EP2311564A1 - Système microfluidique doté d'une chambre et moyen pour générer des champs magnétiques alternatifs - Google Patents

Système microfluidique doté d'une chambre et moyen pour générer des champs magnétiques alternatifs Download PDF

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Publication number
EP2311564A1
EP2311564A1 EP09172166A EP09172166A EP2311564A1 EP 2311564 A1 EP2311564 A1 EP 2311564A1 EP 09172166 A EP09172166 A EP 09172166A EP 09172166 A EP09172166 A EP 09172166A EP 2311564 A1 EP2311564 A1 EP 2311564A1
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EP
European Patent Office
Prior art keywords
yoke
processing chamber
magnetic field
magnetically connected
magnet
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Withdrawn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
EP09172166A
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German (de)
English (en)
Inventor
Axel Sebastiaan Lexmond
Paul Keijzer
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Nederlandse Organisatie voor Toegepast Natuurwetenschappelijk Onderzoek TNO
Original Assignee
Nederlandse Organisatie voor Toegepast Natuurwetenschappelijk Onderzoek TNO
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Priority to EP09172166A priority Critical patent/EP2311564A1/fr
Publication of EP2311564A1 publication Critical patent/EP2311564A1/fr
Withdrawn legal-status Critical Current

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    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • B01L3/502—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
    • B01L3/5027—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip
    • B01L3/50273—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip characterised by the means or forces applied to move the fluids
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • B01L3/502—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
    • B01L3/5027—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip
    • B01L3/502761—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip specially adapted for handling suspended solids or molecules independently from the bulk fluid flow, e.g. for trapping or sorting beads, for physically stretching molecules
    • 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
    • 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
    • B01L2200/0668—Trapping microscopic beads
    • 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
    • B01L2300/0816—Cards, e.g. flat sample carriers usually with flow in two horizontal directions
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2400/00—Moving or stopping fluids
    • B01L2400/04—Moving fluids with specific forces or mechanical means
    • B01L2400/0403—Moving fluids with specific forces or mechanical means specific forces
    • B01L2400/043—Moving fluids with specific forces or mechanical means specific forces magnetic forces

