EP2192987B1 - Dispositif et procédé de traitement de liquides avec des particules magnétiques - Google Patents

Dispositif et procédé de traitement de liquides avec des particules magnétiques Download PDF

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EP2192987B1
EP2192987B1 EP08804473.0A EP08804473A EP2192987B1 EP 2192987 B1 EP2192987 B1 EP 2192987B1 EP 08804473 A EP08804473 A EP 08804473A EP 2192987 B1 EP2192987 B1 EP 2192987B1
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Prior art keywords
magnetic particles
central element
magnetic
liquid
ratio
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German (de)
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EP2192987A1 (fr
Inventor
Ralf Himmelreich
Thomas Rothmann
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Qiagen GmbH
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Qiagen GmbH
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    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B03—SEPARATION OF SOLID MATERIALS USING LIQUIDS OR USING PNEUMATIC TABLES OR JIGS; MAGNETIC OR ELECTROSTATIC SEPARATION OF SOLID MATERIALS FROM SOLID MATERIALS OR FLUIDS; SEPARATION BY HIGH-VOLTAGE ELECTRIC FIELDS
    • B03C—MAGNETIC OR ELECTROSTATIC SEPARATION OF SOLID MATERIALS FROM SOLID MATERIALS OR FLUIDS; SEPARATION BY HIGH-VOLTAGE ELECTRIC FIELDS
    • B03C1/00—Magnetic separation
    • B03C1/02—Magnetic separation acting directly on the substance being separated
    • B03C1/28—Magnetic plugs and dipsticks
    • B03C1/288—Magnetic plugs and dipsticks disposed at the outer circumference of a recipient
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B03—SEPARATION OF SOLID MATERIALS USING LIQUIDS OR USING PNEUMATIC TABLES OR JIGS; MAGNETIC OR ELECTROSTATIC SEPARATION OF SOLID MATERIALS FROM SOLID MATERIALS OR FLUIDS; SEPARATION BY HIGH-VOLTAGE ELECTRIC FIELDS
    • B03C—MAGNETIC OR ELECTROSTATIC SEPARATION OF SOLID MATERIALS FROM SOLID MATERIALS OR FLUIDS; SEPARATION BY HIGH-VOLTAGE ELECTRIC FIELDS
    • B03C1/00—Magnetic separation
    • B03C1/005—Pretreatment specially adapted for magnetic separation
    • B03C1/01—Pretreatment specially adapted for magnetic separation by addition of magnetic adjuvants
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B03—SEPARATION OF SOLID MATERIALS USING LIQUIDS OR USING PNEUMATIC TABLES OR JIGS; MAGNETIC OR ELECTROSTATIC SEPARATION OF SOLID MATERIALS FROM SOLID MATERIALS OR FLUIDS; SEPARATION BY HIGH-VOLTAGE ELECTRIC FIELDS
    • B03C—MAGNETIC OR ELECTROSTATIC SEPARATION OF SOLID MATERIALS FROM SOLID MATERIALS OR FLUIDS; SEPARATION BY HIGH-VOLTAGE ELECTRIC FIELDS
    • B03C1/00—Magnetic separation
    • B03C1/02—Magnetic separation acting directly on the substance being separated
    • B03C1/025—High gradient magnetic separators
    • B03C1/031—Component parts; Auxiliary operations
