WO1994018565A1 - Method and means for magnetic particle specific binding assay - Google Patents

Method and means for magnetic particle specific binding assay Download PDF

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Publication number
WO1994018565A1
WO1994018565A1 PCT/FI1994/000048 FI9400048W WO9418565A1 WO 1994018565 A1 WO1994018565 A1 WO 1994018565A1 FI 9400048 W FI9400048 W FI 9400048W WO 9418565 A1 WO9418565 A1 WO 9418565A1
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WO
WIPO (PCT)
Prior art keywords
vessel
remover
particles
equipment
medium
Prior art date
Application number
PCT/FI1994/000048
Other languages
French (fr)
Inventor
Jukka Tuunanen
Original Assignee
Labsystems Oy
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
Priority claimed from FI930440A external-priority patent/FI930440A0/en
Priority claimed from FI932866A external-priority patent/FI932866A0/en
Application filed by Labsystems Oy filed Critical Labsystems Oy
Priority to DE69429159T priority Critical patent/DE69429159T2/en
Priority to JP06517693A priority patent/JP3142873B2/en
Priority to EP94905132A priority patent/EP0681700B1/en
Publication of WO1994018565A1 publication Critical patent/WO1994018565A1/en
Priority to NO19953014A priority patent/NO318762B1/en
Priority to FI953669A priority patent/FI953669A0/en
Priority to US09/479,615 priority patent/US6447729B1/en

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Classifications

    • 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
    • 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
    • B01L3/02—Burettes; Pipettes
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
    • G01N33/543—Immunoassay; Biospecific binding assay; Materials therefor with an insoluble carrier for immobilising immunochemicals
    • G01N33/54313—Immunoassay; Biospecific binding assay; Materials therefor with an insoluble carrier for immobilising immunochemicals the carrier being characterised by its particulate form
    • G01N33/54326—Magnetic particles
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
    • G01N33/543—Immunoassay; Biospecific binding assay; Materials therefor with an insoluble carrier for immobilising immunochemicals
    • G01N33/54366—Apparatus specially adapted for solid-phase testing
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • G01N35/02—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor using a plurality of sample containers moved by a conveyor system past one or more treatment or analysis stations
    • G01N35/026—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor using a plurality of sample containers moved by a conveyor system past one or more treatment or analysis stations having blocks or racks of reaction cells or cuvettes
    • 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
    • B01L2200/0657—Pipetting powder
    • 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
    • B01L2300/04—Closures and closing means
    • B01L2300/041—Connecting closures to device or container
    • B01L2300/044—Connecting closures to device or container pierceable, e.g. films, membranes
    • 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
    • B01L2300/0829—Multi-well plates; Microtitration plates
    • 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
    • B01L2300/0848—Specific forms of parts of containers
    • 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
    • B01L2300/16—Surface properties and coatings
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • B01L3/508—Containers for the purpose of retaining a material to be analysed, e.g. test tubes rigid containers not provided for above
    • B01L3/5085—Containers for the purpose of retaining a material to be analysed, e.g. test tubes rigid containers not provided for above for multiple samples, e.g. microtitration plates
    • B01L3/50853—Containers for the purpose of retaining a material to be analysed, e.g. test tubes rigid containers not provided for above for multiple samples, e.g. microtitration plates with covers or lids
    • 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
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • G01N35/10—Devices for transferring samples or any liquids to, in, or from, the analysis apparatus, e.g. suction devices, injection devices
    • G01N2035/1027—General features of the devices
    • G01N2035/1048—General features of the devices using the transfer device for another function
    • G01N2035/1055—General features of the devices using the transfer device for another function for immobilising reagents, e.g. dried reagents
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • G01N35/0098—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor involving analyte bound to insoluble magnetic carrier, e.g. using magnetic separation
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • G01N35/10—Devices for transferring samples or any liquids to, in, or from, the analysis apparatus, e.g. suction devices, injection devices
    • G01N35/1065—Multiple transfer devices
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • G01N35/10—Devices for transferring samples or any liquids to, in, or from, the analysis apparatus, e.g. suction devices, injection devices
    • G01N35/1081—Devices for transferring samples or any liquids to, in, or from, the analysis apparatus, e.g. suction devices, injection devices characterised by the means for relatively moving the transfer device and the containers in an horizontal plane
    • G01N35/109—Devices for transferring samples or any liquids to, in, or from, the analysis apparatus, e.g. suction devices, injection devices characterised by the means for relatively moving the transfer device and the containers in an horizontal plane with two horizontal degrees of freedom
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
    • Y10S—TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10S436/00—Chemistry: analytical and immunological testing
    • Y10S436/806—Electrical property or magnetic property
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
    • Y10S—TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10S436/00—Chemistry: analytical and immunological testing
    • Y10S436/807—Apparatus included in process claim, e.g. physical support structures
    • Y10S436/808—Automated or kit
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
    • Y10T—TECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION
    • Y10T436/00—Chemistry: analytical and immunological testing
    • Y10T436/25—Chemistry: analytical and immunological testing including sample preparation
    • Y10T436/25375—Liberation or purification of sample or separation of material from a sample [e.g., filtering, centrifuging, etc.]

