EP2501475A1 - Système et procédé pour la détection de molécules d'analyte contenues dans des échantillons liquides - Google Patents

Système et procédé pour la détection de molécules d'analyte contenues dans des échantillons liquides

Info

Publication number
EP2501475A1
EP2501475A1 EP10816365A EP10816365A EP2501475A1 EP 2501475 A1 EP2501475 A1 EP 2501475A1 EP 10816365 A EP10816365 A EP 10816365A EP 10816365 A EP10816365 A EP 10816365A EP 2501475 A1 EP2501475 A1 EP 2501475A1
Authority
EP
European Patent Office
Prior art keywords
measuring channel
analyte molecules
permanent magnets
susceptibility
bound
Prior art date
Legal status (The legal status 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 status listed.)
Granted
Application number
EP10816365A
Other languages
German (de)
English (en)
Other versions
EP2501475B1 (fr
Inventor
Frank Sonntag
Udo Klotzbach
Niels Schilling
Mathias Gruchow
Markus Henke
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Fraunhofer Gesellschaft zur Forderung der Angewandten Forschung eV
Original Assignee
Fraunhofer Gesellschaft zur Forderung der Angewandten Forschung eV
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 Fraunhofer Gesellschaft zur Forderung der Angewandten Forschung eV filed Critical Fraunhofer Gesellschaft zur Forderung der Angewandten Forschung eV
Publication of EP2501475A1 publication Critical patent/EP2501475A1/fr
Application granted granted Critical
Publication of EP2501475B1 publication Critical patent/EP2501475B1/fr
Not-in-force legal-status Critical Current
Anticipated expiration legal-status Critical

