EP1974821A1 - Procédé et appareil pour transporter des microbilles magnétiques ou magnétisables - Google Patents

Procédé et appareil pour transporter des microbilles magnétiques ou magnétisables Download PDF

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Publication number
EP1974821A1
EP1974821A1 EP07006148A EP07006148A EP1974821A1 EP 1974821 A1 EP1974821 A1 EP 1974821A1 EP 07006148 A EP07006148 A EP 07006148A EP 07006148 A EP07006148 A EP 07006148A EP 1974821 A1 EP1974821 A1 EP 1974821A1
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EP
European Patent Office
Prior art keywords
poles
electromagnets
capillary tube
row
magnetic
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Withdrawn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
EP07006148A
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German (de)
English (en)
Inventor
Olivier Elsenhans
Goran Savatic
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.)
F Hoffmann La Roche AG
Roche Diagnostics GmbH
Original Assignee
F Hoffmann La Roche AG
Roche Diagnostics GmbH
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 F Hoffmann La Roche AG, Roche Diagnostics GmbH filed Critical F Hoffmann La Roche AG
Priority to EP07006148A priority Critical patent/EP1974821A1/fr
Priority to PCT/EP2008/001706 priority patent/WO2008116543A1/fr
Priority to EP08716225A priority patent/EP2129469A1/fr
Publication of EP1974821A1 publication Critical patent/EP1974821A1/fr
Withdrawn legal-status Critical Current

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    • 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
    • B03C1/23—Magnetic separation acting directly on the substance being separated with material carried by oscillating fields; with material carried by travelling fields, e.g. generated by stationary magnetic coils; Eddy-current separators, e.g. sliding ramp
    • B03C1/24—Magnetic separation acting directly on the substance being separated with material carried by oscillating fields; with material carried by travelling fields, e.g. generated by stationary magnetic coils; Eddy-current separators, e.g. sliding ramp with material carried by travelling fields
    • B03C1/253—Magnetic separation acting directly on the substance being separated with material carried by oscillating fields; with material carried by travelling fields, e.g. generated by stationary magnetic coils; Eddy-current separators, e.g. sliding ramp with material carried by travelling fields obtained by a linear motor
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B03—SEPARATION OF SOLID MATERIALS USING LIQUIDS OR USING PNEUMATIC TABLES OR JIGS; MAGNETIC OR ELECTROSTATIC SEPARATION OF SOLID MATERIALS FROM SOLID MATERIALS OR FLUIDS; SEPARATION BY HIGH-VOLTAGE ELECTRIC FIELDS
    • B03C—MAGNETIC OR ELECTROSTATIC SEPARATION OF SOLID MATERIALS FROM SOLID MATERIALS OR FLUIDS; SEPARATION BY HIGH-VOLTAGE ELECTRIC FIELDS
    • B03C1/00—Magnetic separation
    • B03C1/02—Magnetic separation acting directly on the substance being separated
    • B03C1/025—High gradient magnetic separators
    • B03C1/031—Component parts; Auxiliary operations
    • B03C1/033—Component parts; Auxiliary operations characterised by the magnetic circuit
    • B03C1/0335—Component parts; Auxiliary operations characterised by the magnetic circuit using coils
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B03—SEPARATION OF SOLID MATERIALS USING LIQUIDS OR USING PNEUMATIC TABLES OR JIGS; MAGNETIC OR ELECTROSTATIC SEPARATION OF SOLID MATERIALS FROM SOLID MATERIALS OR FLUIDS; SEPARATION BY HIGH-VOLTAGE ELECTRIC FIELDS
    • B03C—MAGNETIC OR ELECTROSTATIC SEPARATION OF SOLID MATERIALS FROM SOLID MATERIALS OR FLUIDS; SEPARATION BY HIGH-VOLTAGE ELECTRIC FIELDS
    • B03C1/00—Magnetic separation
    • B03C1/02—Magnetic separation acting directly on the substance being separated
    • B03C1/28—Magnetic plugs and dipsticks
    • B03C1/288—Magnetic plugs and dipsticks disposed at the outer circumference of a recipient
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B03—SEPARATION OF SOLID MATERIALS USING LIQUIDS OR USING PNEUMATIC TABLES OR JIGS; MAGNETIC OR ELECTROSTATIC SEPARATION OF SOLID MATERIALS FROM SOLID MATERIALS OR FLUIDS; SEPARATION BY HIGH-VOLTAGE ELECTRIC FIELDS
    • B03C—MAGNETIC OR ELECTROSTATIC SEPARATION OF SOLID MATERIALS FROM SOLID MATERIALS OR FLUIDS; SEPARATION BY HIGH-VOLTAGE ELECTRIC FIELDS
    • B03C2201/00—Details of magnetic or electrostatic separation
    • B03C2201/18—Magnetic separation whereby the particles are suspended in a liquid

Definitions

  • the invention concerns a method for transporting magnetic or magnetisable microbeads immersed in a liquid contained in a capillary tube having a length symmetry axis which defines an axial direction, said transporting being effected in the absence of a static magnetic field in said capillary tube.
