Magnetic substance separator

The magnetic substance separation device optimizes magnetic interaction by arranging cubic components with different magnetization directions, enhancing efficiency and safety while adapting to diverse containers, achieving high magnetic force and low bead residue.

JP2025105583APending Publication Date: 2025-07-10IND TECH RES INST
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Patent Information

Application Number
JP2024231762
Authority / Receiving Office
JP · JP
Patent Type
Applications
Current Assignee / Owner
Priority Date
2023-12-28
Filing Date
2024-12-27
Publication Date
2025-07-10

AI Technical Summary

Technical Problem

Conventional magnetic substance separation devices face challenges in balancing efficiency, convenience, automation, biosafety, and biocompatibility, and struggle to adapt to varying container shapes and magnetic force variations due to sample characteristics.

Method used

A magnetic substance separation device with a casing containing at least one magnetic component assembly, featuring cubic magnetic components arranged in different magnetization directions to form a ferromagnetic surface, allowing for flexible adaptation to different container shapes and enhancing magnetic interaction efficiency.

Benefits of technology

The device increases magnetic force per unit area, improves separation efficiency, and meets requirements of efficiency, convenience, automation, and biosafety, with reduced residual magnetic beads and maintained cell viability.

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Abstract

To provide a magnetic substance separator with high reliability for enhancing efficiency of a magnetic interaction adaptable to different container geometries through a powerful magnetic design with optimized magnet arrangement, and for having a magnetic substance separation experiment.SOLUTION: A magnetic substance separator includes a casing 11 and at least one magnetic component assembly 13. The casing 11 has at least one accommodation compartment, and the magnetic component assembly 13 is disposed in the accommodation compartment. The magnetic component assembly 13 includes at least four cubic magnetic components M1. Furthermore, in the magnetic substance separator, the four cubic magnetic components M1 are arranged linearly in different magnetization directions (Halbach arrangement), enabling magnetic lines of the at least one magnetic component assembly 13 to be concentrated on one side. The magnetic component assembly 13 is configured to form at least one ferromagnetic surface B1 on the casing, and the ferromagnetic surface B1 is configured to attract magnetic substances contained in a sample in a sample container.SELECTED DRAWING: Figure 1
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Description

Technical Field

[0001] The present disclosure relates to a magnetic substance separator.

Background Art

[0002] Conventional magnetic substance separation experiments often face multiple problems. First, when the manufacturers are different, the magnetic force of the magnetic substance varies greatly, and the characteristics of the biological sample (such as the encapsulation phenomenon) affect the magnetic interaction, resulting in a decrease in separation efficiency. Second, the diversity of the experimental containers makes it difficult to optimize the magnetic interaction. Furthermore, the relationship between the magnetic force and the distance also affects the separation effect. Conventional magnetic separation devices often struggle to balance efficiency, convenience, automation, biosafety, and biocompatibility, restricting the progress of magnetic separation experiments.

[0003] Therefore, how to provide a magnetic separation device that meets the requirements such as efficiency, convenience, automation, biosafety, and biocompatibility, and can flexibly select appropriate container shapes, surface materials, and surface treatment methods according to the characteristics of various samples has become an urgent issue in this field for researchers.

Summary of the Invention

Problems to be Solved by the Invention

[0004] The present disclosure provides a magnetic substance separator that optimizes the arrangement of magnets, utilizes a strong magnetic force design, adapts to different container shapes, enhances the efficiency of magnetic interaction, and provides a comprehensive and reliable solution for magnetic substance separation experiments.

Means for Solving the Problems

[0005] One embodiment of the present disclosure provides a magnetic substance separation device configured to attract magnetic substances in a sample within a sample container. The magnetic substance separation device includes a casing and at least one magnetic component assembly. The casing has at least one accommodation compartment. The at least one magnetic component assembly is disposed within the at least one accommodation compartment, and the at least one magnetic component assembly includes at least four cubic magnetic components. Further, the at least four cubic magnetic components are linearly arranged in different magnetization directions, enabling the magnetic field lines of the at least one magnetic component assembly to concentrate on one side, and the at least one magnetic component assembly forms at least one ferromagnetic surface on the casing. The at least one ferromagnetic surface is configured to attract magnetic substances in the sample within the sample container.

Advantages of the Invention

[0006] According to the magnetic substance separation device disclosed in the embodiment of the present disclosure, by arranging the cubic magnetic components in a specific manner, a ferromagnetic surface can be formed on the casing, thereby increasing the magnetic force per unit area with fewer magnetic components. Further, the magnetic substance separation device can be adjusted to adapt to different container shapes, thereby improving the efficiency of magnetic interaction while simultaneously meeting the requirements of efficiency, convenience, automation, biosafety, and biocompatibility.

Brief Description of the Drawings

[0007] The present disclosure will be better understood from the following detailed description shown herein and the accompanying drawings.

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Embodiments for Carrying Out the Invention

[0008] In the following detailed description, for the sake of explanation, numerous specific details are set forth in order to provide a thorough understanding of the disclosed embodiments. However, it will be apparent that one or more embodiments may be practiced without these specific details. In other instances, well-known structures and devices are shown schematically in order to simplify the drawings.

