EP3147028B1 - Method and system for magnetic separation of nano-beads - Google Patents

Description

Technical background

The present invention relates to a method and a system for the magnetic separation of nano-beads (also micro-beads or nano-beads) from a fluid or a solution, and in particular a method and a system for magnetic separation of nano-beads, each allow a faster and more reliable way of working and a beneficial automation of dealing with nano-beads.

Magnetic micro- or nano-beads are used as standard in chemistry and biochemistry. These iron-containing beads with partially functionalized surface, e.g. To bind antibodies must be removed at any given time from the respective reaction vessel. These nano-beads are used in the so-called Magnetic Cell Separation, also known as Magnetic Activated Cell Sorting and often abbreviated as MACS, or in water treatment. Cell separation becomes so much easier because you can pull the labeled with beads cells directly from any vessel. In the treatment of water you can not only remove the unwanted substances, you can also very easily take random samples in the flow process. If the beads have not bound any toxins, they can continue to be used, otherwise they will be replaced.

For this purpose, the prior art uses various magnetic separators which produce a pellet of beads on the bottom or on the side of the reaction vessel. This pellet must be washed so that only the substances bound specifically to the beads (or the nano-beads with the substances) remain there and no nonspecific residues from the respective matrix can disturb the later reactions.

In one example of a conventional process, the nanobeads are initially in a liquid. First, the nano-beads are extracted from the liquid by means of a magnet. To facilitate the later separation, the magnet is surrounded by a kind of shell. The magnet attracts the nano-beads and collects them on the surface of the shell. The magnet is then lifted out of the first fluid, together with the sheath and nano-beads, and into a second fluid, e.g. a wash solution, dipped. The magnet is then pulled out of the shell. The nano-beads are now no longer held on the shell and get into the wash solution. This process of collection and transfer to another liquid may need to be repeated several times until the nano-beads have been sufficiently washed and e.g. can be further processed or reused.

These and other common methods are time consuming, cumbersome and require a mechanical device, e.g. a pipette, magnetic separators, etc. Precise work is essential. In the washing steps beads are lost and clump in the pellet; In addition, at each washing step, the substances bound to the beads, e.g. Bacteria or viruses.

The invention is a simple, fast and inexpensive way to gently remove the beads from any sample vessel and clean. Automation is also much easier with the method and apparatus of the present invention. As well as a simple sample preparation with POCT (point of care testing). The separation and washing of the beads by means of a system or method according to the present invention requires only about 10 seconds. This applies to a single sample as well as to eg 96 samples (in parallel processing). For example, ELISA laboratory systems could also be retrofitted with a system according to the present invention.

US 2014/099658 A1 discloses a method of processing magnetic particles that selectively interact with a substance present in a liquid medium. The particles are collected using a probe with a hollow shield and a probe magnet that can be moved up and down. The lower end of the probe with the collected particles is located on a release point of a plate, below which release point is a release magnet.

Brief description of the invention

The present invention is provided by the appended claims 1 and 8. Advantageous embodiments are disclosed in the dependent claims. Nano-beads are generally all particles which comprise magnetic or magnetizable particles, in particular all iron-, cobalt- or nickel-containing particles. The shape does not necessarily have to be round, so it can also have a polygonal shape. Their average size is usually between 30 nm and 5 μm (diameter).

In a first preferred embodiment of the present invention, there is provided a method of magnetically separating nano-beads from a first fluid, comprising: providing the first fluid having the nano-beads therein; inserting a sleeve body into the first fluid; Sleeve body, a first magnet is arranged, which is displaceable along a longitudinal axis of the sleeve body, collecting nano-beads on the sleeve wall by the force of a first magnetic field of the first magnet, removing the sleeve body with the collected nano-beads from the first fluid, inserting the sleeve body with the collected nano-beads in a second fluid and providing a magnetic field whose magnetic pole alignment opposite to a pole orientation of the first magnet in the sleeve body, so that the first magnet in the sleeve body repelled from the magnetic field and ver in the sleeve body ver is pushed.