  • the invention further concerns an apparatus for transporting magnetic or magnetisable microbeads immersed in a liquid contained in a capillary tube.
  • Magnetic particles e.g. magnetic beads, of a size of several micrometers in diameter are used in biomedical analysis.
  • probe molecules immobilized on the surface of magnetic microbeads are used for performing a method in which probe molecules specifically interact with complimentary target molecules.
  • a method uses for e.g. DNA probes immobilized on the surface of magnetic microbeads for recognition of and hybridization with complimentary target DNA in a solution.
  • microbeads carrying the DNA probes are brought into a solution containing particles which carry on them target.DNA for possible homologous pairing and subsequent identification of the target DNA.
  • the amount of target molecules within a certain volume of solution is determined using electro-optical or electrochemical measurements.
  • the advantage of using magnetic particles in a method of the above mentioned kind is that magnetic particles can be manipulated using magnetic fields independently from any flow pattern of the solution, e.g. for the extraction of target-specific magnetic particles from the solution where the interaction of magnetic particles carrying the probes interact with the target molecules.
  • magnetic particles can be manipulated using magnetic fields independently from any flow pattern of the solution, e.g. for the extraction of target-specific magnetic particles from the solution where the interaction of magnetic particles carrying the probes interact with the target molecules.
  • transport of magnetic particles means that the magnetic particles are effectively moved, that is displaced along a transport path by a magnetic force, and not just retained by a magnetic force at a given place and thereby separated from a liquid solution which flows close to a magnet.
  • Manipulation of magnetic particles in general, and in particular transport of magnetic particles is a difficult task, because the magnetic particles used are usually superparamagnetic microbeads which have a rather weak effective relative magnetic susceptibility ⁇ eff (typically ⁇ eff ⁇ 1, due to demagnetization effects of the mostly spherical particles) and because the volume of a magnetic particle is small.
  • a very small microbead has thus no effective magnetization when there is no external magnetic field applied to it, i.e. it is superparamagnetic.
  • Junho Joung et al. IEEE Transactions on Magnetics, Vol. 36, No. 4, July 2000, pages 2012-2014 , describes an arrangement for displacing clusters of magnetic particles.
  • This arrangement comprises an array of uniformly spaced electromagnetic posts, wherein each post has one electromagnet pole the end of which faces one side of a straight pipe which contains a solution in which magnetic particles are immersed.
  • the poles of the electromagnetic posts are positioned close to, on opposite sides the pipe and are uniformly spaced in an axial direction defined by the length symmetry axis of the pipe.
  • the first pole is located on a first side of the pipe
  • the second pole is located on a second side of the pipe opposite to the first side thereof, and further from the first end of the pipe than the first pole
  • the third pole is located on the first side of the pipe and further from the first end of the pipe than the second pole
  • the fourth pole is located on the second side of the pipe and further from the first end of the pipe than the third pole, and so on.
  • the electromagnetic post are activated one after the other and one at a time by a simple driving circuit which turns them on and off in sequence starting from the electromagnetic post whose pole is the one nearest to the first end of the pipe.
  • a first aim of the invention is to provide a method and an apparatus of the above mentioned kind which do not require the use of large magnets or electromagnets which have to be mechanically moved.
  • aims are achieved by means of a method defined by claim 1.
  • Claims 2 to 5 define preferred embodiments of this method.
  • the above aims are achieved by using an apparatus defined by claim 6 for transporting microbeads having a non-spherical shape.
  • the above aims are achieved by using an apparatus defined by claim 6 for transporting microbeads having a spherical shape.
  • Type 2 microbeads are of similar size as the microbeads of type 1, but differ from them by a non-spherical 'corn flake'-like shape. They are characterized by a product v b ⁇ b , which is estimated from transport experiments to be about a factor 30 higher than the corresponding product for the microbeads of type 1.
