Magnetic separation device and magnetic separation method

Abstract

This magnetic separation device is a device for separating biological particles from a liquid containing the biological particles and magnetic particles capable of binding to the biological particles. The magnetic separation device includes a first magnet, and a second magnet disposed so as to face the first magnet. A space for disposing a flexible container holding the liquid is formed between the first magnet and the second magnet. At least one of the first magnet and the second magnet is relatively movable in a direction toward and a direction away from the other magnet. Each of the first magnet and the second magnet magnetically attracts the magnetic particles bound to the biological particles in the container.

Description

Magnetic separation device and magnetic separation method

[0001] The present disclosure relates to a magnetic separation device and a magnetic separation method.

[0002] 2. Description of the Related Art A magnetic separation method is known for separating bioparticles from a liquid containing bioparticles and magnetic particles capable of binding to the bioparticles (see, for example, Patent Document 1).

[0003] In this magnetic separation method, a liquid (e.g., blood) containing biological particles (e.g., target cells present in blood) and magnetic particles is placed in a container. The biological particles are bound to the magnetic particles in the container. A magnet is then brought close to the outer surface of the container to generate a magnetic field within the container. The magnetic particles bound to the biological particles in the relatively high magnetic field strength region within the container are magnetically attracted to the magnet by the action of the magnetic field within the container.

[0004] In this state, a cleaning liquid such as PBS (Phosphate-Buffered Saline) is poured into and taken out of the container multiple times to remove other particles not bound to the magnetic particles and solvent components such as plasma from the container, thereby separating the target bioparticles from the liquid.

[0005] International Publication No. 2011 / 059076

[0006] In the conventional magnetic separation method described above, the area within the container where the magnetic field strength is relatively high is limited. Therefore, in order to quickly and reliably separate bioparticles from a liquid, it is necessary to use a container with a relatively small volume so that almost the entire area within the container is relatively close to the magnet. However, using such a container with a relatively small volume can take a long time when bioparticles need to be separated from a large amount of liquid.

[0007] The present disclosure provides a magnetic separation device and a magnetic separation method that can efficiently separate biological particles from a liquid.

[0008] A magnetic separation device according to one aspect of the present disclosure is a magnetic separation device for separating biological particles from a liquid containing the biological particles and magnetic particles capable of binding to the biological particles, and comprises a first magnet and a second magnet arranged to face the first magnet, wherein a space is formed between the first magnet and the second magnet for containing the liquid and for placing a flexible container, at least one of the first magnet and the second magnet is movable relative to the other in a direction toward and away from the other, and each of the first magnet and the second magnet magnetically attracts the magnetic particles bound to the biological particles in the container.

[0009] Furthermore, a magnetic separation method according to one aspect of the present disclosure is a magnetic separation method for separating biological particles from a liquid containing the biological particles and magnetic particles capable of binding to the biological particles, the magnetic separation method including the steps of: (a) placing a flexible container containing the liquid in a space between a first magnet and a second magnet arranged to face each other; (b) moving one of the first magnet and the second magnet relatively toward the other magnet, thereby compressing the container between the first magnet and the second magnet, thereby magnetically attracting the magnetic particles bound to the biological particles in the container to each of the first magnet and the second magnet; (c) moving one of the first magnet and the second magnet relatively away from the other magnet, thereby expanding the container between the first magnet and the second magnet; and (d) discharging particles other than the biological particles contained in the liquid that are not bound to the magnetic particles from the container.

[0010] According to the magnetic separation device and the like according to one aspect of the present disclosure, biological particles can be efficiently separated from a liquid.

[0011] FIG. 1 is a schematic diagram showing the configuration of a magnetic separation device according to embodiment 1. FIG. 2 is a flowchart showing the flow of a magnetic separation method using the magnetic separation device according to embodiment 1. FIG. 3 is a schematic diagram showing the configuration of a magnetic separation device according to modified example 1 of embodiment 1. FIG. 4 is a schematic diagram showing the configuration of a magnetic separation device according to modified example 2 of embodiment 1. FIG. 5 is a schematic diagram showing the configuration of a magnetic separation device according to embodiment 2. FIG. 6 is a flowchart showing the flow of a magnetic separation method using the magnetic separation device according to embodiment 2. FIG. 7 is a schematic diagram showing the flow of a magnetic separation method using the magnetic separation device according to embodiment 2. FIG. 8 is a schematic diagram showing the flow of a magnetic separation method using the magnetic separation device according to embodiment 2. FIG. 9 is a schematic diagram showing the flow of a magnetic separation method using the magnetic separation device according to embodiment 2. FIG. 10 is a schematic diagram showing the flow of a magnetic separation method using the magnetic separation device according to embodiment 2. FIG. 11 is a schematic diagram showing the flow of a magnetic separation method using the magnetic separation device according to embodiment 3. FIG. 12 is a schematic diagram showing the configuration of a magnetic separation device according to embodiment 4. FIG. 13 is a schematic diagram showing the configuration of a magnetic separation device according to embodiment 5. FIG. 14 is a schematic diagram showing a state in which the magnetic separation device according to embodiment 5 is in use. 19 is a schematic diagram for explaining the angular relationship between the magnet and the inflow port of the magnetic separation device according to embodiment 5. FIG. 20 is a schematic diagram showing the usage state of the magnetic separation device according to embodiment 5. FIG. 21 is a schematic cross-sectional view of the magnetic separation device according to embodiment 5 taken along line XIX-XIX in FIG. 18. FIG. 22 is a schematic cross-sectional view of a magnetic separation device according to a comparative example. FIG. 23 is a schematic diagram showing the configuration of a magnetic separation device according to embodiment 6. FIG. 24 is a schematic diagram showing the configuration of a magnetic separation device according to embodiment 7.