Definitions

  • the invention concerns a determination method and equipment as well as an adapter for use in these.
  • the invention concerns a determination method and equipment as well as an adapter for use in these.
  • . is especially applicable to automatic immunodetermination systems.
  • Solid-phase immunodetermination is usually performed in one vessel so that the analyte to be determined and possibly contained in the sample is first allowed to react with a separating reagent bound in a solid phase, whereupon the other steps required in the determination are performed in the same vessel.
  • the troublesome thing here is that much dosing and removing of liquids must be performed. When several different determinations are done, a large stock of different reagents is also needed.
  • a system is also known wherein the solution to be used in each determination step is placed in advance in its own vessel.
  • the solid phase is formed by the inside surface of a disposable pipette jet.
  • the pipette jet is brought into the respective vessel, the solution is drawn into the jet and a reaction is allowed to take place, whereafter the jet is emptied and moved into the next vessel.
  • the solution is moved back and forth in the jet.
  • the equipment has several suction cylinders with pumps so that several determina ⁇ tions can be performed in parallel. No exact dosing devices are required in this equipment. Nor are any reagent containers required in the equipment.
  • the drawback is that through a vapour phase samples are in connection with the cylinders of the equipment which can not, however, be washed automatically.
  • a separating reagent means such a substance which reacts with the analyte to be determined and • binds it in a solid phase. In immunodeterminations the separating reagent is usually an antigen or an antibody.
  • a medium here generally means a solution, such as a reaction solution or a washing fluid, to be used in some determination step.
  • the outer surface of solid particles separate from the reaction vessel is used as the solid phase in the method and the determination steps are carried out in two or several vessels.
  • the particles are moved from one vessel to another using a special remover.
  • the particles are kept in the vessel containing the sample and a separating reaction is allowed to take place. Then any other required steps are performed in other vessels, and finally the particles are moved to the measuring vessel. Mediums needed for the determination are dosed beforehand into the vessels.
  • the particles are preferably magnetic particles, whereby the remover preferably contains a magnet which can be moved in relation to the remover.
  • the vessels are preferably formed as one unit. In principle, however, some steps, especially measuring of the formed reaction product, can be performed outside the vessel unit, if desired.
  • An outside measuring vessel could be used especially when the complex is detected directly from the solid phase, for example, fluorometrically or radiometrically.
  • steps can also be performed in the same vessel.
  • a medium can also be dosed into some vessel or removed from it. Separate dosings could possibly- be used in those steps where exact dosing is not necessary and where, for example, the same medium is used in several different determinations. Washes, in particular, could be such steps. However, normally such vessel units are more advantage ⁇ ous where all different mediums are ready in different vessels.
  • At least washes are usually performed in intermediate determination steps.
  • the resulting reaction complex is usually joined in a middle step to a tracer which is then detected in the measuring step.
  • the tracer can be either directly detectable or it can be a tracer which releases a detectable compound from a special substrate. Detection usually takes place fluorometrically, luminometrically, absorptiometrically or radiometrically.
  • the method can be carried out using simple and very reliably-operating automatic equipment.
  • the invention is suitable, for example, for immunologic, DNA-hybridization or hormone determinations.
  • the remover surface is preferably such that liquid will run off it as completely as possible.
  • the bottom of the reaction vessel is advantageously designed with the same shape as the remover, whereby as little medium as possible will be needed.
  • a very large solid-phase surface area is obtained by using solid-phase particles which are separate from the remover.
  • the most advantageous ones are so-called microparticles.
  • Magnetic particles are preferably used which are made to adhere easily to the remover with the aid of a magnet.
  • the remover is provided, for example, with a grid or a filter to separate the particles from the medium.
  • the medium is preferably agitated during the reaction. This is preferably done by moving the remover. It is especially advantageous to move the remover in a vertical direction, whereby the medium must flow through a gap between the vessel and the remover, thus blending very effectively. To make blending more effective the remover is made so wide that a gap of a suitable narrowness is formed between the vessel and the remover. Agitation can also be promoted by a suitable remover and vessel design.
  • the vessel unit forms a plate for use in one determina ⁇ tion.
  • the remover can be packed into some vessel in the plate.
  • the vessels for use in different steps may also be of different sizes.
  • the vessels are preferably closed with a film, which is punctured while carrying out the method.
  • the film can be punctured by using the remover, but a separate puncturing point may also be used.
  • the point may have cutting blades which form strips which tear in a controlled manner.
  • the puncturing point may be attached to the same actuator as the remover in the equipment.
  • the top edge of the vessel preferably has an extension against which the strips of the punctured film can rest. Closed vessels may contain an inert vapour phase to improve durability.
  • the equipment can also have a safeguarding system, which
  • the remover may work conveniently as the indicator of such a system based on electric conductivity measurement.
  • reaction vessel in particular into which the sample is brought some suitable substance may be fastened to the vessel wall or to a separate solid phase remaining in the vessel, which substance binds such substances from the sample or from the formed complex which may disturb later determination steps.
  • the plate vessels are preferably in a single straight row, whereby the remover need be moved only along a straight path in the horizontal plane in relation to the plate.
  • the vessels for the different steps may be located in any order in relation to each other.
  • the vessels are preferably permanently fixed to one another.
  • the plate may be made of some suitable material, preferably of plastic.
  • the plate is advantageously provided with detents and the equipment provided with their counterparts, so that the plate can not be located in a wrong position by mistake.
  • FIG. 1 shows a magnetic particle remover in a reaction vessel for use in implementation of the method
  • FIG. 5 shows a third magnetic particle remover located in a reaction vessel and usable for implementation of the metho .
  • Figure 6 shows a top view of the remover in Figure 5.
  • immunodetermination is performed by using a plate 1, which consists of wells 2 located in a straight line and a remover 3 provided with a cylindrical sheath 4.
  • the remover At its bottom end the remover has a sharp point 5 and the bottom end is shaped as a cone 6.
  • the remover has a handle 7 which is advantageous for robotics and at which the remover can be grasped for exact control of its • horizontal and vertical positions.
  • the well also contains magnetic particles 8 coated with a separating reagent which reacts to form a complex with the analyte to be determined.
  • the remover has a bore 9 containing a movable pin 11 provided with a magnet 10.
  • the magnet 10 in Figure 1 has two magnets one above the other so that identical poles are opposite to one another (SN- NS).
  • SN- NS identical poles are opposite to one another
  • the outside field of the magnet couple weakens in the vertical direction, whereby particles will gather more easily only at the location of the magnets.
  • the sample to be examined is brought first to the first well 2 in plate 1 containing a suitable diluter, if required, whereupon magnetic particles 8 coated with the desired separating reagent and a remover 3 are brought into it.
  • pin 11 is in the upper position, so the particles are moving freely in the well.
  • the analyte possibly contained in the sample is now allowed to react with the separating reagent to form an immunocomplex.
  • the remover is moved in the well to promote blending.
  • the magnet is moved to the lower position, whereby the particles will gather onto the remover surface and they can be moved to the second well.
  • the particles can again be realeased, for example, to perform washing or a tracer reaction, and they can then be reassembled and then moved forward.
  • the measurement required for the determina ⁇ tion is performed in the last well.
  • Plate 1 can be made of some suitable plastic material.
  • the cover 4 diameter is chosen to match the well 2 diameter so that an efficient flow is achieved around the cover when lifting or lowering the cover.
  • several movements back and forth are preferably done with the cover in the well (for example, about 20 times in 10 seconds). - Weakly adhered particles will then drop off, but then they will probably adhere better.
  • Figures 2a and 2b show implementation of the method by using a remover of another design.
  • the first well 2 in plate 1 contains magnetic micropar- ticles 8 coated with a separating reagent for the analyte to be determined, and a diluter, if required.
  • Remover 3.1 has a boring 9 from the top which can receive pin 11 which has a magnet 10 at its lower end. At its lower end the remover has a drop-like extension 12 and its point has a sharp cusp 5. In addition, an annular recess 13 is provided in the extension surface close to its lower end.
  • the sample is brought to the first well 2, whereafter remover 3.1 is pushed into it with pin 11 in the upper position.
  • remover When the remover is moved, the medium and particles 8 will blend effectively to form a suspension.
  • the pin Upon completion of the incubation the pin is pushed down, whereby the particles will gather onto the extension 12 surface pulled by magnet 10 and form a dense mass in recess 13 (see Figure 2b).
  • the remover is now moved to the next well and the pin is pulled up, whereby the particles will again blend with the medium.
  • the particles are taken to the second well containing a first washing fluid, to the third well containing a second washing fluid and to the fourth well containing an enzyme conjugate adhering to the immunocomplex.
  • the remover After tracer incubation the remover is taken through three more reaction and washing wells for measurement in the last well containing an enzyme substrate, from which the- enzyme removes a fluorometrically detectable compound. After the substrate reaction, the remover is moved aside and a fluorometric measurement is performed in such a way that both excitation radiation and emission radiation are led through the well mouth.
  • the material is preferably opaque.
  • Lumino etric determinations can be carried out in a similar manner.
  • the measuring vessel must be transparent or the radiation must be obtained by a special arrangement (for example, a reflecting bottom) from the measuring vessel to the detector.
  • Figure 3 shows a set of equipment where ten determinations may be performed at the same time.
  • Determination plates 1 are located in cassette 14. At the end of the last well in each plate there is a code 15 telling the equipment about the determination in question. In addition, the code may be used to give other data, especially the ageing time.
  • Cassette 14 is pushed into the equipment in the longitudi ⁇ nal direction of the plates with the code end first through opening 16, whereupon the cassette will be moved automatically.
  • the equipment In the plate crosswise direction the equipment has a movable detector head 17 provided with an identifying device 18 for reading the code and a measuring device 19 for establishing the reaction result.
  • Removers and puncturing units for the well closing films, if such are used, and magnet pin moving units, if such are used, are all located on arm 20.
  • the equipment also has a thermostatic heater for keeping the plates at the desired temperature.
  • a remover for each sample plate is attached to arm 20. Samples are dosed into the first well in plates 1 in cassette 14 and the cassette is pushed inside. It moves to its extreme position, where identifying device 18 reads code 15, whereby the control unit receives the information needed for performing the determination.
  • the removers are lowered into the first wells. After incubation the removers are lifted up, the plate is moved one step forward and the second step is performed. The process goes on in this way from one well to the next and finally measurement is performed in the last well.
  • the determination result for each plate is shown on display 21.
  • All determinations may be different provided that they can be performed in the number of wells available in the plate. All wells may not be needed in all determinations, in which case they do not contain any medium.
  • FIG. 4 shows a modular set of equipment where six cassettes can be handled at the same time.
  • plates 1 used in this equipment code 15 is located at the end of the first well.
  • Cassettes 14 are preheated in incubator 22 and they are pushed into the equipment with their code end first through feed opening 16.
  • the removers needed for each cassette are located on arms 20 in the places for the corresponding plates.
  • the equipment has one common detector head 17, which can be moved in a transverse direction and which has an identifying device 18 and a measuring device 19.
  • the identifying device reads code 15 in each plate and the cassette then moves inward to its extreme position, where a sample and possibly also a diluter is dosed into the first well.
  • Dashed line 23 shows the path of movement of the dosing device.
  • the cassette is then moved outward, so that the first well is located under remover arm 20, and the first step is performed.
  • the cassette is then moved step by step inward, until the last well is located at the measuring device.
  • Figure 4 shows a schematic view of the power supplying unit 24, control unit 25, sample dosing pump 25, airing and diluter unit 26 and point washing well 27 in the equipment.
  • Plate 1 in Figure 5 is closed by film 28, which is punctured by using remover 3.2. At the mouth of wells 2 there is an enlarged part 29 against which the punctured film will rest. In the top surface of the plate there is a gap 30 between the wells. It reveals any leakage points that may exist between the wells and it also prevents liquids from moving from one well to another through such points of leakage.
  • the boring in remover 3.2 contains a movable pin 11 with a magnet 10 at its lower end.
  • Remover 3.2 has an extension 12.2 at its lower end. Its lower part is conical with a sharp point 5. In this way, the extension can be used for puncturing film 28 so that magnetic- particles 8 are protected in the sheath above the extension.
  • the extension also functions as an efficient agitating piston.
  • the bottom of wells 2 is shaped conically to match the extension.
  • Edge 31 in extension 12.2 is made sharp to minimize drop adhering.
  • lower edge 32 of the enlarged part of well 2 is suitably flared out downward to remove any remaining drop from remover 3.2 as this is removed from the well .
  • remover 3.2 The upper end of remover 3.2 is provided with a conical outh extension 33, which makes it easier to centralize the sheath in well 2.
  • a plug 34 to close the well mouth is located above the mouth extension.
  • the remover 3.2 surface above extension 12.2 is provided with vertical ridges 35. Magnetic particles 8 are located in grooves 36 between these ridges and are thus protected during transfer.
  • the groove bottoms are shaped suitably flat to facilitate release into the liquid.
  • the protecting ridges may also be threadlike (for example, one thread with two ends).