    • B03C1/033—Component parts; Auxiliary operations characterised by the magnetic circuit
    • B03C1/0332—Component parts; Auxiliary operations characterised by the magnetic circuit using permanent magnets
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B03—SEPARATION OF SOLID MATERIALS USING LIQUIDS OR USING PNEUMATIC TABLES OR JIGS; MAGNETIC OR ELECTROSTATIC SEPARATION OF SOLID MATERIALS FROM SOLID MATERIALS OR FLUIDS; SEPARATION BY HIGH-VOLTAGE ELECTRIC FIELDS
    • B03C—MAGNETIC OR ELECTROSTATIC SEPARATION OF SOLID MATERIALS FROM SOLID MATERIALS OR FLUIDS; SEPARATION BY HIGH-VOLTAGE ELECTRIC FIELDS
    • B03C1/00—Magnetic separation
    • B03C1/02—Magnetic separation acting directly on the substance being separated
    • B03C1/025—High gradient magnetic separators
    • B03C1/031—Component parts; Auxiliary operations
    • B03C1/033—Component parts; Auxiliary operations characterised by the magnetic circuit
    • B03C1/0335—Component parts; Auxiliary operations characterised by the magnetic circuit using coils
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B03—SEPARATION OF SOLID MATERIALS USING LIQUIDS OR USING PNEUMATIC TABLES OR JIGS; MAGNETIC OR ELECTROSTATIC SEPARATION OF SOLID MATERIALS FROM SOLID MATERIALS OR FLUIDS; SEPARATION BY HIGH-VOLTAGE ELECTRIC FIELDS
    • B03C—MAGNETIC OR ELECTROSTATIC SEPARATION OF SOLID MATERIALS FROM SOLID MATERIALS OR FLUIDS; SEPARATION BY HIGH-VOLTAGE ELECTRIC FIELDS
    • B03C1/00—Magnetic separation
    • B03C1/02—Magnetic separation acting directly on the substance being separated
    • B03C1/28—Magnetic plugs and dipsticks
    • B03C1/286—Magnetic plugs and dipsticks disposed at the inner circumference of a recipient, e.g. magnetic drain bolt
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B03—SEPARATION OF SOLID MATERIALS USING LIQUIDS OR USING PNEUMATIC TABLES OR JIGS; MAGNETIC OR ELECTROSTATIC SEPARATION OF SOLID MATERIALS FROM SOLID MATERIALS OR FLUIDS; SEPARATION BY HIGH-VOLTAGE ELECTRIC FIELDS
    • B03C—MAGNETIC OR ELECTROSTATIC SEPARATION OF SOLID MATERIALS FROM SOLID MATERIALS OR FLUIDS; SEPARATION BY HIGH-VOLTAGE ELECTRIC FIELDS
    • B03C2201/00—Details of magnetic or electrostatic separation
    • B03C2201/18—Magnetic separation whereby the particles are suspended in a liquid
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B03—SEPARATION OF SOLID MATERIALS USING LIQUIDS OR USING PNEUMATIC TABLES OR JIGS; MAGNETIC OR ELECTROSTATIC SEPARATION OF SOLID MATERIALS FROM SOLID MATERIALS OR FLUIDS; SEPARATION BY HIGH-VOLTAGE ELECTRIC FIELDS
    • B03C—MAGNETIC OR ELECTROSTATIC SEPARATION OF SOLID MATERIALS FROM SOLID MATERIALS OR FLUIDS; SEPARATION BY HIGH-VOLTAGE ELECTRIC FIELDS
    • B03C2201/00—Details of magnetic or electrostatic separation
    • B03C2201/26—Details of magnetic or electrostatic separation for use in medical or biological applications

