Magnetic carrier for reaction vessel units
Patent Information
- Application Number
- DE202023105800
- Authority / Receiving Office
- DE · DE
- Patent Type
- Utility models
- Current Assignee / Owner
- Filing Date
- 2023-10-06
- Publication Date
- 2025-03-06
- Estimated Expiration
- 2033-10-31
Smart Images

Figure 00000000_0000_ABST
Abstract
Description
[0001] The present invention relates to magnetic carriers for reaction vessel units.
[0002] For laboratory work or experiments, reaction vessel units such as microtiter plates are used. These units consist of reaction vessels arranged in a grid, used to hold samples for chemical, biological, microbiological, and other experiments. A target substance, such as cells, organoids, or spheroids (cell aggregates), or macromolecules like DNA strands or sequences, can be suspended in a liquid, such as a culture medium, within the reaction vessel. It is often desirable to remove the liquid periodically to replace it with fresh liquid or to allow separate access to the target substance. This removal of the liquid is also called "washing" and can be accomplished, for example, by pipetting or centrifugation.
[0003] When washing, whether by pipetting or centrifugation, it is essential to ensure that a residual volume containing the target substance remains in the reaction vessel after the liquid is removed. For this purpose, magnetic particles that bind to the target substance are used. If a magnet is placed below the reaction vessel, it exerts a magnetic attraction on the magnetic particles, causing them to be drawn to the bottom of the vessel along with the bound target substance. This allows the target substance to be collected at the bottom of the reaction vessel. While reaction vessels with a V-shaped bottom are often used for this application, round or flat bottoms are also suitable. The liquid can then be removed by centrifugation or pipetting without carrying the target substance with it.For this process, carriers are known on which a reaction vessel unit can be arranged, wherein the carrier comprises permanent magnets arranged in a matrix. The matrix has a grid of rows or columns that corresponds to the grid of the reaction vessels in the reaction vessel unit. In other words, each magnet in the magnet arrangement corresponds to a reaction vessel in the reaction vessel unit. Typically, the magnets are arranged in a row or column of the matrix with alternating polarity. Such a carrier is also referred to as a magnet carrier and is known, for example, from WO 2015 / 018878 A2.
[0004] When washing reaction vessel assemblies by centrifugation, a centrifuge with a rotor is often used. This rotor has two diametrically opposed mounting positions, each for holding a reaction vessel assembly. More precisely, the rotor's mounting positions are each designed to hold a carrier for a reaction vessel assembly with the reaction vessel assembly mounted on it. US 2021 / 138485 A1 and US 11,132,142 B2, for example, disclose centrifugation devices for washing reaction vessel assemblies. With these centrifugation devices, the reaction vessels are positioned with their openings facing away from the axis of rotation, so that the liquid contained in the reaction vessels is ejected during centrifugation.
[0005] One object of the invention is to provide a magnetic support for receiving a reaction vessel unit with a magnetic arrangement of magnets arranged in a matrix corresponding to a grid of reaction vessels of the reaction vessel unit, in order to selectively influence the contents of the reaction vessels. A further object of the invention is to provide a magnetic support of the aforementioned type that enables the targeted sedimentation of the magnetic particles in the reaction vessel to be improved and made more uniform across the entire reaction vessel unit.Another object of the invention is to create a magnetic carrier of the type mentioned above which makes it possible to ensure, by the strength of the fixation of the magnetic particles to the bottom of the reaction vessel, that no magnetic particles unintentionally leave the reaction vessel unit during the washing process, in order to further improve the reliability and safety of the washing of the reaction vessel unit.
[0006] One or more of the problems of the invention are solved, at least in part, by the features of the independent claims. Preferred embodiments and advantageous further developments are specified in the dependent claims.
[0007] In practical applications of magnetic carriers, the inventors discovered that when washing by centrifugation, the magnetic particles were not retained equally reliably in all reaction vessels. Finding the correct speed setting for centrifugation proved difficult, as did determining the correct suction setting for pipetting. Through investigations and experiments, the inventors discovered that the magnetic field in a conventional magnetic carrier array is not homogeneous. In particular, the magnetic field can be weaker at the edge of the matrix than in its interior. As mentioned above, the magnets in each row and column are alternately polarized. This means that each magnet has several direct neighbors with opposite polarization (neighboring magnets in a row or column of the matrix are referred to here as direct neighbors).This causes the magnetic field lines to partially pass through neighboring magnets and, if necessary, through a yoke plate positioned beneath the magnets, thus reducing the distance they have to travel freely through the air. This results in an intensification of the magnetic effects close to the end faces of the magnets, i.e., in the area where the bottom of the reaction vessels of the reaction vessel arrangement is located. The magnets in the center of the matrix have four direct neighbors, magnets at the edge have only three direct neighbors, and magnets in the corner have only two direct neighbors. According to the inventors, this weakens the magnetic field at the edge and especially in the corners of the magnet arrangement. According to the inventors' further findings, this coincides with a characteristic of washing by centrifugation.Firstly, it must be ensured that the liquid to be removed is reliably extracted from each reaction vessel within the reaction vessel unit. Secondly, the magnetic particles in all reaction vessels must be securely fixed during the centrifugation process to prevent them from being ejected, even partially, with the liquid. For example, during washing by centrifugation, the rotational speed in the centrifuge must remain below a certain limit to prevent a reaction vessel located in an area of weaker magnetic force from experiencing such a high centrifugal acceleration that the target substance is washed out.Even during washing by pipetting, which is usually performed using automated pipetting systems with an array of pipettes that are controlled together, at least in rows, the suction effect must remain below a certain threshold to prevent a reaction vessel located in an area of weaker magnetic field from experiencing such a strong suction that the target substance is unintentionally removed from the reaction vessel unit. Equally important is ensuring that, given a certain level of suction, the pipette tip is not placed too close to the pellet.
[0008] Another special feature of washing by centrifugation, whereby during centrifugation the reaction vessels located transversely to the axis of rotation in the outer row have a greater distance from the axis of rotation and therefore experience a greater centrifugal acceleration than the reaction vessels located in the center of the magnet arrangement, makes it even more difficult, according to the inventors' findings, to find and maintain the optimal speed of the centrifuge.
