WO1990014891A1 - Separator device for magnetic particles - Google Patents

Separator device for magnetic particles Download PDF

Info

Publication number
WO1990014891A1
WO1990014891A1 PCT/NO1990/000098 NO9000098W WO9014891A1 WO 1990014891 A1 WO1990014891 A1 WO 1990014891A1 NO 9000098 W NO9000098 W NO 9000098W WO 9014891 A1 WO9014891 A1 WO 9014891A1
Authority
WO
WIPO (PCT)
Prior art keywords
tubes
rack
separation device
particles
magnet
Prior art date
Application number
PCT/NO1990/000098
Other languages
French (fr)
Inventor
Øivind Fylling JENSEN
Original Assignee
Dynal As
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Dynal As filed Critical Dynal As
Publication of WO1990014891A1 publication Critical patent/WO1990014891A1/en

Links

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
    • B03C1/288—Magnetic plugs and dipsticks disposed at the outer circumference of a recipient
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L9/00—Supporting devices; Holding devices
    • B01L9/06—Test-tube stands; Test-tube holders
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B03—SEPARATION OF SOLID MATERIALS USING LIQUIDS OR USING PNEUMATIC TABLES OR JIGS; MAGNETIC OR ELECTROSTATIC SEPARATION OF SOLID MATERIALS FROM SOLID MATERIALS OR FLUIDS; SEPARATION BY HIGH-VOLTAGE ELECTRIC FIELDS
    • B03C—MAGNETIC OR ELECTROSTATIC SEPARATION OF SOLID MATERIALS FROM SOLID MATERIALS OR FLUIDS; SEPARATION BY HIGH-VOLTAGE ELECTRIC FIELDS
    • B03C2201/00—Details of magnetic or electrostatic separation
    • B03C2201/26—Details of magnetic or electrostatic separation for use in medical applications
    • 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

Definitions

  • Present invention relates a separation device, more specific a separation device where a magnetic or magnetizable carrier aterial in the form of particles are being separated from a liquid composition.
  • the magnetic carrier in the form of magnetic particles will in such an application be coated with a reactive coating that can have affinity to certain proteins, cells, vira etc. that when a suspension containing the magnetic carrier particles the component for which the particles have affinity, be bound to the particles whereafter these can be separated form the suspension by means of one ore more magnets.
  • a reactive coating that can have affinity to certain proteins, cells, vira etc. that when a suspension containing the magnetic carrier particles the component for which the particles have affinity, be bound to the particles whereafter these can be separated form the suspension by means of one ore more magnets.
  • the magnets When the vial is fixed in the rack, the magnets will be in immediate proximity to the vial and the magnetic filed can affect the suspended magnetic particles that are dispersed in an solution in the vial.
  • the particles will be collected and concentrated along the wall of the vial and can be collected i the bottom of the vial if it is gently pulled up of the rack, if this is wanted.
  • the liquid in the vial after concentration of the particles along the wall, can be decanted from or aspired while the particles still are fixed to the wall and new liquid can be delivered to wash the particles etc.
  • the present separation device eliminates these disadvantages and make it possible to fixate numerous vials or "Eppendorf" tubes for simultaneous treatment.
  • the centre distance between each tube is such that the liquid can be. drawn off by means of an automatic standard pipette.
  • the separation device contains a block with numerous semi circular apertures that can receive a "Eppendorf” tube, when a section of the aperture has a design that is corresponding to the outer contour of the "Eppendorf” tube.
  • the block it is arranged strong permanent and electro ⁇ magnets that will be adjacent to the sidewall in a "Eppen ⁇ dorf" tube when this is placed in one of the apertures.
  • the tubes will be fixated by means of an elastic plate arranged in front of the tubes that apply an elastic force and fixate the tubes in the rack.
  • reference number 1 designate a block of a non-magnetic material which material preferably is easy to keep clean and easy machineable.
  • An example of such a material is "Teflon”.
  • the block 1 is provided with an aperture 2 which extends in the longitudinal direction.
  • this aperture 2 is provided a number of vertical extending apertures 3 to receive "Eppendorf” tubes 5.
  • Adjacent each aperture 3 is provided at least one magnet 4 that will adjacent the sidewall of the "Eppendorf" tube 5 when this is inserted in an aperture 3.
  • the block 1 For fixation of a tube 5, the block 1 is provided with a longitudinal slot in which it is inserted an fixed a suitable designed plate 6 which upper edge will elasticly be resting against a tube 5 inserted in the aperture 3.
  • the plate 6 consists of a elastic material that can apply an elastic force to the tube 5.
  • the plate consists of a transparent material that allows visual inspection of the material in the "Eppendorf" tubes when these are inserted in the apertures 3.
  • the plate 6 is supplied with a number of slots 8, so that the tubes will be affected of segments that are independent of each other and defined between to adjacent slots 8.
  • the balls are also coated with a material that has affinity to the macromolecules, proteins etc. that is intended to be separated from the liquid in which the particles are suspended.
  • the particles will be affected by the magnet 4 and collect along the inner wall of the tube adjacent the magnet 4.
  • the magnet 4 is a strong permanent magnet since this makes the separation device simple to handle and simple to produce, but for certain purposes it can also be used electro-magnets. This can be advantageously i certain cases where it is wanted that the particles or balls are present in the separation device, so that the balls can float freely and the surface active coating can be i contact with the solution for a desired period of time.
  • the electromagnets can for instance be activated simultaneously or in sequens according to a previous determined sequens.
  • the separation device with the inserted tubes can be shaken carefully, be turned so that possible particles fixed to the liquid surface, bubbles and so on can be brought into the suspension and thereafter move in the direction of the magnet 4 so that the most of or all the particulate material will be collected adjacent the inner wall of the tube adjacent the magnet.
  • the supernatant liquid can be decanted, sucked up by means of a pipette or removed otherwise if this is wanted.
  • the separation device can of course have a design to receive a much larger number of tubes or be designed in such a way that other types of tubes can be accommodated in a larger model of the separation device than shown in the drawing.
  • the separation device need not be designed as rectilinear, but the tubes can for instance be arranged circumferentially in a carousel if this is preferred.