Definitions

  • the present invention relates to an apparatus and a method for treating liquids with magnetic particles.
  • the device and the method are suitable, for example, for applications in biochemistry, clinical chemistry, molecular biology, microbiology, medical diagnostics or forensic medicine.
  • the basic principle of magnetic separation of substances from complex mixtures is based on the fact that magnetic particles e.g. by chemical treatment of their surface with specific binding properties for the target substances to be separated.
  • the size of such magnetic particles is generally in the range from approximately 0.05 to 500 ⁇ m, so that they provide a large surface for the binding reaction.
  • the magnetic particles can have a density that is similar to the density of the liquid in which they are suspended. In this case, sedimentation of the magnetic particles can take a few hours.
  • the magnetic particles are immobilized at one point by using magnetic forces or a magnetic field, for example by means of a permanent magnet.
  • This accumulation of magnetic particles is also referred to as a pellet or magnetic sediment.
  • the liquid supernatant is then separated off and discarded, for example by suction or decanting. Since the magnetic particles are immobilized by the magnetic forces, magnetic particles are largely prevented from being separated off together with the supernatant.
  • the immobilized magnetic particles are typically subsequently resuspended.
  • An elution liquid or an elution buffer is used to enrich the bound target substances.
  • the bond between the target substance and the magnetic particles are released and the target substance molecules are released from the magnetic particles.
  • the target substance molecules can then be separated together with the elution liquid, while the magnetic particles are immobilized by the action of a magnetic field.
  • the target substance molecules can not only be enriched, but also concentrated.
  • One or more washing steps can be carried out before the elution step.
  • the magnetic rod attracts the magnetic particles so that the magnetic particles adhere to the rod.
  • the magnetic rod together with the magnetic particles adhering to it, is then pulled out of the reaction vessel and introduced into a second reaction vessel. There the magnetic force of the rod is then reduced or switched off, so that the magnetic particles detach from the rod and are suspended in a liquid in the reaction vessel. Similar procedures are also out of the US 6,065,605 and the WO 2005/005049 known.
  • EP 0 965 842 a device is known in which the magnetic particles are drawn up together with the liquid in which they are suspended in a pipette.
  • the pipette tip has a special separation area that can be acted upon by a magnet with a magnetic field. This turns the magnetic particles into pellets or magnetic sediments immobilized on the inside of the pipette tip.
  • the aspirated liquid is then removed from the pipette tip by the pipetting function of the device.
  • the magnetic field in the separation area can then be removed again, as a result of which the magnetic particles immobilized in the pellet are released again.
  • a similar method and a similar device are in the US 6,187,270 described.
  • the magnetic particles remain in the same reaction vessel while the liquid in this vessel is exchanged.
  • the magnetic sediments can be immobilized at a desired height on the side wall of the reaction vessel in order to adapt to a respective process step. This is done by providing magnets which are arranged on different arms of a rotatably mounted carrier at different distances from the axis of rotation. By rotating the carrier, a specific arm - and thus a specific magnet - can be brought near the side wall of the reaction vessel. At this point, the magnetic particles are then immobilized as a pellet.
  • WO 2007/063174-A describes an enrichment unit for biological components in which a magnetic rod is inserted through an opening into a bag.
  • WO 99/42832-A describes a method for transferring magnetic particles with the aid of a magnet inserted into a vessel from the outside.
  • WO 2004/035217-A describes a method for metering magnetic particles with the aid of a magnet inserted into a vessel from the outside.
  • WO 03/072531-A1 describes an apparatus and a method for obtaining magnetic particles in a slurry phase reactor, in which the magnetic particles suspended in a liquid are guided past magnetic bars.
  • the present invention is based on the object of overcoming the disadvantages arising from the prior art and, in particular, of creating a device and a method for a wide range of applications in which the treatment of liquids with magnetic particles is possible in a simple manner is.
  • a device for treating a liquid with magnetic particles comprising a vessel containing the liquid and a multiplicity of magnetic particles arranged in the liquid and at least one rod-shaped, dumbbell-shaped and / or ellipsoid-shaped magnetic and / or magnetizable central element , wherein the ratio of the longest diameter d2 of the at least one central element to the ratio of the average diameter dl of the magnetic particles at least d 2nd mm ⁇ 15 ⁇ d 1 mm , the central element being located completely inside the vessel, the device additionally comprising at least one external magnet which is designed to interact with the at least one central element, so that the central element can be moved by the external magnet.