[0009] The following description is to be understood as providing various embodiments or examples for implementing different aspects of the present disclosure. The specific components and arrangements described below are merely simplified descriptions of the present disclosure and are provided for illustrative purposes and not for limitation. The term "about" as used in the present disclosure refers to a value that includes the recited value and values within an acceptable deviation range, taking into account measurement problems and errors (i.e., the limitations of the measurement system) by those skilled in the art. For example, "about" can mean within one or more standard deviations of the recited value, or within ±5% of the recited value. The amounts provided herein are approximate values, and even if terms such as "about," "substantially," or "approximately" are not explicitly recited, they may be implied. Further, the expression "from a to b" as used in the present disclosure indicates a range from "a" or more to "b" or less.

[0010] Terms such as "first," "second," "third," etc. may be used herein to describe various components, regions, layers, and / or parts, but it is to be understood that these components, regions, layers, and / or parts should not be limited by these terms. These terms are only used to distinguish one component, region, layer, and / or part from another. Thus, a "first" component, region, layer, and / or part described hereinafter may be referred to as a "second" component, region, layer, and / or part without departing from the teachings of the embodiments of the present disclosure.

[0011] The present disclosure provides a magnetic substance separation device for the purpose of attracting magnetic substances in a sample within a sample container, thereby separating the magnetic substances from the sample, but its use is not limited to separating magnetic substances from the sample. In some aspects, the magnetic substance separation device can also be configured to separate substances attracted to the magnetic substance or substances linked to the magnetic substance, and whether to retain or discard the separated substances depends on the purpose of the experiment.

[0012] According to the present disclosure, the magnetic substance separator includes a casing and at least one magnetic component assembly. The casing has at least one accommodation compartment. The at least one magnetic component assembly is disposed within the at least one accommodation compartment, and the at least one magnetic component assembly includes at least four cubic magnetic components. Further, the at least four cubic magnetic components are linearly arranged with different magnetization directions, enabling the magnetic field lines of the at least one magnetic component assembly to concentrate on one side, such that the magnetic component assembly forms at least one ferromagnetic surface on the casing, and the at least one ferromagnetic surface is configured to attract magnetic substances in the sample within the sample container. The linear arrangement of the cubic magnetic components with different magnetization directions may refer to the magnetization directions of each cubic magnetic component rotating according to a specific pattern. For example, the magnetization direction of each sequentially arranged cubic magnetic component rotates by 90° with respect to the magnetization direction of the preceding cubic magnetic component.

[0013] In one aspect, the at least four cubic magnetic components are arranged, for example, in a Halbach array.

[0014] In one aspect, the magnetic component assembly may further form a diamagnetic surface on the casing, and the diamagnetic surface and the ferromagnetic surface may be located on opposite sides of the casing. It should be noted that in a configuration where the casing is, for example, plate-shaped, the ferromagnetic surface is defined as being located on a reference plane formed by the X-axis and the Y-axis. The extending direction of the accommodation compartment within the casing may be parallel to, for example, the X-axis or the Y-axis, whereby the magnetic component assembly can have a more flexible configuration based on actual design requirements, but the present disclosure is not limited to the aforementioned extending direction of the accommodation compartment within the casing.

[0015] In one aspect, at least one magnetic component assembly may include a plurality of magnetic component assemblies, at least one receiving compartment may include a plurality of receiving compartments, and the magnetic component assemblies are respectively disposed in the receiving compartments. In other words, the number of magnetic component assemblies may be plural, and the number of receiving compartments may also be plural. Further, the number of magnetic component assemblies may correspond to the number of receiving compartments, whereby each magnetic component assembly can be disposed in a respective receiving compartment. Further, the cubic magnetic components in one of the receiving compartments may be arranged aligned with another cubic magnetic component in another one of the receiving compartments, but the present disclosure is not limited thereto. In other configurations, the cubic magnetic components within a receiving compartment in one of the receiving compartments may be arranged in an offset configuration with respect to the cubic magnetic components in another one of the receiving compartments.

[0016] In one aspect, each two adjacent cubic magnetic components within the same receiving compartment may be physically in contact with each other, but the present disclosure is not limited thereto. In other configurations, there may be a gap between each two adjacent cubic magnetic components within the same receiving compartment, and the gap may be, for example, greater than 0 mm and less than or equal to 2.0 mm.

[0017] In a configuration where the number of receiving compartments is plural, the casing can have a plurality of partitions, and the partitions are respectively disposed between two adjacent receiving compartments. In other words, the partitions of the casing can divide the internal space of the casing into a plurality of receiving compartments, and each receiving compartment is designed to accommodate a magnetic component assembly. Further, the thickness of each of the partitions can range from 1.0 mm to 10.0 mm. Preferably, the thickness of each of the partitions can be in the range of 1.5 mm to 7.9 mm. For example, in one configuration, the thickness of each partition of the casing may be substantially 1.5 mm, in another configuration, the thickness of each partition of the casing may be substantially 1.8 mm, in yet another configuration, the thickness of each partition of the casing may be substantially 4.8 mm, and in yet another configuration, the thickness of each partition of the casing may be substantially 7.9 mm.

[0018] According to the magnetic substance separation device of the present disclosure, the thickness of the casing on the ferromagnetic surface may be in the range of 1.0 mm to 2.0 mm. For example, in one configuration, the thickness of the casing on the ferromagnetic surface may be substantially 1.0 mm, in another configuration, the thickness of the casing on the ferromagnetic surface may be substantially 1.5 mm, in still another configuration, the thickness of the casing on the ferromagnetic surface may be substantially 1.8 mm, and in still another configuration, the thickness of the casing on the ferromagnetic surface may be substantially 2.0 mm.

[0019] In one configuration, the magnetic component assembly may be in physical contact with the inner peripheral surface of the accommodation section, but the present disclosure is not limited thereto. In other configurations, there may be a gap between the magnetic component assembly and at least a part of the inner peripheral surface of the accommodation section.