  • a capillary tube 3 is used as chamber within which the transport of the magnetic microbeads takes place.
  • the capillary tube is e.g. a glass capillary having an inner diameter of 0.58 millimeter and an outer diameter of 1 millimeter.
  • a first embodiment of an apparatus according to the invention for transporting magnetic or magnetisable microbeads immersed in a liquid contained in a capillary tube is described hereinafter with reference to Figures 1a to 3 and 7 .
  • Fig. 1a shows a first electromagnet 1.1 comprising a coil 10 wound around magnetic core 9 having poles 11 and 12.
  • Fig. 1a shows this electromagnet in a first polarity state designated by 1.1+ and indicated by the sense of the excitation current applied to coil 10 and by the corresponding direction of the magnetic flux indicated by arrows in poles 11 and 12.
  • electromagnet 1.1 belongs to a first row 1 of electromagnets which are arranged on a first side of a capillary tube 3 having a length axis A as represented in the arrangement shown by Fig. 3 .
  • Fig. 1b shows the same first electromagnet 1.1 as in Fig. 1a , but when this electromagnet is in a second polarity state designated by 1.1- which is opposite to the first polarity state designated by 1.1+ and shown by Fig. 1a .
  • Fig. 2a shows a second electromagnet 2.1 comprising a coil 10 wound around magnetic core 9 having poles 11 and 12.
  • Fig. 2a shows this electromagnet in a first polarity state designated by 2.1+ and indicated by the sense of the excitation current applied to coil 10 and by the corresponding direction of the magnetic flux indicated by arrows in poles 11 and 12.
  • electromagnet 2.1 belongs to a second row 2 of electromagnets which are arranged on a second side of the capillary tube 3, the second side being opposite to the first side thereof.
  • Fig. 2b shows the same second electromagnet 2.1 as in Fig. 2a , but when this electromagnet is in a second polarity state designated by 2.1- which is opposite to the first polarity state designated by 2.1+ and shown by Fig. 2a .
  • an apparatus comprises the following components: a capillary tube 3, a first row 1 of uniformly spaced electromagnets forming a first linear array of poles 11, 12 located on a first side of the capillary tube 3, a second row 2 of uniformly spaced electromagnets forming a second linear array of poles 11, 12 located on a second side of the capillary tube 3, the second side being opposite to the first side.
  • Capillary tube 3 has a length symmetry axis A and is adapted for receiving a liquid containing an amount of magnetic or magnetisable microbeads to be transported.
  • the first linear array of poles 11, 12 and the second linear array of poles 11, 12 extend in an axial direction defined by the length symmetry axis A of the capillary tube 3.
  • Each of the electromagnets has an electromagnetic circuit which comprises a magnetic core 9 which has two poles 11, 12, which are neighboring poles in the first or the second linear array of poles, and a coil 10 coupled with that magnetic core 9.
  • Magnetic core 9 is e.g. a ferrite core or any other suitable soft magnetic material. The dimensions of each magnetic core are in the millimeter-centimeter-range.
  • At least two successive poles 11, 12 of the first array of poles are portions of a first one-piece magnetic core 9 and at least two successive poles 11, 12 of the second array of poles are portions of a second one-piece magnetic core 9.
  • Each of poles 11, 12 has an outer end surface that faces capillary tube 3, and each of poles 11, 12 defines a magnetic axis which is perpendicular to the length symmetry axis A of the capillary tube 3.
  • the magnetic axis of all poles lie in a common plane which passes through the length symmetry axis A of capillary tube 3.
  • the poles 11, 12 of the first row 1 of electromagnets and the poles 11, 12 of the second row 2 of electromagnets are axially offset with respect to each other.
  • Fig. 3 which shows that B is the center-to-center distance between neighbor electromagnets of the same row, and that the electromagnets of rows on opposite sides of capillary tube 3 are shifted of a distance B/2 with respect to each other.
  • This feature is important for achieving the desired effect, i.e. the transport of the magnetic microbeads in the axial direction.
  • Fig. 7 shows a schematic representation of an electrical circuit which is adapted for applying to the coils 10 of the electromagnetic circuits of the first row 1 of electromagnets, and to the coils 10 of the electromagnetic circuits of the second row 2 of electromagnets, periodical electrical current pulses of uniform duration.
  • the electrical circuit represented therein comprises a DC current source 15, an AC current source 16 and switches 13 and 14 actuated by a control circuit 17.
