WO2008116543A1

WO2008116543A1 - Method and apparatus for transporting magnetic or magnetisable microbeads

Info

Publication number: WO2008116543A1
Application number: PCT/EP2008/001706
Authority: WO
Inventors: Olivier Elsenhans; Goran Savatic; Martin Gijs; Amar Rida; Victor Fernandez
Original assignee: F. Hoffmann-La Roche Ag; Roche Diagnostics Gmbh
Priority date: 2007-03-26
Filing date: 2008-03-04
Publication date: 2008-10-02
Also published as: EP1974821A1; EP2129469A1

Abstract

A method and an apparatus 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, the transporting being effected in the absence of a static magnetic field in the capillary tube.

Description

METHOD AND APPARATUS FOR TRANSPORTING MAGNETIC OR MAGNETISABLE MICROBEADS

Field of the invention

The invention concerns a method for transporting magnetic or magnetisable microbeads being capable of binding a biological probe and/or a biological analyte, said magnetic or magnetisable microbeads being immersed in a liquid comprising a biological probe and/or a biological analyte, said liquid being 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 being capable of binding a biological probe and/or a biological analyte, said magnetic or magnetisable microbeads being immersed in a liquid comprising a biological probe and/or a biological analyte, said liquid being contained in a capillary tube.

Background Particles, e.g. magnetic beads, of a size of several micrometers in diameter are used in biomedical analysis.

In such analysis, magnetic microbeads may be used, as non- limiting examples, for generically binding a biological probe or a biological analyte. This method can be used to separate a biological analyte from a liquid sample. Alternatively, magnetic microbeads having a biological probe molecule immobilized on their surface may bind to a biological analyte comprised in a liquid. In a preferred embodiment, said biological analyte is RNA or DNA. In a further preferred embodiment, said biological probe is an oligonucleotide which is complementary to a target RNA or DNA. The biological probe can be immobilized on the magnetic particles and hybridized to the target RNA or DNA. A specific target RNA or DNA can thus be separated from a complex liquid. The separated biological analyte can then be quantitated. One method known in the art for quantitating a target RNA or DNA is amplification, such as, as non-limiting example, real time PCR.

The advantage of using magnetic particles in a method according to the present invention is that magnetic particles can be manipulated using magnetic fields independently from any flow pattern of the solution. Thus, by manipulation of the magnetic particles with controlled magnetic fields an important relative motion of the magnetic particles with respect to the fluid and thereby with respect to the target molecules can be created, and this effect strongly increases the probability of capturing a biological probe or a biological analyte with the magnetic particles, or to bind a biological analyte to a biological probe immobilized on the magnetic particles. Magnetic particles can then be separated and the bound analyte eluted for further processing, or directly processed.

In the context of the invention transport of magnetic particles, i.e. magnetic or magnetisable microbeads, 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 χ_eff (typically Xeff < 1/ due to demagnetization effects of the mostly spherical particles) and because the volume of a magnetic particle is small. The magnetic moment induced in a microbead is given by μ=Vχ_effB_o/μo, with B₀ the magnetic f ield generated by the permanent magnet, χ_eff the magnetic permeability and V the magnetic microbead volume. A very small microbead has thus no effective magnetization when there is no external magnetic field applied to it, i.e. it is superparamagnetic. The magnetic force on an induced moment in a magnetic induction field is given by

F =μWB

From (1) it is apparent that to create a strong magnetic force on a magnetic particle it is necessary to have a large magnetic moment //and a large gradient of the magnetic induction .

For this reason relatively important magnetic fields of about 10^~2 T and large magnetic field gradients from 10 to 100 T/m have to be generated locally, e.g. within a capillary tube used for the transport of a solution containing target molecules, in order to generate magnetic forces which are sufficiently strong for manipulating magnetic particles in a solution. Prior art solutions for the separation and sorting of magnetic microbeads exist, but most of them require use of large permanent magnets or electromagnets which are mechanically moved.