In one embodiment of the present invention, the method comprises further rinsing the pod body with the collected nano-beads after the step of removing the pod body with the collected nano-beads from the first fluid and before the step of inserting the pod body with the collected nano-beads in the second fluid.

In one embodiment of the present invention, the sleeve body has a cylindrical hollow central portion and the first magnet comprises a bar magnet whose diameter is slightly less than the inner diameter of the central portion of the sleeve body.

In one embodiment of the present invention, the second magnetic field is provided by a second magnet which is displaced in a longitudinal axis to the sleeve body with the collected nano-beads in the second fluid.

In an embodiment of the present invention, the second magnetic field is provided by at least one electromagnet.

In one embodiment of the present invention, the second magnetic field is provided by a plurality of electromagnets which generate a multipole field rotating about the longitudinal axis of the sleeve body which rotates by cyclically turning on and off individual electromagnets or by rotating the electromagnets about the longitudinal axis of the sleeve body.

In one embodiment of the present invention, the sleeve body has an elongate shape, the pole orientation of the first magnet is parallel to the longitudinal axis of the sleeve body, and the nano-beads are collected at a lower end of the sleeve body by one of the poles of the first magnet.

In a second preferred embodiment, there is provided a system for magnetically separating nano-beads from a first fluid comprising at least one sleeve body in which a first magnet is disposed along a longitudinal axis (A) of the first Sleeve body (110) is movable, and at least one second magnetic field providing device, wherein the magnetic pole orientation of the second magnetic field opposite to the polar orientation of the first magnet in the sleeve body and the second magnetic field providing device and the sleeve body in one direction do not overlap perpendicular to the longitudinal axis.

In one embodiment of the present invention, the sleeve body has a cylindrical hollow central portion and the first magnet comprises a bar magnet whose diameter is slightly less than the inner diameter of the central portion of the sleeve body. The axial length of the central portion of the sleeve body is preferably selected so that the first magnet is sufficiently displaceable in the sleeve body, depending on the application of the present invention, e.g. Penetration depth into the fluid and magnetic strength. Preferably, the axial play of the magnet in the central part of the sleeve body is 0.1 cm to 5 cm, more preferably 0.2 cm to 3 cm, and most preferably 0.5 cm to 2 cm.

In an embodiment of the present invention, the device providing the second magnetic field comprises a second magnet slidable in a longitudinal axis to the sleeve body.

In an embodiment of the present invention, the device providing the second magnetic field comprises an electromagnet.

In one embodiment of the present invention, the device providing the second magnetic field comprises a plurality of electromagnets which generate a multipole field rotating about the longitudinal axis of the sleeve body by cycling individual electromagnets on and off or by rotating the electromagnets about the longitudinal axis of the sleeve body rotates.

In one embodiment of the present invention, the sleeve body has an elongated shape, the pole orientation of the first magnet being parallel to the longitudinal axis of the first magnet Sleeve body and the nano-beads are collected at a lower end of the sleeve body by at least one of the poles of the first magnet, depending on the depth of immersion of the sleeve body with the first magnet in the first or second fluid, for example by both poles of the first magnet.

In a third preferred embodiment, there is provided an automated system for magnetically separating nano-beads from a first fluid, comprising: a plurality of systems for magnetically separating nano-beads from a first one Fluid according to a system as described above, wherein the sleeve bodies and the devices providing the second magnetic field are each provided in a holder, a transport means which can move the holder with the sleeve bodies from a first position to a second position wherein the second position is directly above a position of the support with the devices providing the second magnetic field, and a control unit controls the movement of the transport device and the provision of the second magnetic field. In a preferred embodiment, the magnetic fields are provided not by individual second magnets but by a single second magnet or a number of sufficiently large and strong second magnets that is less than the number of first magnets.

In a fourth preferred embodiment, a computer readable storage medium is provided that includes program code that, when executed, performs a method as described above.