[0012] <First Disclosure> The first disclosure, which corresponds to the following techniques 1 to 6, provides a magnetic separation device and a magnetic separation method that can efficiently separate biological particles from a liquid.

[0013] (Technology 1) A magnetic separation device for separating biological particles from a liquid containing the biological particles and magnetic particles that can bind to the biological particles, the magnetic separation device comprising: a first magnet; and a second magnet arranged to face the first magnet; a space for accommodating the liquid and for placing a flexible container is formed between the first magnet and the second magnet; at least one of the first magnet and the second magnet is movable relative to the other in a direction toward and away from the other; and each of the first magnet and the second magnet magnetically attracts the magnetic particles that have bound to the biological particles in the container.

[0014] According to Technology 1, a container containing a liquid is placed between a first magnet and a second magnet, and each of the first magnet and the second magnet magnetically attracts magnetic particles bound to bioparticles in the container. This allows a container with a certain volume to be configured so that most of the interior of the container is relatively close to the first magnet and the second magnet, and the magnetic particles bound to the bioparticles can be effectively magnetically attracted to the first magnet and the second magnet. As a result, even when treating a large amount of liquid, bioparticles can be efficiently separated from the liquid.

[0015] (Technology 2) A magnetic separation device according to Technology 1, wherein when one of the first magnet and the second magnet moves relative to the other in a direction toward the other, the container is compressed between the first magnet and the second magnet, and when one of the first magnet and the second magnet moves relative to the other in a direction away from the other, the container is expanded between the first magnet and the second magnet.

[0016] According to Technology 2, when one of the first magnet and the second magnet moves relatively toward the other, the container is compressed between the first magnet and the second magnet. This allows almost all areas within the container to be configured to be relatively close to the first magnet and the second magnet, effectively magnetically attracting the magnetic particles bound to the bioparticles to each of the first magnet and the second magnet. Furthermore, when one of the first magnet and the second magnet moves relatively away from the other, the container expands between the first magnet and the second magnet. When a cleaning solution is introduced into the container in this state, the flow rate of the cleaning solution within the container becomes relatively slow, thereby preventing the magnetic attraction between the magnetic particles and each of the first magnet and the second magnet from being unexpectedly released due to the flow of the cleaning solution.

[0017] (Technology 3) A magnetic separation device according to Technology 2, wherein the first magnet and the second magnet each have a first magnetic pole portion and a second magnetic pole portion that are magnetized to different magnetic poles, and the first magnetic pole portion of the first magnet and the second magnetic pole portion of the second magnet are arranged to face each other.

[0018] According to the third technique, the magnetic particles bound to the bioparticles can be magnetically attracted more effectively by each of the first magnet and the second magnet.

[0019] (Technology 4) The magnetic separation device according to Technology 3, further comprising: a first support plate that supports the first magnet; a second support plate that is arranged opposite the first support plate and that supports the second magnet; and a spacer that is arranged between the first support plate and the second support plate, wherein when one of the first magnet and the second magnet moves relatively in a direction approaching the other, the spacer is sandwiched between the first support plate and the second support plate.

[0020] According to Technology 4, when one of the first magnet and the second magnet moves relatively in a direction approaching the other, the gap between the first support plate and the second support plate can be adjusted as desired by adjusting the thickness of the spacer.

[0021] (Technology 5) The magnetic separation device according to any one of Technologies 1 to 4, further comprising: a first non-magnetic plate disposed between the first magnet and the container; and a second non-magnetic plate disposed opposite the first non-magnetic plate and between the second magnet and the container.

[0022] According to the fifth technique, it is possible to prevent the container from being deformed in accordance with the shapes of the first magnet and the second magnet.

[0023] (Technology 6) A magnetic separation method for separating biological particles from a liquid containing the biological particles and magnetic particles that can bind to the biological particles, the magnetic separation method comprising: (a) a step of placing a flexible container that holds the liquid in a space between a first magnet and a second magnet that are arranged to face each other; (b) a step of moving one of the first magnet and the second magnet relatively toward the other magnet in a direction toward the other magnet, thereby compressing the container between the first magnet and the second magnet, thereby magnetically attracting the magnetic particles that have been bound to the biological particles in the container to each of the first magnet and the second magnet; (c) a step of moving one of the first magnet and the second magnet relatively away from the other magnet, thereby expanding the container between the first magnet and the second magnet; and (d) a step of discharging particles other than the biological particles that are contained in the liquid and that are not bound to the magnetic particles from the container.