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  • Chemical Kinetics & Catalysis (AREA)
  • Clinical Laboratory Science (AREA)
  • Automatic Analysis And Handling Materials Therefor (AREA)
  • Investigating Or Analysing Biological Materials (AREA)
  • Investigating Or Analyzing Materials By The Use Of Magnetic Means (AREA)
  • Sampling And Sample Adjustment (AREA)

Abstract

The invention concerns a determination method and equipment and an adapter for use in these. In the method, the sample is allowed to react with a separating reagent bound in a solid phase to the outer surface of particles (8) which are separated from the vessel, whereafter the particles are removed from the vessel using a remover (3.2) and they are taken to a measuring vessel, if required through one or several intermediate step vessels. At least one vessel contains a medium needed in a determination step to be performed therein when the particles are brought into this vessel. The invention is especially suitable for use in automatic immunodetermination systems.

Description

METHOD AND MEANS FOR MAGNETIC PARTICLE SPECIFIC BINDING ASSAY.
TECHNICAL FIELD
The invention concerns a determination method and equipment as well as an adapter for use in these. The invention
. is especially applicable to automatic immunodetermination systems.
TECHNICAL BACKGROUND
Solid-phase immunodetermination is usually performed in one vessel so that the analyte to be determined and possibly contained in the sample is first allowed to react with a separating reagent bound in a solid phase, whereupon the other steps required in the determination are performed in the same vessel. The troublesome thing here is that much dosing and removing of liquids must be performed. When several different determinations are done, a large stock of different reagents is also needed.
A system is also known wherein the solution to be used in each determination step is placed in advance in its own vessel. The solid phase is formed by the inside surface of a disposable pipette jet. In each step the pipette jet is brought into the respective vessel, the solution is drawn into the jet and a reaction is allowed to take place, whereafter the jet is emptied and moved into the next vessel. During the step the solution is moved back and forth in the jet. The equipment has several suction cylinders with pumps so that several determina¬ tions can be performed in parallel. No exact dosing devices are required in this equipment. Nor are any reagent containers required in the equipment. However, the drawback is that through a vapour phase samples are in connection with the cylinders of the equipment which can not, however, be washed automatically. This can cause a risk of contamination. Liquid will also remain in the pipette jet and will move along to the following step. In addition, piston pumps wear easily and unpredictably, for which reason their condition must be checked often. Another problem is the sealing of the pipette jet to the suction cylinder. All things considered, much trouble can occur in this device. Besides, there is only limited solid-phase surface area available on the inner surface of the pipette jet. DESCRIPTION OF THE INVENTION
A method of determination as defined in claim 1 has now been invented. Advantageous applications of the same are presented in the other claims.
As used herein, a separating reagent means such a substance which reacts with the analyte to be determined and • binds it in a solid phase. In immunodeterminations the separating reagent is usually an antigen or an antibody. A medium here generally means a solution, such as a reaction solution or a washing fluid, to be used in some determination step.
The outer surface of solid particles separate from the reaction vessel is used as the solid phase in the method and the determination steps are carried out in two or several vessels. The particles are moved from one vessel to another using a special remover. The particles are kept in the vessel containing the sample and a separating reaction is allowed to take place. Then any other required steps are performed in other vessels, and finally the particles are moved to the measuring vessel. Mediums needed for the determination are dosed beforehand into the vessels.
The particles are preferably magnetic particles, whereby the remover preferably contains a magnet which can be moved in relation to the remover.
The vessels are preferably formed as one unit. In principle, however, some steps, especially measuring of the formed reaction product, can be performed outside the vessel unit, if desired. An outside measuring vessel could be used especially when the complex is detected directly from the solid phase, for example, fluorometrically or radiometrically.
Correspondingly, several steps, e.g. washes, can also be performed in the same vessel. A medium can also be dosed into some vessel or removed from it. Separate dosings could possibly- be used in those steps where exact dosing is not necessary and where, for example, the same medium is used in several different determinations. Washes, in particular, could be such steps. However, normally such vessel units are more advantage¬ ous where all different mediums are ready in different vessels.
At least washes are usually performed in intermediate determination steps. In addition, the resulting reaction complex is usually joined in a middle step to a tracer which is then detected in the measuring step. The tracer can be either directly detectable or it can be a tracer which releases a detectable compound from a special substrate. Detection usually takes place fluorometrically, luminometrically, absorptiometrically or radiometrically.
There is no risk of contamination in the method, because the sample is not drawn into the equipment from the plate vessels. In addition, the method can be carried out using simple and very reliably-operating automatic equipment.
The invention is suitable, for example, for immunologic, DNA-hybridization or hormone determinations.
The remover surface is preferably such that liquid will run off it as completely as possible. Preferably there is also a tip at the bottom end. The bottom of the reaction vessel is advantageously designed with the same shape as the remover, whereby as little medium as possible will be needed.
A very large solid-phase surface area is obtained by using solid-phase particles which are separate from the remover. The most advantageous ones are so-called microparticles. Magnetic particles are preferably used which are made to adhere easily to the remover with the aid of a magnet.
When using non-magnetic separate particles, the remover is provided, for example, with a grid or a filter to separate the particles from the medium.
To speed up mass transfer and thus also the necessary reaction time, the medium is preferably agitated during the reaction. This is preferably done by moving the remover. It is especially advantageous to move the remover in a vertical direction, whereby the medium must flow through a gap between the vessel and the remover, thus blending very effectively. To make blending more effective the remover is made so wide that a gap of a suitable narrowness is formed between the vessel and the remover. Agitation can also be promoted by a suitable remover and vessel design.
The vessel unit forms a plate for use in one determina¬ tion. The remover can be packed into some vessel in the plate. The vessels for use in different steps may also be of different sizes.
The vessels are preferably closed with a film, which is punctured while carrying out the method. The film can be punctured by using the remover, but a separate puncturing point may also be used. The point may have cutting blades which form strips which tear in a controlled manner. The puncturing point may be attached to the same actuator as the remover in the equipment. The top edge of the vessel preferably has an extension against which the strips of the punctured film can rest. Closed vessels may contain an inert vapour phase to improve durability.
The equipment can also have a safeguarding system, which
• will make sure before the step is started that the vessel contains a medium. The remover may work conveniently as the indicator of such a system based on electric conductivity measurement.
If desired, in that reaction vessel in particular into which the sample is brought some suitable substance may be fastened to the vessel wall or to a separate solid phase remaining in the vessel, which substance binds such substances from the sample or from the formed complex which may disturb later determination steps.
The plate vessels are preferably in a single straight row, whereby the remover need be moved only along a straight path in the horizontal plane in relation to the plate. The vessels for the different steps may be located in any order in relation to each other. The vessels are preferably permanently fixed to one another. The plate may be made of some suitable material, preferably of plastic.
The plate is advantageously provided with detents and the equipment provided with their counterparts, so that the plate can not be located in a wrong position by mistake.
Some applications of the invention will be described in the following by way of example. In the drawings of the description
- Figure 1 shows a magnetic particle remover in a reaction vessel for use in implementation of the method,
- Figures 2a and 2b show implementation of the method by using magnetic particles and another remover,
- Figure 3 shows a set of equipment usable in implementa¬ tion of the method,
- Figure 4 shows another set of equipment of greater capacity,
- Figure 5 shows a third magnetic particle remover located in a reaction vessel and usable for implementation of the metho , and