Links

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
    • B01L3/502—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
    • 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
    • B03C1/28—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
    • B03C1/32—Magnetic separation acting on the medium containing the substance being separated, e.g. magneto-gravimetric-, magnetohydrostatic-, or magnetohydrodynamic separation
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2200/00—Solutions for specific problems relating to chemical or physical laboratory apparatus
    • B01L2200/06—Fluid handling related problems
    • B01L2200/0647—Handling flowable solids, e.g. microscopic beads, cells, particles
    • B01L2200/0652—Sorting or classification of particles or molecules
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00—Additional constructional details
    • B01L2300/06—Auxiliary integrated devices, integrated components
    • B01L2300/0627—Sensor or part of a sensor is integrated
    • B01L2300/0636—Integrated biosensor, microarrays
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00—Additional constructional details
    • B01L2300/08—Geometry, shape and general structure
    • B01L2300/0809—Geometry, shape and general structure rectangular shaped
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00—Additional constructional details
    • B01L2300/08—Geometry, shape and general structure
    • B01L2300/0861—Configuration of multiple channels and/or chambers in a single devices
    • B01L2300/0877—Flow chambers
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2400/00—Moving or stopping fluids
    • B01L2400/04—Moving fluids with specific forces or mechanical means
    • B01L2400/0403—Moving fluids with specific forces or mechanical means specific forces
    • B01L2400/043—Moving fluids with specific forces or mechanical means specific forces magnetic forces
    • 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 invention relates to a system and a method for detecting analyte molecules contained in liquid samples. These may in particular be proteins or DNA. Particularly advantageous use is possible with very small molecules.
  • the procedure is such that a liquid sample flows through a measuring channel in which ligands specific for the respective analyte molecules are immobilized on measuring surfaces to which the
  • analyte molecules can bind analyte molecules. After binding, a detection is carried out in which it can be determined whether the respective analyte molecules are contained in the sample or not. A quantitative determination can also be made.
  • the analyte molecules are more or less evenly distributed in the liquid sample and the measurement channel has a certain required volume. As a result, the liquid sample flows through the measuring channel with a minimum layer thickness. However, a complete filling of measuring channels is preferred.
  • the transport of analyte molecules to the immobilized ligands takes place essentially by convection and diffusion. In the vicinity of the surface of measuring surfaces on which ligands are immobilized, a layer is formed in which essentially diffusion occurs. This is called Nernstsche diffusion boundary layer. The transport of analyte molecules to ligands is thereby hindered, whereby this effect increases with increasing thickness of the
  • AI proposed to lead through a flow channel formed with an inert liquid main stream.
  • main streams free of analyte molecules, a feed for liquid sample should then be arranged in front of the actual measuring surfaces.
  • Main flow can be achieved displacement of the liquid sample in the direction of the measuring surfaces with the ligands immobilized there.
  • the liquid sample can thus flow as a thin film over the measuring surfaces.
  • Sample can not be avoided. Besides, can not be influenced specifically or selectively on the binding behavior of certain analyte molecules.
  • Nanoparticles or biomolecules is possible.
  • a suitable device is described in the unpublished DE 10 2008 062 620. It should upper and possibly also below one
  • Measuring channels strip-shaped electrodes arranged at intervals to each other and each acted upon by an electrical AC voltage. The polarity changes from electrode to electrode. In this case, with a certain frequency taking into account the respective Clausius-Mossotti factor, a force is to be exerted on molecules in order to move them away when passing through them to a measuring surface or non-specifically bound foreign molecules.
  • DE 697 29 101 T2 discloses a device and a method for separating, immobilizing and quantifying biological substances. This is to be achieved by means of external and internal magnetic fields, which can be achieved with permanent magnets, which are connected to a separating magnet in relation to a ferromagnetic catcher construction. are arranged vessel to be formed.
  • the catcher construction should preferably be formed with a grid formed of a ferromagnetic material, which is to be attached to the upper inner wall of the separation vessel.
  • the force effect of the magnetic field is intended to draw molecules or cells which are coupled with magnetically reacting particles in the direction of the capture structure and to immobilize there. Subsequently, a preferred optical detection of the molecules can then be carried out.
  • At least one opening for their supply and removal is present at the beginning and end of a measuring channel within a housing in the flow direction of a fluid containing analyte molecules.
  • a sample that Analyte molecules and a liquid can be passed through the measuring channel.
  • at the bottom of the measuring channel there is a sensitive area on which ligands for the respective analyte molecules can be immobilized in the measuring channel.
  • the housing should be formed of a non-magnetic and non-magnetizable material.
  • suitable polymers and / or aluminum can be used.
  • At least one element made of a ferromagnetic material is arranged in the housing material or on the upper wall of the measuring channel.
  • two permanent magnets are arranged on both sides of the measuring channel parallel to the flow direction, or they can be arranged there temporarily.
  • a magnetic field should be formed within the measurement channel at least in the area in which the / the element (s) is arranged from ferromagnetic material. In this case, the
  • the analyte molecules and / or particles therefore have paramagnetic, supermagnetic or ferromagnetic properties.
  • a plurality of permanent magnets are arranged in a series arrangement above the measuring channel. assigns.
  • the permanent magnets are alternately magnetized alternately. The polar alignment of juxtaposed permanent magnets is therefore set against.
  • This series arrangement should be arranged at least in the region of the sensitive surface area.
  • Analyte molecules are included which have a
  • the analyte molecules and / or particles have diamagnetic properties. As it flows through, in the case of both alternative embodiments of the invention, the sample enters the area of influence of the magnetic field which is formed with the permanent magnets, so that the analyte molecules act on a force acting in the direction of the bottom of the measuring channel and the sensitive area immobilized by ligands for analyte molecules become.
  • a magnetic field formed with magnets can be influenced with ferromagnetic elements which are arranged in the magnetic field. These elements are magnetized and can lead to magnetic field intensity gradients in certain directions, depending on the particular arrangement of the magnets and the ferromagnetic elements. In the plane aligned parallel to the external magnetic field, the gradient becomes a ferromagnetic element. Perpendicular to this, the gradient of the magnetic field strength points away from the ferromagnetic element.
  • the direction-dependent force F is given by
  • X P - X f i can be positive or negative, whereby the direction of the acting force F can be changed according to the sign according to 180 °.
  • a suitable parameter for this is a corresponding selection of a liquid for the respective sample with a smaller or greater susceptibility Xf i, than the susceptibility ⁇ ⁇ of the analyte molecules.
  • One or more elements of ferromagnetic material should preferably be arranged in the flow direction in front of the sensitive surface area.
  • the ferromagnetic elements which can be used in the invention can have a very flat design and can be aligned parallel to the bottom of the measuring channel. They may, for example, be aligned in a strip shape and parallel to the flow direction of the sample.
