GB2300258A - A separation device for magnetisable particles - Google Patents

A separation device for magnetisable particles Download PDF

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Publication number
GB2300258A
GB2300258A GB9508726A GB9508726A GB2300258A GB 2300258 A GB2300258 A GB 2300258A GB 9508726 A GB9508726 A GB 9508726A GB 9508726 A GB9508726 A GB 9508726A GB 2300258 A GB2300258 A GB 2300258A
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GB
Grant status
Application
Patent type
Prior art keywords
separation device
microplate
means
magnetic separation
base
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.)
Withdrawn
Application number
GB9508726A
Other versions
GB9508726D0 (en )
Inventor
Philip John Jewess
Limited Scigen
Original Assignee
Scigen Ltd
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

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Classifications

    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/50Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • B01L3/508Containers for the purpose of retaining a material to be analysed, e.g. test tubes rigid containers not provided for above
    • B01L3/5085Containers 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
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B03SEPARATION 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
    • B03CMAGNETIC OR ELECTROSTATIC SEPARATION OF SOLID MATERIALS FROM SOLID MATERIALS OR FLUIDS; SEPARATION BY HIGH-VOLTAGE ELECTRIC FIELDS
    • B03C1/00Magnetic separation
    • B03C1/02Magnetic separation acting directly on the substance being separated
    • B03C1/28Magnetic plugs and dipsticks
    • B03C1/288Magnetic plugs and dipsticks disposed at the outer circumference of a recipient
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00Investigating or analysing materials by specific methods not covered by the preceding groups
    • G01N33/48Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/53Immunoassay; Biospecific binding assay; Materials therefor
    • G01N33/543Immunoassay; Biospecific binding assay; Materials therefor with an insoluble carrier for immobilising immunochemicals
    • G01N33/54313Immunoassay; Biospecific binding assay; Materials therefor with an insoluble carrier for immobilising immunochemicals the carrier being characterised by its particulate form
    • G01N33/54326Magnetic particles
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • G01N35/0098Automatic 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

Abstract

A magnetic separation device comprises a 96-well microplate 5 and a transparent base plate 1 (Figure 2) to which a number of magnets 2 are affixed, the base plate 1 fitting onto the base of the microplate 5 (Figure 3) with the magnets symmetrically arrayed such that each magnet is surrounded by four wells 6 of the microplate. The device is used for separating magnetisable particles provided with a coating for selective affinity for one or more compounds to be removed from the liquid in which the particles are suspended. The device causes the particles to be attracted to one side of a well for analysis to be made by a photometric, fluorometric or luminometric microplate reader.

Description

SEPARATION DEVICE FOR MAGNETISABLE PARTICLES This invention relates to a separation device for magnetisable particles.

DESCRIPTION In the fields of biochemistry, molecular genetics, cell, organelle and virus separation, environmental analysis and medical diagnostics the use of magnetic attraction is becoming widespread and increasingly accepted as a simple and rapid small-scale separation method with a number of advantages compared with other methods such as the use of columns or centrifugation.

These magnetic methods usually take the form of the use of magnetic particles coated with a reactive substance which has an affinity for certain proteins, cells, virus particles, pesticides, environmental contaminants or other materials which it is desired to analyse. Thus, when a suspension containing the magnetic carrier particles is added to the analyte, the component for which the particles have affinity is bound to the said particles and can then be separated from the rest of the suspension by means of suitable magnets. Such reactive substances which can be used in this way often have remarkable avidity and specificity for certain compounds, examples of which are antibodies (immunoglobulins) and oligonucleotides.The assays performed for the target compound present in the sample are effected by reactions using a labelled reagent, the assay being performed by measuring the amount of label either bound to the solid phase or unbound in solution.

An additional advance in this field of analysis is the ability to be able to analyse much smaller samples than could be used with earlier technology. A corollary of this has been the widespread use of methods which use and handle large numbers of small samples and which lend themselves to automation, an example of which has been the widespread adoption of standardised 96-well microplates such as Microtitres plates for such analyses. These plates permit the near simultaneous photometric, fluorometric or luminometric analysis of all 96 samples containing as little as 50 1 of solution in a few seconds when used in conjunction with suitable electronic microplate readers.

Although existing apparatuses are known for the simultaneous performing of multiple magnetic separations in a plurality of containers for heterogeneous assays, the known methods have limitations of scale or problems of adaptability to microtitre type assays. In particular, the devices already described either use sample tubes containing 1 ml or greater or, if designed for use with 96-well microplates such as Microtitrez plates or MicronicX type tubes are not adaptable for the simultaneous analysis of samples and the separation of magnetisable particles. It would be a tremendous advantage in convenience, accuracy and time if such analyses could be performed in the same sample container as is used to effect the magnetic separation.The present invention describes a means by which such magnetic separation may be effected and the analysis performed without the transfer of liquid samples contained in 96-well microplates.