[0020] According to the magnetic substance separation device of the present disclosure, the side length of each cubic magnetic component may be in the range of 1 mm to 15 mm. Preferably, the side length of each cubic magnetic component may be in the range of 3 mm to 10 mm. For example, in one configuration, the side length of each cubic magnetic component of the magnetic component assembly may be substantially 3 mm, in another configuration, the side length of each cubic magnetic component of the magnetic component assembly may be substantially 5 mm, and in still another configuration, the side length of each cubic magnetic component of the magnetic component assembly may be substantially 10 mm.

[0021] In one configuration, the magnetic substance separation device may further include a holder disposed on the casing, and the holder is configured to fix the sample container on the ferromagnetic surface of the casing.

[0022] In a configuration where the magnetic substance separation device includes a holder, the holder may include a central post, and the sample container may be a flexible tube. The central post may be disposed in the central region of the ferromagnetic surface, and the central post is configured such that the sample container is wound around it. In some configurations, the holder may further include a cover disposed on the casing, and an accommodation space may be formed between the cover and the ferromagnetic surface. Further, the cover may have a first through-hole and a second through-hole reaching the accommodation space, the central post may be disposed so as to penetrate the cover, and the central post may have a winding groove. The first through-hole of the cover is configured such that the sample container passes through and extends into the accommodation space, the winding groove of the central post is disposed in the accommodation space and is configured such that the sample container is wound, and the second through-hole of the cover is configured such that the sample container passes through and extends from the accommodation space.

[0023] According to the magnetic substance separation device of the present disclosure, in a configuration where the sample container is a flexible tube, the flexible tube can be connected to an automatic processing device (such as a cell culture device), whereby the magnetic substance separation device can continuously and automatically remove magnetic substances (for example, magnetic beads) used in the culture process. For example, the automatic processing device can continuously introduce a sample into the flexible tube and cause the sample to flow through the flexible tube at a specific flow rate. When the sample passes through the magnetic component assembly, the magnetic beads in the sample are attracted and held in the flexible tube, while the sample after the magnetic beads are separated is output from the flexible tube and recovered. By this process, the magnetic substance separation device can effectively utilize the automatic processing device to perform automatic magnetic substance separation, thereby improving the efficiency of magnetic substance separation for the sample. Further, the automatic processing device is interlocked with the flow path length of the flexible tube, controls the flow rate of the sample in the flexible tube, and can meet the required magnetic bead residue standard.

[0024] In a configuration where both the number of magnetic components assemblies and the number of accommodation compartments are plural, the accommodation compartments can be configured in a two-layer arrangement such that the magnetic components assemblies respectively accommodated in the two-layer accommodation compartments can form two ferromagnetic surfaces on the casing, and the two ferromagnetic surfaces are located on the opposing surfaces of the casing. However, the present disclosure is not limited to the aforementioned numbers. For example, in other configurations, the accommodation compartments can be arranged in three or more rows, and the rows of these accommodation compartments are arranged adjacent to different surfaces of the casing. As a result, the magnetic components assemblies accommodated in the accommodation compartments can form three or more ferromagnetic surfaces on the casing.

[0025] In one configuration, the casing may be plate-shaped, and the sample container may be, for example, a flexible tube. Further, the casing is configured such that the sample container (e.g., a flexible tube) can be wound around it, whereby the sample container (e.g., a flexible tube) can be positioned at least partially on the ferromagnetic surface.

[0026] In one configuration, the casing may be cylindrical and have an outer peripheral surface, and the accommodation compartments may be arranged in the vicinity of the outer peripheral surface such that the ferromagnetic surface can be located on the outer peripheral surface of the casing. In this configuration, the sample container may be, for example, a flexible tube, and the casing is configured such that the sample container (e.g., a flexible tube) can be wound around the outer peripheral surface (i.e., the ferromagnetic surface) with the sample container (e.g., a flexible tube) in a wound state. Further, in a configuration where the casing is cylindrical and has an outer peripheral surface, the magnetic substance separation device can be arranged on the casing and further include a holder for fixing the sample container to the ferromagnetic surface of the casing. The holder may be a quick-release outer cover and include a support base and at least one extension arm. The support base is arranged detachably on the end surface of the casing, and the extension arm is connected to the support base and suspended above the ferromagnetic surface configured such that the sample container (e.g., a flexible tube) can be wound around it.

[0027] In one configuration, the casing may be cylindrical and have an inner circumferential surface, and the accommodation section may be arranged near the inner circumferential surface such that the ferromagnetic surface can be positioned on the inner circumferential surface of the casing. Further, in a configuration where the casing is cylindrical and has an inner circumferential surface, the magnetic substance separator may further include a holder. The inner circumferential surface of the casing may be formed to surround the accommodation space, and the holder is configured to fix the sample container on the ferromagnetic surface of the casing. For example, the sample container may be, for example, a flexible tube, and the holder may be a quick-release shaft detachably disposed in the accommodation space and configured such that the sample container (e.g., flexible tube) can be wound around it.

[0028] <First Embodiment> Referring to FIGS. 1 and 2, FIG. 1 is a perspective view of a magnetic substance separator according to the first embodiment of the present disclosure, and FIG. 2 is an exploded perspective view of the magnetic substance separator shown in FIG. 1.

[0029] In the present embodiment, the magnetic substance separator 1 is configured to attract magnetic substances in a sample in a sample container (not shown). The magnetic substance separator 1 includes a casing 11 and a plurality of magnetic component assemblies 13.