  • AC current source 16 optionally comprises a phase shifter which introduces a phase shift ⁇ .
  • the electrical circuit just described has output terminals which are connected with the input terminals of the electromagnets of the first and the second row of electromagnets in such a way that periodical electrical current pulses delivered at the output terminals of the electrical circuit are applied to the coils 10 of the electromagnets in the order of their position in the axial direction. Under the control of control circuit 17, switches 13 and 14 change the polarity of the current pulses applied to the coils 10 of the electromagnets.
  • Successive current pulses delivered at the output terminals of the electrical circuit shown by Fig. 7 extend over overlapping time intervals and the phase difference between successive pulses is constant and is comprised between 90 and 180 degrees.
  • the electrical circuit of Fig. 7 provides direct current pulses or a superposition of direct current pulses and AC current pulses to the coils 10 of the electromagnets in the sequences described in detail hereinafter with reference to Figures 4a to 6 in the description of a first example of a method according to the invention.
  • a first embodiment of a method according to the invention for transporting magnetic or magnetisable microbeads immersed in a liquid contained in a capillary tube is described hereinafter with reference to Figures 4a to 6 .
  • the method according to this first embodiment is carried out e.g. with an apparatus of the type described above with reference to Figures 1a to 3 and 7 and comprises:
  • step (c) the electrical current pulses of uniform duration are applied to the coils 10 in the order of the position of the corresponding electromagnets in the axial direction, successive pulses extend over overlapping time intervals, and the phase difference between successive pulses is constant and is comprised between 90 and 180 degrees.
  • the application of the electrical current pulses to the coils 10 of the electromagnets generates a magnetic field within capillary tube 3. The amplitude, polarity and position of this magnetic field varying so with time that the magnetic field moves forward in the axial direction, and thereby causes transport of the microbeads in the axial direction.
  • the magnetic microbeads introduced into capillary tube 3 comprise magnetic microbeads having a non-spherical shape.
  • the magnetic microbeads introduced into capillary tube 3 comprise magnetic microbeads having a spherical shape.
  • the electrical current pulses applied to the coils 10 have a frequency in the range of 0.1 to 5 cycles per second.
  • an alternating current signal having a frequency in the range of 1 to 100 cycles per second is superposed onto said electrical current pulses.
  • Figures 4a to 4g illustrate transport of microbeads along the capillary tube shown in Fig. 3 . This transport is achieved by successively actuating the electromagnet arrangements so that these are successively in the polarity states represented in Figures 4a to 4g .
  • the polarity states of the electromagnets are indicated in the same way as in Figures 1a to 2b , that is by a + or a - sign on the right of the reference number which designates the electromagnet, e.g. 1.1+, 2.2-, etc.
  • Fig. 5 shows direct current intensities I 1 .(t), I 2 .(t), I 3 .(t) applied to the electromagnet arrangements represented in Figures 4a to 4g in order that these are successively in the polarity states shown by Figures 4a to 4g .
  • the letters a , b , c , d , e , f and g designate time intervals.
  • Fig. 5 shows three direct current intensities which have a phase difference of 120° with respect to each other.
  • four direct current intensities which have a phase difference of 90° with respect to each other are applied to the electromagnets. This embodiment provides a more efficient transport.
  • Fig. 4a show the polarity states of the electromagnets during time interval a in Fig. 5 .
  • Figures 4b to 4g show the polarity states of the electromagnets during each of the time intervals b , c , d , e , f and g respectively.
  • Fig. 4a shows a cluster 5 of distributed magnetic microbeads formed by the magnetic fields generated by the current intensities I 1 . (t), I 2 . (t), I 3 . (t) applied to the electromagnets during time interval a in Fig. 5 .
  • Figures 4b to 4g show the position of the cluster 5 of distributed magnetic microbeads formed by the magnetic fields generated by the current intensities I 1 . (t), I 2 . (t), I 3 . (t) applied to the electromagnets during each of the time intervals b , c , d , e , f and g respectively.
  • the cluster 5 of distributed magnetic microbeads shown in each of Figures 4a to 4g is composed of magnetic microbeads distributed over a the cross-section of the capillary tube 3 and over a short segment thereof.
  • the cluster 5 of distributed magnetic microbeads has approximately the shape of a column or a disk.
  • the cluster 5 is not a compact mass of magnetic microbeads, but a swarm of magnetic microbeads spaced from each other and moving as a group.