Abstract

Separation device for separating magnetizable particles provided with a coating for selective affinity for one or more compounds to be removed from a liquid in which the particles are suspended, consisting of a rack (1) for tubes (5), preferably 'Eppendorf' tubes and which rack is provided with at least one magnet that will affect the magnetizable particles when a tube is inserted in the rack, where the rack for receiving a number of tubes (5) is provided with a number of apertures (3), which tubes intersect the fields of forces from the magnet (4).

Description

χ
SEPARATOR DEVICE FOR MAGNETIC PARTICLES.
Present invention relates a separation device, more specific a separation device where a magnetic or magnetizable carrier aterial in the form of particles are being separated from a liquid composition.
In the fields of chemistry, biochemistry and gen anipulation such a technique for separation has a wide application. The magnetic carrier in the form of magnetic particles will in such an application be coated with a reactive coating that can have affinity to certain proteins, cells, vira etc. that when a suspension containing the magnetic carrier particles the component for which the particles have affinity, be bound to the particles whereafter these can be separated form the suspension by means of one ore more magnets. In Us patent application 064.040 filed June 12, 1987 titled "Magnetic Particles Concentrator", it is described a device suited for such separation. This device consists of a rack where a series of magnets are positioned in a row in vertical direction and which device is designed to receive a vial which is fixed by means of a springloaded clip. When the vial is fixed in the rack, the magnets will be in immediate proximity to the vial and the magnetic filed can affect the suspended magnetic particles that are dispersed in an solution in the vial. The particles will be collected and concentrated along the wall of the vial and can be collected i the bottom of the vial if it is gently pulled up of the rack, if this is wanted.
The liquid in the vial, after concentration of the particles along the wall, can be decanted from or aspired while the particles still are fixed to the wall and new liquid can be delivered to wash the particles etc.
The disadvantage with the known rack or separation device is that it is relatively large and not suitable for utilization of the so-called "Eppendorf-tubes" or micro test tubes which 14891
are widely used in the field of acromolecular research. It is also difficult with this known device to arrange more vials in one rack due to the manually operated fix/clip- device for fixation of the vials with content.
It is therefore a need for a simple separation device which can contain more vials or "Eppendorf-tubes" and where fixation of one tube by means of manually operated fixing- device can be avoided.
The present separation device eliminates these disadvantages and make it possible to fixate numerous vials or "Eppendorf" tubes for simultaneous treatment. Preferably the centre distance between each tube is such that the liquid can be. drawn off by means of an automatic standard pipette.
This is accomplished with the separation device according to present invention by that it contains a block with numerous semi circular apertures that can receive a "Eppendorf" tube, when a section of the aperture has a design that is corresponding to the outer contour of the "Eppendorf" tube. In the block it is arranged strong permanent and electro¬ magnets that will be adjacent to the sidewall in a "Eppen¬ dorf" tube when this is placed in one of the apertures.
To avoid that the tubes can fall out of the apertures when the separation device is shaken or turned, the tubes will be fixated by means of an elastic plate arranged in front of the tubes that apply an elastic force and fixate the tubes in the rack.
The invention will be further explained with reference to the accompanying drawing which shows a preferred embodiment of the invention. In the drawing reference number 1 designate a block of a non-magnetic material which material preferably is easy to keep clean and easy machineable. An example of such a material is "Teflon". The block 1 is provided with an aperture 2 which extends in the longitudinal direction. In this aperture 2 is provided a number of vertical extending apertures 3 to receive "Eppendorf" tubes 5. Adjacent each aperture 3 is provided at least one magnet 4 that will adjacent the sidewall of the "Eppendorf" tube 5 when this is inserted in an aperture 3. For fixation of a tube 5, the block 1 is provided with a longitudinal slot in which it is inserted an fixed a suitable designed plate 6 which upper edge will elasticly be resting against a tube 5 inserted in the aperture 3. The plate 6 consists of a elastic material that can apply an elastic force to the tube 5. Preferably the plate consists of a transparent material that allows visual inspection of the material in the "Eppendorf" tubes when these are inserted in the apertures 3.