Figure 6 shows a top view of the remover in Figure 5. In accordance with Figure 1, immunodetermination is performed by using a plate 1, which consists of wells 2 located in a straight line and a remover 3 provided with a cylindrical sheath 4. At its bottom end the remover has a sharp point 5 and the bottom end is shaped as a cone 6. At its top end the remover has a handle 7 which is advantageous for robotics and at which the remover can be grasped for exact control of its • horizontal and vertical positions. The well also contains magnetic particles 8 coated with a separating reagent which reacts to form a complex with the analyte to be determined. The remover has a bore 9 containing a movable pin 11 provided with a magnet 10.
The magnet 10 in Figure 1 has two magnets one above the other so that identical poles are opposite to one another (SN- NS). In this way a powerful change of the magnetic field is created at the junction of the magnets and also an advantageous situation for pulling the particles to this point on the remover 3 surface. Correspondingly, the outside field of the magnet couple weakens in the vertical direction, whereby particles will gather more easily only at the location of the magnets. Several magnets can be placed similarly after each other. This is advantageous when a narrow structure is desired.
The sample to be examined is brought first to the first well 2 in plate 1 containing a suitable diluter, if required, whereupon magnetic particles 8 coated with the desired separating reagent and a remover 3 are brought into it. At this stage pin 11 is in the upper position, so the particles are moving freely in the well. The analyte possibly contained in the sample is now allowed to react with the separating reagent to form an immunocomplex. During the reaction the remover is moved in the well to promote blending. After incubation the magnet is moved to the lower position, whereby the particles will gather onto the remover surface and they can be moved to the second well. In the second well the particles can again be realeased, for example, to perform washing or a tracer reaction, and they can then be reassembled and then moved forward. Finally, the measurement required for the determina¬ tion is performed in the last well.
During reactions and washes the remover 3 is moved back and forth in well 2, whereby the medium will blend effectively.
Plate 1 can be made of some suitable plastic material.
No liquid transfers are required during the determination, whereby a safe, simple and reliably-operating system can be constructed.
The cover 4 diameter is chosen to match the well 2 diameter so that an efficient flow is achieved around the cover when lifting or lowering the cover. When separating particles, several movements back and forth are preferably done with the cover in the well (for example, about 20 times in 10 seconds). - Weakly adhered particles will then drop off, but then they will probably adhere better.
Figures 2a and 2b show implementation of the method by using a remover of another design.
The first well 2 in plate 1 contains magnetic micropar- ticles 8 coated with a separating reagent for the analyte to be determined, and a diluter, if required.
Remover 3.1 has a boring 9 from the top which can receive pin 11 which has a magnet 10 at its lower end. At its lower end the remover has a drop-like extension 12 and its point has a sharp cusp 5. In addition, an annular recess 13 is provided in the extension surface close to its lower end.
The sample is brought to the first well 2, whereafter remover 3.1 is pushed into it with pin 11 in the upper position. When the remover is moved, the medium and particles 8 will blend effectively to form a suspension. Upon completion of the incubation the pin is pushed down, whereby the particles will gather onto the extension 12 surface pulled by magnet 10 and form a dense mass in recess 13 (see Figure 2b). The remover is now moved to the next well and the pin is pulled up, whereby the particles will again blend with the medium. The particles are taken to the second well containing a first washing fluid, to the third well containing a second washing fluid and to the fourth well containing an enzyme conjugate adhering to the immunocomplex. After tracer incubation the remover is taken through three more reaction and washing wells for measurement in the last well containing an enzyme substrate, from which the- enzyme removes a fluorometrically detectable compound. After the substrate reaction, the remover is moved aside and a fluorometric measurement is performed in such a way that both excitation radiation and emission radiation are led through the well mouth.
Light need not be led through the well wall in the determination. For this reason, as cheap a material and as simple a manufacturing technology as possible may be used. To reduce background radiation, the material is preferably opaque.
Lumino etric determinations can be carried out in a similar manner.
If the reaction result is measured absorptiometrically, the measuring vessel must be transparent or the radiation must be obtained by a special arrangement (for example, a reflecting bottom) from the measuring vessel to the detector.
Figure 3 shows a set of equipment where ten determinations may be performed at the same time.
Determination plates 1 are located in cassette 14. At the end of the last well in each plate there is a code 15 telling the equipment about the determination in question. In addition, the code may be used to give other data, especially the ageing time.
Cassette 14 is pushed into the equipment in the longitudi¬ nal direction of the plates with the code end first through opening 16, whereupon the cassette will be moved automatically. In the plate crosswise direction the equipment has a movable detector head 17 provided with an identifying device 18 for reading the code and a measuring device 19 for establishing the reaction result. Removers and puncturing units for the well closing films, if such are used, and magnet pin moving units, if such are used, are all located on arm 20. The equipment also has a thermostatic heater for keeping the plates at the desired temperature.
A remover for each sample plate is attached to arm 20. Samples are dosed into the first well in plates 1 in cassette 14 and the cassette is pushed inside. It moves to its extreme position, where identifying device 18 reads code 15, whereby the control unit receives the information needed for performing the determination. The removers are lowered into the first wells. After incubation the removers are lifted up, the plate is moved one step forward and the second step is performed. The process goes on in this way from one well to the next and finally measurement is performed in the last well. The determination result for each plate is shown on display 21.
All determinations may be different provided that they can be performed in the number of wells available in the plate. All wells may not be needed in all determinations, in which case they do not contain any medium.
Such equipment can of course also be used where both the detector head and the removers are mounted on the same arm. Figure 4 shows a modular set of equipment where six cassettes can be handled at the same time.
In plates 1 used in this equipment code 15 is located at the end of the first well. Cassettes 14 are preheated in incubator 22 and they are pushed into the equipment with their code end first through feed opening 16. The removers needed for each cassette are located on arms 20 in the places for the corresponding plates.
The equipment has one common detector head 17, which can be moved in a transverse direction and which has an identifying device 18 and a measuring device 19. The identifying device reads code 15 in each plate and the cassette then moves inward to its extreme position, where a sample and possibly also a diluter is dosed into the first well. Dashed line 23 shows the path of movement of the dosing device. The cassette is then moved outward, so that the first well is located under remover arm 20, and the first step is performed. The cassette is then moved step by step inward, until the last well is located at the measuring device.
Figure 4 shows a schematic view of the power supplying unit 24, control unit 25, sample dosing pump 25, airing and diluter unit 26 and point washing well 27 in the equipment.
Plate 1 in Figure 5 is closed by film 28, which is punctured by using remover 3.2. At the mouth of wells 2 there is an enlarged part 29 against which the punctured film will rest. In the top surface of the plate there is a gap 30 between the wells. It reveals any leakage points that may exist between the wells and it also prevents liquids from moving from one well to another through such points of leakage.
The boring in remover 3.2 contains a movable pin 11 with a magnet 10 at its lower end.
Remover 3.2 has an extension 12.2 at its lower end. Its lower part is conical with a sharp point 5. In this way, the extension can be used for puncturing film 28 so that magnetic- particles 8 are protected in the sheath above the extension. The extension also functions as an efficient agitating piston. The bottom of wells 2 is shaped conically to match the extension.
Edge 31 in extension 12.2 is made sharp to minimize drop adhering. Correspondingly, lower edge 32 of the enlarged part of well 2 is suitably flared out downward to remove any remaining drop from remover 3.2 as this is removed from the well .
The upper end of remover 3.2 is provided with a conical outh extension 33, which makes it easier to centralize the sheath in well 2. A plug 34 to close the well mouth is located above the mouth extension.
The remover 3.2 surface above extension 12.2 is provided with vertical ridges 35. Magnetic particles 8 are located in grooves 36 between these ridges and are thus protected during transfer. The groove bottoms are shaped suitably flat to facilitate release into the liquid. The protecting ridges may also be threadlike (for example, one thread with two ends).