  • the current intensities applied to the electromagnets are not the direct current pulses shown in Fig. 5 , but current pulses formed by multiplication of the current pulses shown in Fig. 5 with an alternating current signal.
  • Fig. 6 shows current pulses I 1 . (t), I 2 . (t), I 3 . (t) which are the result of this multiplication.
  • a second embodiment of an apparatus according to the invention for transporting magnetic or magnetisable microbeads immersed in a liquid contained in a capillary tube is described hereinafter with reference to Figures 8a to 10 , 14 and 15 to 23 .
  • Fig. 8a shows a first electromagnet 1.1 comprising a planar coil 20 wound around a magnetic core element 19.
  • Fig. 8a shows this electromagnet in a first polarity state designated by 1.1+ and indicated by the sense of the excitation current applied to planar coil 20 and by the corresponding direction of the magnetic flux indicated by arrows in pole 21.
  • electromagnet 1.1 belongs to a first row 1 of electromagnets which are arranged on a first side of a capillary tube 3 having a length axis A as represented in the arrangement shown by Fig. 10 .
  • Fig. 8b shows the same first electromagnet 1.1 as in Fig. 8a , but when this electromagnet is in a second polarity state designated by 1.1- which is opposite to the first polarity state designated by 1.1+ and shown by Fig. 8a .
  • Fig. 9a shows a second electromagnet 2.1 comprising a planar coil 20 wound around a magnetic core element 19.
  • Fig. 9a shows this electromagnet in a first polarity state designated by 2.1+ and indicated by the sense of the excitation current applied to planar coil 20 and by the corresponding direction of the magnetic flux indicated by arrows in pole 21.
  • electromagnet 2.1 belongs to a second row 2 of electromagnets which are arranged on a second side of the capillary tube 3, the second side being opposite to the first side thereof.
  • Fig. 9b shows the same second electromagnet 2.1 as in Fig. 9a , but when this electromagnet is in a second polarity state designated by 2.1- which is opposite to the first polarity state designated by 2.1+ and shown by Fig. 9a .
  • an apparatus comprises the following components: a capillary tube 3, a first linear array of uniformly spaced poles 21 of a first row 1 of electromagnets located on a first side of the capillary tube 3, a second linear array of uniformly spaced poles 21 of a second row 2 of electromagnets located on a second side of the capillary tube 3, the second side being opposite to the first side.
  • Capillary tube 3 has a length symmetry axis A and is adapted for receiving a liquid containing an amount of magnetic or magnetisable microbeads to be transported.
  • the first linear array of poles 21 and the second linear array of poles 21 extend in an axial direction defined by the length symmetry axis A of the capillary tube 3.
  • Each one of the electromagnets has an electromagnetic circuit which comprises a magnetic core element 19 and a planar coil 20 coupled therewith.
  • At least two successive poles 21 of the first row 1 of electromagnets are portions of a first one-piece magnetic core 23, and at least two successive poles 21 of the second row 2 of electromagnets are portions of a second one-piece magnetic core 23.
  • Each of poles 21 has an outer end surface that faces capillary tube 3, and each of poles 21 defines a magnetic axis which is perpendicular to the length symmetry axis A of the capillary tube 3.
  • the magnetic axis of all poles lie in a common plane which passes through the length symmetry axis A of capillary tube 3.
  • the poles 21 of the first row 1 of electromagnets and the poles 21 of the second row 2 of electromagnets are axially offset with respect to each other.
  • Fig. 10 which shows that B is the center-to-center distance between neighbor poles of the same row, and that the poles of rows on opposite sides of capillary tube 3 are shifted of a distance B/2 with respect to each other.
  • This feature is important for achieving the desired effect, i.e. the transport of the magnetic microbeads in the axial direction.
  • all magnetic core elements 19 of the first row 1 of electromagnets are portions of a first one-piece magnetic core 23 and all magnetic core elements 19 of the second row 2 of electromagnets are portions of a second one-piece magnetic core 23.
  • Magnetic core 23 is e.g. a ferrite core or any other suitable soft magnetic material. Magnetic core 23 can also be formed by assembling together a ferrite plate and a wafer on which pin-shaped poles have been formed, e.g. by the powder blasting process described hereinafter.
  • each of the magnetic core elements 19 has the shape of a pin that terminates in a sharp pointed tip.
  • the distance between the tip of a pole 21 of the first row of electromagnets and the next tip of a pole 21 of the second row of electromagnets is at most two times the width of the capillary tube 3.