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. Starting from a first end of the pipe which is the inlet thereof, 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. In order to transport the magnetic particles along the pipe, 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. When an electromagnetic post of this arrangement is turned on, the pole thereof attracts magnetic particles which form a cluster on the portion of the inner side of the pipe wall which is close to that pole. When the electromagnetic posts are turned on and off in sequence as mentioned above, the magnetic forces successively exerted by the poles on the magnetic particles causes motion of a cluster of magnetic particles back and forth along a zigzag path between opposite side walls of the pipe. The motion of the cluster of magnetic particles in the axial direction defined by the length axis of the pipe is thus rather slow. The utility of this arrangement is thus limited to applications in which a very slow motion of the magnetic particles is acceptable. In the above mentioned zigzag movement the magnetic particles keep the form of a cluster and are thus not homogeneously distributed over the cross- section of the pipe. This is an important drawback, because it strongly reduces the probability of biological interactions of probesor analytes with the magnetic particles , or magnetic particles with DNA immobilized on their surface with target molecules carried by a liquid flowing through the pipe. A further limitation of the above mentioned arrangement described by Joung et al . is that the magnetic forces that can be created with such an arrangement are relatively weak and are effective only within a very limited spatial range. The utility of this arrangement is thus limited to applications in which pipes of very small diameter are used. Otherwise, the magnetic forces created by the arrangement would not be sufficiently strong to achieve a movement of the cluster of magnetic particles.

Summary of the invention

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.

According to a first aspect of the invention the above aims are achieved by means of a method defined by claim 1. Claims 2 to 5 define preferred embodiments of this method.

According to a second aspect of the invention the above aims are achieved by means of an apparatus defined by claim 6. Claims 7 to 10 define preferred embodiments of this apparatus.

According to a third aspect of the invention the above aims are achieved by using an apparatus defined by claim 6 for transporting microbeads having a non-spherical shape.

According to a fourth aspect of the invention the above aims are achieved by using an apparatus defined by claim 6 for transporting microbeads having a spherical shape.

The main advantages obtained with a method and an apparatus according to the invention are as follows:

- use of large magnets or electromagnets which have to be mechanically moved is not required,

- the apparatus comprises a miniaturized and low-price electromagnetic arrangement made by using coils made on simple printed circuit boards and ferrite microstructures patterned from ferrite wafers using a batch-type powder blasting micro-erosion technology,

- the magnetic particles are displaced over several millimeters in a single attraction event between neighboring poles, and - average transport velocities of about 1 millimeter per second are achievable,

- the magnetic particles can be displaced back and forth within one or more liquids contained in a capillary tube.

The efficient transport of magnetic microbeads achieved with instant invention is particularly useful in biochemical reactions wherein as many as possible interactions between magnetic microbeads which may interact with probe molecules or analytical target molecules, or which carry e.g. probe molecules (e.g. single stranded DNA) on their surface and which specifically interact with complementary target molecules (e.g. a complementary target DNA) .

In a preferred embodiment of the invention the magnetic or magnetisable microbeads transported are electrically non- conductive microbeads. Such microbeads are e.g. non-metallic magnetic or magnetisable particles having a resistivity larger than 2 milliohm.cm.

The small dimensions of an apparatus according to the invention make possible to build with it a compact bioanalysis system.

Brief description of the drawings

The subject invention will now be described in terms of its preferred embodiments with reference to the accompanying drawings. These embodiments are set forth to aid the understanding of the invention, but are not to be construed as limiting.

Brief description of the drawings

The subject invention will now be described in terms of its preferred embodiments with reference to the accompanying drawings. These embodiments are set forth to aid the understanding of the invention, but are not to be construed as limiting. Fig. Ia shows a first embodiment of a first electromagnet of a first row of electromagnets in a first polarity state.

Fig. Ib shows the first electromagnet of Fig. Ia in a second polarity state.

Fig. 2a shows a first embodiment of a first electromagnet of a second row of electromagnets in a first polarity state.

Fig. 2b shows the first electromagnet of Fig. 2a in a second polarity state.

Fig. 3 shows a cross-sectional view of a portion of a first embodiment of an apparatus according to the invention comprising a capillary tube located between a first row of electromagnets and a second row of electromagnets.

Figures 4a to 4g illustrate transport of beads along the capillary tube shown in Fig. 3 achieved by successively actuating the electromagnet arrangements so that these are successively in the states represented in Figures 4a to 4g.

Fig. 5 shows direct current intensities applied to the electromagnet arrangements represented in Figures 4a to 4g in order that these are successively in the states shown by Figures 4a to 4g.

Fig. 6 shows current pulses formed by multiplication of the current pulses shown in Figure 5, with an alternating current signal .

Fig. 7 a schematic representation of the circuit used for applying direct current voltages and alternating current voltages to the electromagnet arrangements shown in Figures 4a to 4g.

Fig. 8a shows a second embodiment of a first electromagnet of a first row in a first polarity state. Fig. 8b shows the first electromagnet of Fig. 8a in a second polarity state.