Brief description of the drawings

• Fig. 1 ist eine Perspektivansicht eines Hülsenkörpers mit einem Magneten gemäß einer Ausführungsform der vorliegenden Erfindung.
• Fig. 2A-2D sind schematische Querschnittsansichten, die ein Verfahren gemäß einer Ausführungsform der vorliegenden Erfindung zeigen.
• Fig. 3A-3D sind schematische Querschnittsansichten, die ein Verfahren gemäß einer anderen Ausführungsform der vorliegenden Erfindung zeigen.
• Fig. 4 ist ein Flussdiagramm eines Verfahrens gemäß einer Ausführungsform der vorliegenden Erfindung.

All drawings shown here are schematic in nature and components shown should only be interpreted in relation to each other. The drawings and the description use reference numerals to facilitate the understanding of the present invention. Wherever appropriate, like reference numerals have been used to designate the same or similar parts.

• Fig. 1 is a perspective view of a sleeve body with a magnet according to an embodiment of the present invention.
• Fig. 2A-2D FIG. 15 are schematic cross-sectional views showing a method according to an embodiment of the present invention. FIG.
• Fig. 3A-3D FIG. 15 are schematic cross-sectional views showing a method according to another embodiment of the present invention. FIG.
• Fig. 4 FIG. 10 is a flowchart of a method according to an embodiment of the present invention. FIG.

Detailed description of the invention

The subject of the invention is a simple, quick and inexpensive way of gently removing nano-beads from any sample vessel and using e.g. to clean or further process. Also, automation is much simpler by the method and apparatus of the present invention and a corresponding automated system is provided by the present invention. The separation and washing of the beads by means of a system or method according to the present invention requires only about 10 seconds. This applies to a single sample as well as e.g. 96 samples (parallel processing). If e.g. If 1 billion beads were added to 1000 liters of water and 1 million beads were needed for an analysis, one would normally need to remove and examine one liter of water. But such a large volume is very unwieldy. With the method and system of the present invention, it is only necessary to move the sleeve body with the magnet through the water for a few seconds to bind enough beads.

Fig. 1 is a perspective view of a sleeve body with a magnet according to an embodiment of the present invention. In the illustrated embodiment, a sleeve body 110 is formed substantially cylindrical and closed at the top and bottom, respectively. The sleeve body 110 may have a collar at a lower end (at which later the nano-beads are collected), which makes it difficult to collect nano-beads on the side wall of the sleeve body. It should be noted, however, that the shape of the sleeve body is not limited herein. Other oblong shapes with polygon cross section (rectangular, square, triangular, pentagonal, etc.) are also possible.

In the sleeve body 110, a magnet 112 is provided. The magnet 112 is arranged in the sleeve body along the longitudinal axis A movable or displaceable. In Fig. 1 the magnet 112 is shown as a bar magnet with Polausrichtung along the longitudinal axis A. Instead of a bar magnet, any other magnetic shape may be used as long as the magnet has opposite magnetic poles with respect to the longitudinal axis A (in FIG Fig. 1 exemplified by "N" and "S", without limitation) and is designed such that the poles can not be reversed. In the present embodiment, this is achieved by the magnet has a diameter which is only slightly smaller than the inner diameter of the sleeve body, so that the magnet can not be reversed and the magnetic poles of the magnet with respect to the longitudinal axis A are aligned. The axial length of a central portion of the sleeve body 110, in which the first magnet 112 can move, is preferably selected so that the first magnet 112 is sufficiently displaceable in the sleeve body 110, depending on the application of the present invention, eg penetration depth into the Fluid 152 and magnetic strength of the first and second magnets, respectively. Preferably, the axial play of the first magnet 112 in the central portion of the sleeve body 110 is 0.1 cm to 5 cm, more preferably 0.2 cm to 3 cm, and most preferably 0.5 cm to 2 cm. The magnets used here are preferably neodymium bar magnets having a diameter which approximately corresponds to the inner diameter of the sleeve body used. Thus, for example, for small reaction vessels with about 0.5 ml to 1.5 ml magnets with a diameter between 2 mm and 4 mm and a length between 5 mm and 15 mm. The adhesive force of the first magnets 112 is in each case preferably between 250 g and 750 g, particularly preferably between 350 g and 600 g.

