing them from re-entering the membrane. Only small uncharged molecules can pass through the membrane and only molecules which are soluble in the membrane and in the acceptor solution can be enriched. Water soluble neutral substances remain in the matrix. Neutral hydrophobic substances partition into the membrane and not into the acceptor phase. Substances with the opposite charge as the analytes remain in the matrix. LLLME is thus a powerful clean-up technique.
  • the driving force for the extraction is dependant on the product of the analyte partition coefficients between the membrane and the sample solution and between the acceptor phase and the membrane which is equivalent to the analyte partition coefficient between the acceptor phase and the sample matrix.
  • Compounds having a large partition coefficient between the two aqueous phases will be enriched. This partition coefficient will be large for many drugs. LLLME therefore has the potential to act as both a powerful enrichment and clean-up technique for many ionic drugs.
  • the acceptor/membrane partition coefficient K a l
  • the membrane/sample partition coefficient Ki s
  • the acceptor/sample partition K s
  • the acceptor volume V a
  • the membrane volume Vi
  • the sample volume V s
  • the initial sample concentration C 0
  • the amount of analyte extracted by LLMBE, n is:
  • K as Na + V s Equation 5 can be used to estimate analyte enrichment from a 1 ml sample solution containing 1 ⁇ g/ml of the analyte as a function of acceptor phase volume and the partition coefficient.
  • the results obtained are equivalent to the results shown in Table 1 showing that enrichments from a 1 ml sample into 0.001-0.05 ml of acceptor solution are superior to the enrichments obtained by traditional extraction methods.
  • ionic drugs have partition coefficients larger than 100 between two aqueous phases: one having a pH where the drugs are charged and the other a pH where the drugs are uncharged.
  • an analyte with a partition coefficient of 100 is trapped in 10 ⁇ l acceptor solution from 1 ml sample with a concentration of 1 ⁇ g/ml, analyte concentration in the acceptor phase is 50 ⁇ g/ml.
  • LLLME is able to provide enrichments not obtainable by any other extraction method. LLLME is therefore particularly useful as an extraction technique for modern capillary separation methods such as CE.
  • the chemical nature of the membrane is important in obtaining short analysis times. Extractions should be continued until equilibrium between the three phases is established. If the membrane/sample partition coefficient is low, equilibrium times will be long and will approach infinity for analytes which are very poorly soluble in the membrane. The solvent forming the membrane should therefore be a good solvent for the target analyte. The chemical nature of the membrane is also important for tuning of the selectivity.
  • stirring means preferably a magnetic bar.
  • the container for the acceptor solution is a microporous hollow fibre, optionally of an active polymer.
  • the invention also relates to methods for extraction and thereby relates, in a first extraction aspect, to a method for liquid-liquid micro extraction with high enrichment by using the above described apparatus, and this method is characterised in that a) the container for acceptor solution is lowered into an acceptor solution so that the membrane wall is impregnated with, and the container is filled with, a defined volume of the acceptor solution, b) the container filled under a) is transferred to the container having a defined volume of the sample solution with the analyte that is sought, c) the sample solution with analyte is stirred until extraction equilibrium is established for the analyte in the two solutions, and d) the acceptor solution containing enriched analyte is removed from its container for analysis of the analyte.
  • the invention in a second extraction aspect, relates to a method for liquid-liquid-liquid micro extraction with high enrichment by the use of the apparatus according to claim 1, and this method is characterised in that a) the walls of the container for the acceptor solution are impregnated with, for immobilisation of, a liquid that is immiscible with the sample solution and the acceptor solution, b) the container for acceptor solution is filled with a defined volume thereof and c) is lowered into the container having a defined volume of the sample solution with the analyte that is sought, d) the sample solution with analyte is stirred until extraction equilibrium is established between i) the sample solution and the immobilised liquid, and ii) the immobilised liquid and the acceptor solution, and e) the acceptor solution with enriched analyte is removed from its container for analysis of the analyte.
  • basic analytes can be enriched from basic, aqueous, biological samples by utilising an acceptor liquid in the form of an acidified, aqueous liquid and an organic liquid immobilised in the membrane that is immiscible with the aqueous liquids.
  • microporous hollow fibre it may be advantageous to use a microporous hollow fibre, but it is also possible to use an active polymer.
  • the invention relates to a disposable device for use in liquid-liquid micro extraction, which is characterised in that it has the form of a sponge-like body having a defined pore volume for absorption of an immobilised acceptor solution for an analyte from a volume of a sample solution.
  • Figure 1 shows a comparison between liquid-liquid extraction and liquid-liquid micro extraction
  • Figure 2 shows the principle for liquid-liquid-liquid micro extraction
  • Figure 3 shows a possible device for utilisation in LLLME, or LLME
  • Figure 4 shows another possible device for LLLME, or LLME
  • Figure 5 shows chromatograms obtained in connection with Example 1,
  • Figure 6 shows electropherograms obtained in connection with Example 2.
  • Devices for LLLME should accomplish extraction from a large sample volume through a negligible volume of a membrane into a small volume of an aqueous acceptor solution.
  • the membrane should be a thin film with a large surface area.
