Rod arrangement and method for extracting magnetizable particles from solutions

Abstract

Rod arrangement (1) for extracting magnetizable particles (70) from solutions (60) in at least one cavity (50), the rod arrangement (1) comprising: - at least one guide element (90) which is fixed to a guide element traverse (100) and which is movable to a distal guide element position (90d) by means of the guide element traverse (100) which is driven by a guide element drive group (900) consisting of up to three independent and separately controllable drives (m9x, m9y, m9z), wherein the guide element traverse (100) is movable in the direction parallel to the guide element (90) and in at least one direction perpendicular to the guide element (90); - at least one rod element (20), wherein the rod element (20) is fixed to a rod element traverse (30), which is driven by a rod element drive group (200) with up to three drives (m2x, m2y, m2z) acting orthogonally to each other, and thus the rod element (20) is movable at least in one direction parallel to the at least one guide element (90) and in at least one direction perpendicular to the guide element (90) and is thereby insertable into and removed from the at least one guide element (90); - a magnetic element (110) which is arranged at a distal end section of the at least one rod element (20), wherein the magnetic element (110) is movable to a distal magnetic element position (110d) and wherein the distal magnetic element position (110d) is located at a distal end section of the at least one guide element (90); and - a covering (80) which closes the distal end section of the guide element (90).

Description

Field of invention

[0001] The invention relates to rod arrangements for extracting magnetizable particles from solutions in at least one cavity. Furthermore, the invention relates to methods for extracting magnetizable particles from a solution in at least one cavity. Finally, the invention relates to magnetic elements for extracting magnetizable particles. Background of the invention

[0002] Rod arrangements are known in the art for the extraction of biomolecules using magnetizable particles. The magnetizable particles are initially contained in a solution within a cavity. Under suitable conditions, the biomolecules bind to these magnetizable particles. Suitable conditions include the addition of a binding buffer and possibly lysis of the biomolecules, as is known in the art.

[0003] The magnetizable particles are bound to the biomolecules. A magnetic element in the rod assembly attracts the magnetizable particles and, consequently, the bound biomolecules. Multiple purification steps are typically used to extract the magnetizable particles. The purity of the magnetizable particles on the rod assembly increases with each purification step. The magnetizable particles, along with the bound biomolecules, are typically moved from one cavity to the next using the rod assembly.

[0004] Simple magnetizable rod assemblies are known in the prior art. These rod assemblies are used, for example, in laboratory automation equipment to transport magnetizable particles. In the prior art, a rod is often encased in a shell that is closed at the bottom but open at the top. The rod is then placed in a solution containing magnetizable particles. A magnetic element inside the rod is moved to a region near the lower end, i.e., the distal end of the rod. The magnetic attraction enables the magnetizable particles to be transported from the solution into further cavities. To release the magnetizable particles into the further cavity, the magnetic element is switched off. Switching off the magnetic element can be achieved by removing it from the shell.Alternatively, it is possible to switch off the current flow through the magnetic element, provided that the magnetic element is implemented as an electromagnet.

[0005] WO 198705536 (Carbomatrix, 1986) describes a method for manipulating magnetizable particles using magnetic elements. A plastic sheath is used for the magnetizable rod. The plastic sheath is essentially non-magnetic. It is typically made of thin-walled, non-magnetizable, and remanent material. The Carbomatrix system further describes a mobility of the magnetic element within the non-magnetic sheath. A distal end of the plastic sheath has a stepped profile. This stepped profile ensures that the magnetizable particles adhere primarily to the tip and not to the side of the plastic sheath.

[0006] US 20060266130 (Festo, 2005) describes an automated processing device with magnetizable rods and magnetizable particles. Furthermore, this patent application provides a comprehensive overview of the development of so-called "magnetic beads" technologies. In first-generation magnetic beads, magnets were attached from below to attract the magnetizable particles downwards. These were followed by various arrangements with magnetizable rods that could be inserted into cavities from above. The Festo system from 2005 is designed for relatively large magnetizable particles that achieve high velocities within a solution. The Festo system from 2005 also provides only a small magnetically effective area. A magnetically effective area is defined as an area of ​​the enclosure that is permeated with a sufficiently strong and inhomogeneous magnetic field to attract magnetizable particles.The magnetically effective area is determined by the extent of a region sufficiently permeated by an inhomogeneous magnetic field and essentially by the intersection of this sufficiently inhomogeneous magnetic field-permeated region with the casing or the walls of the cavities. The Festo system from 2005 is not suitable for use with small magnetizable particles.

[0007] The magnetizable particles known in the prior art have a diameter in the range of a few micrometers to a few tens of micrometers. In the following, small magnetizable particles will be understood to mean magnetizable particles with a diameter of less than one micrometer, for example, in the range of 100 to 500 nm. These magnetizable particles with a diameter of less than one micrometer are also referred to as "nanobeads".

[0008] WO 8606493 (Labsystems, 1986) describes a method for performing immunoassays using magnetizable particles and magnetizable rods. The Labsystems system from 1986 also allows for radiation measurement of the magnetizable particles that adhere to the magnetizable rod. The magnetizable rod has a magnetic element at its tip. This magnetic element is a short bar magnet, meaning its length is comparable to or less than the diameter of the bar magnet. In the Labsystems system from 1986, the magnetically effective area for extracting magnetizable particles is limited to the distal end of the rod.

[0009] EP 0787296 (Thermo, 1994) describes a magnetizable rod made of ferromagnetic material. At one distal end of the magnetizable rod is a long bar magnet whose length is at least twice its diameter. A ferromagnetic shaft of the magnetizable rod concentrates the magnetic field lines within the ferromagnetic material, causing the magnetic field lines to emerge proximally from a cavity at the distal end of the magnetizable rod. Similarly, in the Thermo system from 1994, the effective magnetic field is limited to the distal end of the magnetizable rod.

[0010] EP 0687505 (Roche, 1994) discloses a downwardly open cavity in which a solution is drained downwards after the magnetizable particles contained therein have been deposited on a chain of alternating magnets. The chain of alternating magnets is protected from the solution by a protective sheath.

[0011] WO 2002066165 (Dexter Magnetic, 2002) discloses a layer carrying alternating magnetizations. The alternating magnetization of the layer is caused by alternatingly magnetized magnetic elements. The layer can be placed beneath multiwell plates so that magnetic fields penetrate the cavities of the multiwell plate from below. The magnetic field lines run perpendicular to the plane of the multiwell plate. Within the cavities, the magnetic field lines run vertically. Consequently, the magnetizable particles collect at the bottom of the cavities.

[0012] EP 1185372 (Thermo, 2001) discloses a magnetizable rod used in conjunction with a vessel for collecting magnetizable particles from a solution or for releasing magnetizable particles into a solution. The magnetizable rod has a tapered end. The magnetizable particles accumulate at this tapered end. The tapered end of the magnetizable rod limits the magnetically effective area to this area. Simultaneously, the tapered end of the rod increases the magnetic field strength, as is known to those skilled in the art. With the Thermo system of 2001, the collection of magnetizable particles is limited to a very small tip area. Here, too, only a very small area is available for collecting the magnetizable particles. The Thermo system of 2001 further discloses a planar cavity.The shallow depression of the cavity creates, for example, a ring-shaped free space between the tapered end of the magnetizable rod and the bottom of the cavity. This ring-shaped free space is permeated by an inhomogeneous magnetic field, allowing the magnetizable particles to be collected within it.

[0013] WO 2008045742 (Promega, 2006) describes a magnetizable rod with a distal magnetic element. A magnet with transverse magnetization is embedded in the distal magnetic element. A characteristic feature of the Promega system from 2006 is that the north-south orientation of the magnetic poles is essentially perpendicular to the longitudinal axis of the magnetizable rod. In the Promega system from 2006, the magnetizable rod is also surrounded by a casing, which is made, for example, of plastic.