[0009] The invention is based on the consideration of at least partially compensating for the weakening of the magnetic effect of the magnets of the magnetic arrangement located at two opposite edges of the matrix. According to the invention, this is achieved by providing magnetic force-enhancing means which are designed to increase the magnetic effect of the magnets of the magnetic arrangement located at one edge, preferably several edges, and particularly preferably opposite edges of the matrix.
[0010] Accordingly, a magnetic support for a reaction vessel unit with multiple reaction vessels is proposed, wherein the magnetic support has a receiving area for receiving a reaction vessel unit and a magnetic arrangement with magnets arranged in a matrix, wherein each reaction vessel of the reaction vessel unit is assigned exactly one magnet or exactly one group of magnets, which is arranged below the reaction vessel. According to the invention, magnetic force enhancers are provided, which are designed to increase the magnetic effect of the magnets of the magnetic arrangement located at at least one edge of the matrix. This allows a weakening of the magnetic effect of the magnets of the magnetic arrangement located at the edge of the matrix to be at least partially compensated. The magnetic force enhancers are preferably provided to increase the magnetic effect at several edges, particularly preferably opposite edges.The decision as to which edge(s) the magnetic force enhancers are intended for depends on the circumstances, such as technical aspects of handling (e.g. centrifugation, pipetting, etc.) or the type of assay.
[0011] The magnets are arranged below the reaction vessels, in particular below a plane defined by the bottom walls of the reaction vessels of a reaction vessel unit mounted on the magnet support. The position of the magnets can be axially central or eccentric in the axial extension within the cross-sectional area of the reaction vessel, or laterally offset below. The magnets (more precisely: the upper surfaces or poles of the magnets) are preferably arranged in one plane. Several magnets in a magnet group can also be assigned to one reaction vessel. However, the invention assumes that one magnet is assigned to each reaction vessel. A pattern of the matrix thus corresponds to a grid of reaction vessel units of a reaction vessel unit recorded in the recording area.The grid of the matrix can refer to all individual magnets if exactly one magnet is assigned to each reaction vessel, or to a center, such as the center of a surface, of the respective magnet groups if several magnets are assigned to each group.
[0012] The receiving area can have a lateral support structure extending from the base wall of the magnetic support. This allows the reaction vessel assembly to be held laterally in a defined position. The lateral support structure can comprise one or more side walls surrounding the reaction vessel assembly and / or one or more structures engaging in a recess on the underside of the reaction vessel assembly, such as one or more protrusions. The magnets can be arranged on, under, or at least partially within the base wall of the magnetic support.
[0013] The increase in magnetic effect can be achieved particularly in an area above the magnets of the magnetic arrangement, corresponding to the bottom of reaction vessels of a reaction vessel unit arranged in the receiving area. On a side of the magnets facing away from the receiving area, i.e., from the reaction vessel unit, a planar or mesh-like magnetic yoke can be provided, which ensures that the magnetic effect is primarily developed on the side of the reaction vessels.
[0014] The increase in magnetic strength at the edges can roughly correspond to a difference in centrifugal acceleration experienced by the outer reaction vessels compared to the centrally located reaction vessels of a reaction vessel unit, when the reaction vessel unit is mounted on a centrifuge rotor at a predetermined center distance and the rotor is rotating at a predetermined speed. Depending on the dimensions of the auxiliary magnets, the overall magnetic strength, i.e., the sum of the magnet array and the auxiliary magnet array, can be stronger, approximately the same, or weaker at the edge of the magnet array than in the center.
[0015] In embodiments, the magnetic force enhancement means can comprise an auxiliary magnet arrangement consisting of auxiliary magnets arranged outside the main magnet arrangement.
[0016] The auxiliary magnet arrangement can include auxiliary magnets arranged in a straight line extending from a row of the matrix of magnets in the arrangement. The matrix can have several rows in which the magnets (or groups of magnets) are arranged at regular intervals. The rows are preferably aligned parallel to each other. Due to the regularity of the magnets in the rows, lines can be drawn through the locations of the magnets (or groups of magnets) in different directions, which can be defined as rows (and columns) of the matrix. Preferably, the magnet support has a longitudinal direction and a transverse direction that are perpendicular to each other, with the longitudinal extent of the magnet support preferably being greater than the transverse extent, and the rows of the matrix comprise transverse rows or columns in the transverse direction and longitudinal rows or columns in the longitudinal direction.The magnet carrier is preferably arranged on a centrifuge rotor such that its longitudinal direction is parallel to the rotor's axis of rotation and its transverse direction is circumferential. However, embodiments are also conceivable in which the magnet carrier is arranged with its transverse direction along the axis of rotation, particularly when several magnet carriers are arranged simultaneously on one plane of the rotor, with their longitudinal sides abutting each other along the axis of rotation. The auxiliary magnets can be arranged as extensions of the transverse rows, the longitudinal rows, or both. In principle, one auxiliary magnet outside the edge of the matrix, extending from each row, is sufficient and also represents the simplest solution from a manufacturing perspective. However, configurations are also conceivable in which further auxiliary magnets are arranged between the aforementioned auxiliary magnets, for example, to fine-tune the shape of the magnetic field.
[0017] In some embodiments, for each of the magnets arranged at two opposite edges of the matrix of the magnet arrangement, an auxiliary magnet is provided beyond the respective edge. In principle, all edge-side magnets of the magnet arrangement can be assigned an auxiliary magnet, i.e., all around the edges. When used for arrangement in a centrifuge, it may also be sufficient to provide auxiliary magnets only at the edges where the greatest centrifugal force acts during centrifugation.
[0018] However, it can be advantageous to have two auxiliary magnets for each magnet located in a corner of the matrix. One of these auxiliary magnets is arranged longitudinally and the other transversely in the matrix, i.e., extending both the corresponding transverse and longitudinal rows. Since the magnets in the corners of the matrix are missing not just one, but two neighbors in their respective rows, the weakening of the magnetic field is particularly pronounced there. At the same time, the corners are always located where the greatest centrifugal force acts during centrifugation. To counteract this, the two auxiliary magnets arranged diagonally can be provided, as mentioned above. If necessary, a third auxiliary magnet can be provided for the magnets in the corners to fill in the gaps created by the magnets "missing" in the matrix diagonally.