A specific example of the invention will now be described with reference to the accompanying figures in which: Fig, 1 shows the device in plan view.

Fig. 2 shows the device in horizontal section.

Fig. 3 shows the device as in Fig. 2 but when placed against the base of a microplate.

Fig. 4 shows the layout of the magnets contained within the device relative to the sample wells of a microplate.

Fig. 5 and Fig. 6 show the principle of operation of the device.

Referring to the drawings, the separation device consists of base plate 1 made of clear transparent plastic cut and rebated to form a flange 3 to enable it to fit on or in the base of a 96-well microplate and drilled with holes 4 to accommodate magnets 2, Fig. 1. The magnets 2 are cut or cast to fit the holes 4 in the base plate and of such a size that they will fit in the spaces between the wells of the microplate. The magnets are optimally high intensity magnets such as those made of Neodymium/Iron/Boron or Samarium/Cobalt. These magnets would typically be between 1 and 4 mm in diameter or square and 1 and 12 mm in length. Optimally, the upper edge of each magnet is chamfered or radiused to improve location of the magnets within the recesses between the microplate wells.The magnets are attached in the recesses of the base plate by a suitable adhesive and in conjunction with the base plate constitute the invention. Alternatively, the plastic base plate may be cast directly around the array of magnets. The magnets are optimally placed in an array so that each magnet is surrounded by four microplate wells. The illustration, Fig. 4 shows the preferred configuration of the devicesuch that each magnet in the device is surrounded by four receiving wells or orifices 6 in the plate 5 and thus has a total of 24 magnets. Alternative geometries are also possible such that more magnets may be evenly arrayed between the receiving wells but surprisingly, such geometries were not found to aid significantly the separation of the magnetisable particles.The base plate 1 is machined of such dimensions that it recesses into the base of the microplate and contributes minimally to the total thickness when the device is placed on the plate, although the presence of the thin flange 3 enables the convenient disassembly of the device from the microplate. This arrangement is shown in Fig. 3 and contributes a particular advantage so that the device being thin, transparent and flat that, when placed on the microplate enables the plate to be inserted in a suitable photometric microplate reader. Such a principle is shown in Fig. 5 and Fig. 6. Fig. 5 shows a suspension of magnetisable particles or microspheres 7 contained within the receiving orifices or wells of a microplate. Fig. 6 shows the same microplate with the magnetisable device in place. It can thus be seen that the magnetisable particles are drawn to one side, allowing the light beam AoB produced by the photometric microplate reader to pass unimpeded through the solution. Such principles are well known as the basis of methods by which light-absorbing or emitting materials may be quantified when in solution by spectrophotometric, spectrofluorometric or luminometric means and its use in conjunction with the claimed device and magnetisable particles represents a peculiar advantage over other devices previously claimed.

Claims (11)

CLAIMS A SEPARATION DEVICE FOR MAGNETISABLE PARTICLES
1 A magnetic device for separating magnetisable particles provided with a coating for selective affinity for the compounds to be removed for the suspension solution consisting of (a) a base means consisting of a sheet of clear, transparent flat plastic (1) adapted to fit in or on the base of a 96-well microplate (5) adapted in turn to contain the magnetisable particles or microspheres (b) a plurality of magnet means (2) attached to the base means and spaced equidistantly around the edge of each microplate well (6) and as substantially described herein with reference to Figs. 1-6 of the accompanying drawings.
2 A magnetic separation device according to claim 1 such that each magnet means is surrounded by four microplate wells (6).
3 A magnetic separation device according to claims 1 to 2 whereby the base means is rebated to form a flange (3) to fit the base of a 96-well microplate such that when attached, the total thickness of the microplate is increased by no more than 4 mm.
4 A magnetic separation device according to claims 1 to 3 in which, when attached to a 96-well microplate, the microplate together with the device may be inserted into and the solution contained therein may be analysed by a photometric, fluorometric or luminometric microplate reader.
5 A magnetic separation device as claimed in claims 1 to 4 in which the magnet means (2) are attached to the base means by means of press fitting into suitably sized holes (4) impressed, machined or drilled into the base means (1).
6 A magnetic separation device as claimed in claims 1 to 5 in which the magnet means (2) are fixed into the holes (4) by the use of an adhesive.
7 A magnetic separation device as claimed in claims 1 to 6 in which the base means (1) is constructed by means of injection moulding around the magnet means (2).
8 A magnetic separation device as claimed in claims 1 to 7 in which the magnet means (2) are constructed of Iron.
9 A magnetic separation device as claimed in claims 1 to 8 in which the magnet means (2) are constructed of Samarium and Cobalt.
10 A magnetic separation device as claimed in claims 1 to 9 in which the magnet means (2) are constructed of Iron, Neodymium and Boron.
11 A magnetic separation device as claimed in claims 1 to 10 in which the upper surfaces of the magnet means (2) are chamfered or radiused.
GB9508726A 1995-04-28 1995-04-28 A separation device for magnetisable particles Withdrawn GB2300258A (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
GB9508726A GB2300258A (en) 1995-04-28 1995-04-28 A separation device for magnetisable particles

