Magnetic substance separation device

Abstract

The invention discloses a magnetic substance separation device which is used for attracting magnetic substances in a sample in a sample container. The magnetic substance separation device comprises a shell part and at least one magnetic part group. The shell part is provided with at least one containing groove. The at least one magnetic piece set is arranged in the at least one containing groove, and the at least one magnetic piece set comprises at least four cubic magnetic pieces. Wherein the at least four cubic magnetic parts are linearly arranged in different magnetization directions, so that magnetic lines of force of the at least one magnetic part group are concentrated on a single side, and the at least one magnetic part group forms at least one strong magnetic surface on the shell part. And the at least one strong magnetic surface is used for attracting magnetic substances in a sample in the sample container.

Description

Technical Field

[0001] The present invention relates to a magnetic substance separation device, and particularly to a magnetic substance separation device in which magnetic components are linearly arranged in different magnetization directions. Background Art

[0002] Traditional magnetic substance separation experiments often face multiple challenges. First, there are significant differences in the magnetic force intensity of magnetic substances from different manufacturers, and the characteristics of biological samples (such as coating phenomena) will affect the effect of magnetic force, resulting in reduced separation efficiency. Second, the diversity of experimental containers makes it difficult to optimize the magnetic force. In addition, the relationship between magnetic force and distance also affects the separation effect. Existing magnetic separation devices often cannot balance efficiency, convenience, automation, biological safety, and biocompatibility, which limits the development of magnetic separation experiments.

[0003] Therefore, how to provide a magnetic separation device that can balance requirements such as efficiency, convenience, automation, biological safety, and biocompatibility, and can flexibly select suitable container shapes, surface materials, and surface treatment methods according to the characteristics of different samples is an urgent issue for researchers in this field to overcome. Summary of the Invention

[0004] The present invention aims to provide a magnetic substance separation device, which optimizes array magnets and adopts a strong magnetic force design, and can be adaptively adjusted for different container shapes, so as to improve the efficiency of magnetic force action and provide a more comprehensive and reliable solution for magnetic substance separation experiments.

[0005] The magnetic substance separation device disclosed in an embodiment of the present invention is used to attract magnetic substances in a sample in a sample container, and the magnetic substance separation device includes a housing member and at least one magnetic component group. The housing member has at least one accommodating groove. The at least one magnetic component group is disposed in the at least one accommodating groove, and the at least one magnetic component group includes at least four cubic magnetic components. Among them, the at least four cubic magnetic components are linearly arranged in different magnetization directions, so that the magnetic force lines of the at least one magnetic component group are concentrated on a single side, and thus at least one strong magnetic surface is formed on the housing member. The at least one strong magnetic surface is used to attract magnetic substances in the sample in the sample container.

[0006] According to the magnetic substance separation device disclosed in the above embodiment, by arranging the cubic magnetic components in a specific manner, a strong magnetic surface can be formed on the housing member, so as to provide a strong magnetic force per unit area with fewer magnetic components. In addition, the magnetic substance separation device can be adaptively adjusted for different container shapes to improve the efficiency of magnetic force action, so as to balance requirements such as efficiency, convenience, automation, biological safety, and biocompatibility.

[0007] The above description of the content of the present invention and the following description of the embodiments are used to demonstrate and explain the principles of the present invention and provide a further explanation of the scope of the patent application of the present invention. Description of the Drawings

[0008] Figure 1 A three-dimensional schematic diagram of the magnetic substance separation device according to the first embodiment of the present invention;

[0009] Figure 2 is Figure 1 A disassembled schematic diagram of the magnetic substance separation device of

[0010] Figure 3 A schematic diagram of the magnetic force distribution formed by linearly arranging four cube magnetic members in different magnetization directions;

[0011] Figure 4 A schematic diagram of the magnetic force distribution formed by linearly arranging five cube magnetic members in different magnetization directions;

[0012] Figure 5 A three-dimensional schematic diagram of the magnetic substance separation device and the sample container according to the second embodiment of the present invention;

[0013] Figure 6 A three-dimensional schematic diagram of the magnetic substance separation device according to the third embodiment of the present invention;

[0014] Figure 7 A three-dimensional schematic diagram of the magnetic substance separation device according to the fourth embodiment of the present invention;

[0015] Figure 8 is Figure 7 A disassembled schematic diagram of the magnetic substance separation device of

[0016] Figure 9 A three-dimensional schematic diagram of the magnetic substance separation device according to the fifth embodiment of the present invention;

[0017] Figure 10 is Figure 9 A disassembled schematic diagram of the magnetic substance separation device of

[0018] Symbol Description

[0019] 9g: Sample container

[0020] 1, 1g, 1h, 1k, 1p: Magnetic substance separation device

[0021] 11, 11g, 11h, 11k, 11p: Housing part

[0022] 110: Base

[0023] 111: Main housing

[0024] 112, 112g, 112h: Partition wall

[0025] 13, 13g, 13h, 13k, 13p: Magnetic component group

[0026] 15g, 15k, 15p: Fixing part

[0027] 151g: Upper cover

[0028] 153g: Middle column

[0029] 155k: Base

[0030] 157k: Extension arm

[0031] B1: Strong magnetic surface

[0032] B2: Weak magnetic surface

[0033] G1: First wire hole

[0034] G2: Second wire hole

[0035] H1: Through hole

[0036] K1: Outer ring surface

[0037] M1: Cubic magnetic component

[0038] P1: Inner ring surface

[0039] S1: Accommodating groove

[0040] S2, S3: Accommodating space Detailed implementation manner

[0041] The following details the detailed features and advantages of the embodiments of the present invention in the implementation manner. The content is sufficient for any person with ordinary knowledge in the art to understand the technical content of the embodiments of the present invention and implement it accordingly. And according to the content disclosed in this specification, the claims and the drawings, any person with ordinary knowledge in the art can easily understand the relevant purposes and advantages of the present invention. The following embodiments further illustrate the viewpoints of the present invention, but do not limit the scope of the present invention in any way.