Fig. 9a shows a second embodiment of a first electromagnet of a second row in a first polarity state.

Fig. 9b shows the first electromagnet of Fig. 9a in a second polarity state.

Fig. 10 shows a cross-sectional view of a portion of a second embodiment of an apparatus according to the invention comprising a capillary tube located between a first row of electromagnets of the type shown in Fig. 8a and a second row of electromagnets of the type shown in Fig. 9a.

Figures 11a to Hh illustrate transport of beads along the capillary tube shown in Fig. 10 achieved by successively actuating the electromagnet arrangements so that these are successively in the states represented in Figures Ha to Hh.

Fig. 12 shows direct current intensities applied to the electromagnet arrangements represented in Figures Ha to Hh in order that these are in the states shown by Figures Ha to Hh.

Fig. 13 shows additional alternating current intensities applied to the electromagnet arrangements shown in Figures Ha to Hh.

Fig. 14 shows a schematic representation of the circuit used for applying direct current voltages and alternating current voltages to the electromagnet arrangements shown in Figures Ha to Hh.

Fig. 15 shows a perspective exploded view showing the components of an embodiment the apparatus shown by Fig. 10.

Fig. 16 shows an enlarged view of a portion of Fig. 15. Fig. 17 shows a cross-sectional view of an apparatus according to Figures 15 and 16.

Fig. 18 shows a cross-sectional view along plane XVIII- XVIII represented in Fig. 17.

Fig. 19 shows a perspective view of a coil arranged on both sides of a printed circuit board.

Fig. 20 illustrates a first step of the fabrication of pole tips on a ferrite wafer.

Fig. 21 illustrates a second step of the fabrication of pole tips on a ferrite wafer.

Fig. 22 shows a ferrite wafer 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.

Reference numerals used in drawings

1 first row of electromagnets

1.1 electromagnet

1.2 electromagnet

1.3 electromagnet 2 second row of electromagnets

2.1 electromagnet 2.2 electromagnet 2.3 electromagnet

2.4 electromagnet 3 capillary tube

4 liquid

4a first liquid

4b second liquid

4c third liquid 5 cluster of beads

9 magnetic core

10 coil 11 pole

12 pole

13 polarity reversal switch

14 polarity reversal switch 15 direct -current source

16 alternating current source

17 control unit

19 magnetic core element / portion of magnetic core 23

20 coil 21 pole / pole tip

22 printed circuit board

23 magnetic core / ferrite plate

24 bore hole 30a ferrite wafer 30b ferrite wafer

30c ferrite wafer

31 mask

32 web of mask 31 33 ridge 34 mask

35 web of mask 34

36 projection

A symmetry axis of capillary tube

B distance between electromagnets

Detailed description of the invention

Preferred embodiments of the invention are described hereinafter with reference to the accompanying drawings.

The operation of the apparatus and methods described hereinafter is based on the following principles:

The magnetic force exerted in the direction X (e.g. along the length axis of the capillary tube 3 in the examples described hereinafter) on a magnetic microbead in a magnetic field is given by: 3 H

F . = M X _> H (D d x

Where μ_Q is the permeability in vacuum Vj_b is the volume of the microbead X_b is the magnetic susceptibility of the microbead H is the vector of the external magnetic field.

In addition to the magnetic force, the magnetic microbead in motion with a velocity vector v experiences a hydrodynamic drag force. If there is no macroscopic motion of the liquid solution containing the microbeads, the hydrodynamic viscous force acting on a spherical particle of radius R_b, is given by:

F _mccui = 6 πη R_b v (2)

Where η is the viscosity of the fluid (for water, η = 8.9 x 10 ^"4 N s/m²) .

When the microbead is subjected to a magnetic attraction force, it will accelerate till the force associated with viscosity equals the magnetic force. For example, to displace a magnetic particle having a radius R_b=O.5 μm with a velocity of 0.5 mm/s requires a magnetic force of about 4 pN. This equilibrium velocity in the x-direction can be found by equalizing eq. (1) with the x-axis projection of eq. (2) , giving a stationary microbead velocity

3H v - H (3)

6πηR_b dx

In the examples described below two types of magnetic microbeads are used:

Type 1 microbeads are spherical 10 micrometer size, magnetic latex particles micromer^®-M microbeads with a susceptibility Xb = 0.045, and a volume v_b = 523 cubic micrometer purchased from Micromod Partikeltechnologie GmbH, Rostock, Germany. Micromer^®-M microbeads are monodisperse particles which consist of magnetite in an organic matrix from a styrene- maleic acid-copolymer .