[0019] In some embodiments, the magnets and auxiliary magnets are embedded in the base wall. This can offer advantages, particularly in terms of manufacturing and space requirements. The magnets and auxiliary magnets can be exposed on their upper surface facing the receiving area, and in particular, protrude. This allows the magnets to be positioned close to the reaction vessels of a reaction vessel unit mounted on the magnet support. The height at which the magnetic force is concentrated can also be controlled by adjusting the position (height) of the upper pole.
[0020] It is advantageous if the auxiliary magnets of the auxiliary magnet arrangement are polarized in the opposite direction to the magnet of the magnet arrangement adjacent to it in the longitudinal or transverse direction of the matrix. This ensures that the magnetic field lines are tightly closed at the edge.
[0021] In some embodiments, the auxiliary magnets are neodymium magnets. Alternatively, other rare-earth magnets or materials with high coercivity can be used. All of these share the characteristic of exhibiting a strong magnetic effect. The magnets of the matrix of the magnet arrangement can also be neodymium or other rare-earth magnets. The auxiliary magnets can be smaller in size and / or strength than the magnets of the magnet arrangement, provided this is sufficient to support the magnetic field at the periphery. In this sense, the auxiliary magnets also include components that do not exhibit their own magnetic effect but enhance the magnetic effect of the magnets (retaining magnets). These can be, for example, components made from a yoke material arranged on one side of the magnets.Unlike the auxiliary magnets, the magnets themselves are usually true magnets with high remanence in order to exert their original holding effect.
[0022] In some embodiments, the magnets of the magnetic arrangement are arranged in a row and have different thicknesses in the transverse and / or longitudinal direction. This can further contribute to homogenizing the magnetic field. It can be provided that magnets of the magnetic arrangement at the edge of the matrix, particularly in the transverse direction, have a greater thickness than magnets arranged within the edge of the matrix. It can also be provided that the thickness of the magnets of the magnetic arrangement increases continuously, particularly linearly, from the center of the matrix to the edge of the matrix, particularly in the transverse direction. Furthermore, it can be provided that magnets of the magnetic arrangement at the corners of the matrix have a greater thickness than magnets arranged within the corners, particularly in a row at the transverse edge of the matrix.The idea of controlling and equalizing the magnetic strength by adjusting the strength of the individual magnets as described above, particularly by increasing it at the edges, can also be an independent aspect of the invention. This design of the magnets in the magnetic arrangement can constitute an independent embodiment of the magnetic force-enhancing means within the meaning of the invention.
[0023] In some embodiments, the magnets of the magnetic arrangement are alternately polarized in a longitudinal and transverse direction of the matrix. This results in a harmonically and densely formed magnetic field.
[0024] The advantages of the invention can be particularly realized when the magnet carrier is designed for insertion into a rotor of a centrifuge.
[0025] Selected embodiments of the present invention are described in detail below with reference to the accompanying drawings. The drawings show: Fig. 1 a magnetic carrier for a reaction vessel unit according to an embodiment of the invention in a perspective view from an oblique angle above; Fig. 2 the magnetic carrier from Fig. 1 in a perspective low angle view; Fig. 3 the magnetic carrier Fig. 1 in a top view; Fig. 4 the magnetic carrier Fig. 1 in a cross-sectional view along a section plane IV-IV in Fig. 3; Fig. 5A an exemplary reaction vessel unit for use on the magnetic carrier made of Fig. 1 in a top view; Fig. 5B the reaction vessel unit Fig. 5A in a cross-sectional view along a section plane BB in Fig. 5A; Fig. 5C a modification of the reaction vessel unit made of Fig. 5A in a cross-sectional view accordingly Fig. 5B; Fig. 6 a centrifuge with a reaction vessel unit arranged outside a rotor chamber on a support; Fig. 7A an arrangement of the magnet carrier of Fig. 1 and a balancing weight on a rotor of a centrifuge; Fig. 7B the order from Fig. 7A in a cross-sectional view.
[0026] Reaction vessel units 50 can have the form of a microtiter plate ( Fig. 5), however, the application of the invention is not limited to this. The individual reaction vessels 51 of a microtiter plate are also referred to as wells, which are usually arranged in a predetermined, regular grid of rows 52 and columns 53. The grid thus determines the number of reaction vessels 51.
[0027] Microtiter plates are available in various sizes and designs. The base area usually conforms to the ANSI standards recommended by the Society for Biomolecular Screening (SBS) of L = 27.76 mm × W = 85.48 mm × H = 14.35 mm, where the length (L) and width (B) are fixed, but the height (H) can vary. Common microtiter plate sizes are listed in the table below: Näpfchen Anzahl Raster Füllvolumen (µl) 6 2×3 2000...5000 12 3×4 2000...4000 24 4×6 500...3000 48 6×8 500...1500 96 8×12 100...300 384 31×24 30...100 1536 32×48 5...15 3456 48×72 1...5
[0028] The naming of a microtiter plate depends on the number of wells. For example, a microtiter plate with 24 wells is called a 24-well plate, a microtiter plate with 384 wells a 384-well plate, and so on. The wells can have different bottom shapes, such as F-bottom (flat bottom), C-bottom (flat bottom with minimally rounded edges), V-bottom (conical bottom, see below). Fig. 5B) or U-shaped base (U-shaped depression, cf. Fig. 5C). The cups can have different cross-sectional shapes, such as round, oval, elliptical, square, diamond-shaped, hexagonal, with polygonal shapes also having rounded edges.
[0029] In such microtiter plates, assays are performed, among other things, in which magnetic particles (“beads”) are suspended in solutions to adsorb biomolecules from these solutions onto their surface for further analysis.
[0030] These assays also require washing steps to desorb unwanted molecules that have bound to the magnetic particles. The conditions under which these washings take place must be precisely controlled. Influencing factors include temperature, ion concentration in the washing solution, mixing of the contents of reaction vessel 51, and the strength and orientation of the magnetic field. Only when all influencing factors are correctly adjusted can it be ensured that unwanted compounds are removed while the desired reactants remain bound to the magnetic particles.