  • central element is understood in particular to mean any object which is capable of acting through the action of a magnetic field - possibly under the action of a further “external” magnet (as described below) - to bind at least the majority of the magnetic particles to itself in the idle state.
  • the at least one central element comprises a magnet, preferably a permanent magnet; According to an alternative, preferred embodiment of the invention, the at least one central element comprises a magnetizable material, such as e.g. Iron.
  • liquids is understood to mean, but not limited to, in particular aqueous solutions, suspensions and / or two-phase emulsions with water as a phase which contain biomolecules.
  • treatment in the sense of the present invention means in particular that certain biomolecules can attach to the magnetic particles in a separation step; however, the present invention is expressly not limited to this.
  • diameter of the magnetic particles means in particular if the magnetic particles are not spherical or essentially spherical, the longest diameter of the magnetic particles in each case.
  • average diameter means in particular the arithmetic mean of the diameter of the magnetic particles, which can be measured in particular (but not limited to) on a sample basis.
  • the ratio of the longest diameter d2 of the at least one central element to the ratio of the average diameter d1 of the magnetic particles is advantageously d2 (mm) 50 50 ⁇ d1 (mm), more preferably d2 (mm) ⁇ 100 ⁇ d1 (mm), further preferably d2 (mm) ⁇ 200 ⁇ d1 (mm), and most preferably d2 (mm) ⁇ 300 ⁇ d1 (mm).
  • the number of magnetic particles per central element is ⁇ 10 4 , advantageously up to ⁇ 10 8 , preferably ⁇ 5 x 10 5 to ⁇ 5 x 10 6 .
  • the magnetic particles contain a material selected from the group consisting of paramagnetic materials, superparamagnetic materials, ferromagnetic materials, ferrimagnetic materials and mixtures thereof.
  • the average saturation magnetization of the magnetic particles is advantageously ⁇ 1 Am 2 / kg and 250 Am 2 / kg, preferably ⁇ 10 Am 2 / kg and 240 Am 2 / kg, and most preferably ⁇ 20 Am 2 / kg and 235 Am 2 / kg kg. This has been found to be advantageous for many applications of the present invention.
  • the at least one central element is rod-shaped, dumbbell-shaped and / or ellipsoid-shaped and the ratio of the longest diameter a to the ratio of the shortest diameter b is advantageously from a / b ⁇ 1.1 to a / b ⁇ 10.
  • the ratio of the longest diameter a to the ratio of the shortest diameter b is advantageously from a / b 1.5 1.5 to a / b 8 8, preferably a / b 2 2 to a / b 5 5.
  • the magnetic particles and the at least one central element are advantageously arranged in a closed vessel.
  • the added volume V m of the magnetic particles and that of the at least one central element are 0 0.25% to 50 50% of the total volume V G of the vessel. This has proven to be favorable for many applications.
  • the added volume V m of the magnetic particles and that of the at least one central element are preferably 0 0.5% to 20 20%, even more preferably 1 1% to 15 15%, of the total volume V G of the vessel.
  • the device according to the invention further comprises at least one external magnet which is designed to interact with the at least one central element.
  • the central element is a permanent magnet
  • the ratio of the magnetic strength H 3 of the at least one external magnet to the magnetic strength H 2 of the at least one central element is according to a preferred embodiment of the invention H 3 ⁇ 1.1 ⁇ H 2 to H 3 ⁇ 10 ⁇ H 2
  • the ratio of the magnetic strength H 3 of the at least one external magnet to the magnetic strength H 2 of the at least one central element is advantageously H 3 1.5 1.5 ⁇ H 2 to H 3 8 8 ⁇ H 2 , even more preferably H 3 2 2 ⁇ H 2 to H 3 ⁇ 5 ⁇ H 2 .
  • the at least one external magnet is and / or comprises an electromagnet (s) which is operated under alternating voltage for the homogenization of the magnetic particles.
  • the central element is then preferably a (permanent) magnet.
  • the at least one external magnet is and / or comprises a permanent magnet (s).
  • the central element remains in the container throughout the process.
  • step a) comprises resuspending the magnetic particles in the liquid.
  • the magnetic particles were at least partially, preferably almost completely, attached to the at least one central element, and step a) takes place by the action of an external force on the at least one central element, which during the entire process the container remains.
  • Step b) is advantageously supported by means of a further, external permanent magnet.
  • a further, external permanent magnet is brought into the vicinity of the vessel in which the magnetic particles and the at least one central element are located.
  • this allows the magnetic particles to be deposited on the at least one central element much more quickly.
  • This embodiment has also proven to be particularly advantageous when the at least one central element is not a permanent magnet.