[0014] WO 2004035217 (BioNobile, 2002) describes a magnetizable rod with a long bar magnet at its distal end. The long bar magnet is significantly longer than its width. It is enclosed by a ferromagnetic sheath, which can be removed proximally. Removing the sheath releases the magnetic field of the tip. The ferromagnetic sheath concentrates the field lines of the long bar magnet within its interior, thus preventing inhomogeneous magnetic field distributions at the distal end of the magnetizable rod once the sheath substantially encloses the entire length of the long bar magnet.

[0015] EP 1726963 (Festo, 2006) discloses a transfer unit for transferring a sample from a source vessel to a target vessel. The transfer unit comprises a distally closed guide element and a magnetic element. The Festo system from 2006 is suitable for extracting common magnetizable particles. The magnetic element is movable within the guide element. The magnetic element always remains spaced from a distal end of the guide element. This limits the strength of the inhomogeneous magnetic field in the magnetically effective area. Therefore, the use of the Festo system from 2006 is limited with small magnetizable particles.

[0016] DE 699 26 218 T2 relates to a method for transferring a substance immobilized on microparticles from a first vessel to a second vessel, wherein the microparticles consist of magnetic or magnetizable material or the microparticles are attached to a magnetic or magnetizable body, and the microparticles on which the substance is immobilized are captured by means of a magnet immersed in the first vessel, the magnet together with the captured microparticles is transferred to the second vessel, and the microparticles are released from the influence of the magnet, wherein the surface of the magnet is separated from the microparticles either by a membrane or a magnetic coating, such that the membrane or coating, which is firmly in contact with the surface of the magnet, separates the magnet from the microparticles but does not significantly weaken the magnetic field directed on the microparticles.where the substance is an enzyme.

[0017] US 7,347,338 B2 relates to a method for opening an opening using an elastic plug whose outer diameter in the static state is larger than the diameter of the opening and which has a cavity at its end. An extension device is inserted into the cavity of the plug so that the plug is pressed tightly around the extension device. The plug is extended by inserting the extension element of the extension device into the cavity of the plug to such a depth that the outer diameter of the plug is equal to or smaller than the diameter of the opening. The extended plug is inserted into the opening, and its extension is reduced until the plug closes the opening and adheres so tightly to it that the extension device can be removed from the plug. A method for opening the opening when it is closed by the plug is also disclosed.

[0018] US Patent 5,647,994 A. The invention relates to a method and an apparatus for separating magnetic particles from one solution and transferring these particles into another solution. The apparatus comprises a pipette container, a partition wall defining a separation chamber, and a magnet arranged at a first location adjacent to an outer surface of the partition wall or at a second location within the separation chamber. The magnet is designed such that it can be brought into a state in which a magnetic field is applied to the solution, causing the particles to collect either on an inner surface of the partition wall when arranged at the first location, or on a collecting surface of the magnet when arranged at the second location, or such that the magnetic field no longer holds the magnetic particles to the partition wall or collecting surface.The pipette container comprises a suction cylinder for drawing the solution into the container and for drawing the solution out of the container via a jet channel. The invention can be applied in various areas of biotechnology where solid particles are used as the solid phase for binding biomaterial.

[0019] DE 44 21 058 A1 relates to a method for separating a component of a liquid from other components by immobilizing the component on magnetic suspended particles in a vessel, immersing a magnetic device in the vessel, wherein the device is separated from the liquid by a protective sleeve made of non-magnetic material, and removing non-immobilized components, as well as a device suitable for carrying out the method, which has the advantage of simple and efficient resuspension.

[0020] US Patent 6,033,574 A discloses an apparatus and method for performing affinity separation of a target substance from a liquid test medium by mixing magnetic particles with a surface-immobilized ligand or receptor within the test medium to promote an affinity binding reaction between the ligand and the target substance. The test medium containing the magnetic particles in a suitable container is removably mounted in a device that generates a magnetic field gradient in the test medium. This magnetic field gradient is used to excite the magnetic particles to movement, thereby causing mixing. The mixing is achieved either by moving a magnet relative to a stationary container or by moving the container relative to a stationary magnet. In both cases, the magnetic particles undergo a continuous change in angular position relative to the magnet.Simultaneously with the relative angular movement between the magnet and the magnetic particles, the magnet is also moved along the length of the container, causing the magnetic field gradient to sweep across the entire length of the container. After the desired time, sufficient for the affinity reaction to occur, the movement of the magnetic gradient is stopped, immobilizing the magnetic particles on the inner wall of the container near the magnet source. The remaining test medium is removed, while the magnetic particles are retained on the container wall. The test medium or the particles can then be subjected to further processing.

[0021] US Patent 6,409,925 B1 relates to a device for collecting magnetic particles. The invention further relates to a system for transferring material from a plurality of source containers to a plurality of target containers, wherein the device comprises a plurality of collection elements, each of which can be manipulated independently. The invention further relates to a method for detecting fluorescently labeled biological units, wherein the units are bound to magnetic particles. The fluorescent emission is concentrated by clustering the magnetic particles using the magnetic force. Summary of the invention

[0022] The invention relates to a rod assembly for extracting magnetizable particles from a solution in at least one cavity. The rod assembly comprises at least one guide element, at least one rod element, a magnetic element, and a casing. The at least one guide element is fixed to a guide element traverse and can be moved to a distal guide element position by means of the guide element traverse, which is driven by a guide element drive group consisting of up to three independent and separately controllable drives, wherein the guide element traverse is movable in the direction parallel to the guide element (90) and in at least one direction perpendicular to the guide element (90).The at least one rod element is fixed to a rod element traverse, which is driven by a rod element drive group with up to three drives acting orthogonally to each other, and thus the rod element is movable at least in one direction parallel to the at least one guide element and in at least one direction perpendicular to the guide element and can therefore be inserted into and removed from the at least one guide element (90). The magnetic element is arranged on a distal end section of the at least one rod element, wherein the magnetic element is movable to a distal magnetic element position and wherein the distal magnetic element position is located on a distal end section of the at least one guide element. The covering closes the distal end section of the guide element.

[0023] The invention further relates to a method for extracting magnetizable particles from solutions in at least one cavity. The method comprises picking up coatings at a distal end section of at least one of the guide elements. The method further comprises inserting at least one rod element into the at least one guide element, wherein the rod element is fixed to a rod element traverse, the rod element traverse being driven by a rod element drive group with up to three drives acting orthogonally to one another, and wherein the rod element is movable at least in one direction parallel to the at least one guide element and in at least one direction perpendicular to the at least one guide element and is thereby insertable into the at least one guide element.wherein a magnetic element is arranged at a distal end section of the at least one rod element. Furthermore, in one step, the sheaths are immersed in the solutions by driving the at least one guide element by means of a guide element traverse to which the guide element is fixed, wherein the guide element traverse is driven by a guide element drive group consisting of up to three independent and separately controllable drives. In a next step, the method comprises moving the guide element into a distal guide element position by means of the guide element drive group, provided that the at least one guide element is not already in the distal guide element position.This is followed by moving the magnetic element through an opening in the guide element beyond the distal end of the guide element into a distally exposed magnetic element position by driving at least one rod element by means of the rod element traverse to which the rod element is fixed, unless the magnetic element is already in the distal magnetic element position (110d). In a final step, the magnetizable particles are collected by the magnetic element in a distally exposed magnetic element position. The method may include mixing the solutions. Collection of the hulls may include closing the opening at the distal end of the guide element with a closing element. Closing the opening at the distal end may also replace collection of the hulls.