[0042] It should be understood that the following description provides many different embodiments or examples for implementing different aspects of the present invention. The specific elements and arrangements described below are only for a simple description of the present invention, and these are only for illustrative purposes and not limitations of the present invention. The term "about" used in the present invention means including the stated value and values within an acceptable deviation range when those skilled in the art consider measurement problems and measurement errors (i.e., the limitations of the measurement system). For example, "about" can represent values within one or more standard deviations of the stated value or within ±5% of the stated value. The quantities given herein are approximate quantities, that is, the meaning of "about", "approximately", or "substantially" can still be implied without specifically stating "about", "approximately", or "substantially". Additionally, the expression "a to b" in the present invention means including values greater than or equal to a and less than or equal to b.

[0043] It can be understood that although terms such as "first", "second", "third", etc. may be used herein to describe various elements, regions, layers, and / or parts, these elements, regions, layers, and / or parts should not be limited by these terms, and these terms are only used to distinguish different elements, regions, layers, and / or parts. Therefore, a first element, region, layer, and / or part discussed below can be referred to as a second element, region, layer, and / or part without departing from the teachings of the embodiments of the present invention.

[0044] Embodiments of the present invention provide a magnetic substance separation device for attracting magnetic substances in a sample in a sample container to separate the sample from the magnetic substances, but not limited to separating the sample and the magnetic substances. In some embodiments, the magnetic substance separation device can also be used to separate substances adsorbed or linked to the magnetic substances, and whether this substance is to be retained or discarded depends on the experimental purpose.

[0045] The magnetic substance separation device disclosed in the present invention includes a housing member and at least one magnetic member group. The housing member has at least one accommodation groove, and the at least one magnetic member group is disposed in the at least one accommodation groove, and the at least one magnetic member group includes at least four cubic magnetic members. Among them, the at least four cubic magnetic members are linearly arranged in different magnetization directions, so that the magnetic field lines of the at least one magnetic member group are concentrated on a single side, thereby forming at least one strong magnetic surface on the housing member to attract magnetic substances in the sample in the sample container. The linear arrangement of the cubic magnetic members in different magnetization directions can mean that the magnetization direction of each cubic magnetic member rotates according to a certain rule. For example, the magnetization direction of each sequentially arranged cubic magnetic member rotates 90 degrees relative to the magnetization direction of the previous cubic magnetic member.

[0046] In one embodiment, the at least four cubic magnetic members are arranged in a Halbach array, for example.

[0047] In one embodiment, a weak magnetic surface can be further formed on the housing member by the magnetic member group, and the weak magnetic surface and the strong magnetic surface can be located on opposite two surfaces of the housing member. Additionally, it should be noted that in the embodiment where the housing member is plate-shaped, the strong magnetic surface is defined to be located on the reference plane formed by the X-axis and the Y-axis. Among them, the extending direction of the accommodating groove in the housing member can be parallel to the X-axis or parallel to the Y-axis, for example, so that the magnetic member group can have a more flexible configuration according to actual design requirements, but the present invention is not limited to the above-mentioned extending direction of the accommodating groove in the housing member.

[0048] In one embodiment, the at least one magnetic member group can include a plurality of magnetic member groups, the at least one accommodating groove can include a plurality of accommodating grooves, and these magnetic member groups are respectively disposed in these accommodating grooves. That is to say, the number of magnetic member groups can be multiple groups, and the number of accommodating grooves can be multiple. Among them, the number of magnetic member groups can correspond to the number of accommodating grooves, so that these magnetic member groups can be respectively disposed in these accommodating grooves. In addition, the cubic magnetic members located in one accommodating groove and the cubic magnetic members located in another accommodating groove can be aligned with each other, but the present invention is not limited thereto. In other embodiments, the cubic magnetic members located in one accommodating groove and the cubic magnetic members located in another accommodating groove can be offset from each other.

[0049] In one embodiment, any two adjacent cubic magnetic members located in the same accommodating groove can be in physical contact with each other, but the present invention is not limited thereto. In other embodiments, there can be a gap between any two adjacent cubic magnetic members located in the same accommodating groove, and the gap is greater than 0 millimeter (mm) and less than or equal to 2.0 millimeters, for example.

[0050] In the embodiment where the number of accommodating grooves is multiple, the housing member can have a plurality of partition walls, and these partition walls are disposed between any two adjacent accommodating grooves. In other words, these partition walls of the housing member can divide the internal space of the housing member into a plurality of accommodating grooves to respectively accommodate these magnetic member groups. Among them, the thickness of each partition wall can be any value from 1.0 millimeter to 10.0 millimeters. Preferably, the thickness of each partition wall can be any value from 1.5 millimeters to 7.9 millimeters. For example, in one embodiment, the thickness of the partition wall of the housing member can be substantially 1.5 millimeters; in another embodiment, the thickness of the partition wall of the housing member can be substantially 1.8 millimeters; in yet another embodiment, the thickness of the partition wall of the housing member can be substantially 4.8 millimeters; in still another embodiment, the thickness of the partition wall of the housing member can be substantially 7.9 millimeters.