Claims

1. Method of determination wherein the sample possibly containing the analyte to be determined is allowed to react in a medium contained in a vessel with a separating reagent for the analyte which is bound to a solid phase separate from the vessel to form an analyte-εeparating-reagent-complex, one or several intermediate steps are performed, if required, whereupon any formed complex is established, characterized in that
- the sample is allowed to react with the separating reagent bound in a solid phase on the outer surface of solid particles,
- after the reaction the particles are removed from the vessel using a remover, to which the particles are made to adhere,
- taken to a measuring vessel, through one or several intermediate step vessels, if required, performing intermediate steps in a medium contained in these, and
- any formed complex is detected in the measuring vessel, whereby at least one vessel contains a medium required in a determination step to be performed therein when the particles are brought into this vessel.
2. Method as defined in claim 1, characterized in that the particles are magnetic particles, whereby they are made to adhere to the remover preferably using a magnet.
3. Method as defined in anyone of claims 1 - 2, charac¬ terized in that a medium is agitated in a vessel in at least some step of the determination.
4. Method as defined in claim 3, characterized in that the medium is agitated by using the remover, preferably by moving - li ¬ he remover vertically.
5. Method as defined in anyone of claims 1 - 4, charac¬ terized in that in one or several determination steps, preferably in the first step, from which the particles are moved to the next step, the sample or any formed complex is allowed to react with a substance bound to a solid phase which is added to the vessel wall or to the medium, which remains in
- the vessel, which substance will bind any substances disturbing later steps in the determination.
6. Equipment for determination of an analyte from a sample possibly containing it by allowing the sample to react in a medium contained in a vessel with a separating reagent for the analyte bound to a solid phase which is separate from the vessel to form an analyte-separating-reagent-complex, and possibly after any required intermediate steps, by establishing any formed complex, characterized in that the equipment comprises
- a reaction vessel (2) to be placed in the equipment and particles (8) for the reaction vessel on whose outer surface the separating reagent is bound in a solid phase,
- a measuring vessel and a measuring device to detect any formed complex,
- one or several vessels for any intermediate steps to be performed in a medium, and
- a remover (3) and its actuator for removing particles from the vessel and moving them to another vessel, whereby at least one vessel contains a medium for use in a determination step to be performed therein.
7. Equipment as defined in claim 6, characterized in that the particles are magnetic particles (8) and that a magnet (10) is connected to the remover for making the particles adhere to the remover after the reaction.
8. Equipment as defined in claim 7, characterized in that the remover comprises a magnetic grasping means (11) vertically movable inside the remover.
9. Equipment as defined in claim 7 or 8, characterized in that the remover surface has a profiled area (36/13) for making the particles adhere to the remover as a dense mass.
10. Equipment as defined in anyone of claims 6 - 9, characterized in that to promote flowing of liquid the remover surface is essentially downward sloping everywhere and that it is preferably also provided with a sharp nodule (5) at its lowest point.
11. Equipment as defined in anyone of claims 6 - 10, characterized in that it is provided with an agitator to agitate the medium in the vessel.
12. Equipment as defined in claim 11, characterized in that the remover (3.1/3.2) functions as agitator.
13. Equipment as defined in anyone of claims 6 - 12, ' characterized in that the reaction vessel and at least one more vessel required in the determination, preferably all vessels required in the determination, are joined together into one vessel unit (1) .
14. A set of means for use in the determination of an analyte from a sample possibly containing it by allowing the sample to react in a medium contained in a vessel with a separating reagent for the analyte bound to a solid phase which is separate from the vessel to form an analyte-separating- reagent-co plex, and possibly after any required intermediate steps, by establishing any formed complex, characterized in that the set of means comprises
- a reaction vessel (2) and solid particles (8) for it on whose outer surface the separating reagent is bound in a solid phase,
- one or several vessels (2) for any intermediate steps to be performed in a medium or a measuring vessel for detecting any formed complex, and
- a remover (3) for removing the particles from the vessel and for moving them to another vessel, whereby at least one vessel contains a medium required in a determination step to be performed therein.
15. Set of means as defined in claim 14, characterized in that the vessels contain all the mediums needed for measure¬ ment.
16. Set of means as defined in claim 14 or 15, charac¬ terized in that at least one vessel, and preferably all vessels are closed with a film (28) which can be punctured.
17. Set of means as defined in claim 16, characterized in that at least some closed vessel contains an inert vapour phase.
PCT/FI1994/000048 1993-02-01 1994-02-01 Method and means for magnetic particle specific binding assay WO1994018565A1 (en)

Priority Applications (6)

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DE69429159T DE69429159T2 (en) 1993-02-01 1994-02-01 Method for a specific magnetic particle binding test
JP06517693A JP3142873B2 (en) 1993-02-01 1994-02-01 Method and apparatus for assay by specific binding of magnetic particles
EP94905132A EP0681700B1 (en) 1993-02-01 1994-02-01 Method for magnetic particle specific binding assay
NO19953014A NO318762B1 (en) 1993-02-01 1995-07-31 Method for determining an analyte.
FI953669A FI953669A0 (en) 1993-02-01 1995-08-01 Methods and devices for carrying out binding determination using magnetic particles
US09/479,615 US6447729B1 (en) 1993-02-01 2000-01-07 Method and means for magnetic particle specific binding assay

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FI930440A FI930440A0 (en) 1993-02-01 1993-02-01 BESTAEMNINGSFOERFARANDE
FI930440 1993-02-01
FI932866 1993-06-21
FI932866A FI932866A0 (en) 1993-06-21 1993-06-21 Separeringsfoerfarande

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EP (2) EP0681700B1 (en)
JP (1) JP3142873B2 (en)
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FI (1) FI953669A0 (en)
NO (1) NO318762B1 (en)
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Cited By (31)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1996012958A1 (en) * 1994-10-20 1996-05-02 Labsystems Oy Separation device for microparticles involving a magnetic rod
WO1996012959A1 (en) * 1994-10-20 1996-05-02 Labsystems Oy Magnetic particle transfer device
WO1996012961A1 (en) * 1994-10-20 1996-05-02 Labsystems Oy Two-stage separation method
US5837144A (en) * 1994-06-16 1998-11-17 Boehringer Mannheim Gmbh Method of magnetically separating liquid components
WO1999004239A2 (en) * 1997-07-16 1999-01-28 Heermann Klaus Hinrich Magnetic pin for concentrating and separating particles
EP0965842A1 (en) * 1996-05-20 1999-12-22 Precision System Science Co., Ltd. Method and apparatus for controlling magnetic particles by pipetting machine
US6020211A (en) * 1994-10-20 2000-02-01 Labsystems Oy Separation of magnetic microparticles involving a preconcentration step
US6040192A (en) * 1993-02-01 2000-03-21 Labsystems Oy Method and means for magnetic particle specific binding assay
US6197597B1 (en) 1993-02-01 2001-03-06 Labsystems Oy Solid phase immunoassay with carriers matching the shape of sample wells
WO2001068263A1 (en) * 2000-03-14 2001-09-20 Thermo Labsystems Oy Vessel and rod
EP1198566A2 (en) * 1999-07-05 2002-04-24 Max-Planck-Gesellschaft zur Förderung der Wissenschaften e.V. Method for high-throughput selection of interacting molecules
WO2005019836A2 (en) * 2003-08-21 2005-03-03 The Secretary Of State For Defence Apparatus for processing a fluid sample
WO2009021998A1 (en) * 2007-08-14 2009-02-19 Qiagen Gmbh Method for suspending or re-suspending particles in a solution and apparatus adapted thereto
US7534081B2 (en) 2005-05-24 2009-05-19 Festo Corporation Apparatus and method for transferring samples from a source to a target
US20090181359A1 (en) * 2007-10-25 2009-07-16 Lou Sheng C Method of performing ultra-sensitive immunoassays
US7597520B2 (en) 2005-05-24 2009-10-06 Festo Corporation Apparatus and method for transferring samples from a source to a target
WO2010012641A1 (en) * 2008-07-31 2010-02-04 Eads Deutschland Gmbh Device and method for the automatic detection of biological particles
US7709212B2 (en) 2004-12-03 2010-05-04 Orion Diagnostica Oy Particle based binding assay
WO2010089138A1 (en) * 2009-02-09 2010-08-12 Caprotec Bioanalytics Gmbh Devices, systems and methods for separating magnetic particles
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US8404198B2 (en) 2008-08-27 2013-03-26 Life Technologies Corporation Apparatus for and method of processing biological samples
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US8722347B2 (en) 1997-12-09 2014-05-13 Massachusetts Institute Of Technology Optoelectronic sensor
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US9329194B2 (en) 2007-11-05 2016-05-03 Abbott Laboratories Automated analyzer for clinical laboratory
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US11235323B2 (en) 2008-08-27 2022-02-01 Life Technologies Corporation Apparatus for and method of processing biological samples