[0024] Essentially non-magnetic is understood here to mean materials whose electron system does not produce a noticeable magnetic moment. Essentially non-magnetic materials are therefore not ferromagnetic. Furthermore, essentially non-magnetic materials are not paramagnetic. Likewise, essentially non-magnetic materials are not antiferromagnetic. Provided that only atomic diamagnetism is present, which is not superimposed by a magnetic moment of the electron system, the atomic diamagnetic contributions are considered permissible. Examples of essentially non-magnetic materials are stainless steel and plastics.

[0025] The rod arrangement according to the invention can include a cylindrical tube as a guide element. In the following, a thin-walled cylindrical tube is understood to mean a cylindrical tube whose length is considerably greater than its wall thickness. For practical implementation of the invention, a length of approximately 80 mm is suitable, for example. The wall thickness of the thin-walled cylindrical tube is, for example, 0.2 mm. To increase the magnetic field strength available outside the guide element, the wall thickness of the cylindrical tube, i.e., the guide element, should be chosen to be as thin as possible. For a typical thin-walled cylindrical tube, this results in a length-to-wall-thickness ratio of 400:1. Of course, other length-to-wall-thickness ratios are also possible without restriction, as long as the length is significantly greater than the wall thickness.Sufficient dimensional stability of the thin-walled cylindrical tube is important for the guide element. Sufficient dimensional stability of the guide element is desirable when receiving the coverings.

[0026] The rod element according to the rod arrangement can comprise a rod-like element. Furthermore, the rod element can comprise a cylindrical tube, for example, a thin-walled cylindrical tube. In the case of the rod element, a thin-walled cylindrical tube also comprises a significantly greater length of the rod element relative to its wall thickness. The rod element can also be implemented in the form of a wire element or a cord, with the magnetic element fixed at one end of the cord.

[0027] Biomolecules bound to magnetizable particles are also referred to as a particle-biomolecule complex. In the following, the term "magnetizable particles" should be understood as encompassing the particle-biomolecule complex.

[0028] Extracting magnetizable particles from a solution requires an inhomogeneous magnetic field to exert a force on them. Rod arrays therefore provide at least one region with an inhomogeneous field distribution that can be introduced into a solution containing magnetizable particles. By introducing this inhomogeneous field distribution into the solution, the magnetizable particles are induced to move due to a magnetic force acting upon them. This force can either attract the magnetizable particles, causing them to adhere to the rod, or repel them. In the case of repulsion, the magnetizable particles are pushed away from the magnetically active area.In the case of repulsion, for example, a concentration of magnetizable particles can occur in a bottom area of ​​a cavity.

[0029] The rod arrangement for extracting biomolecules from solutions according to the present invention is suitable to provide the largest possible magnetic effective area to the circumferential surfaces of the guide element.

[0030] The rod arrangement allows the use of small magnetizable particles. The diameter of these particles is on the order of a few hundred nanometers. These small particles place particularly high demands on the strength of the inhomogeneous magnetic field. Due to their small size, they can only move very slowly within the solution. Furthermore, they require the largest possible magnetically effective surface area to which the particles, and thus the biomolecules, can adhere. The distally open design of the guide element allows for an increase in the strength of the inhomogeneous magnetic field at the distal end of the guide element.

[0031] Therefore, this rod arrangement is better suited for purifying small magnetizable particles than rod arrangements known in the prior art. The improvements over the prior art apply to both common magnetizable particles and small magnetizable particles.

[0032] The present invention is described below with reference to the drawings and selected embodiments. Fig. Figure 1 shows a rod arrangement according to the state of the art. Fig. Figure 2 shows a detail of the rod arrangement according to the state of the art. Fig. 1. Fig. Figure 3 shows a rod arrangement. Fig. 4 shows a detail of the in Fig. 3 shown rod arrangement. Fig. Figure 4a shows a clamping device. Fig. Figure 5 shows a field line pattern for a magnetic element. Fig. Figure 6 shows areas where the magnetizable particles are deposited on the circumferential surfaces of the guide element, more precisely on the circumferential surfaces of a covering. Fig. Figure 7 shows the guide element in the distal guide element position and the magnet element in the distal magnet element position. Fig. Figure 8 shows the guide element in the distal guide element position and the magnet element in a proximal magnet element position. Fig. Figure 9 shows the guide element in a proximal guide element position and the magnet element in the distal magnet element position. Fig. Figure 10 shows a comparison of the magnetic field line pattern for a magnetic element in a rod arrangement according to the present invention with a magnetic element according to the prior art. Fig. Figure 11 shows various drives for moving the magnetic elements and the guide elements. Fig. Figure 12 shows the magnetic element in a position for changing the magnetic elements. Fig. Figure 13 shows the magnetic element in a distally exposed magnetic element position. Fig. Figure 14 shows a flowchart of the procedure. Fig. Figure 15 shows details of the step for mixing the solution. Fig. Figure 16 shows details of a step for collecting the magnetizable particles. Detailed description of the invention

[0033] Fig. Figure 1 shows a rod arrangement 1. The rod arrangement 1 comprises a magnetic element 110. In the prior art, the magnetic element 110 is designed as a long permanent magnet or bar magnet. In the case of a long bar magnet, the length of the bar magnet is significantly greater than its diameter. The bar magnet can, for example, be cylindrical. Other bar magnet shapes are also conceivable without limitation. The length of the magnetic element 110 is aligned parallel to a rod element 20. The magnetic element 110 is arranged at a distal end section of the rod element 20. The rod element 20 is held by a rod element mechanism. The rod element mechanism can, without limitation, be designed as a crossbeam 30. The north-south direction of the magnetic element 110 in Fig. 1 is aligned parallel to a longitudinal axis of the rod element 20. The north pole N is located proximally, i.e., at the top. The south pole S, on the other hand, is located in Fig. 1 below or distally. Of course, a reverse orientation would also be conceivable for the magnetic element 110. In Fig. Figure 1 shows a magnetic field line distribution 40 of the magnetic element 110. The magnetic field distribution indicates that an inhomogeneous magnetic field of the magnetic element 110 results, particularly at the two poles N and S. The magnetically effective surfaces are therefore located in the Fig. Figure 1 shows the magnetic element 110, essentially on its distal end section and a proximal end section. For the magnetic element 110, which is in the form of a long bar magnet, only the distal end section is available as a magnetically active surface. This is because only the distal end section of the magnetic element 110 is immersed in a solution 60 containing biomolecules 70. The solution 70 is located in a cavity 50 in which the magnetic element 110 is immersed.

[0034] The magnetic field in Fig. 1, and thus the field line distribution 40 of the magnetic element 110 is asymmetrical in the north-south direction. The field line distribution 40 extends significantly further into a proximal region above the magnetic element 110. The asymmetrical field line distribution is caused by the rod element 20, which is made of a ferromagnetic material. Ferromagnetic materials concentrate a field line distribution in their interior. The ferromagnetic material of the rod element 20 causes the inhomogeneous magnetic field in the distal end section of the magnetic element 110 to increase. The increased inhomogeneous magnetic field intensifies the force acting on the magnetizable particles 70 in the solution 60, so that the magnetizable particles 70 increasingly adhere to the distal end section of the magnetic element 110.