  • the membrane can either be a solid (liquid-solid-liquid micro extraction, LSLME) or a liquid (liquid- liquid-liquid micro extraction, LLLME).
  • the solvent forming the liquid membrane should be immobilised. Any material able to immobilise a water immiscible solvent can be used. Hydrophobic hollow fibres are particularly useful.
  • the fibres can be made of a polymeric materials such as Teflon, polypropylene or polyethylene.
  • the inner diameter of the hollow fibre is in the range of 0.05 - 1 mm, the wall thickness is typically in the range of 0.01 - 0.3 mm and the average pore size is in the range of 0.01 - 10 ⁇ m.
  • the length of the fibre is typically 2 - 10 cm to allow fixed volumes of acceptor solution in the range of 5 - 50 ⁇ l to be filled into the hollow fibre.
  • the membrane may be a polymeric film made of a multitude able to sorb uncharged compounds. Examples of such materials are polydimethylsiloxane (PDMS), polyacrylate or polystyrene divinyl benzene. These materials are also used as well known sorbents in SPME.
  • the membrane thickness is preferably 0.5 - 50 ⁇ m.
  • the membrane may be supported by a rigid framework and formed into tubes with the same dimensions as the hollow fibres described above.
  • Devices for LLLME should be disposable. Impurities from one sample may be trapped in the membrane and these impurities may contaminate other samples. One sample pre- treatment device should therefore be used for each sample. Disposable devices should also be connected to commercially available sample preparation vials.
  • Disposable devices for LLLME are shown in Figures 3a and 4a.
  • Figures 3b and 4b show the devices connected to sample vials filled with sample solution.
  • the guiding rod can be a stainless steel rod or a rod made of a polymeric material.
  • the top of the guiding rod can be connected to a needle guide to allow filling of the hollow fibre with acceptor solution from a syringe.
  • the hollow fibre in Fig. 3b is connected at both ends to guiding rods.
  • the membrane can be used as it is.
  • LLLME the liquid membrane is formed by dipping the hollow fibre into the organic solvent for 5-30 sec. to allow the solvent to penetrate into the pores of the fibre.
  • Acceptor solution is then filled into the fibre by a syringe. Normally, fibres with an inner tube volume of 10 ⁇ l are preferred, since 10 ⁇ l of acceptor solution gives high analyte enrichments and 10 ⁇ l volumes can be handled with commercially available syringes.
  • the acceptor solution has a pH where the target analytes are charged. Extraction is performed by connecting the LLLME device to the sample vial. The sample filled into the sample vial is buffered to a pH where the analytes are neutral.
  • Typical sample volumes are 0.5 - 5 ml of a biological fluid.
  • An internal standard is always added to the sample solution before extraction to compensate for fluctuations in the procedure.
  • Extraction is performed by stirring, for example with a magnetic stir bar placed in the sample vial. Extraction is continued until equilibrium between the three phases is established. When equilibrium is reached (15- 60 min) the acceptor solution is collected with a syringe and filled into autosampler vials for automated injection into the analytical instrument.
  • the device shown in Figure 4a was used to demonstate the potential of liquid-liquid micro extraction and liquid-liquid-liquid micro extraction.
  • the hollow fibre used was a polypropylene fibre with pore size 0.2 ⁇ m (Accurel PP Q3/2) and was purchased from Akzo Nobel (Wuppertal, Germany).
  • the inner diameter was 600 ⁇ m
  • the wall thickness was 200 ⁇ m
  • the length was 5.5 cm.
  • Example 1 Liquid - liquid micro extraction (LLME)
  • LLME is demonstrated by the extraction of 5 nmol/ml sample solutions of diazepam (D) and prazepam (P) prepared in 1.0 M acetate buffer pH 5.5, in urine and in human plasma.
  • a standard solution in octanol (5 nmol/ml) was prepared as a reference solution for direct injection into the gas chromatograph.
  • the pH of the standard solution in urine was adjusted to pH 5.5 before extraction.
  • To an aliquote of plasma (1080 ⁇ l) was added 120 ⁇ l methanol to reduce the protein binding of the benzodiazepines prior to extraction and the mixture was agitated for 1 min.
  • LLME was accomplished by placing 1.2 ml of the sample solutions in 2 ml autosampler vials (Chromacol, Trumball, CT., USA).
  • the hollow fibre was filled with 10 ⁇ l of 1 -octanol. After 1 min, to ensure that the solvent would completely penetrate the pores, the hollow fibre was immersed into the autosampler vials.
  • the sample solution was stirred with a magnetic stir bar during extraction. After 30 min 1 ⁇ l of octanol was withdrawn from the hollow fibre with a GC syringe and injected into the gas chromatograph.
  • the gas chromatographic separation was achieved on a poly-(dimethylsiloxane) column (30 x 0.25 mm i.D., 0.25 mm film thickness) and the compounds were detected with a nitrogen-phosphorous detector (NPD). Helium (1 ml/min) was used a carrier gas.
  • the chromatographic separation was achieved by temperature programming. The temperature was held at 180 C for 1 min and increased at 20 C /min to 300 C.
  • Figure 5 shows chromatograms of the reference solution in octanol (5 nmol/ml) and chromatograms of the sample solutions (5 nmol/ml) of diazepam and prazepam in acetate buffer, in urine and plasma after enrichment by LLME. The chromatograms demonstrate preconcentration by a factor of 100 and 70, respectively, for diazepam and prazepam from the acetate buffer, urine and the plasma sample.
  • LLLME is performed with 1 -octanol as the immobilised liquid.
  • the hollow fibre was immersed for 5 sec in 1 -octanol which is sufficient for 1 -octanol to penetrate and fill the pores of the fibre.
  • 10 ⁇ l of 0.1M HC1 was used as acceptor solution and was filled into the impregated fibre with a syringe.
  • a standard solution of 4 ⁇ g/ml of diphenhydramine in 0.1 M HC1 was prepared as a reference for direct injection into the CE instrument.
  • sample solutions of diphenydramine (4 ⁇ g/ml) were prepared in 0.1 M NaOH, in urine and plasma.