[0024] According to Technology 6, a container containing a liquid is placed between a first magnet and a second magnet, and each of the first magnet and the second magnet magnetically attracts magnetic particles bound to bioparticles in the container. This allows a container with a certain volume to be configured so that most of the container's interior is relatively close to the first magnet and the second magnet, and the magnetic particles bound to the bioparticles can be effectively magnetically attracted to the first magnet and the second magnet. As a result, bioparticles can be efficiently separated from the liquid, even when treating a large amount of liquid, for example.

[0025] <Second Disclosure> In the conventional magnetic separation method described above, in order to recover all of the bioparticles remaining in the container, a large amount of recovery solution needs to be poured into the container. However, when such a large amount of recovery solution is used, the concentration of bioparticles in the recovery solution recovered from the container decreases.

[0026] Therefore, in the second disclosure corresponding to the following techniques 7 to 12, a magnetic separation device and a magnetic separation method are provided that can increase the recovery concentration of bioparticles.

[0027] (Technology 7) A magnetic separation device for separating biological particles from a liquid containing the biological particles and magnetic particles that can bind to the biological particles, the magnetic separation device comprising: a magnet that is placed near a container that holds the liquid, and that forms a magnetic field inside the container to magnetically attract the magnetic particles that have bound to the biological particles inside the container; and an adjustment unit that adjusts the magnetic field strength of the magnet inside the container so that the magnetic particles that have bound to the biological particles are collected in a specific region inside the container.

[0028] According to Technology 7, the adjusting unit adjusts the magnetic field strength of the magnet inside the container so that magnetic particles bound to bioparticles are collected in a specific region inside the container. As a result, when, for example, a recovery solution is injected into the container to recover bioparticles, the bioparticles collected in the specific region inside the container can be discharged to the outside of the container together with the recovery solution present in the specific region (i.e., a portion of the recovery solution injected into the container). As a result, the bioparticles remaining inside the container can be recovered in a state where they are dispersed in a relatively small amount of recovery solution, thereby increasing the recovery concentration of bioparticles.

[0029] (Technology 8) A magnetic separation device according to Technology 7, wherein the magnet is a permanent magnet, and the adjustment unit displaces one of the container and the permanent magnet relative to the other so as to collect the magnetic particles bound to the biological particles in the specific region inside the container.

[0030] According to Technique 8, magnetic particles bound to biological particles can be easily collected in a specific region inside the container using a relatively simple configuration in which one of the container and the permanent magnet is displaced relative to the other.

[0031] (Technology 9) The magnetic separation device according to Technology 8, wherein a plurality of the permanent magnets are provided, and the magnetic separation device further includes a plurality of yokes attached to the plurality of permanent magnets respectively and connected to each other.

[0032] According to the ninth technique, the magnetic particles bound to the bioparticles inside the container can be magnetically attracted to the multiple permanent magnets more efficiently.

[0033] (Technology 10) A magnetic separation device according to Technology 7, wherein the magnet is an electromagnet and a plurality of electromagnets are provided, the plurality of electromagnets are arranged two-dimensionally near the container, and the adjustment unit controls the flow of current to each of the plurality of electromagnets so as to collect the magnetic particles bound to the biological particles in the specific region inside the container.

[0034] According to Technique 10, magnetic particles bound to bioparticles can be easily collected in a specific region inside a container with a relatively simple configuration in which the energization of each of a plurality of electromagnets is controlled.

[0035] (Technology 11) A magnetic separation method for separating biological particles from a liquid containing the biological particles and magnetic particles that can bind to the biological particles, the magnetic separation method comprising: (a) a step of placing a magnet near a container that contains the liquid and forming a magnetic field inside the container, thereby magnetically attracting the magnetic particles that have bound to the biological particles inside the container to the magnet; and (b) a step of adjusting the magnetic field strength of the magnet inside the container so that the magnetic particles that have bound to the biological particles are collected in a specific region inside the container.

[0036] According to Technology 11, the magnetic field strength of the magnet inside the container is adjusted so that magnetic particles bound to bioparticles are collected in a specific region inside the container. As a result, when, for example, a recovery solution is injected into the container to recover bioparticles, the bioparticles collected in the specific region inside the container can be discharged to the outside of the container together with the recovery solution present in the specific region (i.e., a portion of the recovery solution injected into the container). As a result, the bioparticles remaining inside the container can be recovered in a state where they are dispersed in a relatively small amount of recovery solution, thereby increasing the recovery concentration of bioparticles.

[0037] (Technology 12) The magnetic separation method according to Technology 11, wherein the container includes a port communicating with the interior of the container and an on-off valve disposed in the port, and the magnetic separation method further includes the step of (c) switching the on-off valve to discharge the bioparticles collected in the specific region inside the container from the port to the outside of the container and recover them.

[0038] According to Technique 12, by switching the on-off valve, bioparticles collected in a specific region inside the container can be easily discharged from the port to the outside of the container.