To avoid that the force from the plate 6 shall be dependant of the number of tubes inserted i the device, the plate 6 is supplied with a number of slots 8, so that the tubes will be affected of segments that are independent of each other and defined between to adjacent slots 8.
In use the "Eppendorf" tubes containing a suspension of small balls, for instance the balls ore particles known as "Ugelstad's" balls, that for the present aim has been made super paramagnetic to be able to move in a magnetic field, but are separated from each other when the magnetic field cease to exist.
Dependant of the purpose, the balls are also coated with a material that has affinity to the macromolecules, proteins etc. that is intended to be separated from the liquid in which the particles are suspended. When a tube is inserted in an aperture 3, the particles will be affected by the magnet 4 and collect along the inner wall of the tube adjacent the magnet 4.
In the preferred embodiment the magnet 4 is a strong permanent magnet since this makes the separation device simple to handle and simple to produce, but for certain purposes it can also be used electro-magnets. This can be advantageously i certain cases where it is wanted that the particles or balls are present in the separation device, so that the balls can float freely and the surface active coating can be i contact with the solution for a desired period of time. The electromagnets can for instance be activated simultaneously or in sequens according to a previous determined sequens.
Due to the fixation of the tube by the plate 6, the separation device with the inserted tubes can be shaken carefully, be turned so that possible particles fixed to the liquid surface, bubbles and so on can be brought into the suspension and thereafter move in the direction of the magnet 4 so that the most of or all the particulate material will be collected adjacent the inner wall of the tube adjacent the magnet. The supernatant liquid can be decanted, sucked up by means of a pipette or removed otherwise if this is wanted.
Even if the temporary preferred embodiment is designed as shown in the drawing, the separation device can of course have a design to receive a much larger number of tubes or be designed in such a way that other types of tubes can be accommodated in a larger model of the separation device than shown in the drawing.
The separation device need not be designed as rectilinear, but the tubes can for instance be arranged circumferentially in a carousel if this is preferred.

Claims

5 C l a i m s
1. Separation device for separating magnetizable particles provided with a coating for selective affinity for the compound or compounds to be removed form a liquid in which the particles are suspended, consisting of a rack (1) for tubes (5) , preferably "Eppendorf" tubes, which rack is provided with at least one magnet (4) provided to affect the mag- netizable particles when a tube is inserted in the rack, c h a r a c t e r i z e d i n t h a t the rack for receiving a number of tubes (5) is provided with a number of apertures (3) , which tubes (5) intersects the magnets (4) fields.
2. Separation device according to claim 1, c h a r a c t e r i z e d i n t h a t a resting- plate (6) , preferably a transparent elastic material is provided to push a tube (5) against the wall of the aperture (3) towards the direction of a magnet (4)
3. Separation device according to claim 2 , c h a r a c t e r i z e d i n t h a t the plate (6) is provided with a number of slots (8) .
4. Separation device according to the previous claims, c h a r a c t e r i z e d i n t h a t the magnet (4) is a permanent magnet.
Separation device according to claim 1 - 4, c h a r a c t e r i z e d i n t h a t the magnet (4) is a electromagnet.
PCT/NO1990/000098 1989-05-31 1990-05-28 Separator device for magnetic particles WO1990014891A1 (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
NO892202A NO168811C (en) 1989-05-31 1989-05-31 Separation device for separating magnetizable particles
NO892202 1989-05-31

