EP2501475B1 - System und ein verfahren zur detektion von in flüssigen proben enthaltenen analytmolekülen - Google Patents

System und ein verfahren zur detektion von in flüssigen proben enthaltenen analytmolekülen Download PDF

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Publication number
EP2501475B1
EP2501475B1 EP10816365.0A EP10816365A EP2501475B1 EP 2501475 B1 EP2501475 B1 EP 2501475B1 EP 10816365 A EP10816365 A EP 10816365A EP 2501475 B1 EP2501475 B1 EP 2501475B1
Authority
EP
European Patent Office
Prior art keywords
analyte molecules
measurement channel
susceptibility
permanent magnets
molecules
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.)
Not-in-force
Application number
EP10816365.0A
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German (de)
English (en)
French (fr)
Other versions
EP2501475A1 (de
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 Foerderung der Angewandten Forschung eV
Original Assignee
Fraunhofer Gesellschaft zur Foerderung der Angewandten Forschung eV
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Publication of EP2501475A1 publication Critical patent/EP2501475A1/de
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Publication of EP2501475B1 publication Critical patent/EP2501475B1/de
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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
    • B01L3/502—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. After binding, a detection is carried out in which it can be determined whether the respective analyte molecules in the sample are included 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. Near the surface of measurement surfaces where ligands are immobilized, a layer is formed in which diffusion substantially occurs. This is called the Nernst-type diffusion barrier layer. The transport of analyte molecules to ligands is thereby hindered, whereby this effect increases with increasing thickness of the diffusion layer.
  • strip-shaped electrodes should be arranged at intervals above one another and optionally also below a measuring channel at intervals from one another and in each case acted upon by an electrical alternating voltage.
  • the polarity changes from electrode to electrode.
  • a force action 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.
  • a device and a method for separating, immobilizing and quantifying biological substances are known. This should be done with help be achieved by external and internal magnetic fields, which are to be formed with permanent magnets, which are arranged with respect to a ferromagnetic catcher construction on a separation vessel.
  • 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.
  • FR 2 863 117 - A1 describes a microsystem for displacing fluids, the microsystem having a micro-conduit with at least one fluid and means used to establish a primary displacement of the fluid between an inlet and an outlet of the micro-conduit. Furthermore, the microsystem has magnetohydrodynamic means which cause at least a secondary displacement of the fluid.
  • the invention can be used in the field of microfluidics, inter alia for mixing fluids and for scanning particles on the surface of reactors.
  • At least one opening for supplying and discharging thereof is present in a housing in the flow direction of a fluid containing analyte molecules at a measuring channel at its beginning and end.
  • a sample comprising analyte molecules and a liquid can thus be passed through the measurement 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.
  • the measuring channel 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 within the measurement channel at least in the region in which the / the element (s) is arranged / are made of ferromagnetic material, are formed.
  • the analyte molecules have a susceptibility> 0 or particles are bound to analayt molecules whose susceptibility is> 0.
  • the total susceptibility should be> 0.
  • the analyte molecules and / or particles therefore have paramagnetic, supermagnetic or ferromagnetic properties.
  • a plurality of permanent magnets may be arranged in a series arrangement above the measuring channel.
  • 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.
  • a sample is used in which analyte molecules are present which have a susceptibility which is ⁇ 0 or particles which have a susceptibility ⁇ 0 are bound to analyte molecules.
  • the total susceptibility should be ⁇ 0.
  • the analyte molecules and / or particles have diamagnetic properties.
  • a force acting on magnetic or magnetized particles can be influenced by the gradient of the magnetic field strength within a magnetic field.
  • the respective force is dependent on the ratio of the susceptibility of the particles and the surrounding medium.
  • 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 away from the ferromagnetic element.
  • ⁇ p is the susceptibility (magentizability) of the analyte molecules or of the magnetizable particles / particles bound to them
  • ⁇ fl - the acceptability of the sample liquid in each case as dimensionless volume magnetizability in SI unit
  • ⁇ p - ⁇ fl be positive or negative, whereby the direction of the acting force F can be changed by 180 ° in accordance depending on the sign.
  • a suitable parameter for this is a corresponding selection of a liquid for the respective sample with a smaller or larger susceptibility ⁇ fl . as the susceptibility ⁇ p 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.
  • a force acting on the analyte molecules which in this case have a higher susceptibility ⁇ p as the susceptibility ⁇ fl of the sample liquid from the one or more ferromagnetic element (s) away in towards the bottom of the measuring channel and because of the flow in the direction ligands immobilized on the sensitive area are exercised.
  • the respective analyte molecules can thereby be better and more securely bound to the ligands.
  • the required sample volume can be kept small and the required time can be reduced.