[0039] <Third Disclosure> In the conventional magnetic separation method described above, when a washing solution is introduced into a container, the flow of the washing solution may unintentionally release the magnetic attraction between the magnet and the magnetic particles, resulting in a decrease in the recovery efficiency of bioparticles.

[0040] Therefore, in the third disclosure corresponding to the following techniques 13 to 19, a magnetic separation device capable of improving the recovery efficiency of bioparticles is provided.

[0041] (Technology 13) A magnetic separation device for separating biological particles from a liquid containing the biological particles and magnetic particles that can bind to the biological particles, the magnetic separation device comprising: a mounting section having a mounting surface on which a container containing the liquid is placed; and a magnet that is placed on the mounting surface and magnetically attracts the magnetic particles that have bound to the biological particles inside the container placed on the mounting surface, wherein the mounting surface has an attraction region where the magnet is placed and magnetically attracts the magnetic particles that have bound to the biological particles inside the container; and a non-adsorption region that is formed between a position directly below a connection between a port connected to the container and the container and the attraction region and that does not magnetically attract the magnetic particles that have bound to the biological particles inside the container.

[0042] Generally, when separating bioparticles from a liquid inside a container, a cleaning solution is introduced into the container through a port, thereby discharging impurity particles other than bioparticles remaining inside the container to the outside of the container. Because the cleaning solution enters the container through a port with a cross-sectional area smaller than the cross-sectional area of ​​the container, the flow rate of the cleaning solution near the connection is relatively fast. According to Technology 13, the mounting surface has a non-adsorption area formed between the position directly below the connection and the adsorption area, so that magnetic particles bound to bioparticles inside the container are not magnetically adsorbed to the non-adsorption area. Therefore, even when the flow rate of the cleaning solution flowing near the connection is relatively fast, the flow of the cleaning solution can be prevented from unintentionally releasing the magnetic adsorption between the magnet and the magnetic particles, thereby improving the efficiency of bioparticle recovery.

[0043] (Technology 14) A magnetic separation device according to Technology 13, wherein the container is formed so that when the liquid flows into the container from the port, the volume of the container increases as the liquid flows in, and the non-adsorption region is formed so as to expand in an approximately fan shape from a position directly below the connection portion toward the adsorption region.

[0044] According to Technology 14, when the volume of the container is variable, the cleaning liquid from the port flows radially into the container, and the volume inside the container increases as the cleaning liquid flows in. At this time, the non-adsorption region is formed to expand in a generally fan shape from a position directly below the connection part toward the adsorption region, so that the flow of the cleaning liquid flowing in radially can be prevented from unintentionally releasing the magnetic adsorption between the magnet and the magnetic particles.

[0045] (Technology 15) The magnetic separation device according to Technology 14, wherein, when the mounting surface is viewed in plan, a radius of the non-adsorption region is longer than a diameter of the port.

[0046] According to Technique 15, the radial flow of the cleaning liquid can effectively prevent the magnetic attraction between the magnet and the magnetic particles from being unintentionally released.

[0047] (Technology 16) A magnetic separation device according to Technology 14 or 15, wherein, when the mounting surface is viewed in a plane, the magnet is formed in an approximately rectangular shape, and one side of the magnet is arranged approximately parallel to a radial line extending radially from a position directly below the connection portion along the mounting surface.

[0048] According to Technology 16, when the cleaning solution from the port flows radially into the container, the magnetic particles that are magnetically attracted to one side of the magnet with a relatively strong magnetic field remain magnetically attracted to the one side of the magnet and move along that side, even if they are subjected to the flow of cleaning solution. This effectively prevents the magnetic attraction between the magnet and the magnetic particles from being unintentionally released.

[0049] (Technology 17) The magnetic separation device according to Technology 16, wherein, when the mounting surface is viewed in a plane, an angle formed by a line connecting a radial center of the port and a center of another side of the magnet opposite the one side of the magnet and the other side of the magnet is 30° or less.

[0050] According to Technique 17, it is possible to more effectively prevent the magnetic attraction between the magnet and the magnetic particles from being unintentionally released.

[0051] (Technology 18) A magnetic separation device according to Technology 13, wherein the container is formed so that when the liquid flows into the container from the port, the volume inside the container does not change with the flow of the liquid, and the non-adsorption region is formed so as to extend linearly from a position directly below the connection portion along the axial direction of the port.

[0052] According to Technology 18, when the volume of the container is not variable, the cleaning liquid from the port flows into the container in a linear fashion along the axial direction of the port, and the volume inside the container does not change as the cleaning liquid flows in. At this time, the non-adsorption region is formed to extend linearly from a position directly below the connection part along the axial direction of the port, so that the magnetic attraction between the magnet and the magnetic particles can be prevented from being unintentionally released by the linear flow of the cleaning liquid flowing in.

[0053] (Technology 19) The magnetic separation device according to Technology 18, wherein, in a plan view of the mounting surface, a length in a lateral direction of the non-adsorption region is longer than a diameter of the port.

[0054] According to Technique 19, the linear flow of the washing liquid can effectively prevent the magnetic attraction between the magnet and the magnetic particles from being unintentionally released.