Publications (1)

Publication Number Publication Date
WO1990014891A1 true WO1990014891A1 (en) 1990-12-13

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Application Number Title Priority Date Filing Date
PCT/NO1990/000098 WO1990014891A1 (en) 1989-05-31 1990-05-28 Separator device for magnetic particles

Country Status (2)

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NO (1) NO168811C (en)
WO (1) WO1990014891A1 (en)

Cited By (16)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0577643A1 (en) * 1991-03-25 1994-01-12 Immunicon Corp Apparatus and methods for magnetic separation featuring external magnetic means.
US5458785A (en) * 1992-09-24 1995-10-17 Amersham International Plc Magnetic separation method
WO1996017959A2 (en) * 1994-12-09 1996-06-13 Gamera Bioscience Corporation An apparatus for performing magnetic cycle reaction
JP2003144968A (en) * 2001-11-16 2003-05-20 Jsr Corp Magnetic stand
US6776174B2 (en) 1998-08-21 2004-08-17 Paul E. Nisson Apparatus for washing magnetic particles
WO2008145709A3 (en) * 2007-05-29 2009-02-12 Invitrogen Dynal As A magnetic separation rack
DE102008061714A1 (en) 2008-12-12 2010-06-17 Siemens Healthcare Diagnostics Inc., Deerfield Process for the purification of nucleic acids, in particular from fixed tissue
US7985340B2 (en) 2005-12-02 2011-07-26 Invitrogen Dynal As Magnetic separator
WO2013019346A1 (en) * 2011-07-29 2013-02-07 Corning Incorporated Magnetic separation device and methods
WO2013171123A1 (en) 2012-05-15 2013-11-21 Life Technologies As Sample holder with magnetic base and magnetisable body
JP2014018692A (en) * 2012-07-12 2014-02-03 Tamagawa Seiki Co Ltd Magnetic stand
US8691969B2 (en) 1994-12-12 2014-04-08 Life Technologies As Isolation of nucleic acid
JP2014100704A (en) * 2012-11-20 2014-06-05 Qiagen Gmbh Magnetic rack system and usage of the same
WO2015088201A1 (en) * 2013-12-09 2015-06-18 (주)바이오니아 Magnetic particle separating device, and method of separating and purifying nucleic acid or protein using same
US9199247B2 (en) 2007-05-29 2015-12-01 Invitrogen Dynal As Magnetic separation rack
CN108970815A (en) * 2018-07-20 2018-12-11 深圳市第二人民医院 A kind of GMP Multi-functional centrifuge tube shelf with timer

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4297337A (en) * 1979-04-13 1981-10-27 Corning Glass Works Solid-phase immunoassays using magnetic glass
DE3102029A1 (en) * 1981-01-22 1982-08-26 Europäisches Laboratorium für Molekularbiologie (EMBL), 6900 Heidelberg Appliance for separating ferromagnetic particles
US4438068A (en) * 1979-11-13 1984-03-20 Technicon Instruments Corporation Test-tube assembly for immunoassays utilizing magnetically attractable particles
EP0136126A2 (en) * 1983-09-09 1985-04-03 Corning Glass Works Magnetic separator for solid phase immunoassays
US4895650A (en) * 1988-02-25 1990-01-23 Gen-Probe Incorporated Magnetic separation rack for diagnostic assays

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4297337A (en) * 1979-04-13 1981-10-27 Corning Glass Works Solid-phase immunoassays using magnetic glass
US4438068A (en) * 1979-11-13 1984-03-20 Technicon Instruments Corporation Test-tube assembly for immunoassays utilizing magnetically attractable particles
DE3102029A1 (en) * 1981-01-22 1982-08-26 Europäisches Laboratorium für Molekularbiologie (EMBL), 6900 Heidelberg Appliance for separating ferromagnetic particles
EP0136126A2 (en) * 1983-09-09 1985-04-03 Corning Glass Works Magnetic separator for solid phase immunoassays
US4895650A (en) * 1988-02-25 1990-01-23 Gen-Probe Incorporated Magnetic separation rack for diagnostic assays