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_bχ_b, which is estimated from transport experiments to be about a factor 30 higher than the corresponding product for the microbeads of type 1.

In the examples described below 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.

First Example of an apparatus according to the invention

A first embodiment of an apparatus according to the invention for transporting electrically non-conducting, magnetic or magnetisable microbeads immersed in a liquid contained in a capillary tube is described hereinafter with reference to Figures Ia to 3 and 7.

Fig. Ia shows a first electromagnet 1.1 comprising a coil 10 wound around magnetic core 9 having poles 11 and 12. Fig. Ia 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. As will be described hereinafter with reference to Fig. 3, 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. Ib shows the same first electromagnet 1.1 as in Fig. Ia, 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. Ia.

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. As will be described hereinafter with reference to Fig. 3, 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.

As shown by Fig. 3 an apparatus according to the invention comprises the following components: a capillary tube 3, a first row 1 of uniformly spaced, stationary 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, stationary 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 electrically non-conducting, magnetic 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. In a preferred embodiment 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. This is shown in particular by 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. As shown by Fig. 7, 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 φ. 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. Depending on the method used, 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.

First Example of a method according to the invention

A first embodiment of a method according to the invention for transporting electrically non-conducting, 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 Ia to 3 and 7 and comprises:

(a) positioning a capillary tube 3 having a length symmetry axis A in a space which extends between a first row 1 of uniformly spaced, stationary electromagnets forming a first linear array of poles 11, 12 located on a first side of the capillary tube 3, and a second row 2 of uniformly spaced, stationary electromagnets forming a second linear array of poles 11, 12 located on a second side of the capillary tube 3 opposite to the first side,

(b) introducing into the capillary tube 3 a liquid containing an amount of electrically non-conducting, magnetic or magnetisable microbeads to be transported along the axial direction, and

(c) 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.

In 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.

In a preferred embodiment the magnetic microbeads introduced into capillary tube 3 comprise magnetic microbeads having a non-spherical shape.

In another preferred embodiment the magnetic microbeads introduced into capillary tube 3 comprise magnetic microbeads having a spherical shape. In a preferred embodiment the electrical current pulses applied to the coils 10 have a frequency in the range of 0.01 to 5 cycles per second.

In another preferred embodiment an alternating current signal having a frequency in the range of 1 to 2000 cycles per second is superposed onto the 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. In Figures 4a to 4g the polarity states of the electromagnets are indicated in the same way as in Figures Ia 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 I₁. (t), I₂. (t), I₃. (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. In Fig. 5 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. In a preferred embodiment not shown in the accompanying figures, 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.

In order to put the electromagnets shown in Fig. 4a in the polarity states 1.1+, 1.3-, 1.2-, 1.1+, 2.2-, 2.1+, 2.3- shown therein, the current intensities I₁. (t) , I₂. (t) , I₃. (t) shown in Fig. 5 during time the time interval a are applied to the coils 10 of the corresponding electromagnets.

In order to put the electromagnets shown in Fig. 4b in the polarity states 1.1+, 1.3-, 1.2+, 1.1+, 2.2+, 2.1+, 2.3- shown therein, the current intensities I₁. (t), I₂. (t), I₃. (t) shown in Fig. 5 during time the time interval b are applied to the coils 10 of the corresponding electromagnets.

In order to put the electromagnets shown in Fig. 4c in the polarity states 1.1-, 1.3-, 1.2+, 1.1-, 2.2+, 2.1-, 2.3- shown therein, the current intensities I₁. (t), I₂. (t), I₃. (t) shown in Fig. 5 during time the time interval c are applied to the coils 10 of the corresponding electromagnets.

In order to put the electromagnets shown in Fig. 4d in the polarity states 1.1-, 1.3+, 1.2+, 1.1-, 2.2+, 2.1-, 2.3+ shown therein, the current intensities Ii . (t) , I₂. (t) , I₃. (t) shown in Fig. 5 during time the time interval d are applied to the coils 10 of the corresponding electromagnets.

In order to put the electromagnets shown in Fig. 4e in the polarity states 1.1-, 1.3+, 1.2-, 1.1-, 2.2-, 2.1-, 2.3+ shown therein, the current intensities Ii . (t) , I₂. (t) , I₃. (t) shown in Fig. 5 during time the time interval e are applied to the coils 10 of the corresponding electromagnets.