[0051] According to the magnetic substance separation device disclosed by the present invention, the thickness of the housing part at the strong magnetic surface can be any value between 1.0 mm and 2.0 mm. For example, in one embodiment, the thickness of the housing part at the strong magnetic surface can be substantially 1.0 mm; in another embodiment, the thickness of the housing part at the strong magnetic surface can be substantially 1.5 mm; in yet another embodiment, the thickness of the housing part at the strong magnetic surface can be substantially 1.8 mm; in still another embodiment, the thickness of the housing part at the strong magnetic surface can be substantially 2.0 mm.

[0052] In one embodiment, the magnetic member group can be in physical contact with the inner peripheral surface of the receiving groove, but the present invention is not limited thereto. In other embodiments, there can be a gap between the magnetic member group and at least one surface of the inner peripheral surface of the receiving groove.

[0053] According to the magnetic substance separation device disclosed by the present invention, the side length of each cubic magnetic member can be any value between 1 mm and 15 mm. Preferably, the side length of each cubic magnetic member can be any value between 3 mm and 10 mm. For example, in one embodiment, the side length of the cubic magnetic members of the magnetic member group can be substantially 3 mm; in another embodiment, the side length of the cubic magnetic members of the magnetic member group can be substantially 5 mm; in yet another embodiment, the side length of the cubic magnetic members of the magnetic member group can be substantially 10 mm.

[0054] In one embodiment, the magnetic substance separation device can further include a fixing member disposed on the housing part for fixing the sample container on the strong magnetic surface of the housing part.

[0055] In the embodiment where the magnetic substance separation device has a fixing member, the fixing member can include a middle column, and the sample container can be a flexible pipe fitting. Among them, the middle column can be disposed in the central area of the strong magnetic surface for the sample container to wind around. In some embodiments, the fixing member can further include an upper cover, and the upper cover is disposed on the housing part and forms a receiving space with the strong magnetic surface. Moreover, the upper cover can have a first wire passing hole and a second wire passing hole communicating with the receiving space, and the middle column can pass through the upper cover and have a wire groove. Among them, the first wire passing hole of the upper cover is used for the sample container to pass through and extend into the receiving space, the wire groove of the middle column is located in the receiving space and is used for the sample container to wind around, and the second wire passing hole of the upper cover is used for the sample container to pass through and extend out of the receiving space.

[0056] According to the magnetic substance separation device disclosed in the present invention, in an embodiment where the sample container is a flexible pipe fitting, it can be connected to an automated operation device (such as a cell culture device) through the flexible pipe fitting, so that the magnetic substance separation device can continuously and automatically remove magnetic substances (such as magnetic beads) used in the culture process. For example, the automated operation device can continuously input a sample into the flexible pipe fitting, causing the sample to flow through the flexible pipe fitting at a specific flow rate. After the magnetic component group attracts the magnetic beads in the sample, the magnetic beads will adsorb and stay in the flexible pipe fitting, while the sample from which the magnetic beads have been separated is output and collected from the flexible pipe fitting. Thus, the magnetic substance separation device can effectively utilize the automated operation device to implement the automation of magnetic substance separation, so as to improve the efficiency of separating magnetic substances from the sample. In addition, the flow rate of the sample in the flexible pipe fitting can be controlled by the automated operation device, and combined with the flow path length of the flexible pipe fitting, to meet the required standard of the residual amount of magnetic beads.

[0057] In an embodiment where the number of the magnetic component groups and the number of the accommodating grooves are both multiple, these accommodating grooves can be arranged in a double layer, so that these magnetic component groups accommodated in the two layers of accommodating grooves can form two strong magnetic surfaces on the housing member, and these two strong magnetic surfaces can be located on the opposite two surfaces of the housing member. However, the present invention is not limited to the foregoing number. For example, in other embodiments, the accommodating grooves can be arranged in three or more rows, and these three or more rows of accommodating grooves are respectively arranged adjacent to different surfaces of the housing member, so that the magnetic component groups accommodated in these accommodating grooves can form three or more strong magnetic surfaces on the housing member.

[0058] In one embodiment, the housing member can be plate-shaped, and the sample container can be, for example, a flexible pipe fitting. Among them, the housing member can be used for the sample container (flexible pipe fitting) to wind around, so that the sample container (flexible pipe fitting) is at least partially located on the strong magnetic surface.

[0059] In one embodiment, the housing member can be columnar and have an outer ring surface, and the accommodating groove can be arranged adjacent to the outer ring surface, so that the strong magnetic surface can be located on the outer ring surface of the housing member. In this configuration, the sample container can be, for example, a flexible pipe fitting, and the housing member can be used for the sample container (flexible pipe fitting) to wind around, so that the sample container (flexible pipe fitting) winds around the outer ring surface (strong magnetic surface). In addition, in an embodiment where the housing member is columnar and has an outer ring surface, the magnetic substance separation device can further include a fixing member arranged on the housing member for fixing the sample container on the strong magnetic surface of the housing member. Among them, the fixing member can be a quick-release outer cover and include a base and at least one extension arm. The base is detachably arranged on one end surface of the housing member, and the extension arm is connected to the base and suspended above the strong magnetic surface for the sample container (such as a flexible pipe fitting) to wind around.