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
GB9508726A GB2300258A (en) 1995-04-28 1995-04-28 A separation device for magnetisable particles

Publications (2)

Publication Number Publication Date
GB9508726D0 true GB9508726D0 (en) 1995-06-14
GB2300258A true true GB2300258A (en) 1996-10-30

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Family Applications (1)

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GB9508726A Withdrawn GB2300258A (en) 1995-04-28 1995-04-28 A separation device for magnetisable particles

Country Status (1)

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GB (1) GB2300258A (en)

Cited By (16)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1999042219A1 (en) * 1998-02-20 1999-08-26 Florida State University Continuous magnetic separation of components from a mixture
EP0940181A1 (en) * 1998-03-03 1999-09-08 Wolfgang Pache Pin plate with holder attached to it by clamping or gluing
EP0970365A1 (en) * 1997-03-25 2000-01-12 Immunivest Corporation Apparatus and methods for capture and analysis of particulate entities
WO2003090605A2 (en) * 2002-04-26 2003-11-06 Board Of Regents, The University Of Texas System Method and system for the detection of cardiac risk factors
US7651868B2 (en) 2003-12-11 2010-01-26 The Board Of Regents Of The University Of Texas System Method and system for the analysis of saliva using a sensor array
EP2177271A1 (en) * 2008-10-15 2010-04-21 F. Hoffmann-Roche AG Magnetic separation system comprising flexible magnetic pins
EP2191900A1 (en) 2008-11-28 2010-06-02 F. Hoffmann-Roche AG System and method for nucleic acids containing fluid processing
US8101431B2 (en) 2004-02-27 2012-01-24 Board Of Regents, The University Of Texas System Integration of fluids and reagents into self-contained cartridges containing sensor elements and reagent delivery systems
US8105849B2 (en) 2004-02-27 2012-01-31 Board Of Regents, The University Of Texas System Integration of fluids and reagents into self-contained cartridges containing sensor elements
US8377398B2 (en) 2005-05-31 2013-02-19 The Board Of Regents Of The University Of Texas System Methods and compositions related to determination and use of white blood cell counts
EP2565648A1 (en) * 2001-12-28 2013-03-06 BioArray Solutions Ltd. Arrays of microparticles and methods of preparation thereof
US8512558B2 (en) 2010-02-19 2013-08-20 Roche Molecular Systems, Inc. Magnetic separation system comprising flexible magnetic pins
US8658042B2 (en) 2007-08-31 2014-02-25 Tecan Trading Ag Microplate carrier having magnets
CN103675265A (en) * 2013-12-20 2014-03-26 江苏金太生命科技有限公司 Elisa plate shelf applicable to microplate reader
CN103698503A (en) * 2013-12-19 2014-04-02 江苏金太生命科技有限公司 Positioning mechanism of enzyme-linked immunoassay analyzer
GB2515490A (en) * 2013-06-24 2014-12-31 Univ Dublin City An aperture array substrate device, a detection system and a method for detecting analytes in a sample

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN106917062A (en) * 2017-02-21 2017-07-04 成都晟翔科技有限公司 Method for removing furnace slag in nitriding salt bath by utilizing magnetic adsorption principle

Citations (3)

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Publication number Priority date Publication date Assignee Title
EP0030086A1 (en) * 1979-11-13 1981-06-10 TECHNICON INSTRUMENTS CORPORATION (a New York corporation) Test-tube assembly, kit for making it and method of manual immunoassay
EP0317286A2 (en) * 1987-11-16 1989-05-24 Amoco Corporation Magnetic separation device and methods for use in heterogeneous assays
WO1992005443A1 (en) * 1990-09-15 1992-04-02 Medical Research Council Reagent separation