[0055] These general or specific aspects may be realized by an apparatus or a method, or by any combination of an apparatus and a method.

[0056] Each embodiment will be described below with reference to the drawings.

[0057] The embodiments described below are all comprehensive or specific examples. The numerical values, shapes, materials, components, component placement and connection configurations, steps, and step sequences shown in the following embodiments are merely examples and are not intended to limit the scope of the claims. Furthermore, among the components in the following embodiments, components that are not described in the independent claims that represent the highest concepts are described as optional components. Furthermore, the drawings are not necessarily strict illustrations. In each drawing, substantially identical components are designated by the same reference numerals, and redundant descriptions are omitted or simplified.

[0058] First Disclosure First, as a first disclosure, a first embodiment will be described.

[0059] (Embodiment 1) [1-1. Configuration of Magnetic Separator] The configuration of a magnetic separation device 2 according to embodiment 1 will be described with reference to Fig. 1. Fig. 1 is a schematic diagram showing the configuration of a magnetic separation device 2 according to embodiment 1.

[0060] 1, the front-to-rear direction of the magnetic separation device 2 is the X-axis direction, the left-to-right direction of the magnetic separation device 2 is the Y-axis direction, and the up-to-down direction of the magnetic separation device 2 is the Z-axis direction. The positive side of the X-axis is the "front," the negative side of the X-axis is the "rear," the positive side of the Y-axis is the "right," the negative side of the Y-axis is the "left," the positive side of the Z-axis is the "up," and the negative side of the Z-axis is the "down."

[0061] 1, the magnetic separation device 2 includes a first support plate 4, a first magnet 6, a second support plate 8, a second magnet 10, a moving mechanism 12, a driving source 14, and a control unit 16. The magnetic separation device 2 is used as an automated device for separating hematopoietic stem cells from human blood in, for example, the process of establishing iPS cells in regenerative medicine.

[0062] The first support plate 4 is a plate-like member made of a non-magnetic material such as acrylic resin, etc. A first recess 18 for supporting the first magnet 6 is formed on the lower surface of the first support plate 4 (the surface farther from the second support plate 8).

[0063] The first magnet 6 is, for example, a permanent magnet, and is supported in the first recess 18 of the first support plate 4. An N magnetic pole portion 20n (an example of a first magnetic pole portion) magnetized to an N pole is formed at the upper end portion (the end portion closer to the first support plate 4) of the first magnet 6. Furthermore, an S magnetic pole portion 20s magnetized to an S pole is formed at the lower end portion (the end portion farther from the first support plate 4) of the first magnet 6.

[0064] The second support plate 8 is a plate-shaped member made of a non-magnetic material such as acrylic resin, and is arranged to face the first support plate 4. In the example shown in Fig. 1, the second support plate 8 is arranged above the first support plate 4. A second recess 22 for supporting the second magnet 10 is formed on the upper surface of the second support plate 8 (the surface farther from the first support plate 4).

[0065] The second magnet 10 is, for example, a permanent magnet, and is supported in the second recess 22 of the second support plate 8. This positions the second magnet 10 so that it faces the first magnet 6. An S magnetic pole portion 24s (an example of a second magnetic pole portion) magnetized to an S pole is formed at the lower end of the second magnet 10 (the end portion closer to the second support plate 8). Furthermore, an N magnetic pole portion 24n magnetized to an N pole is formed at the upper end of the second magnet 10 (the end portion farther from the second support plate 8).

[0066] That is, the N magnetic pole 20n of the first magnet 6 and the S magnetic pole 24s of the second magnet 10 are magnetized to different magnetic poles and are arranged to face each other, so that a magnetic field is generated between the N magnetic pole 20n of the first magnet 6 and the S magnetic pole 24s of the second magnet 10 due to magnetic forces in the directions of attraction.

[0067] Conversely, the N magnetic pole 20n may be formed at the lower end of the first magnet 6, and the S magnetic pole 20s (an example of a first magnetic pole) may be formed at the upper end of the first magnet 6. Alternatively, the S magnetic pole 24s may be formed at the upper end of the second magnet 10, and the N magnetic pole 24n (an example of a second magnetic pole) may be formed at the lower end of the second magnet 10. In this case, the S magnetic pole 20s of the first magnet 6 and the N magnetic pole 24n of the second magnet 10 are magnetized to different magnetic poles and are arranged to face each other.

[0068] The movement mechanism 12 is an actuator for relatively moving one of the first support plate 4 and the second support plate 8 in a direction toward or away from the other. The first magnet 6 and the second magnet 10 move integrally with the first support plate 4 and the second support plate 8, respectively. In other words, the movement mechanism 12 allows one of the first magnet 6 and the second magnet 10 to move relatively toward or away from the other.