[0031] In reality, magnetic assays exhibit an edge effect where reaction vessels located at the periphery of the reaction vessel unit 51 can produce false results. This is due to the differing quality of the magnetic fields at the periphery of the reaction vessel unit 50, as described in the prior art. The invention described herein can align the magnetic fields located at the periphery with those located in the center of the reaction vessel unit 50 and thus also remedy this problem.
[0032] When washing the microtiter plates, these magnetic particles should remain in the reaction vessel 51, while the supernatant is removed and replaced, for example, with fresh medium. In accordance with the invention, this is achieved by mounting the reaction vessel unit 50 on a magnetic support 1 ( Fig. 1-4) is placed under the microtiter plate, which has magnets 15 in a magnet arrangement 14 with a grid that corresponds to the grid of the reaction vessels 51. The magnets 15 attract the magnetic particles with the analytes bound to them, so that the reaction vessel unit 50 is centrifuged and the liquid is ejected, but the magnetic particles remain in the reaction vessels 51.
[0033] A magnetic carrier 1 according to the invention has a base body 2 with a bottom wall 3 and a side wall 4, which can also form a contact surface for a reaction vessel unit 50. Recesses 5 are formed in the side wall 4, which allow or facilitate gripping a reaction vessel unit 50 held by the magnetic carrier 1. The bottom wall 3 and the side wall 4 define a receiving area 6 for a reaction vessel unit 50.
[0034] To facilitate the assignment, directions with respect to the magnetic support are defined as follows using a Cartesian coordinate system x, y, z. Coordinates x, y span a horizontal plane x, y, with the base wall 3 lying in this horizontal plane x, y. For a rectangular magnetic support 1, the coordinate x runs along the shorter edge and defines a latitude direction, lateral direction, or transverse direction, while the coordinate y runs along the longer edge of the base wall 3 and defines a longitudinal direction, with the positive direction x defining a "front" and the negative direction x defining a "back". End faces located in the longitudinal direction x are also called end faces, and end faces located in the transverse direction y are called cheeks. Thus, the side wall 4 has two end faces 4b, 4d and two cheeks 4a, 4c. The wall recesses 5 are each formed in one cheek 4a, 4c.The coordinate z runs perpendicular to the bottom wall 3 and defines a vertical or height direction, where the positive direction z defines "above" and the negative direction y defines "below".
[0035] The receiving area 6 for the reaction vessel unit is thus defined on the upper side of the base wall 3. On the underside of the base plate 3, two longitudinally extending steps 7 are formed at the lateral edges, which can serve to receive guide rails or the like, for example, on a receiving area on the rotor of a centrifuge, or rollers of a roller conveyor in a transport system. The steps 7 have respective approach ramps 20 at their ends ( Fig. 2) on.
[0036] In this embodiment, the base body 2 of the magnet carrier 1 is made of plastic, preferably a thermoplastic or a thermoset.
[0037] A coupling 8 for manipulation by a gripper or the like is provided on the front end face 4b. For this purpose, the coupling has a retaining hole 9. The coupling 8 is preferably magnetic or made of a ferromagnetic material to facilitate coupling. In this embodiment, the coupling 8 is designed as a sheet metal part that is mounted to the front end face 4b by means of fastening screws 10. Alternatively, the coupling 8 can also be integrally formed with the front end face 4b and, for example, have a magnetic sleeve.
[0038] A plinth 11 is formed in the base wall 3, which leads via a step 12 to a depression or recess 13. The height of the step 12 is dimensioned such that the reaction vessel unit 50 rests on the undersides 56 of the reaction vessels 51 and not on the skirt 55 (cf. Fig. 5B, Fig. 5C).
[0039] The magnet carrier 1 has a magnet arrangement 14 with a plurality of magnets 15. The magnets 15 are embedded in respective bores or recesses in the base plate 3 or cast into the base plate 3 during manufacturing. The magnets 15 of the magnet arrangement 14 are arranged in a matrix 30 ( Fig. 3) The matrix 30 of the magnet arrangement 14 corresponds to the grid of the reaction vessels 51 of a reaction vessel unit 50 ( Fig. 5A-5C) and thus has rows or transverse rows 31 and columns or longitudinal rows 32. In this respect, the magnetic carrier 1 is adapted to a specific shape of reaction vessel unit 50. The rows 31 run in the longitudinal direction y of the magnetic carrier 1 and the columns 32 in the transverse direction x. The outermost row 31 in the matrix 30 forms a border row 34 and the outermost column 32 of the matrix forms a border column 35. The magnets 15 in the border rows 34 and border columns 35 are also referred to as border magnets 15r. Where a border row 34 and a border column 35 meet, there is a corner 36 of the matrix with a corner magnet 15e. The area within the borders 34, 35 is an interior region 37 of the matrix 30 with interior magnets 15i.
[0040] An auxiliary magnet arrangement 16 with a plurality of auxiliary magnets 17 is arranged around the magnet assembly 14. The auxiliary magnets 17 are embedded in respective bores or recesses in the base plate 3 or cast into the base plate 3 during manufacturing. Each auxiliary magnet 17 is arranged outside an edge of the matrix 30 of the magnet assembly 14, extending along a row 31 or column 32. The auxiliary magnets 17 arranged at the edge of the matrix 30 of magnets 15 homogenize, reinforce, or stabilize the edge-side magnetic field of the magnet assembly 14. They thus form magnetic force-enhancing means designed to increase the magnetic effect of the magnets 15 located at the edges of the matrix of the magnet assembly 14.
[0041] In the present embodiment, an auxiliary magnet 17 is provided at the ends of each column 32 and at the ends of the outer rows 31 in the transverse direction x, i.e., the outermost rows 34, but not at the ends of the inner rows 31 in the transverse direction. This is designed for centrifugation in a centrifuge in which the magnet carrier 1 and a reaction vessel unit 50 arranged thereon are mounted on a rotor at a distance from the axis of rotation of the centrifuge, and the longitudinal axis y runs parallel to the rotor axis. During centrifugation in such an arrangement, the magnetic forces acting on the reaction vessels 51 are strongest at the outer transverse edge of the reaction vessel unit 50, while they decrease towards the center. Here, the intensification of the magnetic effect at the longitudinal edges 34 is most important in order to reliably retain the magnetic particles in the reaction vessels.For other applications, it may be advantageous to occupy additional or all positions at the edge of the matrix 30 with auxiliary magnets 17 or to leave other positions free.