Families Citing this family (60)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2001509891A (en) * 1997-01-30 2001-07-24 メルク パテント ゲゼルシャフト ミット ベシュレンクテル ハフトング Methods for immunological measurement of analytes
JP4856831B2 (en) * 1999-07-19 2012-01-18 オルガノン・テクニカ・ベー・ヴエー Apparatus and method for mixing magnetic particles with a fluid
US7410807B2 (en) * 2000-07-24 2008-08-12 D Aurora Vito J Pregnancy and sex identification test based on saliva or other bodily fluids
DE10057396C1 (en) * 2000-11-18 2002-04-04 Karlsruhe Forschzent Separation of e.g. biomolecules from dispersion or solution, employs magnetic particles onto which substance is sorbed, and electromagnet for their extraction
US6649419B1 (en) 2000-11-28 2003-11-18 Large Scale Proteomics Corp. Method and apparatus for protein manipulation
WO2002060585A1 (en) * 2001-01-25 2002-08-08 Senomyx, Inc. Method and apparatus for solid or solution phase reaction under ambient or inert conditions
US6962674B2 (en) * 2001-02-28 2005-11-08 Varian, Inc. Dissolution test apparatus
GB0110476D0 (en) 2001-04-30 2001-06-20 Secr Defence Reagent delivery system
US6790413B2 (en) 2001-05-03 2004-09-14 Beckman Coulter, Inc. Sample presentation unit
US20030040129A1 (en) * 2001-08-20 2003-02-27 Shah Haresh P. Binding assays using magnetically immobilized arrays
US20060188875A1 (en) * 2001-09-18 2006-08-24 Perlegen Sciences, Inc. Human genomic polymorphisms
JP2005522679A (en) * 2002-04-12 2005-07-28 インストゥルメンテイション ラボラトリー カンパニー Immunoassay probe
FI120863B (en) * 2002-10-18 2010-04-15 Biocontrol Systems Inc Magnetic transfer method and microparticle transfer device
JP4732755B2 (en) 2002-11-07 2011-07-27 三菱化学メディエンス株式会社 Magnetic body for collecting magnetic particles and use thereof
KR100483684B1 (en) * 2003-01-29 2005-04-18 (주)바이오넥스 Kit for separating and purifying nucleic acids or various biological materials, and system for automatically performing separation or purification of biological materials using the same
US7601491B2 (en) * 2003-02-06 2009-10-13 Becton, Dickinson And Company Pretreatment method for extraction of nucleic acid from biological samples and kits therefor
US20040157219A1 (en) * 2003-02-06 2004-08-12 Jianrong Lou Chemical treatment of biological samples for nucleic acid extraction and kits therefor
FI20040159A0 (en) 2003-10-20 2004-02-02 Bio Mobile Oy Magnetic transfer method, microparticle transfer device, and reaction unit
US20050239091A1 (en) * 2004-04-23 2005-10-27 Collis Matthew P Extraction of nucleic acids using small diameter magnetically-responsive particles
US8211386B2 (en) 2004-06-08 2012-07-03 Biokit, S.A. Tapered cuvette and method of collecting magnetic particles
US20060024776A1 (en) * 2004-08-02 2006-02-02 Mcmillian Ray Magnetic particle capture of whole intact organisms from clinical samples
WO2006017427A1 (en) * 2004-08-03 2006-02-16 Becton, Dickinson And Company Use of magnetic material to fractionate samples
AU2005271688B2 (en) * 2004-08-03 2011-10-06 Becton, Dickinson And Company Use of magnetic material to direct isolation of compounds and fractionation of multipart samples
GB0503986D0 (en) * 2005-02-26 2005-04-06 Secr Defence Reaction apparatus
AU2006350038B2 (en) * 2005-11-30 2011-09-15 Massachusetts Institute Of Technology Pathogen detection biosensor
EP2069041A4 (en) * 2006-10-06 2013-04-24 Promega Corp Apparatus and method for separating magnetic particles from a solution
US8283185B2 (en) * 2006-10-30 2012-10-09 Stc.Unm Magnetically susceptible particles and apparatuses for mixing the same
DK2171098T3 (en) * 2007-06-29 2018-05-22 Becton Dickinson Co PROCEDURES FOR EXTRACTION AND CLEANING COMPONENTS IN BIOLOGICAL SAMPLES
US8691149B2 (en) * 2007-11-06 2014-04-08 Abbott Laboratories System for automatically loading immunoassay analyzer
US8685322B2 (en) 2007-11-13 2014-04-01 Stratec Biomedical Ag Apparatus and method for the purification of biomolecules
US8071395B2 (en) * 2007-12-12 2011-12-06 The Board Of Trustees Of The Leland Stanford Junior University Methods and apparatus for magnetic separation of cells
KR101384142B1 (en) * 2007-12-28 2014-04-14 삼성디스플레이 주식회사 Display substrate, method for manufacturing the display substrate and display apparatus having the display substrate
WO2009094642A2 (en) * 2008-01-25 2009-07-30 Luminex Corporation Assay preparation plates, fluid assay preparation and analysis systems, and methods for preparing and analyzing assays
JP2011516075A (en) * 2008-04-09 2011-05-26 バイオニア コーポレーション Automatic purification apparatus, multiwell plate kit, and method for extracting hexane from biological sample
DE102009001864A1 (en) * 2009-03-25 2010-09-30 Qiagen Gmbh Overlay for particle separation
US9011771B2 (en) * 2009-05-15 2015-04-21 Gen-Probe Incorporated Method and apparatus for effecting automated movement of a magnet in an instrument for performing a magnetic separation procedure
US20100297778A1 (en) * 2009-05-20 2010-11-25 Abbott Laboratories Conjugate Having Cleavable Linking Agent
JP2011013042A (en) * 2009-06-30 2011-01-20 Beckman Coulter Inc Automatic analysis device and measurement method
EP2565260B1 (en) * 2010-04-30 2020-12-23 Bioneer Corporation Automatic biological sample purification device having a magnetic-field-applying unit, a method for extracting a target substance from a biological sample, and a protein expression and purification method
US8784734B2 (en) 2010-05-20 2014-07-22 Abbott Laboratories Reusable sheaths for separating magnetic particles
KR101279577B1 (en) * 2010-11-25 2013-06-27 삼성테크윈 주식회사 Magnetic beads separator
US9804179B2 (en) 2011-01-08 2017-10-31 Access Medical Systems, Ltd. Systems for immunoassay tests
FI20115175A0 (en) 2011-02-23 2011-02-23 Helsinki Thermo Fisher Scient Oy Particle processing
JP5650056B2 (en) * 2011-05-30 2015-01-07 株式会社日立ハイテクノロジーズ Sample processing apparatus and sample processing method
US8920751B2 (en) * 2011-07-08 2014-12-30 Life Technologies Corporation Automated enrichment for nucleic acid sequencing
RU2528885C2 (en) * 2011-10-04 2014-09-20 Общество с ограниченной ответственностью "Инноград Пущино" Method for detecting analyte from particle solution and device for implementing it
AU2013215159B2 (en) 2012-01-30 2018-07-12 Exact Sciences Corporation Modification of DNA on magnetic beads
CN103657548A (en) * 2012-08-31 2014-03-26 艾博生物医药(杭州)有限公司 Method and equipment for automatically adding liquid reagent
CN103805498B (en) * 2013-08-23 2015-11-25 常州金麦格生物技术有限公司 Grabbing device and there is the instrument of extraction biologically active substance of this grabbing device
KR102323205B1 (en) * 2014-08-22 2021-11-08 삼성전자주식회사 Apparatus for separating target matter and Method for separating target matter
US9656267B2 (en) * 2015-09-17 2017-05-23 Nvigen, Inc. Magnetic rack
CN105527150B (en) * 2015-12-10 2018-10-23 南京医科大学 A kind of high-throughput magnetic extracting and enriching device and enrichment method
WO2017204111A1 (en) * 2016-05-26 2017-11-30 株式会社Ｉｆｇ Apparatus and method for non-contact electrical stimulation of cells in liquid culture medium
LU93333B1 (en) * 2016-12-06 2018-06-08 Stratec Biomedical Ag Transfer Tool for use in automated analyser systems
DE202017001238U1 (en) * 2017-03-09 2017-05-05 Ritter Gmbh Plastic magnetic separation plate for performing automatic magnetic separation processes
EP3605107A4 (en) * 2017-04-28 2020-12-30 Ezdia Tech Inc. Automated immunoassay device and method using large magnetic particle complex
KR102256776B1 (en) 2018-07-26 2021-05-27 (주)바이오니아 Target Material Extraction Apparatus with exchangeable Magnetic-Rod-Block
ES2975426T3 (en) 2019-03-15 2024-07-05 Siemens Healthcare Diagnostics Inc Method and apparatus for manipulating magnetic beads
WO2021113290A1 (en) 2019-12-03 2021-06-10 Alamar Biosciences, Inc. Nucleic acid linked immune-sandwich assay (nulisa)
CN118591548A (en) * 2022-01-17 2024-09-03 南京金斯瑞生物科技有限公司 Purification method