[0035] Fig. 2 shows a detail of the rod arrangement from Fig. 1. The magnetic element 110 and a distal end section of the rod element 20 are covered with a casing 80. The casing 80 consists of a substantially non-magnetic material, e.g., plastic. The wall thickness of the casing is chosen to be as thin as possible in order to minimize the reduction of the strength of the inhomogeneous magnetic field acting on the magnetizable particles 70 in the solution 60. For the same reason, it is advantageous to choose a substantially non-magnetic material for the casing 80. The casing 80 serves to facilitate the separation of the magnetizable particles 70, which are deposited on the outer surfaces of the casing 80, from the magnetic element 110. Once the covering 80 is provided, it is sufficient to detach the covering 80 from the magnetic element and the distal end section of the rod element 20 to separate the magnetizable particles 70 and the magnetic element 110.Therefore, by using the covering 80, the otherwise necessary cleaning of the magnetic element 110 is eliminated, whereas cleaning is made more difficult by the attractive interaction between the magnetizable particles and the magnetic element 110.

[0036] Fig. Figure 3 shows the rod arrangement 1 according to the invention. The rod arrangement 1 comprises a rod element 20 which is fixed to a rod element mechanism. The rod element mechanism is in Fig. 3 is designed as a rod element traverse 30. A magnetic element 110 is arranged at a distal end of the rod element 20. The magnetic element 110 comprises a first magnetic pole at a distal end d, for example, the south pole. At a proximal end p, on the other hand, a second magnetic pole is located, for example, the north pole. A longitudinal axis of the rod element 20 and a longitudinal axis of the magnetic element 110 are essentially coaxial with each other.

[0037] The rod element 20 can be designed as a cylindrical tube. It can also be designed as a thin-walled cylindrical tube or as a rod. Furthermore, it is conceivable to replace the rod element 20 with a wire element or a cord (not shown), with the magnetic element 110 fixed to a distal end section of the cord. Movement of the rod element traverse 30 in the z-direction is transmitted to the rod element 20 and thus also to the magnetic element 110. The rod element traverse 30 therefore allows movement of the magnetic element 110 essentially along a longitudinal axis of the magnetic element 110.

[0038] The magnetic element 110 is located inside a guide element 90. The guide element 90 comprises in Fig. 3 a thin-walled cylindrical tube. Of course, rectangular designs are also possible. The use of the thin-walled cylindrical tube for the guide element 90 is advantageous in order to provide the magnetic field supplied by the magnetic element 110 with as little attenuation as possible at the outer surface of the casing 80. The guide element 90 and the rod element 20 are movable relative to each other. The movement of the rod element 20 can be independent of any movement of the guide element 90. The rod element 20 can be pulled upwards by means of the rod traverse 30, while the guide element 90 can remain in the cavity 50. Likewise, the movement of the rod element 20 and the guide element can occur simultaneously. It is advantageous to provide a certain amount of play between the guide element 90 and the rod element 20 with the magnetic element 110.The play between the rod element 20 and the magnetic element 110 inside the guide element 90 prevents either the rod element 20 or the magnetic element 110 from becoming jammed. This play thus ensures the mobility of the rod element 20 and the magnetic element 110 within the guide element 90.

[0039] The guide element 90 is fixed to a guide element mechanism. The guide element mechanism includes, for example, a guide element crossbeam 100. Movement of the guide element crossbeam 100 is transmitted to the guide element 90 as well as to a distal end section of the guide element 90, which is enclosed by a covering 80. By providing the guide element 90, it is no longer necessary for the covering 80 itself to be sufficiently dimensionally stable to enclose the magnetic element 110. Rather, it is sufficient if a releasable connection is established between the covering 80 and the guide element 90, which prevents the solution 70 from penetrating to the magnetic element 110.

[0040] Furthermore, the guide element 90 enables highly accurate positioning of the covering 80 within the cavity 50. This highly accurate positioning of the covering 80 prevents the magnetizable particles 70 from being stripped from the covering 80 by contact with a wall of the cavity 50.

[0041] In contrast to the prior art, the rod arrangement 1 allows the magnetic element 110 to extend through an opening 91 beyond the distal end of the guide element 90 into a distally exposed magnetic element position 110d*, as shown in Fig. As shown in Figure 13, the magnetic element 110 can be moved even closer to the casing 80. It is also advantageous to move the magnetic element 110 out through the opening 91 of the guide element 90 when the casing is picked up. This prevents edges of the guide element 90 from damaging the casing 80.

[0042] In Fig. Figure 3 shows the magnetic element 110 in a distal magnetic element position 110d. The distal magnetic element position 110d is located in a distal end section of the guide element 90. The distal magnetic element position 110d causes the solution 60 to be permeated with an inhomogeneous magnetic field from the magnetic element 110. Thus, a force acts on the magnetizable particles 70 in the solution. In other words, the distal end section of the guide element 90 is magnetically switched when the magnetic element 110 is in the distal magnetic element position 110d.

[0043] The in Fig. Figure 3 shows the magnetic element 110 in the distal magnetic element position 110d. The distal magnetic element position 110d is located in a distal end section of the guide element 90. The inhomogeneous magnetic field of the magnetic element 110 in the distal magnetic element position 110d permeates the distal end section of the guide element 90. It should be noted that the distal magnetic element position 110d is defined only in relation to the distal end section of the guide element 90. In other words, as soon as the magnetic element 110 is located in the distal magnetic element position 110d, the distal end section of the guide element 90 is magnetized, i.e., the magnetic field is switched on. The guide element 90 is in Fig. Figure 3 shows the guide element in a distal position 90d. The distal guide element position 90d means that the distal end section of the guide element 90 is at least partially immersed in the solution 60 containing the magnetizable particles 70, which is located within the cavity 50.

[0044] The distal magnet element position 110d corresponds to a distal rod element position 20d as shown in Fig. Figure 3 shows that from the distal rod element position 20d, the rod element 20 can be moved in a proximal direction to a proximal rod element position 20p, as shown in Figure 3. Fig. Figure 8 shows that the distal rod element position 20d results in a proximal magnet element position 110p for the magnet element 110, as for example in Fig. Figure 8 shows the distal magnet element position 110d, which is clearly defined as shown in Figure 8. Fig. Figure 3 shows that in the distal magnet element position 110d, the distal end section of the guide element 90 is permeated by the magnetic field of the magnet element 110. Obviously, this results in a multitude of positions for the magnet element 110, which correspond to the proximal magnet element position 110p. Consequently, there are also a multitude of proximal rod element positions 110p for the rod element 20, as exemplified in Figure 3. Fig. 8 shown.

[0045] The magnetic element 110 in the distally exposed magnetic element position 110d* helps to prevent damage to the covering 80 by the edges of the guide element 90 at the distal opening 91 of the guide element. This allows the use of thinner and less dimensionally stable coverings 80 compared to the prior art. At the same time, the manufacturing costs for the coverings 80 are reduced, as the dimensions no longer need to meet such tight tolerances as before.

[0046] Furthermore, it is possible to increase the magnetic field strength of the inhomogeneous magnetic field over the circumference of the casing 80 by moving the magnetic element 110 to the distally exposed magnetic element position 110d*. Naturally, this requires that the casing 80 is not damaged by moving the magnetic element 110 to the distally exposed magnetic element position 110d*. The described movement of the magnetic element 110 must therefore only occur within the elastic range of the casing 80. The in Fig. Figure 3 shows a rod arrangement 1, which only shows a single rod element 20. Of course, it is possible that the rod arrangement 1 comprises a plurality of guide elements 90, a plurality of rod elements 20 and a plurality of magnetic elements 110.