[0030] In this embodiment, the casing 11 has four accommodation compartments S1, and the four accommodation compartments S1 are parallel to each other. Specifically, the casing 11 includes a main housing 111, three partitions 112, and a base 110. The three partitions 112 are arranged in the main housing 111 so as to form four parallel and elongated grooves in the main housing 111. The base 110 is fixed to the main housing 111 by, for example (but not limited to), screws, whereby four accommodation compartments S1 are formed together with the main housing 111 and the partitions 112. Further, the partitions 112 are respectively arranged between two adjacent accommodation compartments S1. Further, the base 110 has four openings H1 respectively connected to the four accommodation compartments S1, whereby the magnetic component assembly 13 can be inserted into the accommodation compartment S1 through the openings H1.

[0031] As shown in FIG. 1, the length direction and the width direction of the casing 11 respectively correspond to the X-axis direction and the Y-axis direction. In this embodiment, the extending direction of the accommodation compartment S1 is substantially parallel to the X-axis direction and can be considered to extend along the length direction of the casing 11, but the present disclosure is not limited thereto. In other embodiments, the extending direction of the accommodation compartment in the casing may be substantially parallel to the Y-axis direction, which means that the accommodation compartment can extend along the width direction of the casing.

[0032] In this embodiment, the partition 112 is integrally formed with the main housing 111, but the present disclosure is not limited to the foregoing structural configuration. In other embodiments, the main housing, the partition, and the base may be integrally formed as a single casing.

[0033] In this embodiment, the four magnetic component assemblies 13 are respectively arranged in the four accommodation compartments S1. Further, each magnetic component assembly 13 includes at least four cubic magnetic components M1. In other words, each accommodation compartment S1 accommodates at least four cubic magnetic components M1. During assembly, the cubic magnetic components M1 are inserted into the accommodation compartment S1 through the opening H1. Further, the cubic magnetic components M1 are linearly arranged with different magnetization directions, whereby the magnetic field lines of the magnetic component assembly 13 are concentrated on one side.

[0034] Further, referring to FIGS. 3 and 4, FIG. 3 shows a schematic diagram of the magnetic field distribution formed by linearly arranging four cubic magnetic components with different magnetization directions, and FIG. 4 shows a schematic diagram of the magnetic field distribution formed by linearly arranging five cubic magnetic components with different magnetization directions. As shown in FIGS. 3 and 4, by linearly arranging the cubic magnetic components M1 with different magnetization directions, a ferromagnetic region can be formed on one surface of the cubic magnetic components M1, and a weak magnetic region can be formed on the other surface of the cubic magnetic components M1. A strong magnetic force can be generated in one acting direction (acting surface) with a small number of magnetic components, and the magnetic force per unit area can be increased. To linearly arrange cubic magnetic components with different magnetization directions, as shown in FIGS. 3 and 4, a plurality of cubic magnetic components having N poles and S poles are arranged in a specific pattern (for example, a Halbach array may be used). The number of the cubic magnetic components M1 in FIG. 3 or FIG. 4 is only provided as an example, and the present disclosure is not limited to a specific number as shown in FIGS. 3 and 4. In some embodiments of the present disclosure, each magnetic component assembly may include six or more cubic magnetic components. The aforementioned cubic magnetic components M1 may be, for example, magnets having N poles and S poles, but the present disclosure is not limited thereto.

[0035] Due to the above arrangement of the cubic magnetic components M1, the four magnetic component assemblies 13 form a ferromagnetic surface B1 and a diamagnetic surface B2 on the opposing faces of the casing 11. The ferromagnetic surface B1 is configured to attract magnetic substances in the sample within the sample container. Specifically, the ferromagnetic surface B1 is located on the surface of the main housing 111 farthest from the base 110, and the diamagnetic surface B2 is located on the surface of the base 110 farthest from the main housing 111.

[0036] In this embodiment, all of the cubic magnetic components M1 are cubes. In other words, each face of the cubic magnetic component M1 is a square. Note that the term "cube" may refer not only to a perfect cube but also to a rectangular parallelepiped whose shape approximates a perfect cube due to manufacturing tolerances.

[0037] In this embodiment, the cubic magnetic component M1 in one of the accommodation compartments S1 is offset with respect to the cubic magnetic component M1 in another adjacent one of the accommodation compartments S1, but the present disclosure is not limited thereto. In other embodiments, the cubic magnetic components in two adjacent accommodation compartments of the accommodation compartments may be arranged in alignment with each other.

[0038] In this embodiment, each two adjacent cubic magnetic components M1 within the same accommodation compartment S1 are in physical contact with each other, but the present disclosure is not limited thereto. In other embodiments, there may be a gap between each two adjacent cubic magnetic components. The distance between two adjacent cubic magnetic components within a single accommodation compartment can be controlled, for example, by restricting these cubic magnetic components using the wall surfaces at both ends of the accommodation compartment. For example, when the length of the accommodation compartment is substantially equal to the total length of the cubic magnetic components within the accommodation compartment, the wall surfaces at both ends of the accommodation compartment press against the outermost cubic magnetic components, and the cubic magnetic components within the accommodation compartment will be closely adjacent to each other. Conversely, when the length of the accommodation compartment is greater than the total length of the cubic magnetic components within the accommodation compartment, there may be a gap between two adjacent cubic magnetic components, for example, due to repulsive forces.