In Fig. 1 is indicated by the downward arrow P1 that the sleeve body is immersed in a first step of a method according to the present invention in a first vessel 150 with a first fluid 152. In the first fluid, usually a liquid, nano-beads are distributed. With nano-beads (also nano-beads) are in the present invention, all kinds of substantially meant spherical and magnetizable (or magnetized) bodies. Their size can range from one nm to a few microns in diameter, depending on the application. In chemistry and biochemistry they are used to selectively bind substances by means of functional surfaces or to attach themselves to surfaces of certain chemical compositions (hybridization reactions).

In one embodiment of the present invention, the sleeve body 110, e.g. in a manual operation, so far immersed in the fluid 152 that both poles of the first magnet 112 are below the surface of the fluid with the nano-beads. The nano-beads then bind at the north pole and the south pole when the sleeve body 110 is immersed deep enough and then form two bands. One can thus use the sleeve body 110 with its magnet 112 like a spoon in a beaker for stirring; in a few seconds so bind all the beads. However, in the present invention, immersion of the sleeve body 110 into the fluid 152 is preferably only to be performed so far that only one pole of the magnet 112 lies below the surface of the fluid 152. Thus, the nano-beads bind to only one pole of the magnet 112.

Fig. 2A-2D FIG. 15 are schematic cross-sectional views showing a method according to an embodiment of the present invention. FIG. In Fig. 2A the situation is shown in which the sleeve body 110 is immersed with the magnet 112 in the vessel 150 with the first fluid 152. Through the points in the fluid, it is indicated in the drawings that the nano-beads are still distributed in the fluid. In Fig. 2B The nano-beads are already collected by the magnetic attraction of the magnet 112 on the lower surface of the sleeve body 110, which is represented by a pellet 154. The upward arrow in Fig. 2B indicates that the sleeve body 110 can be removed with the bead pellet 154 and the magnet 112 from the first fluid.

In Fig. 2C For the first time, a complete system according to the present invention is shown. The sleeve body 110 with the bead pellet 154 and the magnet 112 is in Fig. 2C immersed in a second fluid 162 in a second vessel 160. The second fluid is eg a washing solution or a liquid, in which further reactions between substances in the liquid and the nano-beads should proceed. In the lower area, a second magnet 120 is shown, which is opposite to the polar orientation of the magnet 112 in its polar alignment and which, as indicated by the upward arrow, is moved in the direction of the second vessel 160. When the magnetic field of the second magnet 120 comes close enough to the magnet 112 in the sleeve body, the magnet 112 in the sleeve body becomes repulsive by the same poles of the first magnet 112 and the second magnet 120 (here, the N poles, whereupon the magnet) Invention is not limited), as indicated by the narrow arrow in Fig. 2D will be shown.

This lifting of the magnet 112 has two important and synergetic effects. Firstly, the nanobeads are no longer held by the first magnet 112 on the sleeve body wall and can be detached therefrom. On the other hand, this solution process is promoted by the attractive effect of the second magnet, so that the nano-beads quickly collect in the lower region of the second vessel 160. This speeds up the process altogether. Optionally, the second magnet 120 may be moved up and down several times so as to create a movement of the nano-beads through the fluid, which may, for example, accelerate rinses. To remove the nano-beads from the second fluid 162, the second magnet 120 is simply lowered again, so that the first magnet 112 attracts the nano-beads again and can then be removed from the second fluid (see FIGS. 2A and 2B ).