[0047] Fig. Figure 4 shows the guide element 90 in the distal guide element position 90d as well as the magnet element 110 in the distal magnet element position 110d. Previously discussed elements of the Fig. 4 are provided with the same reference symbols as before. Fig. Figure 4 shows details of the magnetic element 110 according to the present invention. The magnetic element 10 can comprise a plurality of bar magnets 130. Fig. Figure 4 shows four bar magnets. It is of interest to arrange the plurality of bar magnets 130 such that like poles of the bar magnets 130 face each other. Furthermore, the magnetic element 110 optionally includes a plurality of spacer elements 150 between individual bar magnets 130. The arrangement of like poles relative to each other for the bar magnets 130, in conjunction with the spacer element 150, is of interest in order to increase the magnetically effective areas on the covering 80, as will be discussed below. Other magnets 130 are also conceivable instead of a bar magnet. The in Fig. The four bar magnets 130 shown are therefore to be understood only as exemplary embodiments. It is of interest to achieve the highest possible magnetic field strengths for the magnets 130. The magnets 130 should therefore possess a high specific magnetic moment. One possible embodiment of the magnets 130 thus comprises, for example, rare earth materials. It is known to those skilled in the art that rare earth materials possess a high specific magnetic moment. By achieving the highest possible specific magnetic moment for the magnet 130, a high inhomogeneous field strength can be achieved on the circumferential surfaces of the guide element 90 and thus on the circumferential surfaces of the casing 80. Consequently, the deposition of the magnetizable particles 70 on the circumferential surfaces of the casing 80 is facilitated. The casing 80 is again adapted in size to the dimensions of the guide element 90.The inner diameter of the casing 80 is adapted to the outer diameter of the guide element 90. The guide element 90 and the casing are detachably connected. This detachable connection can be achieved without restriction by positive locking, friction locking, or a clamping device K.

[0048] Fig. Figure 4a shows an example of a clamping bracket K for the detachable connection of the guide element 90 to the housing 80. The brackets K as shown in Fig. The figures shown in 4a are known to those skilled in the art and are therefore not explained in more detail.

[0049] The in Fig. The spacer element 150 shown in Figure 4 essentially comprises non-magnetic material, for example, plastic. Soft magnetic materials are also possible for the spacer element 150. The spacer elements 150 create a gap in the field distribution. The field distribution is described in detail in Figure 4. Fig. 5 discussed. Due to the opposing like poles of the magnets 130, a repulsive force occurs between the individual magnets 130 in the axial direction, in Fig. 4, therefore a repulsion along the vertical. It is therefore necessary to place the individual magnets 130 in the Fig. The arrangement shown in Figure 4 can be forced into place. This can be achieved by mechanically securing the magnets using the rod element 20. Alternatively or additionally, the individual magnets 130 can also be glued together. The magnets 130 can, for example, be implemented as short bar magnets. Short bar magnets are defined as having a length-to-diameter ratio of less than or equal to 1. For example, the length-to-diameter ratio could be 4:5. Of course, other length-to-diameter ratios are also possible. It is possible to manufacture the magnet element 110 as a single piece.

[0050] Fig. Figure 5 shows the magnetic element 110 made of Fig. 4 and additionally the course of the field lines, i.e. the magnetic field distribution 40. From Fig. Figure 5 shows that the magnetic field lines are particularly inhomogeneous in the areas of the spacer elements 150. Therefore, in these sections, i.e., in rings at the level of the spacer elements 150, there will be an increased deposition of the magnetizable particles 70 from the solution 60. The areas of increased magnetic field inhomogeneity are shown in the figure as areas 140b, 140c, and 140d. Area 140a is located above the uppermost magnet 130, i.e., furthest proximal to the Fig. 5 magnetic element 110 shown.

[0051] Area 140a has no magnets 130 with opposite polarity in the proximal direction. Therefore, the magnetic field distribution is less inhomogeneous than in areas 140b, 140c and 140d.

[0052] The area of ​​increased inhomogeneous magnetic field strength 140e is located at the distal end of the magnetic element 110. A magnet 130 with opposite polarity is also missing for the last magnet 130, which adjoins area 140e. Therefore, the inhomogeneity in area 140e is not as high as in areas 140b, 140c, and 140d. Due to the magnetic element 110, as in Fig. As shown in Figure 5, the area of ​​inhomogeneous magnetic field strength 140a, 140b, 140c, 140d, 140e, and thus also the size of the magnetically effective area, can be increased. The magnetic element 110 can be used as shown in Figure 5. Fig. 5 shows, thus increasing the yield of magnetizable particles 70 that attach in the areas of increased inhomogeneous magnetic fields 140a, 140b, 140c, 140d and 140e.

[0053] With N magnets 130, N-1 boundary regions are formed between the magnets 130, that is, N-1 ring-shaped sections 140b, 140c, 140d. The magnetic field lines in these regions 140b, 140c, 140d run essentially radially. Due to the radial orientation of the magnetic fields in regions 140b, 140c, 140d, a volume of the cavity 50 is penetrated. The field lines are drawn pointing from the north pole to the south pole, which determines the direction of the arrowheads. The magnetic field is strong at locations of high field line density. The dimensions of the cavity 50 and the orientation of the magnetic field lines 40 can be adjusted so that the field lines are essentially confined to the volume of the cavity 50. That is, the available magnetic field is used almost optimally for penetrating the volume of the cavity 50. This naturally increases the yield of magnetizable particles 70 that are deposited in areas 140a, 140b, 140c, 140d and 140e.

[0054] It is recommended to provide the 80 mm casing with a profile or radius. In Fig. 6. The casing 80 tapers slightly downwards. This design of the casing 80 allows for better utilization of the inhomogeneous magnetic field available in the 140e region. Furthermore, the Fig. 6 Profiling of the coating 80 shown, to prevent the magnetizable particles 70 from dripping off the coating 80.

[0055] The in Fig. The magnetic element 110 shown in Figure 5 can also be arranged transversely to a longitudinal axis of the rod element 20 or the guide element 90 without restriction. Depending on the dimensions of the guide element 90 and the rod element 20, such an arrangement may be of interest. However, for the cylindrical design of the rod element 20 and the guide element 90, the coaxial alignment of the guide element 90 and the magnetic element 110, as shown in Figure 5, appears to be the most suitable configuration. Fig. 5 shown to be advantageous, since the magnetic fields provided by the magnetic element 110 penetrate the cavity 50 better.

[0056] Fig. Figure 6 shows the magnetic element 110 according to the invention in the distal magnetic element position 110d as already shown in Fig. 5 is shown. However, instead of the field line distribution 40, in Fig. Figure 6 shows the areas in which the magnetizable particles 70 attach themselves. The attachment areas correspond to the areas of increased inhomogeneous magnetic field distributions 140a, 140b, 140c, 140d, and 140e. These areas of increased inhomogeneous magnetic field distributions correspond to the magnetically effective surfaces, as already discussed. It is obvious that this is related to the Fig. In the magnetic element 110 shown in Figure 6, the magnetically effective areas are significantly increased compared to the state of the art, as will be discussed in more detail below.

[0057] With the in Fig. In the magnetic element 110 shown in Figure 6, ring-shaped deposits of magnetizable particles 70 from the solution 60 form on a circumferential surface of the shell 80. The proximal ring 140a is less pronounced than the rings 140b, 140c, and 140d below it.

[0058] In Fig. Figure 7 shows the magnetic element 110 in the distal magnetic element position 110d. It should be noted again that the distal magnetic element position 110d is located in a distal end section of the guide element 90. The magnetic element 110 corresponds to the magnetic element 110 as, for example, in Fig. Figure 6 shows that, for clarity, only the south poles of the individual magnets 130 are indicated. To immerse the magnetic elements 110 in the solution 60, the guide element 90 is additionally moved to the distal guide element position 90d. The guide element traverse 100 can be used for this purpose, for example. To ensure that the magnetic element 110 remains in the distal magnetic element position 110d during this movement of the guide element 90, the rod element 20 must also be moved from a proximal rod element position 20p to a distal rod element position 20d, as shown in Figure 6. Fig. Figure 7 shows that the bar element traverse 30 can be used for the bar element 20 process. Fig. Figure 7 shows eight guide elements 90 and eight rod elements 20 as examples. All further features of the Fig. Figures 7 were already discussed in the earlier figures and are labeled with the same reference symbols. It should be noted again that the rod elements 20 and the guide elements 90 are independently movable.