[0039] In this embodiment, the cubic magnetic component M1 is physically in contact with the inner peripheral surface of the accommodation section S1. By matching the shape of the cubic magnetic component M1 to the shape of the accommodation section S1, unexpected rotation of the cubic magnetic component M1 within the accommodation section S1 can be prevented, thereby ensuring a structural configuration in which the cubic magnetic components M1 are linearly arranged with different magnetization directions.

[0040] In the magnetic substance separation device 1 of this embodiment, the number of accommodation sections S1 is four, each accommodation section S1 houses 10 cubic magnetic components M1, the length of each side of each cubic magnetic component M1 is substantially 10 mm, and the thickness of each partition 112 is substantially 7.9 mm. Further, the thickness of the casing 11 on the ferromagnetic surface B1 is substantially 2.0 mm. In the above-described configuration, the ferromagnetic surface B1 formed by the magnetic component assembly 13 on the casing 11 can achieve a magnetic field strength of about 600 to 1000 gauss. Under the same conditions, in the conventional magnet arrangement, a magnetic field strength of only about 50 to 300 gauss can be formed on a single surface of the casing, which is significantly weaker than the magnetic field strength formed by the magnetic component assembly 13 on the ferromagnetic surface B1 of this embodiment. In the embodiment of the present disclosure, it can be seen that by linearly arranging cubic magnetic components with different magnetization directions, the magnetic force lines of the magnetic component assembly can be concentrated on one side, and the magnetic force per unit area can be increased with fewer magnetic components.

[0041] As an application example, a magnetic bead separation test during cell culture was performed using the magnetic substance separation device 1 of this embodiment. The initial added cell number and the number of magnetic beads were each 5×10 6 . After 14 days of co-culture, magnetic bead separation was performed using the magnetic substance separation device 1 of this embodiment. As a result, if the cell number is 1×10 6 , the number of residual magnetic beads can be reduced to less than 15, and further to less than 10, which meets the recommendation that the number of residual magnetic beads should be less than 30 (Reference: Journal of Hemotherapy, Volume 7, pp437 - 448, 1998).

[0042] According to the present disclosure, the size of the ferromagnetic surface in the magnetic substance separator can be designed to be equal to or larger than the surface area of the sample container according to actual requirements. For example, the size of the ferromagnetic surface can be adjusted by changing the number of accommodation compartments, the number of cubic magnetic components, the size of the cubic magnetic components, and / or the arrangement density of the cubic magnetic components.

[0043] <Second Embodiment> Please refer to FIG. 5, which is a perspective view of the magnetic substance separator and the sample container according to the second embodiment of the present disclosure.

[0044] The magnetic substance separator 1g provided in the second embodiment (corresponding to FIG. 5) is similar to the magnetic substance separator described in the above embodiment. The same or similar reference numerals indicate the same or similar components, and the functions and effects provided by these components are the same as those described above, so the description of this point will not be repeated here. Hereinafter, only the main differences between the magnetic substance separator 1g of the second embodiment and the magnetic substance separator of the above embodiment will be described.

[0045] In the second embodiment, the sample container 9g is, for example, a biocompatibility-certified flexible tube connected to a cell culture device (not shown), and the magnetic beads used during the culture process can be removed by the magnetic substance separator 1g. The cell culture device functioning as an automatic processing device can continuously input a sample into the flexible tube, whereby the sample flows through the flexible tube at a specific flow rate. When the sample passes through the magnetic component assembly 13g, the magnetic beads in the sample are attracted and retained in the flexible tube, while the sample after the magnetic beads are separated is output from the flexible tube and recovered. By this process, the magnetic substance separator 1g can perform automatic magnetic substance separation by effectively utilizing the automatic processing device, and can improve the efficiency of magnetic substance separation for the sample. Further, the automatic processing device can control the flow rate of the sample in the flexible tube in conjunction with the flow path length of the flexible tube, and can satisfy the required magnetic bead residue standard.

[0046] The holder 15g of the magnetic substance separator 1g is configured to fix a sample container (for example, a flexible tube) to the ferromagnetic surface B1 of the casing 11g.

[0047] Specifically, the holder 15g includes a cover 151g and a central post 153g. The cover 151g is disposed on the casing 11g via, for example, at least one positioning pin (not shown), and forms an accommodation space S2 between the cover 151g and the ferromagnetic surface B1. The cover 151g has a first through-hole G1 and a second through-hole G2 that reach the accommodation space S2. The central post 153g is disposed in the central region of the ferromagnetic surface B1 and is disposed so as to penetrate the cover 151g. The central post 153g has a winding groove (not shown) formed on its outer peripheral surface so that the sample container 9g can be wound around it. Further, the first through-hole G1 of the cover 151g is configured such that the sample container 9g passes through and extends into the accommodation space S2, the winding groove of the central post 153g is disposed in the accommodation space S2 and is configured such that the sample container 9g can be wound around it, and the second through-hole G2 of the cover 151g is configured such that the sample container 9g passes through and extends outside the accommodation space S2.

[0048] In the second embodiment, both the number of magnetic component assemblies 13g and the number of accommodation compartments S1 are 8. Each magnetic component assembly 13g includes 8 cubic magnetic components. The side length of each cubic magnetic component is substantially 10 mm. The number of partitions 112g disposed between two adjacent accommodation compartments S1 is 7, and the thickness of each partition 112g is substantially 4.8 mm. Further, the thickness of the casing 11g on the ferromagnetic surface B1 is 2.0 mm. With the above configuration, the ferromagnetic surface B1 formed by the magnetic component assemblies 13g on the casing 11g can achieve a magnetic field strength of about 3500 gauss. Under the same conditions, the conventional magnet arrangement can only form a magnetic field strength of about 50 to 300 gauss on one surface of the casing, which is significantly weaker than the magnetic field strength formed by the magnetic component assemblies 13g on the ferromagnetic surface B1 of this embodiment. In the embodiment of the present disclosure, it can be seen that by linearly arranging cubic magnetic components with different magnetization directions, the magnetic flux lines of the magnetic component assembly 13g can be concentrated on one side, and the magnetic force per unit area can be increased with fewer magnetic components.