It should be noted at this point that a plurality of sleeve body 110 together (parallel) can be used and moved. Thus 96-arrays (8x12) are frequently used in the present technical field. Such arrays or supports can be moved by hand or automatically (by a transport device, eg by a robotic arm or the like). In this case, a suitable computer control is provided which controls the movement of the transport means and the second magnets 120. In other embodiments, the controller may also control other factors, such as currents to activate electromagnets 130, but the invention is not should be limited. It is possible for each sleeve body 110 in a holder to provide a single second magnet 120 as well as a large-area magnet for the entire holder. In the latter case, disturbing edge effects can be minimized.

Fig. 3A-3D FIG. 15 are schematic cross-sectional views showing a method according to another embodiment of the present invention. FIG. This embodiment substantially corresponds to the embodiment of FIG Fig. 2A-2D , In particular, the devices and processes in FIGS. 3A-3B are identical to the devices and processes in Fig. 2A-2B ,

Instead of the second magnet 120 is in Fig. 3C-3D at least one solenoid 130 is provided. Instead of driving the (electric) magnet up and down as in Fig. 2C and 2D , the electromagnet is simply turned on and off to develop the desired effect on nano-beads and first magnets 112. In general, the first magnet 112 and the second magnet 120 and the solenoid 130 are selected and operated so that a sufficient repulsive force (or adhesive force) between the magnet is ensured. For example, in combination with a 96-array, a single, relatively strong magnet can be chosen as the first magnet for the lower magnet. In the case of a 96-array, when the adhesion force of the upper magnets and the lower magnet (s) is 600g in total, the repulsive effect is sufficient for a distance between the first and second magnets of about 1-2 cm (vertical distance between the poles ie only overcoming the gravitational effect on the first magnet and possibly overcoming the attraction force of the nano-beads). Increasing the adhesive force of the lower magnet (s) to a total of 6 kg, the repulsion is sufficient for a distance of about 5 cm. The adhesive force and the weight of the magnets used are also highly dependent on other factors, such as the filling height of the vessel 150. A person skilled in the art can easily adjust the values for weight, adhesive force of the magnets, immersion depth, etc.

Instead of a single electromagnet can also have several electromagnets are provided, which generate a multipole field rotating about the longitudinal axis of the sleeve body, which rotates by cyclically turning on and off of individual electromagnets or by rotating the electromagnets about the longitudinal axis of the sleeve body. Such multipole fields can together (with corresponding pole orientation) achieve the same repulsive effect as the field of a single magnet. The basic function of the present invention would thus be ensured. However, the locally different magnetic action by the multipole magnet creates potentials in the fluid along which the nano-beads flow. Due to the rotation of these multipole fields, the nano-beads can, after detachment from the sleeve body wall in Fig. 3D additionally be moved by the second fluid, which can promote and accelerate a flushing process.

Fig. 4 FIG. 10 is a flowchart of a method according to an embodiment of the present invention. FIG. According to Fig. 4 For example, in a particularly preferred method of the present invention, the first fluid with the nano-beads therein is provided. A sleeve body is inserted into the first fluid, wherein in the sleeve body, a magnet is arranged, which is displaceable along a longitudinal axis A of the sleeve body. The nano-beads are collected at the sleeve wall by the force of the magnetic field of the magnet. The sleeve body is removed with the collected nano-beads from the first fluid. The sleeve body is inserted with the collected nano-beads in a second fluid and an electromagnetic field (magnetic field) is provided, the magnetic pole alignment of which is opposite to the polar orientation of the magnet in the sleeve body. Subsequently, optionally, the sleeve body 110 can be removed from the second fluid 160. Optionally, after the step of removing the pod body 110 with the collected nano-beads from the first fluid 150 and before the step of inserting the pod body 110 with the collected nano-beads into the second fluid 160, rinsing may be performed.