  • each of the electromagnets comprises a planar coil 20 which has a central opening and the pin shaped magnetic core element 19 is inserted through the opening of the planar coil.
  • Fig. 14 shows a schematic representation of an embodiment of the above mentioned electrical circuit which is adapted for applying to the coils 20 of the electromagnetic circuits of the first row of electromagnets 1, and to the coils 20 of the electromagnetic circuits of the second row of electromagnets 2, periodical electrical current pulses of uniform duration.
  • the electrical circuit represented therein comprises a DC current source 15, an AC current source 16 and switches 13 and 14 actuated by a control circuit 17.
  • AC current source 16 optionally comprises a phase shifter which introduces a phase shift ⁇ .
  • the electrical circuit just described has output terminals which are connected with the input terminals of the electromagnets of the first row 1 and the second row 2 of electromagnets in such a way that periodical electrical current pulses delivered at the output terminals of the electrical circuit are applied to the planar coils 20 of the electromagnets in the order of their position in the axial direction. Under the control of control circuit 17, switches 13 and 14 change the polarity of the current pulses applied to the planar coils 20 of the electromagnets.
  • the electrical circuit of Fig. 14 provides direct current pulses or a superposition of direct current pulses and AC current pulses to the planar coils 20 of the electromagnets in the sequences described in detail hereinafter with reference to Figures 11a to 13 in the description of a second example of a method according to the invention.
  • Fig. 15 shows a perspective exploded view showing the components of an embodiment the apparatus shown by Fig. 10 .
  • such an embodiment comprises an upper ferrite plate 23 in which a first row 1 of magnetic poles 21 has been formed, an upper printed circuit board 22 having a thickness of 100 micrometer on which a first row of planar coils 20 having each a thickness of 35 micrometer and a pitch of 200 micrometer has been formed, a capillary tube 3, a lower printed circuit board 22 on which a second row of planar coils 20 has been formed, and a lower ferrite plate 23 in which a second row 2 of magnetic poles 21 has been formed.
  • the magnetic poles of each row belong to portions 19 (shown in Figures 8a to 9b ) of a ferrite plate 23.
  • Portions 19 are magnetic core elements which have the shape of a pin that terminates in a sharp pointed pole tip 21.
  • Fig. 16 shows an enlarged view of a portion of Fig. 15 .
  • Fig. 16 shows the spatial correspondence between the location of the poles 21 and the location of the corresponding planar coils 20.
  • each of the planar coils 20 has a central opening which is aligned with an opening of the printed circuit board and each of the poles 21 having the shape of a pin is inserted through the central opening of the corresponding planar coil 20 and the corresponding opening of the printed circuit board.
  • Fig. 17 shows a longitudinal cross-sectional view of an apparatus comprising components of the type shown in Figures 15 and 16 , wherein the planar coils 20 are arranged on both sides of each printed circuit board 22 (the structure of such a planar coil is shown by Fig. 19 ) in order to generate stronger magnetic fields.
  • capillary tube 3 contains 3 different liquids 4a, 4b and 4c which are e.g. different reagents.
  • Fig. 17 shows a cluster 5 of distributed magnetic microbeads being transported along capillary tube 3 by actuation of the planar coils 20 as described below in a second example of a method according to the invention.
  • Fig. 18 shows a cross-sectional view of the apparatus shown by Fig. 17 along plane XVIII- XVIII represented in Fig. 17 .
  • Fig. 19 shows a perspective view of a planar coil arranged on both sides of a printed circuit board.
  • Figures 20 to 23 illustrate various steps of the process used for forming of magnetic poles 21 on a ferrite wafer by powder blasting micro-erosion technology.
  • Fig. 20 illustrates a first step of the process wherein a first mask 31 having rectilinear web 32 is positioned on a ferrite wafer 30a.
  • the web 32 protects a linear region of the ferrite wafer 30a and after this run a rectilinear ridge 33 results in the wafer now designated as wafer 30b.
  • Fig. 21 illustrates a second step of the fabrication of pole tips 21 on a ferrite wafer.
  • a second mask 34 which has an array of webs parallel to each other and extending in a direction perpendicular to ridge 33, is positioned on ferrite wafer 30b. After powder blasting of wafer 30b with mask 34 on it, the ridge 33 is transformed into an array of ferrite posts or pins 36
  • Fig. 22 shows a ferrite wafer 30c with pole tips fabricated according to the steps shown by Figures 20 and 21 .