Citations (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3985649A (en) * 1974-11-25 1976-10-12 Eddelman Roy T Ferromagnetic separation process and material
US4200613A (en) * 1977-06-03 1980-04-29 Ramco Laboratories Inc. Radioimmunoassay apparatus
EP0027008A1 (en) * 1979-09-28 1981-04-15 Ventrex Laboratories Inc. Apparatus and method for conducting simultaneous solid phase tests for multiple mobile components in fluids
EP0042755A2 (en) * 1980-06-20 1981-12-30 Unilever Plc Processes and apparatus for carrying out specific binding assays
GB2147698A (en) * 1981-11-17 1985-05-15 Unilever Plc Test apparatus for immunoassay
WO1986006493A1 (en) * 1985-04-29 1986-11-06 Labsystems Oy Method and device for carrying out immunological assays
US4649116A (en) * 1983-10-27 1987-03-10 Institut Pasteur Magnetic means for withdrawing magnetic gel beads from an assay fluid
WO1987005536A1 (en) * 1986-03-12 1987-09-24 Carbomatrix Ab Method and apparatus for collecting and dispersing ferromagnetic particles in a fluid medium
US4751053A (en) * 1984-10-23 1988-06-14 Institut Pasteur Magnetic device for removing magnetic gel balls from a medium to be analyzed and transferring them to an immunoenzymatic quantitative anaylsis medium

Family Cites Families (47)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US2471764A (en) * 1946-01-31 1949-05-31 Carl H Miller Magnetic hand pickup tool
US2683618A (en) 1950-12-11 1954-07-13 Louis Slovis Automatic pickup device
US2970002A (en) 1959-01-20 1961-01-31 Laviano Samuel Magnetic pickup
US3826619A (en) * 1971-12-21 1974-07-30 Abbott Lab Test apparatus for direct radioimmuno-assay for antigens and their antibodies
BE791340A (en) * 1972-01-06 1973-03-01 Becton Dickinson Co NEW METHOD AND APPARATUS FOR TAKING A CULTURE AND IDENTIFYING MICRO-ORGANISMS OF MOODS
US3970518A (en) * 1975-07-01 1976-07-20 General Electric Company Magnetic separation of biological particles
US4018886A (en) * 1975-07-01 1977-04-19 General Electric Company Diagnostic method and device employing protein-coated magnetic particles
US4272510A (en) * 1976-04-26 1981-06-09 Smith Kendall O Magnetic attraction transfer process for use in solid phase radioimmunoassays and in other assay methods
US4225575A (en) 1978-05-15 1980-09-30 Ventrex Laboratories, Inc. Method and apparatus for performing in vitro clinical diagnostic tests using a solid phase assay system
US4197287A (en) 1977-06-10 1980-04-08 Ventrex Laboratories Inc. Method and apparatus for performing in nitro clinical diagnostic tests using a solid phase assay system having special utility for use with automatic pipetting equipment
GB1584129A (en) * 1977-06-10 1981-02-04 Nayak P Method and apparatus for performing in vitro clinical diagnostic tests using a solid phase assay system
US4115535A (en) * 1977-06-22 1978-09-19 General Electric Company Diagnostic method employing a mixture of normally separable protein-coated particles
EP0030086B2 (en) * 1979-11-13 1990-03-14 TECHNICON INSTRUMENTS CORPORATION (a New York corporation) Test-tube assembly, kit for making it and method of manual immunoassay
US4261815A (en) 1979-12-31 1981-04-14 Massachusetts Institute Of Technology Magnetic separator and method
JPS585656A (en) * 1981-07-01 1983-01-13 Olympus Optical Co Ltd Deciding method for particle agglomeration
JPS585657A (en) * 1981-07-01 1983-01-13 Toyo Jozo Co Ltd Immunity measuring element and measuring method employing said element
JPS585658A (en) * 1981-07-02 1983-01-13 Japan Synthetic Rubber Co Ltd Carrier for immunity serological inspecting reagent
IL73187A0 (en) * 1983-10-11 1985-01-31 Lilly Co Eli Purification of esters of alkanoic acids
FI842992A0 (en) * 1984-07-26 1984-07-26 Labsystems Oy IMMUNOLOGISKT DEFINITIONSFOERFARANDE.
US4681742A (en) * 1984-10-01 1987-07-21 Cetus Corporation Assay tray
US4839276A (en) * 1984-12-05 1989-06-13 Technicon Instruments Corporation Interference - resistant liposome specific binding assay
JPS635263A (en) * 1986-06-24 1988-01-11 Yasunobu Tsukioka Examination of blood
JPS635265A (en) * 1986-06-25 1988-01-11 Toshiba Corp Method for immunoassay
JPS635266A (en) * 1986-06-25 1988-01-11 Toshiba Corp Analyser
US4891321A (en) * 1987-10-21 1990-01-02 Hubscher Thomas T Apparatus for performing determinations of immune reactants in biological fluids
EP0317286B1 (en) * 1987-11-16 1994-07-13 Amoco Corporation Magnetic separation device and methods for use in heterogeneous assays
US4895650A (en) * 1988-02-25 1990-01-23 Gen-Probe Incorporated Magnetic separation rack for diagnostic assays
DE68916843T2 (en) * 1988-04-26 1995-02-02 Nippon Telegraph & Telephone Microparticles, method and apparatus for collecting samples for use in labeling immune responses and method and apparatus for preparing samples.
EP0351857B1 (en) * 1988-07-20 1994-11-30 Olympus Optical Co., Ltd. Immunoassay method using magnetic marker particles
US5147529A (en) * 1988-08-10 1992-09-15 E. I. Du Pont De Nemours And Company Method for automatically processing magnetic solid phase reagents
EP0418026B1 (en) * 1989-09-13 1994-11-30 Kabushiki Kaisha Tiyoda Seisakusho Apparatus for pretreating cells for flow cytometry
US5066390A (en) 1990-06-04 1991-11-19 Rhodes Keith J Magnetic separator with reciprocating grate
JPH0477225A (en) 1990-07-18 1992-03-11 Nissei Plastics Ind Co Injection molder
US5200084A (en) * 1990-09-26 1993-04-06 Immunicon Corporation Apparatus and methods for magnetic separation
EP0479448A3 (en) * 1990-10-02 1992-12-23 Beckman Instruments, Inc. Magnetic separation device
US5466574A (en) * 1991-03-25 1995-11-14 Immunivest Corporation Apparatus and methods for magnetic separation featuring external magnetic means
JPH0792459B2 (en) * 1991-06-18 1995-10-09 オリンパス光学工業株式会社 Immunological test method
FR2679660B1 (en) * 1991-07-22 1993-11-12 Pasteur Diagnostics METHOD AND MAGNETIC DEVICE FOR IMMUNOLOGICAL ANALYSIS ON A SOLID PHASE.
FI922687A0 (en) * 1992-06-10 1992-06-10 Labsystems Oy AVLAEGSNINGSANORDNING.
DE69434867T2 (en) * 1993-02-01 2007-05-16 Thermo Electron Oy Device for the determination of an analyte in a sample
FI932866A0 (en) * 1993-06-21 1993-06-21 Labsystems Oy Separeringsfoerfarande
FI930440A0 (en) 1993-02-01 1993-02-01 Labsystems Oy BESTAEMNINGSFOERFARANDE
US5316151A (en) 1993-03-09 1994-05-31 The Boeing Company Magnetic particle separator
FI944940A0 (en) * 1994-10-20 1994-10-20 Labsystems Oy Tvaofasigt separeringsfoerfarande
FI944939A0 (en) * 1994-10-20 1994-10-20 Labsystems Oy Foerfarande Foer separering av partiklar
FI944938A0 (en) 1994-10-20 1994-10-20 Labsystems Oy Foerflyttningsanordning
FI944937A0 (en) 1994-10-20 1994-10-20 Labsystems Oy Separeringsanordning

Patent Citations (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3985649A (en) * 1974-11-25 1976-10-12 Eddelman Roy T Ferromagnetic separation process and material
US4200613A (en) * 1977-06-03 1980-04-29 Ramco Laboratories Inc. Radioimmunoassay apparatus
EP0027008A1 (en) * 1979-09-28 1981-04-15 Ventrex Laboratories Inc. Apparatus and method for conducting simultaneous solid phase tests for multiple mobile components in fluids
EP0042755A2 (en) * 1980-06-20 1981-12-30 Unilever Plc Processes and apparatus for carrying out specific binding assays
GB2147698A (en) * 1981-11-17 1985-05-15 Unilever Plc Test apparatus for immunoassay
US4649116A (en) * 1983-10-27 1987-03-10 Institut Pasteur Magnetic means for withdrawing magnetic gel beads from an assay fluid
US4751053A (en) * 1984-10-23 1988-06-14 Institut Pasteur Magnetic device for removing magnetic gel balls from a medium to be analyzed and transferring them to an immunoenzymatic quantitative anaylsis medium
WO1986006493A1 (en) * 1985-04-29 1986-11-06 Labsystems Oy Method and device for carrying out immunological assays
WO1987005536A1 (en) * 1986-03-12 1987-09-24 Carbomatrix Ab Method and apparatus for collecting and dispersing ferromagnetic particles in a fluid medium