[0049] As an application example, a magnetic bead separation test during cell culture was performed using the magnetic substance separation device 1g of this embodiment. The initial number of added cells and the number of magnetic beads were 5×10 6 respectively. After 14 days of co-culture, magnetic bead separation was performed using the magnetic substance separation device 1g of this embodiment. As a result, if the number of cells is 1×10 6 , the number of residual magnetic beads can be reduced to less than 15, and further less than 10, which meets the recommendation that the number of residual magnetic beads should be less than 30.

[0050] <Third Embodiment> Please refer to FIG. 6, which is a perspective view of the magnetic substance separation device according to the third embodiment of the present disclosure.

[0051] The magnetic substance separation device 1h according to the third embodiment (corresponding to FIG. 6) is similar to the magnetic substance separation device described in the above embodiment. The same or similar reference numerals indicate the same or similar components, and the functions and effects provided by these components are the same as those described above, so the description regarding this point will not be repeated. Hereinafter, only the main differences between the magnetic substance separation device 1h according to the third embodiment and the magnetic substance separation devices according to the above embodiments will be described.

[0052] In the third embodiment, the casing 11h is plate-shaped, and the accommodation compartment S1 is configured in a two-layer arrangement. Also, the magnetic component assemblies 13h respectively accommodated in the two-layer accommodation compartments S1 can form two ferromagnetic surfaces B1 on the casing 11h, and the two ferromagnetic surfaces B1 are located on the opposing surfaces of the casing 11h. Therefore, the total area of the ferromagnetic surfaces of the magnetic substance separation device can be increased.

[0053] In the third embodiment, both the number of magnetic component assemblies 13h and the number of accommodation compartments S1 are 14 (for example, 7 per layer). Each of the magnetic component assemblies 13h includes 12 cubic magnetic components, and the length of one side of each cubic magnetic component is substantially 10 mm. In the accommodation compartments S1 of the same layer, the thickness of each partition 112h arranged between two adjacent accommodation compartments S1 is substantially 1.5 mm. Further, the thickness of the casing 11h on the two ferromagnetic surfaces B1 is also substantially 1.5 mm. Under the above-described configuration, the two ferromagnetic surfaces B1 formed by the magnetic component assemblies 13h on the casing 11h can each achieve a magnetic field strength of approximately 4300 gauss. Under the same conditions, the conventional magnet arrangement can only form a magnetic field strength of approximately 50 to 300 gauss on the surface of the casing, which is significantly weaker than the magnetic field strength formed by the magnetic component assemblies 13h on the ferromagnetic surface B1 in this embodiment. In the embodiments of the present disclosure, it can be seen that by linearly arranging cubic magnetic components with different magnetization directions, the magnetic force lines of one magnetic component assembly can be concentrated on one side, and the magnetic force per unit area can be increased with fewer magnetic components.

[0054] In the third embodiment, the magnetic substance separator 1h may be suitable for a flexible tube that functions as a sample container (not shown), for example. For example, the sample container can be directly wound around the casing 11h such that at least a part of the tube corresponds to the two ferromagnetic surfaces B1.

[0055] As an application example, a magnetic bead separation test in a cell culture process was performed using the magnetic substance separator 1h of the present embodiment. The initial added cell number and the number of magnetic beads were 5×10 6 each. After 14 days of co-culture, magnetic bead separation was performed using the magnetic substance separator 1h of the present embodiment. As a result, if the cell number is 1×10 6 the number of residual magnetic beads can be reduced to less than 15, and further to less than 10, which meets the recommendation that the number of residual magnetic beads should be less than 30.

[0056] Furthermore, the extending direction of the accommodation section in the casing shown in the third embodiment is different from the extending direction of the accommodation section shown in the second embodiment. In the second embodiment, the accommodation section extends in a direction parallel to the Y-axis, while in the third embodiment, the accommodation section extends in a direction parallel to the X-axis. As a result, the magnetic component assemblies of these two embodiments exhibit different magnetic field distributions, but the present disclosure is not limited to the extending direction of the accommodation section within the casing. For example, the extending direction of the accommodation section within the casing in the second embodiment can be adjusted to be parallel to the X-axis based on actual design requirements, which means that the accommodation section may extend along the length direction of the casing. Similarly, the extending direction of the accommodation section within the casing in the third embodiment can be adjusted to be parallel to the Y-axis based on actual design requirements, which means that the accommodation section may extend along the width direction of the casing.

[0057] <Fourth Embodiment> Referring to FIGS. 7 and 8, FIG. 7 is a perspective view of a magnetic substance separator according to a fourth embodiment of the present disclosure, and FIG. 8 is an exploded perspective view of the magnetic substance separator shown in FIG. 7.

[0058] The magnetic substance separation device 1k provided in the fourth embodiment (corresponding to FIG. 7) is similar to the magnetic substance separation devices described in the above embodiments. The same or similar reference numerals indicate the same or similar components, and the functions and effects provided by these components are the same as those described above, so the description of this point will not be repeated here. Hereinafter, only the main differences between the magnetic substance separation device 1k according to the fourth embodiment and the magnetic substance separation devices according to the above embodiments will be described.