[0042] The magnets 15 of the magnet arrangement 14 are formed exclusively in the area of the base 11, i.e., in a region of the bottom wall 3 that corresponds to a region of a reaction vessel unit 50 in which reaction vessels 51 are arranged. The auxiliary magnets 17 are formed exclusively in the region of the recess 11, i.e., in a region of the bottom wall 3 that corresponds to a region of a reaction vessel unit 50 in which no reaction vessels 51 are arranged.
[0043] The magnets 15 and / or the auxiliary magnets 17 are preferably designed as rare-earth magnets. Rare-earth magnets are alloys of rare-earth metals such as neodymium or the like with ferrous metals, which exhibit a particularly high magnetic remanence flux density and a high magnetic coercive field strength, and thus a high magnetic energy density. In this embodiment, the magnets 15 are furthermore arranged antiparallel, i.e., with alternating polarity, such that in each row 31 and each column 32, a magnet 15n, whose north pole points upwards, and a magnet 15s, whose south pole points upwards, are always arranged alternately.Accordingly, the auxiliary magnets 17 are also arranged antiparallel to their respective neighbors such that an auxiliary magnet 17s, whose south pole points upwards, is always adjacent to a magnet 15n, whose north pole points upwards, and an auxiliary magnet 17n, whose north pole points upwards, is always adjacent to a magnet 15s, whose south pole points upwards. This antiparallel arrangement increases the field line density in the space directly above and below the magnets, since the field lines run from the north pole of one magnet 15n or auxiliary magnet 17n to the south pole of an adjacent magnet 15s or auxiliary magnet 17s.
[0044] In this embodiment, the magnets 15 each protrude from the top of the base 11 at one end, with the poles of all magnets 15 forming a polar plane 40. The recess 13 ensures that the reaction vessel unit 50, with its bottom wall 56, rests directly on the magnets 15, forming the polar plane 40 (see figure). Fig. 4) thus forms a support surface for a reaction vessel unit 50. Therefore, the magnets 15 are located at a particularly short distance from the reaction vessels 51 of a reaction vessel unit 50 arranged on the magnet support 1. Furthermore, a back plate 21 is arranged below the bottom wall 3. The back plate 21 is screwed to the base body 2 by means of fastening screws 22. The back plate 21 is advantageously designed as a magnetic yoke, which further reinforces the magnetic field generated by the magnets 15 and auxiliary magnets 17 on the upper surface.
[0045] A centrifuge 60, such as the one shown in the following example, can be used to wash reaction vessel units 50. Fig. 6 is shown.
[0046] The centrifuge 60 has a housing 61 comprising a bottom wall 61a, a rear wall 61b, a front wall 61c, and a cover 61d. A drain channel 61e, connected to a drain, is formed in the bottom wall 61a. The housing 61 encloses a rotor chamber 62. A rotor shaft 63 extends between the rear wall 61b and the front wall 61c, each of which is rotatably mounted about a rotor axis R. The rotor shaft 63 is coupled to a rotor drive 64 for rotation about the rotor axis R. A rotor 70 is fixedly mounted to the rotor shaft 63. The rotor 70 has a base frame 71 with two mounting positions 72 for receiving reaction vessel units 50 arranged on a support (see also Fig. 7A, Fig. 7B). The front wall 61c has a window 61f through which the rotor chamber 62 can be accessed from the outside. A balcony 65 is attached to the front wall 61c outside the motor chamber 62. A support, for example a magnetic support 1 according to the present invention, can be arranged on the balcony 65. The balcony 65 is flush with the window 61f at least to the extent that a support arranged thereon, for example the magnetic support 1 according to the present invention, with a reaction vessel unit 50 arranged thereon, can be moved from the balcony 65 into the rotor chamber 62 and back again from the rotor chamber 62 to the balcony 65. The window 61f can be closed by a flap 66. A sliding rod 67 is provided for moving the support, which can be moved through the rotor chamber 62 by means of a linear drive 68. The sliding rod 67 has a coupling element 67a for coupling with the coupling 8 of the carrier.For loading, the rotor 70 is rotated with the sliding rod 67 retracted into a position in which one of the receiving positions 72 is aligned with the window 61f and the balcony 65, then the sliding rod 67 is extended and moved through the rotor chamber 62, the receiving position 72 of the rotor 70 and the window 61f, until the coupling element 67a couples with the coupling 8 on the support 1, the support 1 with the reaction vessel unit 50 arranged on it is pulled onto the receiving position 72, the coupling element 67a is decoupled from the coupling and the sliding rod 67 is fully retracted so that the sliding rod 67 does not interfere with the rotation of the rotor 70.For removal, the rotor 70 is rotated again with the sliding rod 67 retracted into a position in which one of the loaded receiving positions 72 is aligned with the window 61f, then the sliding rod 67 is first extended until the coupling element 67a couples with the coupling 8 on the carrier 1, and then moved further through the rotor chamber 62, the receiving position 72 of the rotor 70 and the window 61f, until the carrier 1 with the reaction vessel unit 50 arranged on it is positioned on the balcony 65, the coupling element 67a is decoupled from the coupling and the sliding rod 67 is either fully retracted so that the sliding rod 67 does not interfere with the rotation of the rotor 70, or only partially retracted to be kept ready for a further loading operation.
[0047] A dispensing module 69 with one or more dispensing heads 69a, each with one or more dispensing nozzles 69b above the balcony 65, can also be mounted on the front wall 61c. The dispensing module can be used to fill the reaction vessels 51 of the reaction vessel unit 50 with a dispensing liquid or different dispensing liquids. Dispensing can be carried out column by column with respect to the columns 53 of the reaction vessels 51 of the reaction vessel unit 50. For this purpose, the sliding rod 67 can also be used, which can be positioned precisely and reliably by means of the positioning drive 68 and due to the rigidity of the sliding rod 67 itself and the coupling element 67a, as well as a low-vibration or vibration-free design of the positioning drive 68, so that precise and closely timed filling by the dispensing unit 69 can take place.