In order to put the electromagnets shown in Fig. 4f in the polarity states 1.1-, 1.3+, 1.2-, 1.1+, 2.2-, 2.1+, 2.3+ shown therein, the current intensities I₁. (t) , I₂. (t), I₃. (t) shown in Fig. 5 during time the time interval f_ are applied to the coils 10 of the corresponding electromagnets.

In order to put the electromagnets shown in Fig. 4g in the polarity states 1.1+, 1.3-, 1.2-, 1.1+, 2.2-, 2.1+, 2.3- shown therein, the current intensities Ii.(t), I₂. (t), I₃. (t) shown in Fig. 5 during time the time interval g are applied to the coils 10 of the corresponding electromagnets.

Fig. 4a show the polarity states of the electromagnets during time interval a in Fig. 5. In the same way, 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 I₁. (t), I₂. (t), I₃. (t) applied to the electromagnets during time interval a in Fig. 5. In the same way, 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 Ii . (t) , I₂. (t) , I₃. (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.

As can be appreciated from Figures 4a to 4g, the result of the actuation of the electromagnets as just described with reference to Figures 4a to 4g and to Fig. 5, is that the magnetic fields generated by the electromagnets transport the cluster 5 of distributed magnetic microbeads in axial direction through the liquid contained in capillary tube 3.

In a preferred embodiment 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 I₁. (t) , I₂. (t) , I₃. (t) which are the result of this multiplication. When the electromagnets in Figures 4a to 4g are actuated which the current pulses shown in Fig. 6, the magnetic fields generated by the electromagnets induce a dynamic vortex- like motion of the microbeads of 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 is advantageous in applications where interaction of the microbeads with target particles is desirable .

Second Example of an apparatus according to the invention

A second embodiment of an apparatus according to the invention for transporting electrically non-conducting, 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. As will be described hereinafter with reference to Fig. 10, 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. As will be described hereinafter with reference to Fig. 3, 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.

As shown by Fig. 10 an apparatus according to the invention comprises the following components: a capillary tube 3, a first linear array of uniformly spaced poles 21 of a first row 1 of stationary 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 stationary 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 electrically non-conducting, 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. In a preferred embodiment 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. This is shown in particular by 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.

In a preferred embodiment 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.

In another preferred embodiment each of the magnetic core elements 19 has the shape of a pin that terminates in a sharp pointed tip.

In a further preferred embodiment 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.

In another preferred embodiment the electromagnetic circuit of 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.

As shown by Fig. 14, 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 φ. 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. Successive current pulsesdelivered at the output terminals of the electrical circuit extend over overlapping time intervals and the phase difference between successive pulses is constant and is comprised between 90 and 180 degrees. Depending on the method used, 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. As shown by Fig. 15 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. As shown by Fig. 16 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. As shown by Fig. 17 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 electrically non-conducting, 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. Ferrite wafer is e.g. a Philips 3F3 ferrite wafer having a high relative permeability (μ_r=1800) and a thickness of 3 millimeter.

During a first powder blasting run 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. In this step 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.

Second Example of a method according to the invention

A second embodiment of a method according to the invention for transporting electrically non-conducting, 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: (a) positioning a capillary tube 3 having a length symmetry axis A in a space which extends between a first linear array of uniformly spaced poles 21 of a first row of stationary electromagnets 1 located on a first side of the capillary tube 3, and a second linear array of uniformly spaced poles 21 of a second row 2 of stationary electromagnets located on a second side of the capillary tube 3 opposite to the first side,

(c) applying to the coils 20 of the electromagnetic circuits of the first row 1 of electromagnets and to the coils 20 of the electromagnetic circuits of the second row 2 of electromagnets periodical electrical current pulses of uniform duration.

In 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.

In a preferred embodiment the magnetic microbeads introduced into capillary tube 3 comprise electrically non-conducting, magnetic microbeads having a non-spherical shape.

In another preferred embodiment the magnetic microbeads introduced into capillary tube 3 comprise electrically nonconducting, magnetic microbeads having a spherical shape. In a preferred embodiment the electrical current pulses applied to the coils 20 have a frequency in the range of 0.01 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.

In another preferred embodiment an alternating current signal having a frequency in the range of 1 to 2000 cycles per second is superposed onto said electrical current pulses .