  • the present invention also relates to the use of a device according to the invention and / or a method according to the invention for at least partial separation of biomolecules from / in a preferably aqueous solution.
  • biomolecules all biomolecules, such as, for. B understood lipids, carbohydrates, metabolites, metabolic products, all types of nucleic acids, all types of peptides and proteins, also substituted or functionalized peptides and / or proteins.
  • biomolecules is further understood - but not limited to this - to mean all molecules which occur naturally or are artificially introduced in biological samples.
  • the device according to the invention and / or the method according to the invention is advantageously used for at least partial separation of nucleic acids from / in a preferably aqueous solution.
  • nucleic acid in the sense of the present invention is particularly - but not limited to - natural, preferably isolated, linear, branched or circular nucleic acids such as RNA, in particular mRNA, siRNA, miRNA, snRNA, tRNA, hnRNA or ribozymes, DNA and Similar, synthetic or modified nucleic acids, for example oligonucleotides, in particular primers, probes or standards used for the PCR, nucleic acids labeled with digoxigenin, biotin or fluorescent dyes or so-called PNAs ( “peptide nucleic acids ”) are understood.
  • RNA in particular mRNA, siRNA, miRNA, snRNA, tRNA, hnRNA or ribozymes, DNA and Similar, synthetic or modified nucleic acids, for example oligonucleotides, in particular primers, probes or standards used for the PCR, nucleic acids labeled with digoxigenin, biotin or fluorescent dyes or so-called PNAs
  • Fig. 1 shows a very schematic view of a device according to the invention according to an embodiment. It should be noted that 1 and 2 are highly schematic and in most applications of the inventors the actual ratios (be it size ratios such as the number of magnetic particles) will be different.
  • the device comprises a plurality of first magnetic particles 10 which are attached to a central element 20 in the “idle state”.
  • Magnetic particles 10 and central magnet 20 are arranged in a (preferably closed) vessel 100, which can optionally have inlets and outlets 110 or 120 (indicated schematically in dashed lines).
  • the vessel 100 is preferably filled with a liquid 150 to such an extent that the magnetic particles 10 and the central element 20 are in the liquid.
  • the central element 20 is a permanent magnet; however, this is not limitative. As already described, the central element 20 can also contain a magnetizable material such as iron.
  • Another embodiment for moving the at least one central element is a one-dimensional oscillating movement. Due to the effect of a magnetic field that moves back and forth on a line, the at least one central element is alternately “hewn” against the opposite vessel walls, as a result of which the magnetic particles are also effectively shaken off the central element 20.
  • a shaking movement of the at least one central element can also take place by means of an electromagnet when it is operated under alternating voltage and the magnetic field polarity changes alternately, insofar this also represents a preferred embodiment of the invention. If the operating mode is changed to direct current, a magnetic separation takes place.
  • the magnetic particles 10 attach themselves to the central element 20 again, so that (essentially) the state of the Fig. 1 is reached again.
  • the liquid 150 can now be removed from the vessel, for example, or additional reagents can be added, depending on the specific application.
  • the present example is also to be understood in a purely illustrative manner with regard to the size / volume / quantity information described or the geometric design of the reaction vessel.
  • the present invention can be applied within a wide range and a person skilled in the art will accordingly choose other dimensions or arrangements.
  • the option to design this as an open system see example I.
  • the present invention also applies to Microsystems, such as micromixers etc., can be used very well in many applications, which is a preferred embodiment of the present invention.
  • Genomic DNA was isolated from 5 ml of whole blood using the following protocol: 5 ml of blood was placed in a 30 ml beaker with a central element (standard Teflon-coated stirring fish; length 2 cm; diameter 7 mm).
  • Buffer AL brand product from QIAGEN
  • QIAGEN Proteinase K
  • An external magnetic stirrer was used for 5 min. stirred to bind the genomic DNA to the magnetic particles.
  • the supernatant was removed again and 15 ml of washing buffer AW2 (QIAGEN) were added.
  • the magnetic particles were then homogenized by stirring for 60 seconds. After the stirring had stopped, the magnetic particles were deposited on the central element.
  • the supernatant was removed, then the magnetic particles were air dried for 20 min.
  • Buffer TE DNA Elution, QIAGEN
  • the UV curve of the supernatant is in Fig. 3 to see.
  • the yield can be estimated on the basis of the UV spectrum, which took place approximately quantitatively in Example 1 (approx. 170 ⁇ g genomic DNA from 5 ml whole blood).