  • ferromagnetic elements should have a thickness of 0.1 mm to 0.4 mm, while their width at least ten times greater. It may also be preferable to use only such a planar ferromagnetic element. Its width should be at least 80% of the width of the measuring channel in the flow direction.
  • One or more ferromagnetic elements should have a thickness of 0.1 mm to 0.4 mm, while their width at least ten times greater. It may also be preferable to use only such a planar ferromagnetic element. Its width should be at least 80% of the width of the measuring channel in the flow direction.
  • One or more ferromagnetic elements should have a thickness of 0.1 mm to 0.4 mm, while their width at least ten times greater. It may also be preferable to use only such a planar ferromagnetic element. Its width should be at least 80% of the width of the measuring channel in the flow direction.
  • One or more ferromagnetic elements should have a thickness of 0.1 mm to
  • Material can be conveniently embedded in the material of the housing. Direct contact with samples can thus be avoided. It can maintain a permanent exact positioning and avoid adhesion problems. However, these elements can also be made in the form of wires with circular be designed like or elliptical cross-section.
  • a magnetic field with a magnetic field strength H of at least 0.5 T should be able to be formed.
  • the magnetization of the permanent magnets should be at least 0.5T.
  • the permanent magnets can be obtained by selection of a suitable liquid with a corresponding greater susceptibility ⁇ £ ⁇ the force action direction which is caused by the gradient of magnetic field strength, with unchanged configuration also be changed. This can be used for rinsing or also removing / detaching unspecifically bound other molecules from the sensitive surface area.
  • a liquid with a larger susceptibility X f i, in which no further molecules, at least no analyte molecules are contained can flow through the measurement channel. Unspecifically bound molecules whose binding forces to ligands are smaller can be easily detached and removed from the measuring channel before the actual detection of the analyte molecules.
  • a complete rinsing of the measuring channel can be achieved and at least the analyte molecules bound to ligands can be removed so that a system thus rinsed and purified can be used again for a detection of another sample .
  • a detection of another sample For example, whole blood samples, blood plasma or other body fluids may be used for detection.
  • samples may also be more or less diluted. This can be achieved with deionized water.
  • Susceptibility X f i for example, manganese (II) chloride or gadolinium (III) complexes can be used.
  • ferromagnetic, paramagnetic or superparamagnetic particles whose size is a few nanometers can be bound to the respective analyte molecules. These particles can be made of iron,
  • the same effects for rinsing and dissolving nonspecifically bound molecules can also be achieved by changing the orientation of the external magnetic field.
  • the two permanent magnets previously arranged on the two sides of the measuring channel can be removed.
  • At least one permanent magnet is then arranged above the one or more elements formed from a ferromagnetic material.
  • the element (s) are then located between this magnet and the measuring channel.
  • the force caused by the gradient of the magnetic field strength thereby changes its direction and is opposite to the direction of force, which is responsible for tying the
  • a third possibility for purging and / or removing nonspecifically bound molecules consists of flowing through the measuring channel with a rinsing liquid in the opposite direction through the measuring channel.
  • FIG. 1 shows force vectors acting on magnetizable particles in a magnetic field, which can be utilized in the invention
  • Figure 2 is a schematic representation of a system according to the invention for deflecting
  • Figure 3 is a schematic representation of a system according to the invention in a second alternative for deflecting analyte molecules in the opposite direction from the bottom of a measurement channel;
  • Figure 4 is an exploded view of an example of a system according to the invention, arranged in the two permanent magnets on the sides of a measuring channel can and can
  • Figure 5 is an exploded view of another example of a system according to the invention.
  • FIG. 1 is intended to illustrate how the direction of forces acting on magnetic or magnetizable particles is in a magnetic field depending on the orientation of the magnetic field. This can be changed by changing the orientation of the magnetic field.
  • a housing 1 made of optically transparent polymer is formed
  • Measuring channel 3 through which a sample 2 is guided.
  • the flow direction is indicated by the arrow.
  • Particles of iron, nickel, an alloy thereof, which can also be used as a mixture with polymer, having a diameter of 5 nm to 500 nm are bound to the respective analyte molecules of sample 2.
  • the thus-prepared analyte molecules had a susceptibility ⁇ ⁇ > 0 to 100.
  • the liquid of the sample had a susceptibility ⁇ .
  • the particles may also be magnetizable polymers or a diamagnetic metal such as gold.
  • a ferromagnetic element 6 formed of iron is embedded in the polymeric material.
  • the element 6 has a thickness of 0.2 mm. Its width should be 2.5 mm.
  • the measuring channel 3 has a length of 8 mm to 10 mm in relation to the flow direction and a height of 50 m.
  • 5 should be at least 0.5 T.
  • a sensitive surface region 7 is formed, on which ligands for analyte molecules are immobilized.
  • the sensitive area 7 may be formed with a thin metal layer, preferably gold or silver.
  • an unillustrated optical waveguide can be arranged below the sensitive surface region 7, via which electromagnetic radiation can be directed at least almost under total reflection conditions onto the underside of the sensitive surface region 7.
  • the evaluation of the SPR analysis can be carried out in be known form.
  • FIG. 3 shows a system according to the invention of a second alternative in schematic form.
  • 3 permanent magnets 5.1 and 5.2 are arranged in the flow direction of the sample 2 in series above the measuring channel.
  • the juxtaposed permanent magnets 5.1 and 5.2 are each magnetized opposite to each other.
  • the susceptibility ⁇ ⁇ of the analyte molecules or possibly also the particles, which are bound to analyte molecules, thereby is less than the susceptibility ⁇ £ ⁇ the liquid or the fluid of the sample 2.
  • Susceptibility of the sample liquid can be used.
  • the sign of the term ( ⁇ ⁇ - X f i) changes and as a result the direction of the acting forces changes in the opposite direction, which can lead to the detachment of nonspecifically bound molecules.
  • ⁇ ⁇ and ⁇ f i With a larger difference of ⁇ ⁇ and ⁇ f i, all molecules can be detached and the measuring channel 3 can be cleaned.
  • FIG. 4 An example of a system according to the invention used for binding analyte molecules to ligands is in Figure 4 in an exploded view.
  • two permanent magnets 5 can be inserted laterally to the right and left of the measuring channel 3 into receptacles 9 arranged there, or used temporarily for detection.
  • a plate-shaped element 6 made of iron is embedded in the lid 1.1 of the housing 1 in the polymer of the lid 1.1.
  • the element 6 has the following dimensions L / B / H 10 / 2.5 / 0.2 mm.
  • a sensitive surface area 7 is again formed at the bottom of the measuring channel 3.
  • a sealing element 1.2 is arranged made of an elastomer, pointing to the underside in the direction of the bottom of a recess 1.3, which forms the measuring channel 3.
  • a sensitive area 7 formed as a thin gold layer. There, ligands can be immobilized.
  • a further receptacle 10 is formed, into which a further permanent magnet 8 can be inserted, if bound analyte molecules or unused specifically bound molecules are to be removed.
  • the permanent magnets 5 previously inserted into the receptacles 9 have been removed therefrom. The direction of the forces has been through the
  • the openings for the supply and removal of samples 2 may be formed in the lid 1.1.
  • FIG. 5 shows a system according to the invention without the two permanent magnets 5 arranged on the sides of the measuring channel 3.
  • permanent magnets 5.1 and 5.2 can be arranged above the measuring channel 3 in a row arrangement.
  • One or more ferromagnetic element (s) 6 are then absent in this example.