• S210 Bereitstellen des ersten Fluids mit darin befindlichen Nano-Beads;
• S220 Einführen eines Hülsenkörpers in das erste Fluid, wobei in dem Hülsenkörper ein erster Magnet angeordnet ist, der entlang einer Längsachse (A) des Hülsenköpers verschiebbar ist;
• S230 Sammeln von Nano-Beads an der Hülsenwand durch die Kraftwirkung eines ersten magnetischen Feldes des ersten Magneten;
• S240 Entfernen des Hülsenköpers mit den gesammelten Nano-Beads aus dem ersten Fluid;
• S250 Einführen des Hülsenköpers mit den gesammelten Nano-Beads in ein zweites Fluid; und
• S260 Bereitstellen eines magnetischen Feldes, dessen magnetische Polausrichtung einer Polausrichtung des ersten Magneten in dem Hülsenkörper entgegengesetzt ist, so dass der erste Magnet in dem Hülsenkörper von dem magnetischen Feld abgestoßen und in dem Hülsenköper verschoben wird.

Fig. 4 shows:

• S210, providing the first fluid having nano-beads therein;
• S220 inserting a sleeve body in the first fluid, wherein in the sleeve body a first magnet is arranged, which is displaceable along a longitudinal axis (A) of the sleeve body;
• S230 collecting nano-beads on the sleeve wall by the force of a first magnetic field of the first magnet;
• S240 removing the sleeve body with the collected nano-beads from the first fluid;
• S250 inserting the sleeve body with the collected nano-beads into a second fluid; and
• S260 providing a magnetic field whose magnetic pole orientation is opposite to a pole orientation of the first magnet in the sleeve body, such that the first magnet in the sleeve body is repelled by the magnetic field and displaced in the sleeve body.

Application example 1

One way of applying the present invention is set forth below with practical reference. However, the example should not be interpreted as limiting the present invention.

An interesting application is to coat the outside of the sleeve body with antibodies: if e.g. Using two different monoclonal antibodies, each capable of binding to a specific epitope of an antigen (e.g., protein), one can bind the first antibody to the beads and the second antibody to the outside of the sleeve body. Then you give the beads with their bound first antibodies in the sample and wait a few minutes. Then immerse the sleeve body, on the outside of which the second antibodies are in the sample.

Through the magnet inside the sleeve body, the beads are attracted. After a few seconds, remove the sleeve body from the sample and immerse it in a washing vessel, under the bottom of which there is a magnet with reverse polarity. If the respective antigen was not in the sample, the beads go into solution ( Fig. 2d ); If however, when the antigen is in the sample, the antigen-antibody reaction has taken place on the outside of the sheath body and the beads to whose antibodies the antigen is bound remain stuck to the sheath body. The antigen acts as a link between the two antibodies. Depending on the concentration of the antigen remain different amounts of beads stick, the rest goes into solution. Pull the sleeve body out of the washing vessel and insert it eg into a Q-MAP device (cf. EP-A-1 664 747 ), where the antigen-antibody binding dissolves and the beads detach from the sheath body after a few seconds and can be measured directly, the measurement result being quantitatively utilizable.

Claims (15)

1. Method for magnetic separation of nanobeads from a first fluid (152), comprising:

   providing (S210) the first fluid (152) containing nanobeads therein; inserting (S220) a sleeve body (110) in the first fluid (152), wherein in the sleeve body (110) a first magnet (112) is disposed, which is moveable along a longitudinal axis (A) of the sleeve body (110);

   collecting (S230) nanobeads on the sleeve wall by the force of a first magnetic field of the first magnet (112);

   removing (S240) the sleeve body (110) with the collected nanobeads from the first fluid (152); inserting (S250) the sleeve body (110) with the collected nanobeads in a second fluid (162); and