[0060] In one embodiment, the housing member may be cylindrical and have an inner annular surface, and the accommodating groove may be disposed adjacent to the inner annular surface such that the strong magnetic surface may be located on the inner annular surface of the housing member. Additionally, in the embodiment where the housing member is cylindrical and has an inner annular surface, the magnetic substance separation device may further include a fixing member. The inner annular surface of the housing member may surround to form an accommodating space, and the fixing member may be used to fix the sample container to the strong magnetic surface of the housing member. For example, the sample container may be a flexible pipe fitting, and the fixing member may be a quick-release shaft member and be detachably disposed in the accommodating space for the sample container (flexible pipe fitting) to wind around.

[0061] <First Embodiment>

[0062] Please refer to Figure 1 and Figure 2 , wherein Figure 1 is a three-dimensional schematic diagram of the magnetic substance separation device according to the first embodiment of the present invention, and Figure 2 is Figure 1 a disassembled schematic diagram of the magnetic substance separation device.

[0063] The magnetic substance separation device 1 of the present embodiment is used to attract magnetic substances in a sample in a sample container (not shown). The magnetic substance separation device 1 includes a housing member 11 and a plurality of magnetic member groups 13.

[0064] The housing member 11 of the present embodiment has four accommodating grooves S1, and these four accommodating grooves S1 are parallel to each other. Specifically, the housing member 11 includes a main housing 111, three partition walls 112, and a base 110. The three partition walls 112 are disposed on the main housing 111 to form four elongated grooves arranged in parallel on the main housing 111, and the base 110 is fixed to the main housing 111, for example, by (but not limited to) screws to jointly form these four accommodating grooves S1 with the main housing 111 and the partition walls 112. Among them, these partition walls 112 are disposed between any two adjacent accommodating grooves S1. In addition, the base 110 has four through holes H1, and these four through holes H1 respectively communicate with these four accommodating grooves S1 for the magnetic member groups 13 to be inserted into the accommodating grooves S1 via the through holes H1.

[0065] As Figure 1 shown, the length direction and width direction of the housing member 11 respectively correspond to the X-axis direction and the Y-axis direction. In the present embodiment, the extending direction of the accommodating groove S1 in the housing member 11 is substantially parallel to the X-axis, which can be regarded as extending along the length direction of the housing member 11, but the present invention is not limited thereto. In other embodiments, the extending direction of the accommodating groove in the housing member may be substantially parallel to the Y-axis, that is, it may be along the width direction of the housing member.

[0066] In this embodiment, the partition wall 112 is integrally formed on the main housing 111. However, the present invention is not limited to the foregoing structural configuration. In other embodiments, the main housing, the partition wall, and the base may be integrally formed as a housing member.

[0067] In this embodiment, these four magnetic member groups 13 are respectively disposed in these four receiving grooves S1. Among them, each magnetic member group 13 includes at least four cubic magnetic members M1. That is to say, at least four cubic magnetic members M1 are received in each receiving groove S1. During assembly, these cubic magnetic members M1 are placed into these receiving grooves S1 through these through holes H1. Among them, these cubic magnetic members M1 are linearly arranged with different magnetization directions, so that the magnetic lines of force of the magnetic member group 13 are concentrated on a single side.

[0068] Please further refer to Figure 3 and Figure 4 , Figure 3 which shows a schematic diagram of the magnetic force distribution formed by linearly arranging four cubic magnetic members with different magnetization directions, and Figure 4 which shows a schematic diagram of the magnetic force distribution formed by linearly arranging five cubic magnetic members with different magnetization directions. As shown in Figure 3 and Figure 4 , by linearly arranging these cubic magnetic members M1 with different magnetization directions, a strong magnetic region can be formed on one side of these cubic magnetic members M1, and a weak magnetic region can be formed on the other side of these cubic magnetic members M1, so as to generate a strong magnetic force in a single acting direction (acting surface) with fewer magnetic members, that is, a stronger magnetic force can be provided per unit area. The linear arrangement of the cubic magnetic members with different magnetization directions is to arrange a number of cubic magnetic members having N poles and S poles in a specific manner (which can be, for example, a Halbach array arrangement), which is, for example, Figure 3 and Figure 4 the arrangement shown. Figure 3 and Figure 4 The number of the cubic magnetic members M1 in Figure 3 and Figure 4 is only an example, and the present invention is not limited to the number of the cubic magnetic members M1 in

[0069] In some embodiments of the present invention, each magnetic member group may also include, for example, six or more cubic magnetic members. The cubic magnetic member M1 may be, for example, a magnet having N poles and S poles, but the present invention is not limited thereto.

[0070] In this embodiment, these cubic magnetic members M1 are all regular cubes. That is to say, each face of these cubic magnetic members M1 is a square. It should be noted that the "cube" can refer to a regular cube and a cuboid whose shape is close to a regular cube due to manufacturing errors, for example.

[0071] In this embodiment, these cubic magnetic members M1 located in one of the receiving grooves S1 and these cubic magnetic members M1 located in the adjacent receiving grooves S1 are arranged in a staggered manner with respect to each other, but the present invention is not limited thereto. In other embodiments, these cubic magnetic members in any two adjacent receiving grooves can be arranged to be aligned with each other.

[0072] In this embodiment, any two adjacent cubic magnetic members M1 located in the same receiving groove S1 are in physical contact with each other, but the present invention is not limited thereto. In other embodiments, there may be a gap between any two adjacent cubic magnetic members. The distance between the cubic magnetic members in a single receiving groove can be controlled, for example, by limiting these cubic magnetic members by the walls at both ends of the receiving groove. For example, when the length of the receiving groove is substantially equal to the total length of the cubic magnetic members in the receiving groove, the walls at both ends of the receiving groove will abut against the outermost cubic magnetic members, causing these cubic magnetic members to be close to each other. When the length of the receiving groove is greater than the total length of the cubic magnetic members in the receiving groove, these cubic magnetic members may have a gap due to repulsive force, for example.