  • Fig. 23 shows an enlarged view of a cut-out XXIII in Fig. 22 .
  • a second embodiment of a method according to the invention for transporting magnetic or magnetisable microbeads immersed in a liquid contained in a capillary tube is described hereinafter with reference to Figures 11a to 13 .
  • the method according to this first embodiment is carried out e.g. with an apparatus of the type described above with reference to Figures 8a to 10 , 14 and 15 to 23 comprises:
  • step (c) the electrical current pulses of uniform duration are applied to the coils 20 in the order of the position of the corresponding electromagnets in the axial direction, successive pulses extending over overlapping time intervals and the phase difference between successive pulses being constant and comprised between 90 and 180 degrees.
  • the application of the electrical current pulses to the coils 20 of the electromagnets generates a magnetic field within capillary tube 3. The amplitude, polarity and position of this magnetic field varying so with time that the magnetic field moves forward in the axial direction, and thereby causes transport of the microbeads in the axial direction.
  • the magnetic microbeads introduced into capillary tube 3 comprise magnetic microbeads having a non-spherical shape.
  • the magnetic microbeads introduced into capillary tube 3 comprise magnetic microbeads having a spherical shape.
  • the electrical current pulses applied to the coils 20 have a frequency in the range of 0.1 to 5 cycles per second. If the coils 20 are mounted on a printed circuit board with no particular cooling other than unforced air convection the maximum current density that can be applied to the coils is about 150 A/square millimeter and that corresponds to a maximum current intensity of about 0.5 A for the coils 20 of the type described above in the second example of an apparatus according to the invention.
  • an alternating current signal having a frequency in the range of 1 to 100 cycles per second is superposed onto said electrical current pulses.
  • Figures 11a to 11g illustrate transport of microbeads along the capillary tube shown in Fig. 10 . This transport is achieved by successively actuating the electromagnet arrangements so that these are successively in the polarity states represented in Figures 11a to 11g .
  • the polarity states of the electromagnets are indicated in the same way as in Figures 8a to 9b , that is by a + or a - sign on the right of the reference number which designates the electromagnet, e.g. 1.1+, 2.2+, etc.
  • Fig. 12 shows direct current intensities I 1 . (t), I 2 . (t), I 3 . (t), I 4 . (t) applied to the electromagnet arrangements represented in Figures 11a to 11g in order that these are successively in the polarity states shown by Figures 11a to 11g .
  • the letters a , b , c , d , e , f , g and h designate time intervals.
  • Figure 12 shows four direct current intensities which have a phase difference of 90° with respect to each other.
  • Figure 11a show the polarity states of the electromagnets during time interval a in Figure 12 .
  • Figures 11b to 11g show the polarity states of the electromagnets during each of the time intervals b , c , d , e , f , g and h respectively.
  • Fig. 11a shows a cluster 5 of distributed magnetic microbeads formed by the magnetic fields generated by the current intensities I 1 . (t), I 2 . (t), I 3 . (t), I 4 . (t) applied to the electromagnets during time interval a in Figure 12 .
  • Figures 11b to 11h show the position of the cluster 5 of distributed magnetic microbeads formed by the magnetic fields generated by the current intensities I 1 . (t), I 2 . (t), I 3 . (t), I 4 . (t) applied to the electromagnets during each of the time intervals b , c , d , e , f , g and h respectively.
  • the cluster 5 of distributed magnetic microbeads shown in each of Figures 11a to 11g is composed of magnetic microbeads distributed over a the cross-section of the capillary tube 3 and over a short segment thereof.
  • the cluster 5 of distributed magnetic microbeads has approximately the shape of a column or a disk.
  • the cluster 5 is not a compact mass of magnetic microbeads, but a swarm of magnetic microbeads spaced from each other and moving as a group.
  • the current intensities applied to the electromagnets are not the direct current pulses shown in Fig. 12 , but current pulses formed by multiplication of the current pulses shown in Fig. 12 with an alternating current signal.
  • Fig. 13 shows current pulses I 1 . (t), I 2 . (t), I 3 . (t), I 4 . (t) which are the result of this multiplication.
  • the magnetic fields generated by the electromagnets induce a dynamic vortex-like motion of the microbeads of the microbead cluster 5 over the entire cross-section of capillary tube 3 and this motion takes place during the transport of cluster 5 in axial direction.
  • the vortex-like motion of the microbeads of the cluster 5 being transported in advantageous in applications where interaction of the microbeads with target particles is desirable.