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  • Physical Or Chemical Processes And Apparatus (AREA)
  • Automatic Analysis And Handling Materials Therefor (AREA)
  • Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
  • Apparatus Associated With Microorganisms And Enzymes (AREA)

Claims (12)

  1. Dispositif de traitement d'un liquide comportant des particules magnétiques, ledit dispositif comprenant un récipient (100), qui contient le liquide (150), et une multitude de particules magnétiques (10) disposées dans le liquide (150) ainsi qu'au moins un élément central magnétique et/ou magnétisable (20) en forme de tige, d'haltère ou d'ellipsoïde, le rapport du plus long diamètre d2 de l'au moins un élément central (20) au diamètre moyen d1 des particules magnétiques (10) étant d'au moins d 2 mm ≥ 15 * d 1 mm ,
    Figure imgb0006
     l'élément central (20) étant situé entièrement à l'intérieur du récipient (100),
    le dispositif comprenant en outre au moins un aimant externe qui est conçu pour interagir avec l'au moins un élément central (20) de sorte que l'élément central (20) peut être déplacé par l'aimant externe.
  2. Dispositif selon la revendication 1, le rapport du volume V2 de l'au moins un élément central (20) au volume moyen V1 d'une particule magnétique (10) étant V 2 mm 3 ≥ 10 * V 1 mm 3 .
    Figure imgb0007
  3. Dispositif selon la revendication 1, le nombre de particules magnétiques (10) par élément central (20) étant ≥ 104.
  4. Dispositif selon l'une des revendications 1 à 3, les particules magnétiques (10) contenant un matériau choisi dans le groupe comprenant les matériaux paramagnétiques, les matériaux superparamagnétiques, les matériaux ferromagnétiques, les matériaux ferrimagnétiques et leurs mélanges.
  5. Dispositif selon l'une des revendications 1 à 4, le volume ajouté Vm des particules magnétiques (10) ainsi que l'au moins un élément central (20) étant ≥ 0,25 % à ≤ 50 % du volume total VG du récipient (100).
  6. Dispositif selon l'une des revendications 1 à 5, l'élément central (20) comprenant au moins un aimant permanent et le rapport de la force magnétique H3 de l'au moins un aimant externe à la force magnétique H2 de l'au moins un élément central (20) étant
    H3 ≥ 1, 1∗H2 à H3 ≤ 10∗H2.
  7. Dispositif selon l'une des revendications 1 à 6, l'au moins un aimant externe étant un électroaimant.
  8. Dispositif selon l'une des revendications 1 à 6, l'au moins un aimant externe étant un aimant permanent.
  9. Procédé de traitement de liquides comportant des particules magnétiques (10) à l'aide d'un dispositif selon l'une des revendications 1 à 8, le procédé comprenant les étapes suivantes :
    a) répartir les particules magnétiques (10) dans le liquide (150) puis
    b) fixer les particules magnétiques (10) à l'au moins un élément central (20).
  10. Procédé selon la revendication 9, caractérisé en ce que l'étape a) comprend une remise en suspension des particules magnétiques (10) dans le liquide (150).
  11. Procédé selon la revendication 9 ou 10, caractérisé en ce que, avant l'étape a), les particules magnétiques (10) étaient fixées au moins partiellement à l'au moins un élément central (20) et l'étape a) est effectuée par action d'une force sur l'au moins un élément central (20).
  12. Utilisation d'un dispositif selon l'une des revendications 1 à 8 et/ou d'un procédé selon l'une des revendications 9 à 11 pour séparer au moins partiellement des biomolécules d'une/dans une solution de préférence aqueuse.
EP08804473.0A 2007-09-21 2008-09-19 Dispositif et procédé de traitement de liquides avec des particules magnétiques Active EP2192987B1 (fr)

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Application Number Priority Date Filing Date Title
DE102007045474A DE102007045474A1 (de) 2007-09-21 2007-09-21 Vorrichtung und Verfahren zum Behandeln von Flüssigkeiten mit magnetischen Partikeln
PCT/EP2008/062539 WO2009040312A1 (fr) 2007-09-21 2008-09-19 Dispositif et procédé de traitement de liquides avec des particules magnétiques

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EP2192987A1 EP2192987A1 (fr) 2010-06-09
EP2192987B1 true EP2192987B1 (fr) 2020-04-22

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US (1) US8361326B2 (fr)
EP (1) EP2192987B1 (fr)
JP (1) JP5336495B2 (fr)
DE (1) DE102007045474A1 (fr)
WO (1) WO2009040312A1 (fr)

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JP2015159733A (ja) * 2014-02-26 2015-09-07 セイコーエプソン株式会社 物質結合用固相担体の凍結乾燥体、物質含有液中の物質を物質結合用固相担体と結合させるための容器、および、物質結合用固相担体を含む凍結乾燥体の製造方法
US10711265B2 (en) 2015-06-01 2020-07-14 Qiagen Gmbh Electrophoresis assisted method for purifying a target nucleic acid using a delayed elution approach
EP3303582A1 (fr) 2015-06-01 2018-04-11 Qiagen GmbH Procédé assisté par électrophorèse et dispositif de purification d'une molécule cible chargées à partir d'un échantillon
KR101834828B1 (ko) 2017-06-02 2018-03-07 한국과학기술원 자력을 이용한 세균 농축방법

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JP2010539502A (ja) 2010-12-16
EP2192987A1 (fr) 2010-06-09
DE102007045474A1 (de) 2009-04-02
US20100307981A1 (en) 2010-12-09
WO2009040312A1 (fr) 2009-04-02
JP5336495B2 (ja) 2013-11-06

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