Figures 11a to Hg 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 Ha to Hg. In Figures Ha to Hg 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_x. (t), I₂. (t), I₃. (t) , I₄. (t) applied to the electromagnet arrangements represented in Figures Ha to Hg in order that these are successively in the polarity states shown by Figures Ha to Hg. In Figure 12 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.

In order to put the electromagnets shown in Fig. Ha in the polarity states shown therein, the current intensities

Ii • (t) , I₂. (t) , I₃. (t) , I₄. (t) shown in Figure 12 during time the time interval a are applied to the coils 20 of the corresponding electromagnets.

In order to put the electromagnets shown in Fig. lib in the polarity states shown therein, the current intensities Ii . (t) , I₂. (t) , I₃. (t) , I₄. (t) shown in Figure 12 during time the time interval b are applied to the coils 20 of the corresponding electromagnets.

In order to put the electromagnets shown in Fig. lie in the polarity states shown therein, the current intensities Ii . (t) , I₂. (t) , I₃. (t) , I₄. (t) shown in Figure 12 during time the time interval c_ are applied to the coils 20 of the corresponding electromagnets.

In order to put the electromagnets shown in Fig. Hd in the polarity states shown therein, the current intensities Ii . (t) , I₂. (t) , I₃. (t) , I₄. (t) shown in Figure 12 during time the time interval d are applied to the coils 20 of the corresponding electromagnets.

In order to put the electromagnets shown in Fig. He in the polarity states shown therein, the current intensities Ii.(t), I₂. (t), I₃. (t), I₄. (t) shown in Figure 12 during time the time interval e are applied to the coils 20 of the corresponding electromagnets.

In order to put the electromagnets shown in Fig. Hf in the polarity states shown therein, the current intensities I₁. (t) , I₂. (t) , I₃. (t) , I₄. (t) shown in Figure 12 during time the time interval _f are applied to the coils 20 of the corresponding electromagnets.

In order to put the electromagnets shown in Fig. Hg in the polarity states shown therein, the current intensities I₁. (t) , I₂. (t) , I₃. (t) , I₄. (t) shown in Figure 12 during time the time interval g are applied to the coils 20 of the corresponding electromagnets. In order to put the electromagnets shown in Fig. Hh in the polarity states shown therein, the current intensities

1₁. (t) , I₂. (t) , I₃. (t) , I₄. (t) shown in Figure 12 during time the time interval h are applied to the coils 20 of the corresponding electromagnets.

Figure Ha show the polarity states of the electromagnets during time interval a in Figure 12. In the same way, Figures Hb to Hg show the polarity states of the electromagnets during each of the time intervals b, £, d, e, f_, g and h respectively.

Fig. Ha shows a cluster 5 of distributed magnetic microbeads formed by the magnetic fields generated by the current intensities Ii . (t) , I₂. (t) , I₃. (t) , I₄. (t) applied to the electromagnets during time interval a in Figure 12. In the same way, Figures Hb to Hh show the position of the cluster 5 of distributed magnetic microbeads formed by the magnetic fields generated by the current intensities I₁. (t) ,

1₂. (t), I₃. (t), I₄. (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 Ha to Hg 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 .

As can be appreciated from Figures Ha to Hh, the result of the actuation of the electromagnets as just described with reference to Figures Ha to Hg and to Figure 12, is that the magnetic fields generated by the electromagnets transport the cluster 5 of distributed electrically non- conducting, magnetic microbeads in axial direction through the liquid contained in capillary tube 3.

In a preferred embodiment 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 Ii . (t) , I₂. (t) , I₃. (t) , I₄. (t) which are the result of this multiplication. When the electromagnets in Figures 11a to Hg are actuated which the current pulses shown in Fig. 13, 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.

Although preferred embodiments of the invention have been described using specific terms, such description is for illustrative purposes only, and it is to be understood that changes and variations obvious to the skilled artisan are to be considered within the scope of the subject application, which is only to be limited by the claims that follow and their equivalents.