[0048] The centrifuge is the subject of several patent applications, with particular reference being made to WO 2017 / 125598 A1 with regard to the design with a sliding rod and positioning drive, to WO 2018 / 234420 A1 with regard to the design with a drainage channel, to EP 4151315 A1 in conjunction with a discharge device, to EP 4151315 A1 and WO 2023 / 020981 A1 with regard to the dispensing unit, insofar as it concerns the illustrated embodiment.
[0049] The mounting positions 72 are diametrically opposed to the rotor axis R on the base frame 71. In the figure, a magnet carrier 1 according to the present invention is mounted at a first (upper) mounting position 72, while a balancing body 73 is mounted at a second (lower) mounting position 72. The balancing body 73 is designed to compensate for an imbalance. For the sake of simplicity, a reaction vessel unit on the magnet carrier 1 and, if applicable, on the balancing body 73 has been omitted from the figures.
[0050] The receiving positions 72 each have a receiving contour 74 that negatively replicates the outer contour of the received magnet carrier 1 with reaction vessel unit 50, at least to the extent necessary for the secure receiving and trouble-free transfer of the magnet carrier 1 into and out of the rotor 70. For further description of the receiving contour 74, directional terms are used as they correspond to the local coordinates x, y, z of a magnet carrier 1 received at the receiving position 72, where a radius with respect to the rotor axis R coincides with the vertical axis z and the longitudinal axis y runs along the rotor axis R. In relation to the rotor, "top" corresponds to a direction away from the axis of rotation R, and "bottom" to a direction towards the axis of rotation R. For example, the receiving contour 74 has two lateral guide surfaces 74a for contact with a side wall 4 of the magnet carrier 1.The lateral guide surfaces 74a are each bounded downwards by a lower guide surface 74b, which extends inwards and serves as a rail-like support for the steps 7 on the bottom wall 3 of the magnet carrier 1. The lateral guide surfaces 74a are each bounded upwards by a first upper stop surface 74c, which extends inwards and serves as a support for the upper edge of a skirt 55 of a reaction vessel unit 50 arranged on the magnet carrier 1. The first upper stop surfaces are each bounded inwards by a lateral boundary surface 74d, which extends upwards and serves as a lateral support for a reaction vessel unit 50 arranged on the magnet carrier 1.The lateral boundary surfaces 74d are each bounded at the top by a second upper stop surface 74e, which extends inwards and serves to guide and secure a reaction vessel unit 50 arranged on the magnetic carrier 1. The lower guide surfaces 74b each terminate inwards in a recess 74f, which extends downwards and exposes further structures of the bottom wall 3 of the magnetic carrier 1. It is understood that the receiving contour 74 can also accommodate carriers that are not magnetic carriers, provided that the outer contour of the carrier is adapted for receiving at one of the receiving positions 72 of the rotor 70.
[0051] The balancing body 73 has an outer contour similar to that of the magnet carrier 1, insofar as this is expedient for its placement on one of the mounting positions 72 of the rotor 70. The balancing body 73 has, in particular, a base body 75 with a side wall 75a and a bottom wall 75b. The base body 75 has an outer contour adapted for placement on one of the mounting positions 72 of the rotor 70. A receiving area 75c for a reaction vessel unit 50 is formed on the upper side of the base body 75. Receiving areas 75d are formed on the underside of the base body 75, in which trim weights 76 are received and secured by a potting compound 77. The balancing body 73 has a coupling 78, which can be configured according to the coupling 8 of the magnet carrier 1.The type of balancing body 73 shown and described here is the subject of another utility model, which was filed on the same day as the present utility model and to whose disclosure content reference is made in full. This balancing body 73, by means of its trimming weights 76, is particularly adapted for balancing comparatively heavy supports, such as the magnetic support 1 of the type presented here. By means of the trimming weights 76, the balancing body 73 can be adapted to the magnetic support 1 according to the invention in terms of mass and / or center of gravity position and / or moment of inertia with respect to the rotor axis R. The trimming weights 76 are preferably made of a non-magnetic or non-magnetic material that has a comparatively high density compared to the base frame 73, such as lead, copper, brass, another metal, an alloy, or other compound.For further balancing, an empty reaction vessel unit 50 or a reaction vessel unit 50, whose reaction vessels 51 are filled in a non-losable manner with a balancing mass whose mass corresponds to an assumed mass of the filling of the reaction vessels 51 of the reaction vessel unit 50 to be washed, can also be attached to the balancing body 73.
[0052] It is understood that the balancing carrier 73 can also be designed differently and is shown here only in a specific embodiment for illustrative purposes. Instead of a special balancing body 73, another magnetic carrier 1 with or without a reaction vessel unit 50 can also be used.
[0053] A reaction vessel unit 50, mounted on the magnet carrier 1 at one of the mounting positions 72, is arranged for centrifugation with the openings of the reaction vessels 51 pointing away from the rotor axis R. Each reaction vessel 51 of the reaction vessel unit 50 is assigned a magnet (holding magnet) 15 of the magnet arrangement 14. Due to the auxiliary magnets 17 of the auxiliary magnet arrangement 16, which are arranged outside the magnet arrangement 14, any edge weakening of the magnet arrangement 14 is compensated for, reduced, or reversed. In this embodiment, the auxiliary magnets 17 are arranged primarily along the longitudinal edges of the magnet arrangement 14 and at the transverse edges only at the outermost magnets in the width direction y (the corner magnets). In variations, it is of course possible to arrange auxiliary magnets 17 around the entire matrix 30 of the magnet arrangement 14.
[0054] If a distance (grid dimension) t between the reaction vessels 51 of the reaction vessel unit 50 in the directions x and y and a smallest axial distance r0 of a bottom of the reaction vessel unit 50 are considered ( Fig. 7B), so an axle spacing r k a k-th row 52 of reaction vessels 51 measured from the yz-plane with an even number of reaction vessels 51 in each column 53 given by rk,g=r02+t2∗(k−12)2.
[0055] In the illustrated embodiments, there are 8 reaction vessels 51 in each column 53, the outermost row 52 in the width direction x therefore has the atomic number k = 4 counted from the middle plane yz.
[0056] If there is an odd number of reaction vessels 51 in each column 53, one reaction vessel 51 in each column 53 lies exactly in the yz-plane; therefore, in this case, the axial distance r ka k-th row 52 of reaction vessels 51 measured from the yz-plane given by rk,u=r02+t2∗k2.