[0069] In this embodiment, the first support plate 4 is fixed to a housing (not shown) of the magnetic separation device 2, and the second support plate 8 is movable in the vertical direction relative to the housing of the magnetic separation device 2. The movement mechanism 12 moves the second support plate 8 relative to the first support plate 4 in a direction toward and away from the first support plate 4. When the first support plate 4 and the second support plate 8 are at their farthest positions (see FIG. 3A, which will be described later), the distance between the first support plate 4 and the second support plate 8 is, for example, about 2 cm. When the first support plate 4 and the second support plate 8 are at their closest positions (see FIG. 3B, which will be described later), the distance between the first support plate 4 and the second support plate 8 is, for example, about 0.5 mm.

[0070] Conversely, the second support plate 8 may be fixed to the housing of the magnetic separation device 2, and the first support plate 4 may be movable in the vertical direction relative to the housing of the magnetic separation device 2. In this case, the movement mechanism 12 may move the first support plate 4 relatively to the second support plate 8 in a direction toward or away from the second support plate 8.

[0071] Alternatively, both the first support plate 4 and the second support plate 8 may be movable in the vertical direction relative to the housing of the magnetic separation device 2. In this case, the movement mechanism 12 may simultaneously move both the first support plate 4 and the second support plate 8 in directions toward and away from each other.

[0072] The driving source 14 is a servo motor for driving the moving mechanism 12 .

[0073] The control unit 16 is a controller for controlling the rotation position, rotation direction, rotation speed, etc. of the drive source 14 .

[0074] A space 28 for arranging a container 26 is formed between the first support plate 4 and the second support plate 8 (i.e., between the first magnet 6 and the second magnet 10). The container 26 is formed, for example, from a flexible non-magnetic material and is shaped like a bag so as to accommodate a liquid (described later). One left-right end of the container 26 is formed with an inlet port 30 for allowing liquid supplied from, for example, a syringe (not shown) to flow into the container 26. The other left-right end of the container 26 is formed with an outlet port 32 for allowing the liquid in the container 26 to flow out of the container 26. Although not shown, the inlet port 30 and the outlet port 32 are respectively provided with an inlet-side valve and an outlet-side valve for switching between flowing and blocking the liquid. Furthermore, an intake / exhaust port 34 for letting air in and out of the container 26 is formed at the upper end of the container 26.

[0075] The container 26 contains a liquid that has flowed in through the inlet port 30. The liquid is, for example, human blood, and is illustrated in FIG. 1 with a dotted pattern. The liquid contains a solvent component such as plasma, a plurality of biological particles 36, a plurality of impurity particles 38, and a plurality of magnetic particles 40. That is, the liquid is produced by mixing a plurality of magnetic particles 40 with human blood that contains a solvent component such as plasma, a plurality of biological particles 36, and a plurality of impurity particles 38. The amount of liquid contained in the container 26 is, for example, approximately 10 ml to several tens of ml.

[0076] For ease of explanation, Fig. 1 shows three each of the biological particles 36, the impurity particles 38, and the magnetic particles 40, but in reality, the liquid contains a large number of biological particles 36, the impurity particles 38, and the magnetic particles 40. For ease of explanation, the sizes of the biological particles 36, the impurity particles 38, and the magnetic particles 40 are exaggerated in Fig. 1.

[0077] The bioparticles 36 are target cells, such as hematopoietic stem cells, that are to be separated by the magnetic separation device 2. For ease of explanation, the bioparticles 36 are simply illustrated as black circles in FIG.

[0078] The impurity particles 38 are all cells other than the biological particles 36 that are not subject to separation by the magnetic separation device 2. For ease of explanation, the impurity particles 38 are simply illustrated as white circles in FIG.

[0079] The magnetic particles 40 are artificial particles that are magnetic, and are so-called magnetic beads. The surfaces of the magnetic particles 40 are formed with modified shapes that correspond to the surface shapes of the biological particles 36, so that the magnetic particles 40 can specifically bind to the biological particles 36. Furthermore, the magnetic particles 40 do not bind to the impurity particles 38. For ease of explanation, the magnetic particles 40 are simply illustrated as white stars in FIG. 1 .

[0080] [1-2. Flow of magnetic separation method] The flow of the magnetic separation method using the magnetic separation device 2 according to embodiment 1 will be described with reference to Figures 2 and 3. Figure 2 is a flowchart showing the flow of the magnetic separation method using the magnetic separation device 2 according to embodiment 1. Figure 3 is a schematic diagram showing the flow of the magnetic separation method using the magnetic separation device 2 according to embodiment 1.

[0081] As a preliminary preparation, a liquid is prepared by mixing a plurality of magnetic particles 40 with human blood containing a solvent component such as plasma, a plurality of biological particles 36, and a plurality of impurity particles 38, and the prepared liquid is left for a certain period of time, whereby the biological particles 36 and the magnetic particles 40 in the liquid are bonded in a one-to-one relationship.

[0082] 2, a liquid prepared in advance is injected into the container 26 through the inflow port 30 (S1). This causes the liquid to be contained in the container 26. At this time, air is sent into the container 26 through the intake / exhaust port 34 so that part of the interior of the container 26 is occupied by air. This allows the liquid to flow effectively within the container 26 when the container 26 is compressed, as will be described later.