Claims

1. A method for transporting magnetic or magnetisable microbeads being capable of binding a biological probe and/or a biological analyte, said magnetic or magnetisable microbeads being immersed in a liquid comprising a biological probe and/or a biological analyte, said liquid being 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, said method comprising:

(a) positioning a capillary tube (3) having a length symmetry axis (A) in a space which extends between a first row (1) of uniformly spaced, stationary electromagnets forming a first linear array of poles (11, 12) located on a first side of said capillary tube (3) , said first linear array extending in an axial direction defined by the length symmetry axis (A) of the capillary tube (3) , and a second row (2) of uniformly spaced, stationary electromagnets forming a second linear array of poles (11, 12) located on a second side of said capillary tube (3), said second linear array extending in said axial direction and said second side being opposite to said first side, each of said electromagnets having an electromagnetic circuit which comprises a magnetic core having two poles (11, 12) and a coil (10) coupled with that magnetic core, said two poles being neighboring poles in said first or said second linear array of poles, at least two successive poles (11, 12) of said first linear array of poles being portions of a first one-piece magnetic core (9) and at least two successive poles (11, 12) of said second linear array of poles being portions of a second one-piece magnetic core (9), each of said poles (11, 12) having an outer end surface that faces said capillary tube (3) , and each of said poles (11, 12) defining a magnetic axis which is perpendicular to the length symmetry axis (A) of said capillary tube (3) , the poles (11, 12) of said first row of electromagnets and the poles (11, 12) of said second row of electromagnets being axially offset with respect to each other,

(b) introducing into said capillary tube (3) a liquid containing an amount of magnetic or magnetisable microbeads to be transported along said axial direction,

(c) applying to the coils (10) of the electromagnetic circuits of said first row (1) of electromagnets and to the coils (10) of the electromagnetic circuits of said second row (2) of electromagnets periodical electrical current pulses of uniform duration, said pulses being applied to the coils (10) in the order of the position of the corresponding electromagnets in said 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 said electrical current pulses to the coils (10) of the electromagnets generating a magnetic field within said capillary tube (3) , the amplitude, polarity and position of said magnetic field varying so with time that said magnetic field moving forward in said axial direction, and thereby causing transport of said microbeads in said axial direction.

2. 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, said method comprising: (a) positioning a capillary tube (3) having a length symmetry axis (A) in a space which extends between a first linear array of uniformly spaced poles (21) of a first row (1) of stationary electromagnets located on a first side of said capillary tube (3) , said first linear array of poles extending in an axial direction defined by the length symmetry axis (A) of the capillary tube (3) , and a second linear array of uniformly spaced poles (21) of a second row (2) of stationary electromagnets located on a second side of said capillary tube (3), said second linear array of poles extending in said axial direction and said second side being opposite to said first side, each one of said poles being part of an electromagnetic circuit which comprises a magnetic core element (19) and a coil (20) coupled therewith, at least two successive poles (21) of said first row (1) of electromagnets being portions of a first one-piece magnetic core (23) and at least two successive poles (21) of said second row of electromagnets being portions of a second one- piece magnetic core (23), each of said poles (21) facing said capillary tube (3), and each of said poles (21) defining a magnetic axis which is perpendicular to the length symmetry axis (A) of said capillary tube (3), the poles (21) of said first row (1) of electromagnets and the poles (21) of said second row (2) of electromagnets being axially offset with respect to each other,

(c) applying to the coils (20) of the electromagnetic circuits of said first row (1) of electromagnets and to the coils (20) of the electromagnetic circuits of said second row (2) of electromagnets periodical electrical current pulses of uniform duration, said pulses being applied to the coils (20) in the order of the position of the corresponding electromagnets in said 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 said electrical current pulses to the coils (10) of the electromagnets generating a magnetic field within said capillary tube (3), the amplitude, polarity and position of said magnetic field varying so with time that said magnetic field moving forward in said axial direction, and thereby causing transport of said microbeads in said axial direction.

3. A method according to any of claims 1 or 2, wherein said magnetic microbeads are electrically non-conducting.

4. A method according to any of claims 1 or 2, wherein said magnetic microbeads comprise magnetic microbeads having a non-spherical shape.

5. A method according to any of claims 1 or 2 , wherein said magnetic microbeads comprise magnetic microbeads having a spherical shape.

6. A method according to any of claims 1 or 2, wherein said electrical current pulses have a frequency in the range of 0.01 to 5 cycles per second.

7. A method according to claim 6, wherein an alternating current signal in the range of 1 to 2000 cycles per second is superposed onto said electrical current pulses.