Cited By (33)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0577643A4 (en) * 1991-03-25 1994-06-08 Immunicon Corp Apparatus and methods for magnetic separation featuring external magnetic means
EP0577643A1 (en) * 1991-03-25 1994-01-12 Immunicon Corp Apparatus and methods for magnetic separation featuring external magnetic means.
US5458785A (en) * 1992-09-24 1995-10-17 Amersham International Plc Magnetic separation method
WO1996017959A2 (en) * 1994-12-09 1996-06-13 Gamera Bioscience Corporation An apparatus for performing magnetic cycle reaction
WO1996017959A3 (en) * 1994-12-09 1996-08-29 Gamera Bioscience Corp An apparatus for performing magnetic cycle reaction
AU691076B2 (en) * 1994-12-09 1998-05-07 Gamera Bioscience Corporation An apparatus for performing magnetic cycle reaction
US8691969B2 (en) 1994-12-12 2014-04-08 Life Technologies As Isolation of nucleic acid
US6776174B2 (en) 1998-08-21 2004-08-17 Paul E. Nisson Apparatus for washing magnetic particles
JP2003144968A (en) * 2001-11-16 2003-05-20 Jsr Corp Magnetic stand
US7985340B2 (en) 2005-12-02 2011-07-26 Invitrogen Dynal As Magnetic separator
CN101678364B (en) * 2007-05-29 2013-12-04 生命技术股份公司 A magnetic separating device
US8574515B2 (en) 2007-05-29 2013-11-05 Life Technologies As Magnetic separating device
US9199247B2 (en) 2007-05-29 2015-12-01 Invitrogen Dynal As Magnetic separation rack
WO2008145711A3 (en) * 2007-05-29 2009-02-19 Invitrogen Dynal As A magnetic separating device
WO2008145709A3 (en) * 2007-05-29 2009-02-12 Invitrogen Dynal As A magnetic separation rack
US9227199B2 (en) 2007-05-29 2016-01-05 Life Technologies As Magnetising portion for a magnetic separation device
DE102008061714A1 (en) 2008-12-12 2010-06-17 Siemens Healthcare Diagnostics Inc., Deerfield Process for the purification of nucleic acids, in particular from fixed tissue
US9416399B2 (en) 2008-12-12 2016-08-16 Siemens Healthcare Diagnostics Inc. Method for purification of nucleic acids, particularly from fixed tissue
EP2998398A1 (en) 2008-12-12 2016-03-23 Siemens Healthcare Diagnostics Inc. Automated system for purifying nucleic acids, particularly from fixed tissue
CN105349404A (en) * 2008-12-12 2016-02-24 西门子保健诊断股份有限公司 Method for purification of nucleic acids, particularly from fixed tissue
US8703931B2 (en) 2008-12-12 2014-04-22 Siemens Healthcare Diagnostics Inc. Method for purification of nucleic acids, particularly from fixed tissue
US9242250B2 (en) 2011-07-29 2016-01-26 Corning Incorporated Magnetic separation device and methods
JP2014521503A (en) * 2011-07-29 2014-08-28 コーニング インコーポレイテッド Magnetic separation apparatus and method
WO2013019346A1 (en) * 2011-07-29 2013-02-07 Corning Incorporated Magnetic separation device and methods
WO2013171123A1 (en) 2012-05-15 2013-11-21 Life Technologies As Sample holder with magnetic base and magnetisable body
US10293344B2 (en) 2012-05-15 2019-05-21 Life Technologies As Sample holder with magnetic base and magnetisable body
JP2014018692A (en) * 2012-07-12 2014-02-03 Tamagawa Seiki Co Ltd Magnetic stand
JP2014100704A (en) * 2012-11-20 2014-06-05 Qiagen Gmbh Magnetic rack system and usage of the same
WO2015088201A1 (en) * 2013-12-09 2015-06-18 (주)바이오니아 Magnetic particle separating device, and method of separating and purifying nucleic acid or protein using same
CN105916972A (en) * 2013-12-09 2016-08-31 株式会社百奥尼 Magnetic particle separating device, and method of separating and purifying nucleic acid or protein using same
CN105916972B (en) * 2013-12-09 2018-12-21 株式会社百奥尼 The separation and method of purification of magnetic particle separator and nucleic acid or protein using the device
US10441957B2 (en) 2013-12-09 2019-10-15 Bioneer Corporation Magnetic particle separating device, and method of separating and purifying nucleic acid or protein using same
CN108970815A (en) * 2018-07-20 2018-12-11 深圳市第二人民医院 A kind of GMP Multi-functional centrifuge tube shelf with timer

Also Published As

Publication number Publication date
NO168811C (en) 1992-04-08
NO892202L (en) 1990-12-03
NO168811B (en) 1991-12-30
NO892202D0 (en) 1989-05-31

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