[0073] In this embodiment, these cubic magnetic members M1 are in physical contact with the inner peripheral surface of the receiving groove S1. Thus, by making the shape of the cubic magnetic member M1 match the shape of the receiving groove S1, unexpected rotation of the cubic magnetic member M1 in the receiving groove S1 can be avoided, thereby ensuring the structural configuration in which the cubic magnetic members M1 are linearly arranged in different magnetization directions.

[0074] In the magnetic material separation device 1 of the present embodiment, the number of the containing slots S1 is four, and each containing slot S1 contains ten cubic magnetic parts M1, the side length of each cubic magnetic part M1 is substantially 10 mm, and the thickness of each partition wall 112 is substantially 7.9 mm. In addition, the shell thickness of the shell part 11 at the strong magnetic surface B1 is substantially 2.0 mm. Under the aforementioned configuration, the strong magnetic surface B1 formed by the magnetic component group 13 on the shell part 11 can have a magnetic field strength of about 600 Gauss to 1000 Gauss. Under the same configuration conditions as the aforementioned, the magnetic field strength generated by the traditional magnet arrangement method on a single surface of the shell part is only about 50 Gauss to 300 Gauss, which is significantly less than the magnetic field strength generated by the magnetic component group 13 on the strong magnetic surface B1 of the present embodiment. It can be seen that the present invention arranges the cubic magnetic parts linearly in different magnetization directions so that the magnetic lines of force of the magnetic component group are concentrated on a single side, so that fewer magnetic parts can be used to provide a stronger magnetic force per unit area.

[0075] In terms of application, during the cell culture process, the magnetic substance separation device 1 of this embodiment is used to perform a magnetic bead separation test. The number of cells and magnetic beads initially added is 5×10 6 After 14 days of co-culture, magnetic beads were separated using the magnetic material separation device 1 of this embodiment. The results showed that at 1×10 6 Under the condition of low cell count, the residual magnetic beads can be less than 15 or even less than 10, which is in line with the recommendation that the residual magnetic beads should be less than 30 (reference: JOURNAL OF HEMATOTHERAPY 7:437-448 (1998)).

[0076] The area of ​​the strong magnetic surface of the magnetic substance separation device of the present invention can be designed to be greater than or equal to the surface area of ​​the sample container according to actual needs. For example, the area of ​​the strong magnetic surface can be changed by adjusting the number of accommodating slots, the number of cubic magnetic elements, the size of the cubic magnetic elements, and / or the density of the arrangement of the cubic magnetic elements.

[0077] <Second Embodiment>

[0078] See also Figure 5 , which is a three-dimensional schematic diagram of a magnetic substance separation device and a sample container according to a second embodiment of the present invention.

[0079] Second embodiment (corresponding to Figure 5 ) is similar to the magnetic substance separation device of the previous embodiment, and the same or similar reference numerals are used to represent the same or similar elements. The functions and effects of the same or similar elements are the same as those described above, and will not be described in detail here. The following only describes the main differences between the magnetic substance separation device 1g of the second embodiment and the magnetic substance separation device of the previous embodiment.

[0080] In the second embodiment, the sample container 9g is a flexible pipe fitting certified for biocompatibility and is connected, for example, to a cell culture device (not shown), so that the magnetic substance separation device 1g can remove the magnetic beads used in the culture process. Among them, automated operation devices such as cell culture devices can continuously input samples into the flexible pipe fitting, causing the samples to flow through the flexible pipe fitting at a specific flow rate. After the magnetic bead group 13g attracts the magnetic beads in the samples, the magnetic beads will be adsorbed and stay in the flexible pipe fitting, while the samples from which the magnetic beads have been separated are output and collected from the flexible pipe fitting. Thus, the magnetic substance separation device 1g can effectively utilize the automated operation device to implement the magnetic substance separation automatically, so as to improve the efficiency of separating magnetic substances from samples. In addition, the flow rate of the samples in the flexible pipe fitting can be controlled by the automated operation device, in cooperation with the flow path length of the flexible pipe fitting, to meet the required standard of the remaining amount of magnetic beads.

[0081] The fixing member 15g of the magnetic substance separation device 1g is used to fix the sample container (flexible pipe fitting) on the strong magnetic surface B1 of the housing member 11g.

[0082] Specifically, the fixing member 15g includes an upper cover 151g and a middle column 153g. The upper cover 151g is arranged on the housing member 11g through at least one positioning pin (not shown) and forms an accommodating space S2 between it and the strong magnetic surface B1. The upper cover 151g has a first wire passing hole G1 and a second wire passing hole G2 that communicate with the accommodating space S2. The middle column 153g is arranged in the central area of the strong magnetic surface B1 and penetrates the upper cover 151g. The middle column 153g has a wire groove (not separately labeled) on its circumferential surface for the sample container 9g to wind around. Among them, the first wire passing hole G1 of the upper cover 151g is used for the sample container 9g to pass through and extend into the accommodating space S2. The wire groove of the middle column 153g is located in the accommodating space S2 and is used for the sample container 9g to wind around. The second wire passing hole G2 of the upper cover 151g is used for the sample container 9g to pass through and extend out of the accommodating space S2.