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Physics & Mathematics (AREA)
  • Fluid Mechanics (AREA)
  • Analytical Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Hematology (AREA)
  • Clinical Laboratory Science (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Investigating Or Analysing Biological Materials (AREA)
  • Investigating Or Analyzing Materials By The Use Of Magnetic Means (AREA)

Abstract

L'invention concerne un système et un procédé pour la détection de molécules d'analyte contenues dans des échantillons liquides. Il peut en particulier s'agir de protéines ou d'ADN. L'invention vise à améliorer le comportement de liaison des molécules d'analyte à des ligands. Le système selon l'invention comprend un conduit de mesure sur le fond duquel se trouve une zone de surface sensible (7). L'enveloppe est formée d'un matériau non magnétique et non magnétisable. Au moins un élément en matériau ferromagnétique peut être placé au-dessus du conduit de mesure, deux aimants permanents servant à former un champ magnétique externe étant placés de part et d'autre du conduit de mesure. Il est également possible de réaliser un champ magnétique par un montage en série d'aimants permanents qui sont respectivement magnétisés en sens contraire en alternance. Selon le champ magnétique formé, les molécules d'analyte ou les particules qui y sont liées présentent une susceptibilité magnétique appropriée de sorte qu'une force orientée vers le fond du conduit de mesure et les ligands qui y sont immobilisés agit sur les molécules d'analyte.
EP10816365.0A 2009-11-18 2010-11-15 Système et procédé pour la détection de molécules d'analyte contenues dans des échantillons liquides Not-in-force EP2501475B1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
DE200910055800 DE102009055800B4 (de) 2009-11-18 2009-11-18 System und ein Verfahren zur Detektion von in flüssigen Proben enthaltenen Analytmolekülen
PCT/DE2010/001366 WO2011060771A1 (fr) 2009-11-18 2010-11-15 Système et procédé pour la détection de molécules d'analyte contenues dans des échantillons liquides

Publications (2)

Publication Number Publication Date
EP2501475A1 true EP2501475A1 (fr) 2012-09-26
EP2501475B1 EP2501475B1 (fr) 2016-03-30

Family

ID=43797833

Family Applications (1)

Application Number Title Priority Date Filing Date
EP10816365.0A Not-in-force EP2501475B1 (fr) 2009-11-18 2010-11-15 Système et procédé pour la détection de molécules d'analyte contenues dans des échantillons liquides

Country Status (4)

Country Link
EP (1) EP2501475B1 (fr)
DE (1) DE102009055800B4 (fr)
PL (1) PL2501475T3 (fr)
WO (1) WO2011060771A1 (fr)

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WO2012079124A1 (fr) * 2010-12-14 2012-06-21 The University Of Queensland Transport d'analyte
CN111999487B (zh) * 2020-08-25 2023-03-28 思远(广东)工程技术有限公司 一种用于蛋白质结晶的永磁封闭实验装置

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Also Published As

Publication number Publication date
DE102009055800A1 (de) 2011-06-22
EP2501475B1 (fr) 2016-03-30
DE102009055800B4 (de) 2013-01-03
WO2011060771A1 (fr) 2011-05-26
PL2501475T3 (pl) 2016-09-30

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