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0030086A1 (en) * 1979-11-13 1981-06-10 TECHNICON INSTRUMENTS CORPORATION (a New York corporation) Test-tube assembly, kit for making it and method of manual immunoassay
EP0317286A2 (en) * 1987-11-16 1989-05-24 Amoco Corporation Magnetic separation device and methods for use in heterogeneous assays
WO1992005443A1 (en) * 1990-09-15 1992-04-02 Medical Research Council Reagent separation

Cited By (28)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0970365A4 (en) * 1997-03-25 2001-01-17 Immunivest Corp Apparatus and methods for capture and analysis of particulate entities
US6623983B1 (en) 1997-03-25 2003-09-23 Immunivest Corporation Apparatus and methods for capture and analysis of particulate entities
EP0970365A1 (en) * 1997-03-25 2000-01-12 Immunivest Corporation Apparatus and methods for capture and analysis of particulate entities
US6036857A (en) * 1998-02-20 2000-03-14 Florida State University Research Foundation, Inc. Apparatus for continuous magnetic separation of components from a mixture
US6129848A (en) * 1998-02-20 2000-10-10 The Florida State University Method for continuous magnetic separation of components from a mixture
US6132607A (en) * 1998-02-20 2000-10-17 The Florida State University System for continuous magnetic separation of components from a mixture
WO1999042219A1 (en) * 1998-02-20 1999-08-26 Florida State University Continuous magnetic separation of components from a mixture
EP0940181A1 (en) * 1998-03-03 1999-09-08 Wolfgang Pache Pin plate with holder attached to it by clamping or gluing
US9611507B2 (en) 2001-12-28 2017-04-04 Bioarray Solutions, Ltd. Arrays of microparticles and methods of preparation thereof
EP2565648A1 (en) * 2001-12-28 2013-03-06 BioArray Solutions Ltd. Arrays of microparticles and methods of preparation thereof
US10138511B2 (en) 2001-12-28 2018-11-27 Bioarray Solutions Ltd. Arrays of microparticles and methods of preparation thereof
WO2003090605A3 (en) * 2002-04-26 2003-12-04 Univ Texas Method and system for the detection of cardiac risk factors
WO2003090605A2 (en) * 2002-04-26 2003-11-06 Board Of Regents, The University Of Texas System Method and system for the detection of cardiac risk factors
US8257967B2 (en) 2002-04-26 2012-09-04 Board Of Regents, The University Of Texas System Method and system for the detection of cardiac risk factors
US7651868B2 (en) 2003-12-11 2010-01-26 The Board Of Regents Of The University Of Texas System Method and system for the analysis of saliva using a sensor array
US8101431B2 (en) 2004-02-27 2012-01-24 Board Of Regents, The University Of Texas System Integration of fluids and reagents into self-contained cartridges containing sensor elements and reagent delivery systems
US8105849B2 (en) 2004-02-27 2012-01-31 Board Of Regents, The University Of Texas System Integration of fluids and reagents into self-contained cartridges containing sensor elements
US8377398B2 (en) 2005-05-31 2013-02-19 The Board Of Regents Of The University Of Texas System Methods and compositions related to determination and use of white blood cell counts
US8658042B2 (en) 2007-08-31 2014-02-25 Tecan Trading Ag Microplate carrier having magnets
EP2177271A1 (en) * 2008-10-15 2010-04-21 F. Hoffmann-Roche AG Magnetic separation system comprising flexible magnetic pins
EP2191900A1 (en) 2008-11-28 2010-06-02 F. Hoffmann-Roche AG System and method for nucleic acids containing fluid processing
US9695467B2 (en) 2008-11-28 2017-07-04 Roche Molecular Systems, Inc. Method for processing nucleic acids-containing fluids
US8921094B2 (en) 2008-11-28 2014-12-30 Roche Molecular Systems, Inc. System and method for nucleic acids containing fluid processing
US8512558B2 (en) 2010-02-19 2013-08-20 Roche Molecular Systems, Inc. Magnetic separation system comprising flexible magnetic pins
GB2515490A (en) * 2013-06-24 2014-12-31 Univ Dublin City An aperture array substrate device, a detection system and a method for detecting analytes in a sample
CN103698503A (en) * 2013-12-19 2014-04-02 江苏金太生命科技有限公司 Positioning mechanism of enzyme-linked immunoassay analyzer
CN103675265B (en) * 2013-12-20 2015-06-03 江苏金太生命科技有限公司 Elisa plate shelf applicable to microplate reader
CN103675265A (en) * 2013-12-20 2014-03-26 江苏金太生命科技有限公司 Elisa plate shelf applicable to microplate reader

Also Published As

Publication number Publication date Type
GB9508726D0 (en) 1995-06-14 application

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