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Abstract

L'invention concerne un appareil permettant d'effectuer une microextraction liquide-liquide ou une microextraction liquide-liquide-liquide hautement enrichie. Cet appareil comprend a) un récipient destiné à une solution à examiner dont le volume Vs contient une substance dissoute à analyser, b) un second récipient, de préférence jetable, disposé dans le premier récipient et pourvu de parois membranaires perméables, destiné à recevoir une solution receveuse présentant un volume Va, dans lequel 1) Vs:Va ≥ 50 et 2) environ 1 νl ≤ Va ≤ 50 νl, c) un dispositif d'agitation, de préférence une barre magnétique. Ce procédé peut être appliqué à une microextraction liquide-liquide et à une microextraction liquide-liquide-liquide hautement enrichie. Dans ce dernier cas, on immobilise un liquide non miscible avec la solution à examiner et la solution receveuse sur la paroi du récipient destiné à la solution receveuse. L'invention concerne également un dispositif jetable permettant d'effectuer une microextraction liquide-liquide. Ce dispositif se présente sous forme d'un corps spongieux présentant une porosité définie destinée à absorber une solution receveuse immobilisée pour une substance à analyser issue d'un volume d'une solution à examiner.
PCT/NO1999/000359 1998-12-01 1999-11-30 Procede et dispositifs jetables permettant d'effectuer une microextraction WO2000033050A1 (fr)

Priority Applications (5)

Application Number Priority Date Filing Date Title
AU16986/00A AU766012B2 (en) 1998-12-01 1999-11-30 Method and disposable devices for micro extraction
JP2000585638A JP2002531823A (ja) 1998-12-01 1999-11-30 ミクロ抽出方法およびそのための使い捨て装置
CA002353130A CA2353130C (fr) 1998-12-01 1999-11-30 Procede et dispositifs jetables permettant d'effectuer une microextraction
EP99960040A EP1137924A1 (fr) 1998-12-01 1999-11-30 Procede et dispositifs jetables permettant d'effectuer une microextraction
AU2004200049A AU2004200049B2 (en) 1998-12-01 2004-01-07 Method and disposable devices for micro extraction