[0059] In the fourth embodiment, the casing 11k is cylindrical and has an outer peripheral surface K1. A housing compartment S1 is arranged in the vicinity of the outer peripheral surface K1, and a ferromagnetic surface B1 is arranged on the outer peripheral surface K1 of the casing 11k. That is, the magnetic component assembly 13k housed in the housing compartment S1 forms the ferromagnetic surface B1 on the outer peripheral surface K1 of the casing 11k.

[0060] In the fourth embodiment, the magnetic substance separation device 1k may be suitable for, for example, a flexible tube that functions as a sample container (not shown). Specifically, the holder 15k is a quick-release outer cover and includes a support base 155k and a plurality of extension arms 157k. The support base 155k is arranged to be detachable from the end face of the casing 11k, and the extension arms 157k are connected to the support base 155k and suspended above the ferromagnetic surface B1. Further, the extension arms 157k are configured such that a sample container (for example, a flexible tube) can be wound around them to fix the sample container on the ferromagnetic surface B1, but the present disclosure is not limited thereto. In other configurations, the magnetic substance separation device 1k may not include the holder (for example, a quick-release outer cover) 15k, and the sample container may be directly wound around the casing 11k and arranged on the ferromagnetic surface B1. In the above-described configuration, the ferromagnetic surface B1 formed by the magnetic component assembly 13k on the casing 11k can achieve a magnetic field strength of about 4300 gauss.

[0061] As an application example, a magnetic bead separation test during cell culture was performed using the magnetic substance separator 1k of the present embodiment. The initial number of added cells and the number of magnetic beads were each 5×10 6 respectively. After 14 days of co-culture, magnetic bead separation was performed using the magnetic substance separator 1k of the present embodiment. As a result, if the number of cells is 1×10 6 , the number of residual magnetic beads can be reduced to less than 15, and further to less than 10, which meets the recommendation that the number of residual magnetic beads should be less than 30.

[0062] <Fifth Embodiment> Referring to FIGS. 9 and 10, FIG. 9 is a perspective view of a magnetic substance separator according to the fifth embodiment of the present disclosure, and FIG. 10 is an exploded perspective view of the magnetic substance separator shown in FIG. 9.

[0063] The magnetic substance separator 1p provided in the fifth embodiment (corresponding to FIG. 9) is similar to the magnetic substance separators described in the above embodiments. The same or similar reference numerals indicate the same or similar components, and the functions and effects provided by these components are the same as those described above, so the description in this regard will not be repeated. Hereinafter, only the main differences between the magnetic substance separator 1p according to the fifth embodiment and the magnetic substance separators according to the above embodiments will be described.

[0064] In the fifth embodiment, the casing 11p is cylindrical and has an inner peripheral surface P1. A housing compartment S1 is arranged in the vicinity of the inner peripheral surface P1, and a ferromagnetic surface B1 is located on the inner peripheral surface P1 of the casing 11p. That is, the magnetic component assembly 13p housed in the housing compartment S1 forms a ferromagnetic surface B1 on the inner peripheral surface P1 of the casing 11p.

[0065] In the fifth embodiment, the magnetic substance separator 1p can be suitably used, for example, for a flexible tube (not shown) that functions as a sample container. Specifically, the holder 15p is a quick-release shaft that is arranged so as to be detachable from the accommodation space S3 formed by being surrounded by the inner peripheral surface P1. Further, the holder 15p is configured such that a sample container (for example, a flexible tube) can be wound around it, and at least a part of the sample container can be placed in the accommodation space S3 together with the holder 15p and fixed onto the ferromagnetic surface B1. In the above-described configuration, the ferromagnetic surface B1 formed by the magnetic component assembly 13p on the inner peripheral surface P1 of the casing 11p can achieve a magnetic field strength of about 4300 gauss.

[0066] As an application example, a magnetic bead separation test during cell culture was conducted using the magnetic substance separator 1p of the present embodiment. The initial added cell number and the number of magnetic beads were 5×10 6 respectively. After 14 days of co-culture, magnetic bead separation was performed using the magnetic substance separator 1p of the present embodiment. As a result, if the cell number is 1×10 6 , the number of residual magnetic beads can be reduced to less than 15, and further less than 10, which satisfies the recommendation that the number of residual magnetic beads should be less than 30.

[0067] As can be seen from the above-described first to fifth embodiments, the magnetic substance separator of the present disclosure can be configured in various ways, enabling the magnetic substance separator to adapt to different situations and sample requirements. Further, the magnetic substance separator is also suitable for use in an automatic sampling device, enabling batch automatic processing. Further, in an experiment conducted using an appropriate sample container, it has been demonstrated that when the cell number is 1×10 6 , the magnetic substance separator can satisfy the recommended number of residual magnetic beads of less than 30. Further, in these experiments, the cell loss rate was suppressed to about 10%, and the cell survival rate was maintained at 94.1% or more.

[0068] According to the magnetic substance separation device disclosed in the above embodiment, by arranging cubic magnetic components in a specific manner, a ferromagnetic surface can be formed on the casing, and the magnetic force per unit area can be increased with a small number of magnetic components. Furthermore, the magnetic substance separation device can be adjusted to adapt to different container shapes, and while meeting requirements such as efficiency, convenience, automation, biosafety, and biocompatibility, the efficiency of magnetic interaction can be enhanced.