[0057] If, in an exemplary dimensioning of the rotor 70, the smallest center distance r0 is to be half the maximum width b, i.e., r0 = b / 2, a maximum center distance r can be max can be estimated by: rmax=B2=r0∗2
[0058] The maximum axle spacing r max is therefore about 41% larger than the smallest axial distance r0. Although this estimate is somewhat larger than the actual axial distance of the outermost row 52 of reaction vessels 51 in the width direction, since it is based on the outer edge of the reaction vessel unit 50, it nevertheless provides a clear indication of the difference between the centrifugal acceleration prevailing in the middle and at the edge of the reaction vessel units 50.
[0059] The centrifugal acceleration az is given for a given angular velocity ω or rotational speed N at any axial distance r from the axis of rotation R by az=r∗ω2=r∗(2πn)2
[0060] The distance therefore correlates linearly with the centrifugal acceleration a. z one. Thus, it can be estimated that the centrifugal acceleration a z The magnetic force at the edge of the reaction vessel unit during centrifugation is approximately 41% greater than in the center. To compensate for this difference in centrifugal acceleration, the magnetic force at the edge of the matrix 30 of magnets 15 is preferably increased by the auxiliary magnets 17.
[0061] The present invention has been explained above with reference to preferred embodiments. It is understood, however, that the invention is not limited by individual features of the embodiments, but is defined solely by the independent claims in their broadest interpretation. Unless included in the respective independent claim, all individual features disclosed in connection with an embodiment or a dependent claim are to be considered optional, even if the feature in question is present in all embodiments.Each individual feature that solves a technical problem compared to the prior art is, in itself or in any combination with other features described and / or shown herein, suitable to define a separate subject matter of the invention, even if it has only been described and / or shown in conjunction with other features of an exemplary embodiment. It is further understood that each feature described and / or shown in connection with an exemplary embodiment may also be applied in any other exemplary embodiment, insofar as this is technically possible, and shall be deemed disclosed to that extent.
[0062] For example, it has been described that the magnetic support 1 has a side wall 4 which can serve as a mounting surface for a reaction vessel unit 50 and, together with the bottom wall 3, forms the receiving area 6 for the reaction vessel unit 50. However, it is conceivable that the magnetic support 1 does not have a side wall 4 and that the receiving area 6 is thus formed only by the bottom wall 3.
[0063] Furthermore, wall recesses 5 were described, each formed in a cheek 4a, 4c. Such wall recesses 5 are entirely optional; they can also be omitted, provided in a different location or in a different number, and in particular adapted to a handling system for reaction vessel units 50, such as a gripper.
[0064] Likewise, the described indentations 7, and even more so the approach ramps 20, are completely optional.
[0065] Similarly, all features described in connection with an embodiment are to be considered optional as long as they are not essential for the claimed invention and the problem solved by it.
[0066] The described and illustrated embodiment assumes that the magnet carrier 1 is arranged on the rotor 70 with its longitudinal direction y parallel to the axis of rotation R of the centrifuge 60, and accordingly, the auxiliary magnets 17 are arranged primarily along the edge rows 34. If the magnet carrier is arranged on the rotor 70 with its longitudinal direction y transverse to the axis of rotation R of the centrifuge 60, the auxiliary magnets 17 can accordingly be arranged primarily along the edge slots 35.
[0067] It is further understood that the centrifuge 60 shown here is purely exemplary and does not in any way limit the invention with respect to the magnet carrier 1, unless expressly described or claimed otherwise. In particular, the rotor 70 shown and described here serves solely to illustrate the application of the magnet carrier 1. The rotor 70 can be designed quite differently in practice. For example, the lower guide surface 74b of the rotor 70 can also be a simple step from which the step 7 is recessed, so that the magnet carrier rests on the recess 74f with the base surface 3 or the magnet yoke 21. The recess 74c can also be omitted entirely, for example. It is evident that numerous other variations are conceivable, which do not affect or limit the present invention.For the use of the magnetic carrier 1 in a centrifuge 60, it is only crucial that a contour of the magnetic carrier 1 is adapted to a contour of a receiving position 72 of the rotor 70. Otherwise, the magnetic carrier 1 according to the invention can be centrifuged in any centrifuge that is fundamentally capable of accommodating the magnetic carrier 1.
[0068] Magnetic force enhancement means can also be implemented in ways other than with auxiliary magnets 17 or additionally by other means. In one embodiment, the edge magnets 15r can have a stronger magnetic field than the inner magnets 15i, and optionally, the corner magnets 15e can have an even stronger magnetic field than the remaining edge magnets 15r. As a further option, the strength of the magnetic fields of the magnets 15 can increase from the center outwards in a transverse direction. Instead of individual auxiliary magnets 17, a ferromagnetic material of continuous extent can also be arranged along the edge of the matrix 30. Ferromagnetic material in the form of the described auxiliary magnets 17 or ferromagnetic material of non-continuous extent can also be used. For example, the yoke plate 21 can be designed in the form of a trough, with the upper edge encompassing the matrix 30 of the magnets 15.Such an edge can preferably be comb-shaped, so that the base body 2 can still be formed in one piece.
[0069] The magnets 15 of the magnet arrangement 14 are retention magnets, each assigned to one of the reaction vessels 51 in the reaction vessel unit 50, in order to influence its contents. The action of the magnets 15 of the magnet arrangement 14 can influence or achieve both the sedimentation of particles in the reaction vessel 51 and their retention during washing.