[0083] 3A, with the first support plate 4 and the second support plate 8 at their farthest positions, the container 26 is placed between the first support plate 4 and the second support plate 8. At this time, the lower end of the container 26 is in contact with the upper surface of the first support plate 4, and the upper end of the container 26 is in contact with the lower surface of the second support plate 8. Furthermore, since the container 26 is placed between the first magnet 6 and the second magnet 10, a magnetic field is generated within the container 26 by the first magnet 6 and the second magnet 10.

[0084] 3(b), the movement mechanism 12 moves the second support plate 8 relatively toward the first support plate 4, causing the container 26 to be compressed in the up-down direction between the first support plate 4 and the second support plate 8 (i.e., between the first magnet 6 and the second magnet 10) (S2). At this time, the container 26 is deformed so that its size in the up-down direction decreases and its size in the left-right and front-to-back directions increases.

[0085] 3B, the container 26 is compressed in the vertical direction, so that almost all areas within the container 26 are relatively close to the first magnet 6 and the second magnet 10. Therefore, magnetic particles 40 bound to bioparticles 36 present at any position within the container 26 are affected by the magnetic field within the container 26 and move within the container 26 toward the first magnet 6 and the second magnet 10. The magnetic particles 40 bound to the bioparticles 36 are then magnetically attracted to each of the first magnet 6 and the second magnet 10, and fixed at the upper and lower ends within the container 26 (i.e., the areas within the container 26 that are closest to the second magnet 10 and the first magnet 6, respectively, and where the magnetic field strength within the container 26 is highest).

[0086] 3(c), the movement mechanism 12 moves the second support plate 8 relatively away from the first support plate 4, causing the container 26 to expand in the vertical direction between the first support plate 4 and the second support plate 8 (S3). At this time, the container 26 is deformed so that the size of the container 26 increases in the vertical direction and decreases in the left-right and front-rear directions.

[0087] In the state shown in (c) of Figure 3, the magnetic particles 40 bound to the biological particles 36 are magnetically attracted to each of the first magnet 6 and the second magnet 10, and remain fixed at the upper and lower ends of the container 26.

[0088] 3(d), a cleaning liquid such as PBS is injected into the container 26 through the inflow port 30 (S4). As a result, solvent components such as plasma and impurity particles 38 present in the liquid in the container 26 are discharged to the outside of the container 26 through the outflow port 32 by the flow of the cleaning liquid. Note that, to enhance the cleaning effect, the cleaning liquid may be injected into the container 26 through the inflow port 30 multiple times while the container 26 is rocked relative to the first support plate 4 and the second support plate 8.

[0089] At this time, since the container 26 is expanded in the vertical direction between the first support plate 4 and the second support plate 8, the size of the XZ cross section within the container 26, which is approximately perpendicular to the flow direction of the cleaning liquid (Y-axis direction), becomes relatively large. Therefore, when the cleaning liquid is flowed into the container 26, the flow rate of the cleaning liquid within the container 26 becomes relatively small compared to the state shown in (b) of FIG. 3. Furthermore, as shown by multiple arrows in (d) of FIG. 3, the flow rate distribution within the container 26 is greatest in the vertical center of the container 26 (i.e., the height positions of the inlet port 30 and the outlet port 32), and the flow rate gradually decreases toward the upper and lower ends of the container 26. Therefore, the magnetic particles 40 can be maintained fixed at the upper and lower ends of the container 26, and the magnetic attraction between the magnetic particles 40 and each of the first magnet 6 and the second magnet 10 can be prevented from being suddenly released by the flow of the cleaning liquid.

[0090] Finally, the container 26 is removed from between the first support plate 4 and the second support plate 8, and the bioparticles 36 are collected from the container 26 (S5). In this manner, the bioparticles 36 are separated from the liquid.

[0091] [1-3. Effects] In this embodiment, as described above, the container 26 containing the liquid is placed between the first magnet 6 and the second magnet 10, and each of the first magnet 6 and the second magnet 10 magnetically attracts the magnetic particles 40 bound to the bioparticles 36 in the container 26.

[0092] As a result, even if the container 26 has a certain volume, it can be configured so that most of the area inside the container 26 is located relatively close to the first magnet 6 and the second magnet 10, and the magnetic particles 40 bound to the bioparticles 36 can be effectively magnetically attracted to each of the first magnet 6 and the second magnet 10. As a result, even when treating a large amount of liquid, for example, the bioparticles 36 can be efficiently separated from the liquid.

[0093] [1-4. Modification 1] The configuration of a magnetic separation device 2A according to Modification 1 of Embodiment 1 will be described with reference to Fig. 4. Fig. 4 is a schematic diagram showing the configuration of a magnetic separation device 2A according to Modification 1 of Embodiment 1. In Fig. 4, the same components as those in Fig. 1 are denoted by the same reference numerals, and their description will be omitted.

[0094] As shown in Fig. 4, the magnetic separation device 2A according to the first modification includes a pair of spacers 42 in addition to the above-described components. The pair of spacers 42 are spacers disposed between the first support plate 4 and the second support plate 8, and are fixed, for example, to the upper surface of the first support plate 4. The thickness of the pair of spacers 42 in the vertical direction is, for example, approximately 0.5 mm. For convenience of explanation, the inlet port 30, the outlet port 32, and the intake / exhaust port 34 are not shown in Fig. 4.