[0083] In the second embodiment, both the number of the magnetic member groups 13g and the number of the receiving grooves S1 are eight. Each magnetic member group 13g includes eight cubic magnetic members, and the side length of each cubic magnetic member is substantially 10 millimeters. The number of the partition walls 112g between any two adjacent receiving grooves S1 is seven, and the thickness of each partition wall 112g is substantially 4.8 millimeters. In addition, the thickness of the housing member 11g at the strong magnetic surface B1 is substantially 2.0 millimeters. Under the foregoing configuration, the strong magnetic surface B1 formed by the magnetic member groups 13g on the housing member 11g can have a magnetic field strength of about 3500 gauss. Under the same configuration conditions as the foregoing, the magnetic field strength generated by the conventional magnet arrangement on a single surface of the housing member is only about 50 gauss to 300 gauss, which is significantly less than the magnetic field strength generated by the magnetic member groups 13g of this embodiment on the strong magnetic surface B1. Thus, it can be seen that the present invention linearly arranges the cubic magnetic members in different magnetization directions, so that the magnetic force lines of the magnetic member groups 13g are concentrated on a single side, so that a smaller number of magnetic members can provide a stronger magnetic force per unit area.

[0084] In terms of application, during the cell culture process, a magnetic bead separation test is performed using the magnetic substance separation device 1g of this embodiment. The number of initially added cells and magnetic beads is both 5×10 6 , and after a total culture for 14 days, the magnetic bead separation is performed using the magnetic substance separation device 1g of this embodiment. The results show that at 1×10 6 cell number, the magnetic bead residue amount can also be less than 15, or even less than 10, meeting the recommendation that the magnetic bead residue amount should be less than 30.

[0085] <Third Embodiment>

[0086] Please refer to Figure 6 , which is a three-dimensional schematic diagram of the magnetic substance separation device according to the third embodiment of the present invention.

[0087] The magnetic substance separation device 1h of the third embodiment (corresponding to Figure 6 ) is similar to the magnetic substance separation device of the foregoing embodiment, and the same or similar components are denoted by the same or similar reference numerals. The functions and effects of the same or similar components are the same as those of the foregoing, and will not be described herein again. The following only describes the main differences between the magnetic substance separation device 1h of the third embodiment and the magnetic substance separation device of the foregoing embodiment.

[0088] In the third embodiment, the housing member 11h is plate-shaped, and the receiving groove S1 is in a double-layer configuration. Among them, the magnetic member groups 13h in these two layers of receiving grooves S1 respectively form two strong magnetic surfaces B1 on the housing member 11h, and these two strong magnetic surfaces B1 are located on the opposite two surfaces of the housing member 11h. Thus, the total area of the strong magnetic surfaces of the magnetic substance separation device can be increased.

[0089] In the third embodiment, the number of magnetic component groups 13h and the number of receiving slots S1 are both fourteen (e.g., seven in each layer). Each magnetic component group 13h includes twelve cubic magnetic components, and the side length of each cubic magnetic component is substantially 10 mm. In the same layer of receiving slots S1, the thickness of the partition wall 112h between any two adjacent receiving slots S1 is substantially 1.5 mm. In addition, the shell thickness of the shell member 11h at the two strong magnetic surfaces B1 is also substantially 1.5 mm. Under the aforementioned configuration, the two strong magnetic surfaces B1 formed by the magnetic component group 13h on the shell member 11h can have a magnetic field strength of about 4300 Gauss. Under the same configuration conditions as the aforementioned, the magnetic field strength generated on the surface of the shell member by the conventional magnet arrangement method is only about 50 Gauss to 300 Gauss, which is significantly smaller than the magnetic field strength generated by the magnetic component group 13h on the strong magnetic surface B1 of this embodiment. It can be seen that the present invention arranges cubic magnetic components linearly in different magnetization directions so that the magnetic force lines of the magnetic component group are concentrated on a single side, thereby using fewer magnetic components to provide a stronger magnetic force per unit area.

[0090] The magnetic substance separation device 1h of the third embodiment can be applied to a sample container (not shown) of a flexible tube. For example, the sample container can be directly wound around the housing 11h and at least part of the tube corresponds to the two strong magnetic surfaces B1.

[0091] In terms of application, during the cell culture process, the magnetic material separation device of this embodiment was used to perform a magnetic bead separation test for 1 h. The number of cells and magnetic beads added initially was 5×10 6 After 14 days of co-culture, magnetic beads were separated using the magnetic material separation device of this embodiment for 1 hour. The results showed that at 1×10 6 At a low cell count, the residual magnetic beads can be less than 15 or even less than 10, which is in line with the recommendation that the residual magnetic beads should be less than 30.

[0092] In addition, the extension direction of the receiving groove of the third embodiment in the shell member is different from the extension direction of the receiving groove of the second embodiment in the shell member, wherein the receiving groove of the second embodiment extends in a direction parallel to the Y axis, while the receiving groove of the third embodiment extends in a direction parallel to the X axis, so that the magnetic component groups in the two embodiments have different magnetic force distributions from each other, but the present invention is not limited to the extension direction of the receiving groove in the shell member. For example, the extension direction of the receiving groove of the second embodiment in the shell member can also be changed to be configured to be parallel to the X axis according to actual design requirements, that is, the receiving groove can, for example, extend along the length direction of the shell member. For another example, the extension direction of the receiving groove of the third embodiment in the shell member can also be changed to be configured to be parallel to the Y axis according to actual design requirements, that is, the receiving groove can, for example, extend along the width direction of the shell member.