[0059] In Fig. Figure 8 shows the magnetic element 110 in an example in a proximal magnetic element position 110p. By moving the magnetic element 110 into the proximal magnetic element position 110p, the distal end section of the guide element 90 is demagnetized. The guide element 90, held in the cavity 50, stabilizes a position of the covering 80. For this purpose, the guide element traverse 100 remains in a position such that the guide elements 90 remain in the distal guide element position 90d. Movement of the rod element traverse 30 can be effected by drive elements, as can movement of the guide element traverse 100 by suitable drive elements, as will be explained further below.

[0060] Fig. Figure 9 shows the guide elements 90 in a proximal guide element position 90p, with the distal end section of the guide elements 90 remaining magnetized. The magnetization of the distal end section of the guide elements 90 is achieved by the magnetic element 110 remaining in the distal magnetic element position 110d. It should be noted again that the distal magnetic element position 110d is determined by positioning the magnetic element 110 within a distal end section of the guide element 90. To achieve a position as shown in Figure 9, the magnetic element 110 is positioned within the distal end section of the guide element 90. Fig. To achieve position 9 of the guide elements 90 with the magnetic element 110 in the distal magnetic element position 110d, a movement in the z-direction of the rod element traverses 30 and the guide element traverses 100 must be coordinated accordingly. Such coordination can be achieved, for example, by suitable control software. In the Fig. In the position of the guide elements 90 and the rod elements 20 shown in Figure 9, the guide elements 90 are in a proximal guide element position 90p and the rod elements 20 are in a proximal rod element position 20p. It should be noted again that there is a plurality of proximal rod element positions 20p for a rod element 20. Likewise, there is a plurality of proximal guide element positions 90p for the guide element 90. The in Fig. The position of the guide elements 90 and the rod elements 20 shown in Figure 9, and thus the position of the magnetic elements 110 in the distal magnetic element position 110d, allows the transport of magnetizable particles 70 attached to the shells 80. This transport can include lifting the magnetizable particles 70 out of the solution 60. Likewise, magnetizable particles 70 attached to the shell 80 can be transported from a first cavity 50 to a second cavity. For example, it is possible to collect additional magnetizable particles 70 from another solution 60, in addition to the magnetizable particles 70 already attached to the circumferential surfaces of the shell 80.

[0061] Fig. Figure 10 shows a comparison of the magnetic element 110 in a rod arrangement according to the present invention with a single bar magnet as the magnetic element 110. Fig. Figure 10 on the left shows a magnetic element 110 in the distal magnetic element position 110d. The magnetic element 110 comprises, by way of example, four short bar magnets 130, as well as the previously discussed spacer elements 150. Furthermore, the field line distribution 40 is shown. The areas of increased inhomogeneous magnetic field regions 140b, 140c, 140d are also indicated. (Right in) Fig. Figure 10 shows a magnetic element 110 in the distal magnetic element position 110d for comparison. In contrast to the left image, the right image includes... Fig. Figure 10 shows a single magnet 130, which is exemplified as a long bar magnet. The field distribution for the single magnet 130 is less inhomogeneous than for the magnetic element 110 in a bar arrangement according to the present invention. Furthermore, the magnetic field lines of the field distribution 40 in the right-hand part of the image extend significantly further beyond the volume of the cavity 50. This means that the available magnetic field strength of the magnetic element 110 is used considerably less effectively for collecting the magnetizable particles 70 from the solution 60.

[0062] In the right-hand part of the image Fig. 10. Only an area of ​​increased inhomogeneous field distribution remains 140. The area of ​​increased inhomogeneous field distribution is significantly smaller for the individual magnet 130. The comparison in Fig. Figure 10 clearly shows that the magnetically effective areas are significantly increased when using the magnetic element 110 in the rod arrangement according to the invention compared to the single bar magnet as known in the prior art.

[0063] The rod arrangement 1 according to the present invention can include drive elements. As shown in Fig. As shown in Figure 11, the beam element traverse 30 with the beam elements 20 is moved by a beam element drive group 200. The beam element drive group 200 can comprise up to three drives acting orthogonally to each other: a first beam element drive m2x for movement in the x-direction, a second beam element drive m2y for movement in the y-direction, and a third beam element drive m2z for movement in the z-direction. These three beam element drives m2x, m2y, and m2z can be driven independently of each other. The guide element traverse 100 can be driven by a guide element drive group 900, resulting in the movement of the guide elements 90. The guide element drive group 900 can comprise up to three independent and separately controllable drives: A first guide element drive m9x, for example, can cause movement of the guide element traverse in the x-direction.A second guide element drive m9y can cause movement of the guide element traverse in the y-direction. A third guide element drive m9z can cause movement of the guide element traverse in the z-direction. The guide element and rod element drive groups 200 and 900 can be controlled independently of each other. A suitable control system for controlling and regulating the two drive elements 200 and 900 can be provided, as is well known to those skilled in the art.

[0064] Fig. Figure 12 shows how it is possible to change the rod elements 20 and thus the magnetic elements 110 (not shown). The rod element drive group 200 for moving the rod element traverse 30 allows a first rod element traverse 30a to move in the proximal direction, away from the guide element traverse 100. This ensures that the rod elements 20a of a first rod element traverse 30a are completely removed from the guide elements 90 of the guide element traverse 100; as shown in Fig. Figure 12, top left, shows that once the first rod elements 20a, connected to the first rod element traverse 30a, have been completely removed from the guide elements 90, a second group of rod elements 20b can be inserted into the guide elements 90 of the guide element traverse 100 by means of a second rod element traverse 30b. The first drive element group 200 allows the rod elements 20 to move freely, as required for changing them. Changing the magnetic elements 110 by changing the rod elements 20 can be useful to ensure that all areas 140 for depositing the magnetizable particles 70 are always covered by solution 60. More generally, changing the magnetic elements 110 allows the magnetic fields of the magnetic elements 110 to be adjusted to the dimensions of a cavity 50 used and / or the fill level of the solution 60 in the cavity 50.

[0065] Furthermore, it is obvious to a person skilled in the art that the drive element groups 200 and 900 also allow circular movement of the guide elements 90 and the rod elements 20 in one plane. This makes, for example, a circular mixing movement possible within the cavities 50.

[0066] Changing the rod elements 20 can be useful, for example, to apply different magnetization strengths to the solutions 60 within the cavities 50. It is advantageous to rigidly connect the guide elements 90 to the guide element traverse 100. As already mentioned, however, attaching the rod elements 20 to the rod element traverse 30 with a slight amount of play is also advantageous. This slight play between the rod elements 20 and the traverse 30 allows the guide element 90 to guide the rod element 20 without causing it to tilt. In essence, this prevents mechanical over-constraint of the guide elements 90 and the rod elements 20.