[0069] It will be apparent to those skilled in the art that various modifications and variations can be made to the disclosed embodiments. The present specification and examples are intended to be considered as illustrative only, and the true scope of the present disclosure is indicated by the following claims and their equivalents.

Claims

1. A magnetic substance separation device configured to attract magnetic substances contained in a sample in a sample container, a casing having at least one accommodation compartment, and at least one magnetic component assembly disposed in the at least one accommodation compartment and including at least four cubic magnetic components, wherein the at least four cubic magnetic components are linearly arranged in different magnetization directions to allow the magnetic field lines of the at least one magnetic component assembly to concentrate on one side, whereby the at least one magnetic component assembly forms at least one ferromagnetic surface on the casing, and the at least one ferromagnetic surface is configured to attract the magnetic substances in the sample in the sample container. A magnetic substance separation device.

2. The magnetic substance separation device according to claim 1, wherein the at least four cubic magnetic components are arranged in a Halbach array.

3. The magnetic substance separation device according to claim 1, wherein the at least one magnetic component assembly further forms a diamagnetic surface on the casing, and the diamagnetic surface and the at least one ferromagnetic surface are located on opposite sides of the casing.

4. The magnetic substance separation device according to claim 1, wherein the at least one magnetic component assembly includes a plurality of magnetic component assemblies, the at least one accommodation compartment has a plurality of accommodation compartments, and the plurality of magnetic component assemblies are respectively arranged in the plurality of accommodation compartments.

5. The magnetic substance separation device according to claim 4, wherein the at least four cubic magnetic components in one of the plurality of accommodation compartments are aligned or offset with respect to the at least four cubic magnetic components in another one of the plurality of accommodation compartments.

6. The magnetic substance separation device according to claim 4, wherein two adjacent cubic magnetic components in the same accommodation compartment are physically in contact with each other.

7. The casing has a plurality of partitions, the plurality of partitions are respectively arranged between two adjacent accommodation compartments, the thickness of each of the plurality of partitions is in the range of 1.0 mm to 10.0 mm, and the thickness of the casing on the at least one ferromagnetic surface is in the range of 1.0 mm to 10.0 mm. The magnetic substance separation device according to claim 4.

8. The magnetic substance separation device according to claim 1, wherein the at least one magnetic component assembly is physically in contact with the inner peripheral surface of the at least one accommodation compartment.

9. The magnetic substance separation device according to claim 1, wherein the side length of each cubic magnetic component ranges from 1 mm to 15 mm.

10. The magnetic substance separation device according to claim 1, further comprising a holder disposed on the casing, the holder being configured to fix the sample container on the at least one ferromagnetic surface of the casing.

11. The magnetic substance separation device according to claim 10, wherein the holder includes a central post disposed in a central region of the at least one ferromagnetic surface, the sample container is a flexible tube, and the central post is configured such that the sample container can be wound around it.

12. The magnetic substance separation device according to claim 11, wherein the holder further has a cover disposed on the casing to form an accommodation space between the cover and the at least one ferromagnetic surface, the cover has a first through-hole and a second through-hole leading to the accommodation space, the central post is disposed to penetrate the cover, the central post has a winding groove, the first through-hole is configured such that the sample container passes through and extends into the accommodation space, the winding groove is located in the accommodation space and is configured such that the sample container can be wound around it, and the second through-hole is configured such that the sample container passes through and extends out of the accommodation space.

13. The at least one magnetic component assembly has a plurality of magnetic component assemblies, the at least one accommodation compartment has a plurality of accommodation compartments, and the plurality of magnetic component assemblies are respectively disposed in the plurality of accommodation compartments. The magnetic substance separation device according to claim 1, wherein the plurality of accommodation compartments are configured in a two-layer arrangement, the at least one ferromagnetic surface has two ferromagnetic surfaces, and the two ferromagnetic surfaces are disposed on opposite surfaces of the casing.

14. The magnetic substance separation device according to claim 13, wherein the casing is plate-shaped, the sample container is a flexible tube, and the casing is configured such that the sample container can be wound around it.

15. The casing is cylindrical, the casing has an outer peripheral surface, the at least one accommodation section is arranged in the vicinity of the outer peripheral surface, and the at least one ferromagnetic surface is arranged on the outer peripheral surface of the casing. The magnetic substance separation device according to claim 1.

16. The sample container is a flexible tube, and the casing is configured such that the sample container can be wound around it. The magnetic substance separation device according to claim 15.

17. Further comprising a holder, the holder is arranged on the casing, and the holder is configured to fix the sample container on the at least one ferromagnetic surface of the casing. The holder is a quick-release outer cover, the holder has a support base and at least one extension arm, the support base is arranged to be detachable from the end face of the casing, the at least one extension arm is connected to the support base and suspended above the at least one ferromagnetic surface, the sample container is a flexible tube, and the at least one extension arm is configured such that the sample container can be wound around it. The magnetic substance separation device according to claim 15.

18. The casing is cylindrical, the casing has an inner peripheral surface, the at least one accommodation section is arranged in the vicinity of the inner peripheral surface, and the at least one ferromagnetic surface is arranged on the inner peripheral surface of the casing. The magnetic substance separation device according to claim 1.

19. Further comprising a holder, the inner peripheral surface of the casing forms and surrounds an accommodation space, and the holder is configured to fix the sample container on the at least one ferromagnetic surface of the casing. The holder is a quick-release shaft, the holder is arranged to be detachable within the accommodation space, the sample container is a flexible tube, and the holder is configured such that the sample container can be wound around it. The magnetic substance separation device according to claim 18.

Citation Information

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