[0093] <Fourth Embodiment>

[0094] Please refer to Figure 7 and Figure 8 , wherein Figure 7 is a three-dimensional schematic diagram of the magnetic substance separation device according to the fourth embodiment of the present invention, and Figure 8 is Figure 7 a disassembled schematic diagram of the magnetic substance separation device of

[0095] The magnetic substance separation device 1k of the fourth embodiment (corresponding to Figure 7 ) is similar to the magnetic substance separation device of the foregoing embodiment, and the same or similar elements are denoted by the same or similar reference numerals. The functions and effects of the same or similar elements are the same as those of the foregoing, and will not be described herein again. The following only describes the main differences between the magnetic substance separation device 1k of the fourth embodiment and the magnetic substance separation device of the foregoing embodiment.

[0096] In the fourth embodiment, the housing member 11k is columnar, and the housing member 11k has an outer ring surface K1. The accommodation groove S1 is disposed adjacent to the outer ring surface K1, and the strong magnetic surface B1 is located on the outer ring surface K1 of the housing member 11k. That is, the magnetic member group 13k in these accommodation grooves S1 forms the strong magnetic surface B1 on the outer ring surface K1 of the housing member 11k.

[0097] The magnetic substance separation device 1k of the fourth embodiment can be applied to a sample container (not shown separately) of a flexible pipe fitting, for example. Specifically, the fixing member 15k is a quick-release outer cover, including a base 155k and a plurality of extending arms 157k. The base 155k is detachably disposed on one end surface of the housing member 11k, and these extending arms 157k are connected to the base 155k and suspended above the strong magnetic surface B1. Among them, the extending arms 157k are used for the sample container (flexible pipe fitting) to wind around to fix the sample container on the strong magnetic surface B1, but the present invention is not limited thereto. In other embodiments, the magnetic substance separation device 1k may not include the fixing member (quick-release outer cover) 15k, and the sample container can be directly wound around the housing member 11k and located on the strong magnetic surface B1. Under the foregoing configuration, the strong magnetic surface B1 formed by the magnetic member group 13k on the housing member 11k can have a magnetic field intensity of about 4300 gauss.

[0098] In terms of application, during the cell culture process, the magnetic bead separation test is performed using the magnetic substance separation device 1k of this embodiment. Among them, the initial number of added cells and the number of magnetic beads are both 5×10 6 . After co-culturing for 14 days, the magnetic bead separation is performed using the magnetic substance separation device 1k of this embodiment. The results show that at a cell number of 1×10 6 , the magnetic bead residue amount can reach less than 15, or even less than 10, meeting the recommendation that the magnetic bead residue amount should be less than 30.

[0099] <The Fifth Embodiment>

[0100] Please refer to Figure 9 and Figure 10 wherein Figure 9 is a three-dimensional schematic diagram of a magnetic substance separation device according to the fifth embodiment of the present invention, and Figure 10 is Figure 9 a disassembled schematic diagram of the magnetic substance separation device.

[0101] The magnetic substance separation device 1p of the fifth embodiment (corresponding to Figure 9 ) is similar to the magnetic substance separation device of the foregoing embodiment, and the same or similar elements are denoted by the same or similar reference numerals. The functions and effects of the same or similar elements are the same as those of the foregoing, and will not be described herein again. The following only describes the main differences between the magnetic substance separation device 1p of the fifth embodiment and the magnetic substance separation device of the foregoing embodiment.

[0102] In the fifth embodiment, the housing member 11p is columnar, and the housing member 11p has an inner ring surface P1. The accommodation groove S1 is disposed adjacent to the inner ring surface P1, and the strong magnetic surface B1 is located on the inner ring surface P1 of the housing member 11p. That is, the magnetic member group 13p in these accommodation grooves S1 forms the strong magnetic surface B1 on the inner ring surface P1 of the housing member 11p.

[0103] The magnetic substance separation device 1p of the fifth embodiment can be applied to, for example, a sample container (not shown separately) of a flexible pipe fitting. Specifically, the fixing member 15p is a quick-release shaft member, which is detachably disposed in an accommodation space S3 formed by surrounding the inner ring surface P1. Among them, the fixing member 15p is used for winding the sample container (flexible pipe fitting), so that at least a part of the sample container can be placed in the accommodation space S3 together with the fixing member 15p and fixed on the strong magnetic surface B1. Under the foregoing configuration, the strong magnetic surface B1 formed by the magnetic member group 13p on the inner ring surface P1 of the housing member 11p can have a magnetic field strength of about 4300 gauss.

[0104] In terms of application, during cell culture, a magnetic bead separation test is performed using the magnetic substance separation device 1p of this embodiment. The initial number of added cells and magnetic beads is both 5×10 6 . After 14 days of co-culture, magnetic bead separation is performed using the magnetic substance separation device 1p of this embodiment. The results show that at a cell number of 1×10 6 , the magnetic bead residue amount can reach less than 15, or even less than 10, meeting the recommendation that the magnetic bead residue amount should be less than 30.

[0105] As can be seen from the above first to fifth embodiments, the magnetic substance separation device of the present invention can have different configurations, so as to be adapted to the needs of different scenarios and samples, and is conducive to being applied to an automated sampling machine, and can be batch-processed automatically. In addition, by conducting experiments with suitable sample containers, the results show that at a cell number of 1×10 6 the magnetic substance separation device of the present invention can meet the recommendation that the residual amount of magnetic beads should be less than 30. Further, in these experiments, the cell loss rate can be controlled at about 10%, and the cell viability is higher than 94.1%.

[0106] According to the magnetic substance separation device of the above embodiment, by arranging the cubic magnetic members in a specific manner, a strong magnetic surface can be formed on the housing member, so as to provide a stronger magnetic force per unit area with fewer magnetic members. In addition, the magnetic substance separation device can be adaptively adjusted according to different container shapes to improve the efficiency of the magnetic force action, so as to take into account requirements such as efficiency, convenience, automation, biosafety, and biocompatibility.