Definitions

  • Microfluidic system comprising a processing chamber and an assembly for generating mutually alternating magnetic fields, provided in the vicinity of the processing chamber.
  • the system may be used for separating bound/free fractions employing magnetizable particles (beads), allowing the particle bound substance to be separated by applying a magnetic field.
  • Magnetizable particles which allow the particle bound substance to be separated by applying a magnetic field.
  • Small magnetizable particles are well known in the art, as is their use in the separations involving immunological and other biospecific affinity reactions. Small magnetizable particles generally fall into two broad categories. The first category includes particles that are permanently magnetized, and the second comprises particles that become magnetic only when subjected to a magnetic field. The latter are referred to as paramagnetic or superparamagnetic particles and are usually preferred over the permanently magnetized particles.
  • paramagnetic beads is coated with a suitable ligand or receptor, such as antibodies, lectins, oligo nucleotides, or other bioreactive molecules, which can selectively bind a target substance in a mixture with other substances.
  • a suitable ligand or receptor such as antibodies, lectins, oligo nucleotides, or other bioreactive molecules, which can selectively bind a target substance in a mixture with other substances.
  • suitable ligand or receptor such as antibodies, lectins, oligo nucleotides, or other bioreactive molecules, which can selectively bind a target substance in a mixture with other substances.
  • small magnetic particles or beads are disclosed in U.S. Pat. Nos. 4230685 , 4554088 , and 4628037 .
  • the use of paramagnetic particles is taught in publications, " Application of Magnetic Beads in Bioassays," by B., Haukanes, and C.
  • the magnetic separation process typically involves mixing the sample with paramagnetic particles in a liquid medium to bind the target substance by affinity reaction, and then separating the bound particle/target complex from the sample medium by applying a magnetic field. All magnetic particles except those particles that are colloidal, settle in time.
  • the liquid medium therefore, must be agitated to some degree to keep the particles suspended for a sufficient period of time to allow the bioaffinity binding reaction to occur. Examples of known agitation methods include shaking, swirling, rocking, rotation, or similar manipulations of a partially filled container.
  • One aim of the present invention to provide a system having improved bead mixing capabilities.
  • Another aim of the invention is to provide a system providing shortened processing times.
  • a microfluidic system comprises a processing chamber and an assembly for generating mutually alternating magnetic fields, provided in the vicinity of the processing chamber.
  • the assembly for generating mutually alternating magnetic fields comprise a yoke at one location relative to the processing chamber and at least one yoke at another location relative to the processing chamber, each of said yokes comprising at least two yoke legs, connected to an alternatable magnetic field source between them, as well as an open end area including a small gap area between both open yoke leg ends, the small gap areas of the yokes involved being located at different locations relative to the processing chamber.
  • the alternatable magnetic field sources involved are arranged that, alternately, in one period a magnetic field is generated in the small gap area at one location of the processing chamber, and in another period a magnetic field is generated in the small gap area at another location of the processing chamber, and so on.
  • the switchable magnetic field source preferably includes a permanent magnet, the magnetic north and south poles being magnetically connected with the yoke legs, which yoke legs, moreover, are magnetically connected with an alternatable magnet, i.e. a magnet which is arranged so that, alternately, in one period its north pole is magnetically connected with a first one of said yoke legs and its south pole is magnetically connected with a second one of said yoke legs, and in another period its north pole is magnetically connected with the second one of said yoke legs and its south pole is magnetically connected with the first one of said yoke legs.
  • an alternatable magnet i.e. a magnet which is arranged so that, alternately, in one period its north pole is magnetically connected with a first one of said yoke legs and its south pole is magnetically connected with a second one of said yoke legs, and in another period its north pole is magnetically connected with the second one of said yoke legs and its south pole is magnetically
  • the alternatable magnet may e.g. be constituted by an alternately energizable electromagnet. In a preferred embodiment, however, the alternatable magnet is constituted by a movable, e.g. rotatable, permanent magnet.
  • Figure 1 shows an embodiment which comprises a processing chamber 1 and an assembly for generating mutually alternating magnetic fields having gradients in mutually different directions, provided in the vicinity of the processing chamber 1.
  • the assembly consisting in two ( figure 1 ) or more ( figure 2 ) modules 2a, 2b etc., provides always changing magnetic fields, generated by said modules 2a, 2b, etc., each having a magnetic gradient pointing towards the relevant module 2a, 2b, etc., i.e.
  • the magnetic field strength is always maximum at the side walls of the processing chamber.
  • the assembly for generating mutually alternating magnetic fields having gradients in mutually different directions, provided in the vicinity of the processing chamber comprises a yoke 3a at one location relative to the processing chamber 1 and at least one yoke 3b at another location relative to the processing chamber 1.
  • Each of the yokes 3 comprises at least two yoke legs 4a, 4b, connected to an alternatable magnetic field source between them, as well as an open end area including a small gap area 5, e.g. having a width of 1 to 5 millimetres, between both open yoke leg ends.
  • the small gap areas 5 of the yokes involved being located at different locations relative to the processing chamber 1.
  • alternatable magnetic field sources involved are arranged that, alternately, in one period a magnetic field is generated in the small gap area at one location of the processing chamber, and in another period a magnetic field is generated in the small gap area at another location of the processing chamber, thus enabling that the beads will be attracted by the maximum field strength area, always generated by one of the alternately energized modules 2a, 2b, etc.
  • the switchable magnetic field source includes a permanent magnet 6, the magnetic north pole N and south pole S being magnetically connected with the yoke legs 4a, 4b.
  • the yoke legs 4a, 4b are magnetically connected with an alternatable magnet, i.e. a rotatable magnet 7, which is arranged (i.e. rotatably driven) so that, alternately, its north pole N is magnetically connected with a first one of the yoke legs 4a and its south pole S is magnetically connected with a second one of the yoke legs 4b, causing that both magnets have the same polarity and thus cause a strong magnetic field in the gap area 5.
  • alternatable magnet i.e. a rotatable magnet 7
  • Figure 1a shows an embodiment comprising two switchable (alternatable) magnet modules 2a and 2b, each comprising a yoke 3 including yoke legs 4a and 4b, as well as a fixedly connected magnet 6 and a rotatable magnet 7. Both magnets 7 are rotated during operation, however having their magnet directions mutually shifted over 180°. Due to this, when both magnets 7 are rotated (always having a mutual "phase shift" of 180°) an alternating magnetic field will occur which alternates between (in figure 1a ) the upper and the lower magnetic modules 2a, 2b.
  • each magnetic module 2a - 2d comprising a yoke 3, including a gap 5, a fixedly connected magnet 6 and a rotatable magnet 7.
  • the rotation means (not shown) which are arranged for rotating the magnets 7 may have a mutual "phase shift" of 90°, instead of -as in figure 1a - 180°.
  • the phase distribution, enabled by the magnets rotation (drive) means may be represented by the sequence 2a - 2b - 2c -2d, indicating that subsequently modules 2a, 2b, 2c, and 2d will have their maximum magnetic force (occurring in their gaps 5) in that sequence 2a - 2b - 2c -2d.
  • Figure 3 shows an alternative embodiment for the modules for generating a variable magnetic field.
  • the switchable magnetic field source includes a permanent magnet 6, the magnetic north (N) and south (S) poles are magnetically connected with the yoke legs 4a and 4b, which are magnetically connected with a switch member 8 which is arranged to, alternately, shortcut both poles of the permanent magnet 6 in one period (left) and to remove said shortcut in another period (right).
  • the rotatable switch member 8 is formed by a body 9 made of a magnetically non-conducting material, e.g.
  • a ceramic or synthetic material holding a magnetically conducting connection member 10 which magnetically interconnects both yokes 4a and 4b and thus shortcuts the permanent magnet 6 (left) in one period and, in another period (right) removes that magnetic shortcut thus causing an alternating magnetic field in the air gap 5.
  • FIG 4 shows another alternative embodiment for the modules for generating a variable magnetic field.
  • the switchable magnetic field source includes a permanent magnet 6, the magnetic north (N) and south (S) poles or which are magnetically connected with the yoke legs via a switch member 8 between a magnet pole and yoke leg 4b.
  • the switch member 8, constituted again by magnetic non-conducting body 9 and magnetically conducting connection member 10, is arranged to, alternately, connect the pole of the permanent magnet 6 to yoke leg 4b in one period and to disconnect that pole of the permanent magnet 6 from the yoke leg 4b in another period, thus causing an alternating magnetic field in the air gap 5.