EP07006148A 2007-03-26 2007-03-26 Procédé et appareil pour transporter des microbilles magnétiques ou magnétisables Withdrawn EP1974821A1 (fr)

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EP07006148A EP1974821A1 (fr) 2007-03-26 2007-03-26 Procédé et appareil pour transporter des microbilles magnétiques ou magnétisables
PCT/EP2008/001706 WO2008116543A1 (fr) 2007-03-26 2008-03-04 Procédé et appareil permettant le transport magnétique ou magnétisable de microbilles
EP08716225A EP2129469A1 (fr) 2007-03-26 2008-03-04 Procédé et appareil permettant le transport magnétique ou magnétisable de microbilles

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WO2010076337A1 (fr) * 2009-01-05 2010-07-08 Gottfried Wilhelm Leibniz Universität Hannover Microsystème électromagnétique pour la manipulation de microperles ou de nanoperles magnétiques
WO2011131411A1 (fr) * 2010-04-22 2011-10-27 Siemens Aktiengesellschaft Dispositif pour séparer des particules ferromagnétiques d'une suspension
WO2012116909A1 (fr) * 2011-03-02 2012-09-07 Siemens Aktiengesellschaft Dispositif de séparation pour séparer des particules magnétiques ou magnétisables contenues dans une suspension
WO2013041983A1 (fr) 2011-09-19 2013-03-28 Centre National De La Recherche Scientifique Système micro-fluidique
WO2015150081A1 (fr) * 2014-03-31 2015-10-08 Basf Se Système d'aimant pour le transport d'un matériau aimanté
US9939439B2 (en) 2012-09-07 2018-04-10 Jean-Louis Viovy Microfluidic system having a magnetic particle bed
US10799881B2 (en) 2014-11-27 2020-10-13 Basf Se Energy input during agglomeration for magnetic separation
US10807100B2 (en) 2014-11-27 2020-10-20 Basf Se Concentrate quality
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EP2208531A1 (fr) 2008-12-30 2010-07-21 Atonomics A/S Distribution de particules dans un canal capillaire par l'application d'un champ magnétique
DE102011076192A1 (de) * 2011-05-20 2012-11-22 Siemens Aktiengesellschaft Filter und Verfahren zum Filtrieren von magnetischen Partikeln

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Cited By (13)

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Publication number Priority date Publication date Assignee Title
WO2010076337A1 (fr) * 2009-01-05 2010-07-08 Gottfried Wilhelm Leibniz Universität Hannover Microsystème électromagnétique pour la manipulation de microperles ou de nanoperles magnétiques
WO2011131411A1 (fr) * 2010-04-22 2011-10-27 Siemens Aktiengesellschaft Dispositif pour séparer des particules ferromagnétiques d'une suspension
US8715494B2 (en) 2010-04-22 2014-05-06 Siemens Aktiengesellschaft Device for separating ferromagnetic particles from a suspension
AU2011244583B2 (en) * 2010-04-22 2014-05-08 Siemens Aktiengesellschaft Device for separating ferromagnetic particles from a suspension
US9028687B2 (en) 2011-03-02 2015-05-12 Siemens Aktiengesellschaft Separating device for separating magnetic or magnetizable particles present in suspension
WO2012116909A1 (fr) * 2011-03-02 2012-09-07 Siemens Aktiengesellschaft Dispositif de séparation pour séparer des particules magnétiques ou magnétisables contenues dans une suspension
WO2013041983A1 (fr) 2011-09-19 2013-03-28 Centre National De La Recherche Scientifique Système micro-fluidique
US9939439B2 (en) 2012-09-07 2018-04-10 Jean-Louis Viovy Microfluidic system having a magnetic particle bed
WO2015150081A1 (fr) * 2014-03-31 2015-10-08 Basf Se Système d'aimant pour le transport d'un matériau aimanté
US10675637B2 (en) 2014-03-31 2020-06-09 Basf Se Magnet arrangement for transporting magnetized material
US10799881B2 (en) 2014-11-27 2020-10-13 Basf Se Energy input during agglomeration for magnetic separation
US10807100B2 (en) 2014-11-27 2020-10-20 Basf Se Concentrate quality
FR3125442A1 (fr) * 2021-07-26 2023-01-27 Airbus Helicopters Procédé et dispositif de captation de particules ferromagnétiques pour un système mécanique, et système mécanique associé

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