Claims

1. A magnetic substance separation device for attracting magnetic substances in a sample in a sample container, the magnetic substance separation device comprising: The housing has at least one receiving groove; and At least one magnetic component set is disposed in the at least one receiving groove, and the at least one magnetic component set includes at least four cubic magnetic components; in, The at least four cubic magnetic parts are arranged linearly with different magnetization directions, so that the magnetic lines of force of the at least one magnetic part group are concentrated on a single side, so that the at least one magnetic part group forms at least one strong magnetic surface on the shell part, and the at least one strong magnetic surface is used to attract the magnetic substance in the sample in the sample container. 2 . The magnetic material separation device as claimed in claim 1 , wherein the at least four cubic magnetic elements are arranged in a Halbach array.

3. The magnetic material separation device as described in claim 1, wherein the at least one magnetic component group further forms a weak magnetic surface on the shell component, and the weak magnetic surface and the at least one strong magnetic surface are located on two opposite surfaces of the shell component. 4 . The magnetic material separation device as described in claim 1 , wherein the at least one magnetic component group includes a plurality of magnetic component groups, the at least one receiving groove includes a plurality of receiving grooves, and the magnetic component groups are respectively disposed in the receiving grooves. 5 . The magnetic material separation device as claimed in claim 4 , wherein the at least four cubic magnetic members located in one receiving groove thereof and the at least four cubic magnetic members located in another receiving groove are arranged in alignment or staggered with each other. 6 . The magnetic material separation device as claimed in claim 4 , wherein any two adjacent cubic magnetic members located in the same receiving groove are in physical contact with each other.

7. A magnetic material separation device as described in claim 4, wherein the shell member has a plurality of partition walls, the partition walls are arranged between any two adjacent accommodating grooves, the thickness of each partition wall is 1.0 mm to 10.0 mm, and the shell thickness of the shell member at the strong magnetic surface is 1.0 mm to 10.0 mm. 8 . The magnetic material separation device as claimed in claim 1 , wherein the at least one magnetic component set is in physical contact with the inner circumference of the at least one receiving groove. 9 . The magnetic material separation device as claimed in claim 1 , wherein the side length of each of the cubic magnetic members is 1 mm to 15 mm. 10 . The magnetic substance separation device as claimed in claim 1 , further comprising a fixing element, wherein the fixing element is disposed on the housing element, and the fixing element is used to fix the sample container on the at least one strong magnetic surface of the housing element. 11 . The magnetic material separation device as claimed in claim 10 , wherein the fixing member comprises a central column, the central column is disposed in a central area of ​​the at least one strong magnetic surface, the sample container is a flexible tube, and the central column is used for the sample container to be wound around.

12. A magnetic material separation device as described in claim 11, wherein the fixing member further includes an upper cover, the upper cover is arranged on the shell member and forms a accommodating space with the at least one strong magnetic surface, the upper cover has a first wiring hole and a second wiring hole connected to the accommodating space, the middle column passes through the upper cover, the middle column has a wiring groove, the first wiring hole is used for the sample container to pass through so as to extend into the accommodating space, the wiring groove is located in the accommodating space and is used for the sample container to be wound, and the second wiring hole is used for the sample container to pass through so as to extend out of the accommodating space.

13. The magnetic material separation device as claimed in claim 1, wherein the at least one magnetic component set comprises a plurality of magnetic component sets, the at least one receiving slot comprises a plurality of receiving slots, and the magnetic component sets are respectively disposed in the receiving slots; and in, The accommodating grooves are double-layered, the at least one strong magnetic surface includes two strong magnetic surfaces, and the two strong magnetic surfaces are located on two opposite surfaces of the shell. 14 . The magnetic substance separation device as claimed in claim 13 , wherein the shell is in a plate shape, the sample container is a flexible tube, and the shell is used for the sample container to be wound around.

15. The magnetic material separation device as claimed in claim 1, wherein the shell is cylindrical, the shell has an outer annular surface, the at least one accommodating groove is disposed adjacent to the outer annular surface, and the at least one strong magnetic surface is located on the outer annular surface of the shell. 16 . The magnetic substance separation device as claimed in claim 15 , wherein the sample container is a flexible tube, and the shell is used for the sample container to be wound around.

17. The magnetic substance separation device as claimed in claim 15, further comprising a fixing member, wherein the fixing member is disposed on the housing member, and the fixing member is used to fix the sample container on the at least one strong magnetic surface of the housing member; and in, The fixing part is a quick-release outer cover, which includes a base and at least one extension arm. The base is detachably arranged on the end surface of the shell part, and the at least one extension arm is connected to the base and suspended above the at least one strong magnetic surface. The sample container is a flexible tube, and the at least one extension arm is used for the sample container to be wound around.

18. The magnetic material separation device as claimed in claim 1, wherein the shell is cylindrical, the shell has an inner annular surface, the at least one accommodating groove is disposed adjacent to the inner annular surface, and the at least one strong magnetic surface is located on the inner annular surface of the shell.

19. The magnetic substance separation device as claimed in claim 18, further comprising a fixing member, wherein the inner annular surface of the shell member surrounds and forms a containing space, and the fixing member is used to fix the sample container on the at least one strong magnetic surface of the shell member; and in, The fixing piece is a quick-release shaft piece, and the fixing piece is detachably arranged in the accommodating space. The sample container is a flexible tube piece, and the fixing piece is used for the sample container to be wound around.

Images