[0067] Fig. Figure 13 shows a guide element 90 with an opening 91 at a distal end. A rod element 20 is inserted into the guide element 90 and carries a magnetic element 110 at a distal end section. For the rod arrangement 1, it is possible to move the magnetic element 110 distally, at least partially, through the opening 91 of the guide element 90 beyond a distal magnetic element position 110d. Fig. Figure 13 shows the magnetic element 110 in the distally exposed magnetic element position 110d*. In the distally exposed magnetic element position 110d*, the magnetic element 110 extends beyond the distal end of the guide element 90. The distally exposed magnetic element position 110d* allows the magnetic element 110 to be moved even closer to the covering 80. With the magnetic element 110 in the distally exposed magnetic element position 110d*, sliding the covering 80 onto the guide element 90, as already described, is facilitated. The magnetic element 110 in the distally exposed magnetic element position 110d* prevents the distal end of the guide element 90 from damaging the covering 80 when the covering 80 is slid onto it. Damage to the casing 80 is particularly likely if the casing 80 itself does not have sufficient dimensional stability.If the casing 80 has sufficient elasticity, the magnetic element 110 can move into the distally exposed magnetic element position 110d* without damaging the casing 80. Furthermore, with the magnetic element 110 in the distally exposed magnetic element position 110d*, the inhomogeneous magnetic field to which the solution 60, and thus the magnetizable particles 70, are exposed increases. The force acting on the magnetizable particles 70 is therefore increased by means of the distally exposed magnetic element position 110d*.

[0068] The invention further discloses a method 500 for extracting magnetizable particles 70 from a solution 60 in at least one cavity 50.

[0069] Fig. Figure 14 shows a sequence of the procedure 500. Step 510 comprises picking up the covers 80 onto at least one of the guide elements 90 and / or closing the opening 91 at the distal end of the at least one guide element 90 by closing elements 92. Closing the opening 91 can replace picking up the cover 80 or be included in addition to picking up the cover in step 510. Step 510 of picking up the cover 80 can, for example, include frictional engagement between the cover 80 and the guide element 90. In addition, to pick up the cover 80, the magnetic element 110 can be inserted into the distally exposed magnetic element position 110d*, as shown in Fig. 13 shown, can be moved. In addition, a clamping bracket K, as shown in , can also be used to hold the casing 80. Fig. As shown in Figure 4a, this is possible. Those skilled in the art are aware of other possibilities for mounting the coverings 80 on the guide element 90, which will not be discussed further here.

[0070] In step 520, solution 60 is mixed. This mixing serves to disperse the magnetizable particles 70 contained within the solution 60. The mixing prevents all magnetizable particles 70 from being concentrated in a single bottom region of cavity 50. Following the mixing of solution 60, step 530 is performed to collect the magnetizable particles 70 from the solution 60. In step 530, the magnetizable particles 70, and consequently the biomolecules bound to them, are extracted from solution 60.

[0071] In step 540, it is checked whether the magnetizable particles 70 and / or the magnetizable particle-molecule complexes that have already been collected should be transported to another cavity 50. If so, the magnetizable particles 70 are transported 550 to the other cavity 50. If no further solution 60 is planned, transport 560 to a target cavity takes place. The target cavity can, for example, contain a result vessel in which the magnetizable particles 70 are concentrated. Following concentration, the biomolecules can be released from the magnetizable particles 70. The magnetizable particles 70 are then separated from the biomolecules in a further step. Transport 560 to the target cavity 50 is possible using the drive units 200 and 900, which allow movement of the guide element traverse 100 and the rod element traverse 30.If a further solution 60 is required, a transport step 550 to the further solution 60 is performed following step 540. This transport step 550 to the further solution 60 can be carried out by the drive elements 200 and 900. After step 550 for transporting to the further solution 60, the process returns to step 530 for collecting the magnetizable particles 70. The transport of the magnetizable particles 70 to the target cavity 50 is followed by step 570 for detaching the magnetizable particles 70 from the coating 80. This detachment can be assisted by mixing, as described in step 520. The detachment of 570 of the magnetizable particles 70 from the coating 80 can also include a detachment of the magnetizable particles 70 from the biomolecules that were bound to the magnetizable particles 70 to form the particle-biomolecule complex.Elution solutions and elution methods are known for detaching the biomolecules from the magnetizable particles 70. These elution methods are not part of the invention but are sufficiently known to those skilled in the art. Therefore, the elution of the biomolecules from the solution 60 containing the magnetizable particles 70 will not be discussed further. In step 580, the guide elements 90 are lifted out of the cavity 50. This can be followed by a step 590 for detaching the coating 80 from the guide elements 90.

[0072] Fig. Figure 15 shows details of step 520 for mixing the solution 60. Step 522 involves moving the magnetizable element 110 to a proximal magnet element position 110p. The proximal magnet element position 110p means that the distal end region of the guide element 90 is no longer penetrated by the magnetic field of the magnet element 110. In step 524, the guide element 90 is moved to a distal guide element position. Typically, in this step, the guide element 90 is immersed in the solution 60 located in the cavity 50. Subsequently, in step 526, the guide element 90 is moved to the proximal guide element position 90p. In other words, in steps 522 to 526, the unmagnetized guide element 90 is immersed in and then lifted out of the solution 60. In step 528, it is checked whether further mixing is necessary. If no further mixing is required, step 520 is complete.If further mixing is required, the procedure returns to step 524.

[0073] Fig. Figure 16 shows details of step 530 for collecting the magnetizable particles 70. Step 532 comprises moving the guide element 90 to the distal guide element position 90d. This is followed in step 533 by moving the magnetic element 110 to the distal magnetic element position 110d, provided the magnetic element 110 is not already in the distal magnetic element position 110d. Step 533 of moving the magnetic element 110 to the distal magnetic element position 110d may also include moving the magnetic element 110 to the distally exposed magnetic element position 110d*, as shown in Fig. 13 shown.

[0074] In step 534, the guide element 90 is moved to the proximal guide element position 90p. The magnet element 110 remains in the distal magnet element position 110d or the distally exposed magnet element position 110d* during step 534.

[0075] In step 535, the guide element 90 is moved to the distal guide element position 90d, while the magnet element 110 remains in the distal magnet element position 110d or the distally exposed magnet element position 110d*. This means that the distal end section of the guide element 90 remains magnetized.

[0076] Step 534 is then repeated to move the guide element into the proximal position.

[0077] In step 536, it is checked whether a further step for collecting 530 is required. If a further step for collecting 530 is required, the procedure returns to step 535.