  • 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. They should have a thickness of 0.1 mm to 0.4 mm have their width at least ten times greater.
  • One or more elements of ferromagnetic 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. These elements can also be formed in the form of wires with a circular 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.
  • a suitable liquid with corresponding greater susceptibility ⁇ fl By selecting a suitable liquid with corresponding greater susceptibility ⁇ fl, the direction of force action which is caused by the gradient of the magnetic field strength can also be changed with an unchanged arrangement of the permanent magnets. This can be used for rinsing or also removing / detaching unspecifically bound other molecules from the sensitive surface area.
  • a liquid with greater susceptibility ⁇ fl in which no further molecules, at least no analyte molecules contained, flow through the measuring 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.
  • such a liquid may also be achieved a complete flushing of the measuring channel and thereby at least the bound ligand analyte molecules are removed so that a so-purged and purified system is used for detection of another sample again.
  • 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.
  • paramagnetic or superparamagnetic particles can be bound to the respective analyte molecules whose size is a few nanometers. These particles can be formed from iron, nickel, cobalt or an alloy of said metals or they can also be used as a mixture with polymer.
  • the same effects for rinsing and dissolving non-specifically bound molecules can also be achieved by adjusting the orientation of the external magnetic field is changed.
  • the previously arranged on the two sides of the measuring channel two permanent magnets 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 has been exploited for binding the analyte molecules to ligands.
  • the magnitude of the acting force is dependent on the achievable with the / the permanent magnet magnetic field strength and / or its / their distance to the / the ferromagnetic element (s).
  • 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 It should be clarified how the direction of forces acting on magnetic or magnetizable particles in a magnetic field is dependent on the orientation of the magnetic field. This can be changed by changing the orientation of the magnetic field.
  • FIG. 2 In the schematic representation after FIG. 2 is shown in a side and front view formed in a housing 1 of optically transparent polymer 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 ⁇ P > 0 to 100.
  • the Liquid of the sample had a susceptibility ⁇ fl ⁇ 0.
  • the particles may also be magnetizable polymers or a diamagnetic metal, such as gold.
  • the improvement of the attachment by liquids with increased susceptibility leads to a negative difference in the term ( ⁇ P - ⁇ fl ) to a deflection of particles or analyte molecules which are diamagnetic or bound to the diamagnetic particles.
  • 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 with respect to the flow direction and a height of 50 microns.
  • the north pole of a permanent magnet 5 points in the direction of the measuring channel 3, whereas the south pole of the permanent magnet 5 arranged on the opposite side of the measuring channel 3 faces the measuring channel 3.
  • the magnetization of the permanent magnets 5 should be at least 0.5 T.
  • FIG. 2 is illustrated by the darker area of the flowing through the measuring channel 3 Sample 2, as analyte molecules move through the forces caused by the gradient of the magnetic field strength towards the bottom of the measuring channel 3.
  • a sensitive area 7 is formed, are immobilized on the ligand for analyte molecules.
  • the sensitive area 7 may be formed with a thin metal layer, preferably gold or silver.
  • an SPR analysis as for example in DE 10 2008 062 620 is described.
  • 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 a manner known per se.
  • FIG. 3 a system not belonging to the invention is shown 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 ⁇ p of the analyte molecules or possibly also of the particles which are bound to analyte molecules is smaller than the susceptibility ⁇ fl of the liquid or the fluid of the sample 2.
  • a force is exerted on the analyte molecules in the sample 2 and can be utilized for a movement in the direction of the sensitive area 7 arranged at the bottom of the measuring channel 3 in order to improve the binding behavior of the analyte molecules to ligands immobilized there.
  • a rinsing liquid with a higher susceptibility ⁇ fl than the susceptibility of the sample liquid instead of the sample only a rinsing liquid with a higher susceptibility ⁇ fl than the susceptibility of the sample liquid can be used.
  • the sign of the term ( ⁇ p - ⁇ fl ) 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.
  • ⁇ p and ⁇ fl With a larger difference of ⁇ p and ⁇ fl , 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 disclosed in US Pat FIG. 4 shown in an exploded view.
  • two permanent magnets 5 can be inserted laterally to the right and left of the measuring channel 3 into recesses 9 arranged there or can be used temporarily for a 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 disposed of an elastomer, pointing to the bottom in the direction of the bottom 1.3 facing a recess is present, 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, in which a further permanent magnet 8 can be used when bound analyte molecules or non-specifically bound molecules to be removed.
  • the permanent magnets 5 previously inserted into the receptacles 9 have been removed therefrom.
  • 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 arranged on the sides of the measuring channel 3 permanent magnets. 5 Otherwise this corresponds to in FIG. 5 shown system by example FIG. 4 , wherein, however, can be additionally dispensed with the formation of shots 9 and 10 in the lid 1.1.