   providing (S260) a magnetic field by means of a device (120, 130) providing a second magnetic field, whose magnetic pole orientation is opposed to the pole orientation of the first magnet (112) in the sleeve body (110), so that the first magnet (112) in the sleeve body (110) is pushed away from the first magnetic field and is moved in the sleeve body (110), wherein the device (120, 130) providing a second magnetic field and the sleeve body (110) do not overlap in a direction perpendicular to the longitudinal axis (A).
2. Method according to claim 1, further comprising:
   rinsing the sleeve body (110) with the collected nanobeads after the step of removing (S240) the sleeve body (110) with the collected nanobeads from the first fluid (152) and before the step of inserting (S250) the sleeve body (110) with the collected nanobeads in the second fluid (162).
3. Method according to one of the preceding claims, wherein the sleeve body (110) comprises a cylindrical hollow central part and the first magnet (112) comprises a rod magnet, whose diameter is slightly less than the inner diameter of the central part of the sleeve body (110).
4. Method according to one of the preceding claims, wherein the second magnetic field is provided by a second magnet (120), which is moved in a longitudinal axis (A) to the sleeve body (110) with the collected nanobeads in the second fluid (162).
5. Method according to one of the claims 1-3, wherein the second magnetic field is provided by at least one electromagnet (130).
6. Method according to claim 5, wherein the second magnetic field is provided by a plurality of electromagnets generating a multi-pole field rotating around the longitudinal axis (A) of the sleeve body (110) by cyclically switching on and off single electromagnets or by rotating of the electromagnets around the longitudinal axis (A) of the sleeve body (110).
7. Method according to one of the preceding claims, wherein the sleeve body (110) has an elongated shape, the pole orientation of the first magnet (112) is parallel to the longitudinal axis (A) of the sleeve body (110) and the nanobeads are collected at a lower end of the sleeve body (110) by one of the poles of the first magnet (112).
8. System for magnetic separation of nanobeads from a first fluid (152), comprising:
   at least one sleeve body (110), in which a first magnet (112) moveable along a longitudinal axis (A) of the sleeve body (110) is disposed; and at least one device (120, 130) providing a second magnetic field, wherein the magnetic pole orientation of the second magnetic field is opposite to the pole orientation of the first magnet (112) in the sleeve body (110) and the device (120, 130) providing a second magnetic field and the sleeve body (110) do not overlap in a direction perpendicular to the longitudinal axis (A).
9. System according to claim 8, wherein the sleeve body (110) has a cylindrical hollow central part and the first magnet (112) comprises a rod magnet, whose diameter is slightly less than the inner diameter of the central part of the sleeve body (110).
10. System according to one of the claims 8-9, wherein the device (120, 130) providing the second magnetic field, comprises a second magnet (120), which is moveable in a longitudinal axis (A) to the sleeve body (110).
11. System according to one of the claims 8-9, wherein the device (120, 130), providing the second magnetic field, comprises an electromagnet (130).
12. System according to claim 11, wherein the device (120, 130) providing the second magnetic field comprises a plurality of electromagnets generating a rotating multi-pole field around the longitudinal axis (A) of the sleeve body (110) by cyclically switching on and off single electromagnets or by rotating the electromagnets around the longitudinal axis (A) of the sleeve body (110).
13. System according to one of the claims 8-12, wherein the sleeve body (110) has an elongated shape, the pole orientation of the first magnet (112) is parallel to the longitudinal axis (A) of the sleeve body (110), whereby the sleeve body (110) is adapted so that the nanobeads are collected at a lower end of the sleeve body (110) by one of the first poles of the first magnet (112).
14. Automated system for magnetic separation of nanobeads from a first fluid (152), comprising:

    a plurality of systems for magnetic separation of nanobeads from a first fluid (152) according to one of the claims 8-13, wherein the sleeve bodies (110) and the devices (120, 130) providing the second magnetic field are each provided in a holder respectively;

    a transport unit, which is able to move the holder with the sleeve bodies (110) from a first position to a second position, wherein the second position is directly above a position of the holder with the devices (120, 130) providing the second magnetic field; and a control unit, which controls the movement of the transport unit and the provision of the second magnetic field.
15. Computer-readable memory device, comprising a program code, which executes a method according to one of the claims 1-7, if executed.

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