[0070] In the described embodiment, each reaction vessel 51 of a reaction vessel 50 is assigned exactly one magnet 15 of the magnet arrangement 14. For finer control of access to the contents of a reaction vessel 51, for example by forming several sedimentation zones, or for a broader distribution of the magnetic effect, a group of several retaining magnets can be provided for each reaction vessel 51 instead of a single magnet 15, particularly in the case of large reaction vessels 51. Reference symbol list 1 magnetic carrier 2 basic shapes 3 Floor wall 4 side wall 5 wall recess 6 Recording area Paragraph 7 8 Clutch 9 retaining holes 10 fastening screws 11 sockets 12th grade 13 Lowering 14 Magnet arrangement 15,15n,15s Magnet / Retaining magnet (n: north pole up, s: south pole up) 15i,15r,15e Magnet / Retaining magnet (i: inner magnet, r: edge magnet, e: corner magnet) 16 Auxiliary magnet arrangement 17,17n,17s Auxiliary magnet (n: north pole upwards, s: south pole upwards) 20 Approach ramp 21 Backplate / Magnetic yoke 22 Mounting screw 30 Matrix 31st line / horizontal row 32 columns / longitudinal rows 33 Marginal line 34 Marginal column 35 Corner 40 Pole plane / support plane 50 reaction vessel units 51 reaction vessel 52nd line Column 53 54 Basic shapes 55 Apron (Skirt) 56 Floor wall 58 stiffening rib 60 centrifuge 61 cases 61a Floor wall 61b Back panel 61c Front wall 61d Cover 61e Drainage channel 61f window 62 Rotor space 63 Rotor shaft 64 Rotor drive 65 Balcony 66 flap 67 Sliding rod 68 Positioning drive 69 Dispensing module 70 Rotor 71 Basic frame 72 recording positions 73 balancing weights 74 Recording contour 74a Side guide surface 74b Lower guide surface 74c First upper stop surface 74d Lateral boundary surface 74e Second upper stop surface 75 Basic body 75a Side wall 75b Floor wall 75c recording area for reaction vessel unit 75d recording range for trim weight 76 trim weight 77 Potting compound 78 Clutch A loading position B Unloading position R Rotor axis b width h height k ordinal number l length r radius t spacing (grid dimension) x transverse direction y longitudinal direction z Vertical direction
[0071] The above list is an integral part of the description. QUOTES INCLUDED IN THE DESCRIPTION
[0000] This list of documents cited by the applicant was automatically generated and is included solely for the reader's convenience. The list is not part of the German patent or utility model application. The DPMA accepts no liability for any errors or omissions. Cited patent literature
[0000] WO 2015 / 018878 A2
[0003] US 2021 / 138485 A1
[0004] US 11,132,142 B2
[0004] WO 2017 / 125598 A1
[0048] WO 2018 / 234420 A1
[0048] EP 4151315 A1
[0048] WO 2023 / 020981 A1
[0048]
Claims
[1] Magnet carrier (1) for a reaction vessel unit (50) with a plurality of reaction vessels (51), wherein the magnet carrier (1) has a receiving area (6) for receiving a reaction vessel unit (50) and a magnet arrangement (14) with magnets (15) arranged in a matrix (30), wherein each reaction vessel (51) of the reaction vessel unit (50) is assigned exactly one magnet (15) or exactly one magnet group, which is arranged below the reaction vessel (51), wherein magnetic force increasing means are provided which are designed to increase a magnetic effect of the magnets (15) of the magnet arrangement (14) located on at least one edge, preferably a plurality of edges, particularly preferably opposite edges, of the matrix (30). [2] Magnet carrier (1) according to claim 1, wherein the magnetic force increasing means comprises an auxiliary magnet arrangement (16) of auxiliary magnets (15) arranged outside the magnet arrangement (14). [3] Magnet carrier (1) according to claim 2, wherein the auxiliary magnet arrangement (16) comprises auxiliary magnets (15) arranged in a straight extension of a row of the matrix (30) of magnets (15) of the magnet arrangement (14). [4] Magnetic carrier (1) according to claim 2 or 3, wherein for each of the magnets (15) of the magnet arrangement (14) arranged at the opposite edges of the matrix (30), an auxiliary magnet (15) is provided beyond the respective edge. [5] Magnet carrier (1) according to one of claims 2 to 4, wherein for each magnet (15) of the magnet arrangement (14) located in a corner of the matrix (30), two auxiliary magnets (15) are provided, one of which is arranged in the longitudinal direction (y) and one in the transverse direction (x) of the matrix (30). [6] Magnet carrier (1) according to one of claims 2 to 5, wherein the magnets (15) and auxiliary magnets (15) are embedded in the bottom wall (3) and are preferably exposed, in particular protruding, on an upper side facing the receiving area (6). [7] Magnet carrier (1) according to one of claims 2 to 6, wherein the auxiliary magnets (15) of the auxiliary magnet arrangement (16) are each polarized inversely to the magnet (15) of the magnet arrangement (14) adjacent in the longitudinal or transverse direction (x) of the matrix (30). [8] Magnet carrier (1) according to one of the preceding claims, wherein the magnets (15) and / or, as far as referred to one of claims 2 to 7, the auxiliary magnets (15) are neodymium magnets (15). [9] Magnet carrier (1) according to one of claims 1 to 8, wherein the magnets (15) of the magnet arrangement (14) in a row have different strengths in the transverse direction (x) and / or longitudinal direction (y). [10] Magnetic carrier (1) according to claim 9, wherein magnets (15) of the magnet arrangement (14) at the edge of the matrix (30), in particular in the transverse direction (x) of the matrix (30), have a greater strength than magnets (15) arranged within the edge of the matrix (30). [11] Magnetic carrier (1) according to claim 9 or 10, wherein the strength of the magnets (15) of the magnet arrangement (14) increases continuously, in particular linearly, from the center of the matrix (30) to the edge of the matrix (30), in particular in the transverse direction (x) of the matrix (30). [12] Magnet carrier (1) according to one of claims 9 to 11, wherein magnets (15) of the magnet arrangement (14) at corners of the matrix (30) have a greater strength than magnets (15) which are arranged within the corners, in particular in a row at the edge of the matrix (30) located in the transverse direction (x) of the matrix (30). [13] Magnetic carrier (1) according to one of the preceding claims, wherein the magnets (15) of the magnet arrangement (14) are each alternately polarized in a longitudinal and transverse direction (x) of the matrix (30). [14] Magnetic carrier (1) according to one of the preceding claims, wherein the magnetic carrier (1) is designed to be received in a rotor (70) of a centrifuge (60).
Citation Information
Patent Citations
Centrifuge and method for cleaning a centrifuge
EP4151315A1
Systems and methods for writing zeros to a memory array
US11132142B2
Centrifuge
US20210138485A1
Centrifuge
WO2017125598A1
Centrifuge
WO2018234420A1