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  • 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 Analyzing Materials By The Use Of Magnetic Means (AREA)
  • Investigating Or Analysing Biological Materials (AREA)
EP10816365.0A 2009-11-18 2010-11-15 System und ein verfahren zur detektion von in flüssigen proben enthaltenen analytmolekülen Not-in-force EP2501475B1 (de)

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 (de) 2009-11-18 2010-11-15 System und ein verfahren zur detektion von in flüssigen proben enthaltenen analytmolekülen

Publications (2)

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

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EP10816365.0A Not-in-force EP2501475B1 (de) 2009-11-18 2010-11-15 System und ein verfahren zur detektion von in flüssigen proben enthaltenen analytmolekülen

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

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WO2012079124A1 (en) * 2010-12-14 2012-06-21 The University Of Queensland Analyte transport
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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DE69729101T2 (de) * 1996-06-07 2005-05-12 Immunivest Corp., Wilmington Magnetische trennung mit hilfe von externen und internen gradienten
TW496775B (en) * 1999-03-15 2002-08-01 Aviva Bioscience Corp Individually addressable micro-electromagnetic unit array chips
US20020001855A1 (en) * 2000-03-22 2002-01-03 Prentiss Mara G. Methods and apparatus for parallel magnetic biological analysis and manipulation
EP1328342A4 (en) * 2000-10-10 2006-03-15 Aviva Biosciences Corp INTEGRATED BIOCHIP SYSTEM FOR SAMPLE PREPARATION AND ANALYSIS
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US20030040129A1 (en) * 2001-08-20 2003-02-27 Shah Haresh P. Binding assays using magnetically immobilized arrays
US20040018611A1 (en) * 2002-07-23 2004-01-29 Ward Michael Dennis Microfluidic devices for high gradient magnetic separation
CN1280428C (zh) * 2003-05-19 2006-10-18 清华大学 一种基于微小颗粒的生物芯片系统及其应用
FR2863117B1 (fr) * 2003-11-28 2006-02-17 Commissariat Energie Atomique Microsysteme pour le deplacement de fluide
JP2006010535A (ja) * 2004-06-25 2006-01-12 Canon Inc 標的物質捕捉方法および装置
DE102004040785B4 (de) * 2004-08-23 2006-09-21 Kist-Europe Forschungsgesellschaft Mbh Mikrofluidisches System zur Isolierung biologischer Partikel unter Verwendung der immunomagnetischen Separation
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BRPI0721509A2 (pt) * 2007-03-26 2013-01-15 Fundacion Gaiker mÉtodo e dispositivo para detecÇço de material genÉtico por reaÇço em cadeia da polimerase
GB0711861D0 (en) * 2007-06-19 2007-07-25 Univ Hull Method of operating a fluidic device and a fluidic device for use in the method
ATE555836T1 (de) * 2007-06-29 2012-05-15 Harvard College Materialtrennungsverfahren auf dichtebasis, überwachung feststoffunterstützter reaktionen und messung der dichte kleiner flüssigkeitsvolumina und feststoffe
DE102008062620B4 (de) 2008-12-10 2012-12-27 Fraunhofer-Gesellschaft zur Förderung der angewandten Forschung e.V. Vorrichtung und Verfahren zur Detektion von in flüssigen Proben enthaltenen Analytmolekülen

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EP2501475A1 (de) 2012-09-26
PL2501475T3 (pl) 2016-09-30
DE102009055800B4 (de) 2013-01-03
DE102009055800A1 (de) 2011-06-22
WO2011060771A1 (de) 2011-05-26

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