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  • Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Dispersion Chemistry (AREA)
  • Analytical Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Hematology (AREA)
  • Clinical Laboratory Science (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Physics & Mathematics (AREA)
  • Fluid Mechanics (AREA)
  • Physical Or Chemical Processes And Apparatus (AREA)
EP09172166A 2009-10-05 2009-10-05 Système microfluidique doté d'une chambre et moyen pour générer des champs magnétiques alternatifs Withdrawn EP2311564A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
EP09172166A EP2311564A1 (fr) 2009-10-05 2009-10-05 Système microfluidique doté d'une chambre et moyen pour générer des champs magnétiques alternatifs

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
EP09172166A EP2311564A1 (fr) 2009-10-05 2009-10-05 Système microfluidique doté d'une chambre et moyen pour générer des champs magnétiques alternatifs

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EP2311564A1 true EP2311564A1 (fr) 2011-04-20

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Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4230685A (en) 1979-02-28 1980-10-28 Northwestern University Method of magnetic separation of cells and the like, and microspheres for use therein
US4554088A (en) 1983-05-12 1985-11-19 Advanced Magnetics Inc. Magnetic particles for use in separations
US4628037A (en) 1983-05-12 1986-12-09 Advanced Magnetics, Inc. Binding assays employing magnetic particles
WO2004078316A1 (fr) * 2003-03-08 2004-09-16 Ecole Polytechnique Federale De Lausanne (Epfl) Dispositif de manipulation et de transport de perles magnetiques
DE10355460A1 (de) * 2003-11-27 2005-06-30 Humboldt-Universität Zu Berlin Mikrofluidsystem
US20080160634A1 (en) * 2006-12-28 2008-07-03 Xing Su Method and device for biomolecule preparation and detection using magnetic array

Patent Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4230685A (en) 1979-02-28 1980-10-28 Northwestern University Method of magnetic separation of cells and the like, and microspheres for use therein
US4554088A (en) 1983-05-12 1985-11-19 Advanced Magnetics Inc. Magnetic particles for use in separations
US4628037A (en) 1983-05-12 1986-12-09 Advanced Magnetics, Inc. Binding assays employing magnetic particles
WO2004078316A1 (fr) * 2003-03-08 2004-09-16 Ecole Polytechnique Federale De Lausanne (Epfl) Dispositif de manipulation et de transport de perles magnetiques
DE10355460A1 (de) * 2003-11-27 2005-06-30 Humboldt-Universität Zu Berlin Mikrofluidsystem
US20080160634A1 (en) * 2006-12-28 2008-07-03 Xing Su Method and device for biomolecule preparation and detection using magnetic array

Non-Patent Citations (6)

* Cited by examiner, † Cited by third party
Title
"Advances in Biomagnetic Separations", 1994, EATON PUBLISHING CO.
B., HAUKANES; C. KVAM: "Application of Magnetic Beads in Bioassays", BIO/TECHNOLOGY, vol. 11, 1993, pages 60 - 63
F. VARTDAL: "Depletion of T Lymphocytes from Human Bone Marrow", TRANSPLANTATION, vol. 43, 1987, pages 366 - 71
J. G. TRELEAVEN: "Removal of Neuroblastoma Cells from Bone Marrow with Monoclonal Antibodies Conjugated to Magnetic Microspheres", LANCET, 14 January 1984 (1984-01-14), pages 70 - 73
SMISTRUP K ET AL: "Microelectromagnet for magnetic manipulation in lab-on-a-chip systems", JOURNAL OF MAGNETISM AND MAGNETIC MATERIALS, ELSEVIER SCIENCE PUBLISHERS, AMSTERDAM, NL, vol. 300, no. 2, 1 May 2006 (2006-05-01), pages 418 - 426, XP024984333, ISSN: 0304-8853, [retrieved on 20060501] *
T. LEA: "Magnetic Monosized Polymer Particles for Fast and Specific Fractionation of Human Mononuclear Cells", SCANDINAVIAN JOURNAL OF IMMUNOLOGY, vol. 22, 1985, pages 207 - 16

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