Claims

[1] Rod arrangement (1) for extracting magnetizable particles (70) from solutions (60) in at least one cavity (50), the rod arrangement (1) comprising: - at least one guide element (90) which is fixed to a guide element traverse (100) and which is movable to a distal guide element position (90d) by means of the guide element traverse (100) which is driven by a guide element drive group (900) consisting of up to three independent and separately controllable drives (m9x, m9y, m9z), wherein the guide element traverse (100) is movable in the direction parallel to the guide element (90) and in at least one direction perpendicular to the guide element (90); - at least one rod element (20), wherein the rod element (20) is fixed to a rod element traverse (30), which is driven by a rod element drive group (200) with up to three drives (m2x, m2y, m2z) acting orthogonally to each other, and thus the rod element (20) is movable at least in one direction parallel to the at least one guide element (90) and in at least one direction perpendicular to the guide element (90) and is thereby insertable into and removed from the at least one guide element (90); - a magnetic element (110) which is arranged at a distal end section of the at least one rod element (20), wherein the magnetic element (110) is movable to a distal magnetic element position (110d) and wherein the distal magnetic element position (110d) is located at a distal end section of the at least one guide element (90); and - a covering (80) which closes the distal end section of the guide element (90). [2] Rod arrangement (1) according to claim 1, wherein the magnetic element (110) is movable through an opening (91) at the distal end of the guide element (90) into a distally exposed magnetic element position (110d*). [3] Rod arrangement (1) according to one of the preceding claims, wherein the at least one guide element (90) is furthermore movable between a proximal guide element position (90p) and the distal guide element position (90d). [4] Rod arrangement (1) according to one of the preceding claims, wherein the magnetic element (110) is further movable between a proximal magnetic element position (110p) and the distal magnetic element position (110d). [5] Rod arrangement (1) according to one of the preceding claims, wherein the at least one rod element (20) is movable relative to the at least one guide element (90) between a proximal rod position (20p) and a distal rod position (20d). [6] Rod arrangement (1) according to one of the preceding claims, wherein the at least one guide element (90) is movable independently of the magnetizable element (110). [7] Rod arrangement (1) according to one of the preceding claims, wherein the at least one rod element (20) is movable independently of the at least one guide element (90). [8] Rod arrangement (1) according to one of the preceding claims, wherein the at least one guide element (90) and the magnetic element (110) are jointly movable along the direction parallel to the at least one guide element (90). [9] Rod arrangement (1) according to one of the preceding claims, wherein a mobility of the at least one guide element (90) comprises a mobility of the at least one guide element (90) with the magnetic element remaining in the distal magnetic element position (110d). [10] Rod arrangement (1) according to one of the preceding claims, wherein the mobility of the at least one guide element (90) comprises mobility of the at least one guide element (90) with the magnetic element (110) remaining in the proximal magnetic element position (110p). [11] Rod arrangement (1) according to one of the preceding claims, wherein the mobility of the at least one guide element (90) comprises mobility of the magnetic element (110) beyond a distal end of the at least one guide element (90), such that the magnetic element (110) is spaced apart from the at least one guide element (90) and the at least one guide element (90) does not follow the movement of the magnetic element (110). [12] Rod arrangement (1) according to one of the preceding claims, wherein the at least one guide element (90) is fixed to a guide element mechanism for moving the at least one guide element (90). [13] Rod arrangement (1) according to claim 12, wherein the guide element mechanism comprises at least the guide element traverse (100). [14] Rod arrangement (1) according to one of the preceding claims, wherein the at least one guide element (90) comprises non-magnetic materials. [15] Rod arrangement (1) according to one of the preceding claims, wherein the at least one guide element (90) comprises a rod-like guide element. [16] Rod arrangement (1) according to one of the preceding claims, wherein the at least one guide element (90) comprises a cylindrical tube. [17] Rod arrangement (1) according to claim 16, wherein the cylindrical tube comprises a thin-walled cylindrical tube. [18] Rod arrangement (1) according to one of the preceding claims, further comprising a rod element mechanism in which the at least one rod element (20) is fixed for movement of the at least one rod element (20), wherein the rod element mechanism comprises at least the rod element traverse (30). [19] Rod arrangement (1) according to one of the preceding claims, wherein the at least one rod element (20) comprises non-magnetic materials. [20] Rod arrangement (1) according to one of the preceding claims, wherein the at least one rod element (20) comprises a cylindrical tube. [21] Rod arrangement (1) according to claim 20, wherein the cylindrical tube comprises a thin-walled cylindrical tube. [22] Rod arrangement (1) according to one of the preceding claims, wherein the opening (91) at the distal end of the at least one guide element (90) is closable. [23] Rod arrangement (1) according to one of the preceding claims, wherein the opening (91) at the distal end of the at least one guide element (90) can be closed by a closing element (92). [24] Rod arrangement (1) according to claim 23, wherein the locking element (92) comprises non-magnetic materials. [25] Rod arrangement (1) according to one of the preceding claims, wherein the at least one guide element (90) has a proximal opening (95), wherein the proximal opening (95) is suitable for inserting the at least one rod element (20) [26] Rod arrangement (1) according to one of the preceding claims, wherein the at least one guide element (90) is detachably connected to the covering (80). [27] Rod arrangement (1) according to one of the preceding claims, wherein a holder detachably connects the at least one guide element (90) and the covering (80). [28] Rod arrangement (1) according to one of the preceding claims, wherein the magnetic element (110) comprises a plurality of bar magnets (130). [29] Rod arrangement (1) according to claim 28, wherein the plurality of bar magnets (130) comprises short bar magnets. [30] Rod arrangement (1) according to one of claims 28 or 29, wherein two or more of the plurality of bar magnets (130) are arranged in the direction parallel to the guide element (90) with repulsive poles to each other. [31] Rod arrangement (1) according to one of claims 28 to 30, wherein at least one spacer element (150) is located between individual rod magnets (130). [32] Rod arrangement (1) according to claim 31, wherein the at least one spacer element (150) comprises non-magnetic material. [33] Rod arrangement (1) according to one of claims 28 to 32, wherein a length of the magnetic element (110) and a quantity of liquid in at least one cavity (50) are matched such that, during the extraction of the magnetizable particles (70) from the solution (60), a rise height of the solution (60) is at least equal to or greater than the length of the magnetic element (110). [34] Method (500) for extracting magnetizable particles (70) from solutions (60) in at least one cavity (50), the method (500) comprising: - Picking up (510) sheaths (80) at a distal end section of at least one guide element (90); - Inserting at least one rod element (20) into the at least one guide element (90), wherein the rod element (20) is fixed to a rod element traverse (30), wherein the rod element traverse (30) is driven by a rod element drive group (200) with up to three drives (m2x, m2y, m2z) acting orthogonally to each other, and wherein the rod element (20) is movable at least in one direction parallel to the at least one guide element (90) and in at least one direction perpendicular to the at least one guide element (90) and is thereby insertable into the at least one guide element (90), wherein a magnetic element (110) is arranged on a distal end section of the at least one rod element (20); - Immersion of the casings (80) into the solutions (60) by driving the at least one guide element (90) by means of a guide element traverse (100) on which the guide element (90) is fixed, wherein the guide element traverse (100) is driven by a guide element drive group (900) consisting of up to three independent and separately controllable drives (m9x, m9y, m9z), and - Moving (532) the guide element (90) into a distal guide element position (90d) by means of the guide element drive group (900), provided that the at least one guide element (90) is not already in the distal guide element position (90d); - Moving the magnetic element (110) through an opening (91) of the guide element (90) beyond the distal end of the guide element (90) into a distally exposed magnetic element position (110d*) by driving the at least one rod element (20) by means of the rod element traverse (30) to which the rod element (20) is fixed, provided that the magnetic element (110) is not already in the distal magnetic element position (110d); - Collection (530) of the magnetizable particles (70) by the magnetic element (110) in the distally exposed magnetic element position (110d). [35] Method (500) according to claim 34, further comprising: - Mixing (520) the solutions (60). [36] Method (500) according to one of claims 34 or 35, further comprising: - Check (540) whether transport (550) of the magnetizable particles (70) to a further cavity (50) is planned, and if so, transport (550) the magnetizable particles (70) to the further cavity (50); otherwise, transport (560) the magnetizable particles (70) to a target cavity (50). [37] Method (500) according to claim 36, further comprising: - Detachment (570) of the magnetizable particles (70) from the shell (80); - Moving (580) the at least one guide element (90) into a proximal guide element position (90p); - Detachment (590) of the shell (80) from the guide element (90). [38] Method (500) according to any one of claims 35 to 37, wherein the mixing (520) further comprises: - Moving (522) the magnetizable element (110) to a proximal magnet element position (110p); - Moving (524) the at least one guide element (90) into the distal guide element position (90d), - Moving (526) the at least one guide element (90) to the proximal guide element position (90p). [39] Method (500) according to claim 38, further comprising: - Check (528) the need for further mixing (520). [40] Method (500) according to any one of claims 34 to 39, wherein the collection (530) of the magnetizable particles (70) further comprises: - Moving (534) the at least one guide element (90) into the proximal guide element position (90p), with the magnet element (110) remaining in the distal magnet element position (110d), - Moving (535) the at least one guide element (90) to the distal guide element position (90d), with the magnet element (110) remaining in the distal magnet element position (110d). [41] Method (500) according to claim 34, wherein the collection (530) of the magnetizable particles (70) further comprises: - Checking (536) the necessity of a further step of collecting (530).

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