8.. An apparatus for transporting magnetic or magnetisable microbeads being capable of binding a biological probe and/or a biological analyte, said magnetic or magnetisable microbeads being immersed in a liquid comprising a biological probe and/or a biological analyte, said liquid being contained in a capillary tube, said apparatus comprising :

(a) a capillary tube (3) adapted for receiving a liquid containing an amount of magnetic or magnetisable microbeads to be transported, said capillary tube has a length symmetry axis (A) ,

(b) a first row (1) of uniformly spaced, stationary electromagnets forming a first linear array of poles (11, 12) located on a first side of said capillary tube (3) , said first linear array of poles extending in an axial direction defined by the length symmetry axis (A) of the capillary tube (3) ,

(c) a second row (2) of uniformly spaced, stationary electromagnets forming a second linear array of poles (11, 12) located on a second side of said capillary tube (3), said second linear array of poles extending in said axial direction and said second side being opposite to said first side, each of said electromagnets having an electromagnetic circuit which comprises a magnetic core (9) having two poles (11, 12) and a coil (10) coupled with that magnetic core, said two poles (11, 12) being neighboring poles in said first or said second linear array of poles, at least two successive poles (11, 12) of said first array of poles being portions of a first one-piece magnetic core (9) and at least two successive poles (11, 12) of said second array of poles being portions of a second one-piece magnetic core (9) , each of said poles (11, 12) having an outer end surface that faces said capillary tube (3) , and each of said poles (11, 12) defining a magnetic axis which is perpendicular to the length symmetry axis (A) of said capillary tube (3), the poles (11, 12) of said first array of poles and the poles (11, 12) of said second array of poles being axially offset with respect to each other, and

(d) an electrical circuit (14, 15, 16, 17) for applying to the coils (10) of the electromagnetic circuits of said first row of electromagnets (1) , and to the coils

(10) of the electromagnetic circuits of said second row of electromagnets (2) , periodical electrical current pulses of uniform duration, said pulses being applied to the coils

(10) in the order of the position of the corresponding electromagnets in said 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.

9. An apparatus for transporting magnetic or magnetisable microbeads immersed in a liquid contained in a capillary tube : (a) a capillary tube (3) adapted for receiving a liquid containing an amount of magnetic or magnetisable microbeads to be transported, said capillary tube has a length symmetry axis (A) ,

(b) a first linear array of uniformly spaced poles (21) of a first row of stationary electromagnets (1) located on a first side of said capillary tube (3), said first linear array of poles extending in an axial direction defined by the length symmetry axis (A) of the capillary tube (3) ,

(c) a second linear array of uniformly spaced poles (21) of a second row of stationary electromagnets (2) located on a second side of said capillary tube (3) , said second linear array of poles extending in said axial direction and said second side being opposite to said first side, each one of said electromagnets having an electromagnetic circuit which comprises a magnetic core element (19) and a coil (20) coupled therewith, at least two successive poles (21) of said first row of electromagnets being portions of a first one-piece magnetic core (23) and at least two successive poles (21) of said second row of electromagnets being portions of a second one-piece magnetic core (23), each of said poles (21) facing said capillary tube (3) , and each of said poles (21) defining a magnetic axis which is perpendicular to the length symmetry axis (A) of said capillary tube (3) , the poles (21) of said first array of poles and the poles (21) of said second array of poles being axially offset with respect to each other, and

(d) an electrical circuit (14, 15, 16, 17) for applying to the coils (20) of the electromagnetic circuits of said first row (1) of electromagnets (1) , and to the coils (20) of the electromagnetic circuits of said second row (2) of electromagnets (2) , periodical electrical current pulses of uniform duration, said pulses being applied to the coils (20) in the order of the position of the corresponding electromagnets in said 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.

10. An apparatus according to any of claims 8 or 9, wherein said magnetic microbeads are electrically non- conducting.

11. An apparatus according to claim 9, wherein all magnetic core elements (19) of said first row (1) of electromagnets are portions of a first one-piece magnetic core (23) and all magnetic core elements (19) of said second row (2) of electromagnets are portions of a second one-piece magnetic core (23)

12. An apparatus according to claim 9, wherein each of said magnetic core elements (19) has the shape of a pin that terminates in a sharp pointed tip.

13. An apparatus according to claim 12, wherein the distance between the tip of a pole (21) of said first row of electromagnets and the next tip of a pole (21) of said second row of electromagnets is at most two times the width of said capillary tube (3) .

14. An apparatus according to claim 12, wherein the electromagnetic circuit of each of the electromagnets comprises a planar coil (20) which has a central opening and said pin shaped magnetic core element (19) is inserted through said opening of said planar coil .

15. An apparatus according to any of claims 8 to 14, characterized in that a liquid in said capillary tube contains magnetic microbeads having a non- spherical shape.

16. An apparatus according to any of claims 8 to 14, characterized in that a liquid in said capillary tube contains magnetic microbeads having a spherical shape.