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
NO19985613A NO311464B1 (no) 1998-12-01 1998-12-01 Fremgangsmåte og engangsinnretning for mikro-ekstrahering
NO19985613 1998-12-01

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WO2000033050A1 true WO2000033050A1 (fr) 2000-06-08

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JP (1) JP2002531823A (fr)
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WO2002042500A2 (fr) * 2000-10-31 2002-05-30 Hitachi Chemical Research Center, Inc. Appareil et procede pour la concentration electrophoretique sur micropoint
WO2002088671A1 (fr) * 2001-04-26 2002-11-07 Esytech Ab Unite de separation, procede de separation et dispositif destine au montage d'une unite de separation dans un appareil de separation
WO2002088672A1 (fr) * 2001-04-26 2002-11-07 Varian, Inc. Dispositifs de preparation d'echantillons constitues de membranes a fibres creuses
WO2007004892A1 (fr) * 2005-06-30 2007-01-11 Uni I Oslo Procédé pour une migration électrocinétique à travers des membranes liquides
US7445939B2 (en) 2004-02-27 2008-11-04 Varian, Inc. Stable liquid membranes for liquid phase microextraction
EP2461150A2 (fr) 2010-12-06 2012-06-06 Greibrokk & Trones Septech AS Dispositif pour extraction de membrane électro (EME)
CN102974127A (zh) * 2012-11-23 2013-03-20 中国计量学院 一种中空纤维膜微萃取器及其应用
CN103877746A (zh) * 2012-12-21 2014-06-25 中国科学院大连化学物理研究所 一种调节电驱动液-液-液萃取极性阴离子选择性的方法
CN104034572A (zh) * 2014-06-24 2014-09-10 广西中烟工业有限责任公司 一种类胡萝卜素的中空纤维膜液相微萃取的方法
EP3384978A2 (fr) 2017-04-04 2018-10-10 Extraction Technologies Norway AS Nouveaux dispositifs d'extraction à électromembrane (eme)

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JP4736130B2 (ja) * 2006-02-20 2011-07-27 株式会社島津製作所 試料水中の有機溶媒易溶成分のクロマトグラフによる分析方法
CN110935194B (zh) * 2019-12-12 2021-08-06 中国计量大学 一种中空纤维膜微萃取系统

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WO1991015745A1 (fr) * 1990-04-02 1991-10-17 Pawliszyn Janusz B Procede et dispositif de micro-extraction et de desorption en phase solide
DE19525771A1 (de) * 1994-09-15 1996-03-28 Hewlett Packard Co Feststoff-Phasen-Extraktion mit reduziertem Lösungsmittel
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WO2002088672A1 (fr) * 2001-04-26 2002-11-07 Varian, Inc. Dispositifs de preparation d'echantillons constitues de membranes a fibres creuses
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WO2007004892A1 (fr) * 2005-06-30 2007-01-11 Uni I Oslo Procédé pour une migration électrocinétique à travers des membranes liquides
EP2461150A2 (fr) 2010-12-06 2012-06-06 Greibrokk & Trones Septech AS Dispositif pour extraction de membrane électro (EME)
US8940146B2 (en) 2010-12-06 2015-01-27 Greibrokk & Trones Septech As Device for electro membrane extraction
CN102974127A (zh) * 2012-11-23 2013-03-20 中国计量学院 一种中空纤维膜微萃取器及其应用
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CN103877746A (zh) * 2012-12-21 2014-06-25 中国科学院大连化学物理研究所 一种调节电驱动液-液-液萃取极性阴离子选择性的方法
CN103877746B (zh) * 2012-12-21 2016-06-15 中国科学院大连化学物理研究所 一种调节电驱动液-液-液萃取极性阴离子选择性的方法
CN104034572A (zh) * 2014-06-24 2014-09-10 广西中烟工业有限责任公司 一种类胡萝卜素的中空纤维膜液相微萃取的方法
EP3384978A2 (fr) 2017-04-04 2018-10-10 Extraction Technologies Norway AS Nouveaux dispositifs d'extraction à électromembrane (eme)
US10272389B2 (en) 2017-04-04 2019-04-30 Extraction Technologies Norway AS Devices for electromembrane extraction (EME)

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AU766012B2 (en) 2003-10-09
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AU1698600A (en) 2000-06-19
NO311464B1 (no) 2001-11-26
NO985613D0 (no) 1998-12-01
CA2353130A1 (fr) 2000-06-08
CA2353130C (fr) 2009-02-17
JP2002531823A (ja) 2002-09-24

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