Cited By (62)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6040192A (en) * 1993-02-01 2000-03-21 Labsystems Oy Method and means for magnetic particle specific binding assay
US6447729B1 (en) 1993-02-01 2002-09-10 Labsystems Oy Method and means for magnetic particle specific binding assay
US6197597B1 (en) 1993-02-01 2001-03-06 Labsystems Oy Solid phase immunoassay with carriers matching the shape of sample wells
US5837144A (en) * 1994-06-16 1998-11-17 Boehringer Mannheim Gmbh Method of magnetically separating liquid components
US6448092B1 (en) 1994-10-20 2002-09-10 Thermo Labsystems Oy Separation device for microparticles involving a magnetic rod
US6207463B1 (en) 1994-10-20 2001-03-27 Labsystems Oy Separation device for microparticles involving a magnetic rod
US5942124A (en) * 1994-10-20 1999-08-24 Labsystems, Oy Magnetic particle transfer device
WO1996012958A1 (en) * 1994-10-20 1996-05-02 Labsystems Oy Separation device for microparticles involving a magnetic rod
WO1996012959A1 (en) * 1994-10-20 1996-05-02 Labsystems Oy Magnetic particle transfer device
US6020211A (en) * 1994-10-20 2000-02-01 Labsystems Oy Separation of magnetic microparticles involving a preconcentration step
WO1996012961A1 (en) * 1994-10-20 1996-05-02 Labsystems Oy Two-stage separation method
US6065605A (en) * 1994-10-20 2000-05-23 Labsystems Oy Two-stage separation method
EP0965842A4 (en) * 1996-05-20 1999-12-22
EP0965842A1 (en) * 1996-05-20 1999-12-22 Precision System Science Co., Ltd. Method and apparatus for controlling magnetic particles by pipetting machine
WO1999004239A2 (en) * 1997-07-16 1999-01-28 Heermann Klaus Hinrich Magnetic pin for concentrating and separating particles
WO1999004239A3 (en) * 1997-07-16 1999-04-08 Heermann Klaus Hinrich Magnetic pin for concentrating and separating particles
US6403038B1 (en) 1997-07-16 2002-06-11 Klaus-Hinrich Heermann Magnetic pin for concentrating and separating particles
US8722347B2 (en) 1997-12-09 2014-05-13 Massachusetts Institute Of Technology Optoelectronic sensor
EP1198566A2 (en) * 1999-07-05 2002-04-24 Max-Planck-Gesellschaft zur Förderung der Wissenschaften e.V. Method for high-throughput selection of interacting molecules
WO2001068263A1 (en) * 2000-03-14 2001-09-20 Thermo Labsystems Oy Vessel and rod
US6596162B2 (en) 2000-03-14 2003-07-22 Thermo Labsystems Oy Vessel and rod
US9005989B2 (en) 2001-02-07 2015-04-14 Massachusetts Institute Of Technology Optoelectronic detection system
US9494579B2 (en) 2001-02-07 2016-11-15 Massachusetts Institute Of Technology Optoelectronic detection system
US8835127B2 (en) 2001-02-07 2014-09-16 Massachusetts Institute Of Technology Optoelectronic detection system
US9291549B2 (en) 2001-02-07 2016-03-22 Massachusetts Institute Of Technology Pathogen detection biosensor
EP1986014A1 (en) 2003-08-21 2008-10-29 The Secretary of State for Defence DSTL Apparatus for processing a fluid sample
AU2004267536C1 (en) * 2003-08-21 2008-12-11 The Secretary Of State For Defence Apparatus for processing a fluid sample
EP1909107A2 (en) 2003-08-21 2008-04-09 The Secretary of State for Defence DSTL Apparatus for processing a fluid sample
AU2004267536B2 (en) * 2003-08-21 2008-04-24 The Secretary Of State For Defence Apparatus for processing a fluid sample
WO2005019836A3 (en) * 2003-08-21 2005-05-12 Sec Dep For Defence Dstl Apparatus for processing a fluid sample
EP1909107A3 (en) * 2003-08-21 2008-04-23 The Secretary of State for Defence DSTL Apparatus for processing a fluid sample
WO2005019836A2 (en) * 2003-08-21 2005-03-03 The Secretary Of State For Defence Apparatus for processing a fluid sample
CN102445556A (en) * 2003-08-21 2012-05-09 英国国防部 Apparatus for processing a fluid sample
CN102445556B (en) * 2003-08-21 2014-02-26 英国国防部 Apparatus for processing a fluid sample
KR101225460B1 (en) 2003-08-21 2013-01-24 더 세크러터리 오브 스테이트 포 디펜스 Apparatus for processing a fluid sample
US8689982B2 (en) 2003-11-11 2014-04-08 Thermo Fisher Scientific Oy Particle separating device
US7709212B2 (en) 2004-12-03 2010-05-04 Orion Diagnostica Oy Particle based binding assay
US7597520B2 (en) 2005-05-24 2009-10-06 Festo Corporation Apparatus and method for transferring samples from a source to a target
US7534081B2 (en) 2005-05-24 2009-05-19 Festo Corporation Apparatus and method for transferring samples from a source to a target
US7841824B2 (en) 2005-05-24 2010-11-30 Festo Corporation Method for transferring magnetic samples from a source to a target
US7799281B2 (en) 2007-01-16 2010-09-21 Festo Corporation Flux concentrator for biomagnetic particle transfer device
CN101772379B (en) * 2007-08-14 2012-09-05 凯杰有限公司 Method for suspending or re-suspending particles in a solution and apparatus adapted thereto
WO2009021998A1 (en) * 2007-08-14 2009-02-19 Qiagen Gmbh Method for suspending or re-suspending particles in a solution and apparatus adapted thereto
AU2008288398B2 (en) * 2007-08-14 2012-11-29 Qiagen Gmbh Method for suspending or re-suspending particles in a solution and apparatus adapted thereto
US8371743B2 (en) 2007-08-14 2013-02-12 Qiagen Gmbh Method for suspending or re-suspending particles in a solution and apparatus adapted thereto
EP2033715A1 (en) * 2007-08-14 2009-03-11 Qiagen GmbH Method for suspending or re-suspending particles in a solution and device adapted therefor
US20090181359A1 (en) * 2007-10-25 2009-07-16 Lou Sheng C Method of performing ultra-sensitive immunoassays
EP2222871A1 (en) * 2007-10-25 2010-09-01 Abbott Laboratories Methods of performing ultra-sensitive immunoassays
EP2222871A4 (en) * 2007-10-25 2012-01-25 Abbott Lab Methods of performing ultra-sensitive immunoassays
EP2765206A1 (en) * 2007-10-25 2014-08-13 Abbott Laboratories Methods of performing ultra-sensitive immunoassays
US9329194B2 (en) 2007-11-05 2016-05-03 Abbott Laboratories Automated analyzer for clinical laboratory
WO2010012641A1 (en) * 2008-07-31 2010-02-04 Eads Deutschland Gmbh Device and method for the automatic detection of biological particles
US8845984B2 (en) 2008-08-27 2014-09-30 Life Technologies Corporation Apparatus for and method of processing biological samples
US8404198B2 (en) 2008-08-27 2013-03-26 Life Technologies Corporation Apparatus for and method of processing biological samples
US9808799B2 (en) 2008-08-27 2017-11-07 Life Technologies Corporation Apparatus for and method of processing biological samples
US10434509B2 (en) 2008-08-27 2019-10-08 Life Technologies Corporation Apparatus for and method of processing biological samples
US11235323B2 (en) 2008-08-27 2022-02-01 Life Technologies Corporation Apparatus for and method of processing biological samples
WO2010089138A1 (en) * 2009-02-09 2010-08-12 Caprotec Bioanalytics Gmbh Devices, systems and methods for separating magnetic particles
US8268264B2 (en) 2009-02-09 2012-09-18 Caprotec Bioanalytics Gmbh Devices, systems and methods for separating magnetic particles
US9011772B2 (en) 2009-05-12 2015-04-21 Life Technologies Corporation Apparatus for and method of automated processing of biological samples
RU2541685C2 (en) * 2009-10-30 2015-02-20 Снекма Apparatus and method of trapping magnetic particles held on magnetic plug
EP3150695A4 (en) * 2014-05-27 2018-01-17 Degree Of Freedom Scientific Machine Co., Ltd. Apparatus and method for magnetic bead method

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US6447729B1 (en) 2002-09-10
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