[0095] When the movement mechanism 12 (see FIG. 1 ) moves the second support plate 8 relatively toward the first support plate 4, the pair of spacers 42 are sandwiched between the first support plate 4 and the second support plate 8. At this time, the gap between the first support plate 4 and the second support plate 8 can be adjusted as desired by adjusting the thickness of the pair of spacers 42 in the vertical direction. Furthermore, if the first magnet 6 and the second magnet 10 are each permanent magnets with relatively strong magnetic force, such as neodymium magnets, the strong magnetic force (attractive force) generated between the first magnet 6 and the second magnet 10 can prevent the container 26 from being completely crushed between the first support plate 4 and the second support plate 8.

[0096] [1-5. Modification 2] The configuration of a magnetic separation device 2B according to Modification 2 of Embodiment 1 will be described with reference to Fig. 5. Fig. 5 is a schematic diagram showing the configuration of a magnetic separation device 2B according to Modification 2 of Embodiment 1. In Fig. 5, the same components as those in Fig. 1 are denoted by the same reference numerals, and their description will be omitted.

[0097] 5, the magnetic separation device 2B according to the second modification includes a plurality of first magnets 6B and a plurality of second magnets 10B. The plurality of first magnets 6B are supported on the upper surface of the first support plate 4 and are spaced apart in the left-right direction. The plurality of second magnets 10B are supported on the lower surface of the second support plate 8 and are spaced apart in the left-right direction.

[0098] The magnetic separation device 2B further includes a first non-magnetic plate 44 and a second non-magnetic plate 46. Each of the first non-magnetic plate 44 and the second non-magnetic plate 46 is a plate-shaped member formed of a non-magnetic material such as acrylic resin. The first non-magnetic plate 44 is supported so as to cover the upper ends of the plurality of first magnets 6B and is disposed between the plurality of first magnets 6B and the lower end of the container 26. The second non-magnetic plate 46 is disposed so as to face the first non-magnetic plate 44. The second non-magnetic plate 46 is supported so as to cover the lower ends of the plurality of second magnets 10B and is disposed between the plurality of second magnets 10B and the upper end of the container 26.

[0099] If the magnetic separation device 2B were not equipped with the first non-magnetic plate 44 and the second non-magnetic plate 46, the plurality of first magnets 6B would be in direct contact with the lower end of the container 26, and the plurality of second magnets 10B would be in direct contact with the upper end of the container 26. At this time, the lower end of the container 26 would deform in an uneven, undulating manner along the uneven surfaces of the plurality of first magnets 6B. Similarly, the upper end of the container 26 would deform in an uneven, undulating manner along the uneven surfaces of the plurality of second magnets 10B. As a result, there is a risk of uneven adsorption between the magnetic particles 40 and the plurality of first magnets 6B and the plurality of second magnets 10B at the lower and upper ends of the container 26, respectively.

[0100] In contrast, in the magnetic separation device 2B according to the second modification, as described above, the first non-magnetic plate 44 is disposed between the plurality of first magnets 6B and the lower end of the container 26, and the second non-magnetic plate 46 is disposed between the plurality of second magnets 10B and the upper end of the container 26. This prevents the lower end of the container 26 from deforming in an uneven, wavy manner by contacting the flat upper surface of the first non-magnetic plate 44. Similarly, the upper end of the container 26 is prevented from deforming in an uneven, wavy manner by contacting the flat lower surface of the second non-magnetic plate 46.

[0101] In this modification, the magnetic separation device 2B is provided with a plurality of first magnets 6B and a plurality of second magnets 10B, but is not limited to this and may be provided with one each of the first magnet 6B and the second magnet 10B. In this case, even if the upper end of the first magnet 6B and the lower end of the second magnet 10B are formed unevenly by, for example, screw holes, the same effect as described above can be obtained.

[0102] <Second Disclosure> Next, as a second disclosure, second to fourth embodiments will be described.

[0103] (Embodiment 2) [2-1. Configuration of Magnetic Separator] The configuration of a magnetic separation device 102 according to embodiment 2 will be described with reference to Fig. 6. Fig. 6 is a schematic diagram showing the configuration of a magnetic separation device 102 according to embodiment 2.

[0104] 6, the left-right direction of the magnetic separation device 102 is the X-axis direction, the front-rear direction of the magnetic separation device 102 is the Y-axis direction, and the up-down direction of the magnetic separation device 102 is the Z-axis direction. The positive side of the X-axis is the "right," the negative side of the X-axis is the "left," the positive side of the Y-axis is the "front," the negative side of the Y-axis is the "rear," the positive side of the Z-axis is the "up," and the negative side of the Z-axis is the "down." That is, FIG. 6 is a plan view of the magnetic separation device 102 viewed from above.

[0105] 6, the magnetic separation device 102 includes a magnet unit 104, a movement mechanism 106 (an example of a control unit), a drive source 108, and a control unit 110. The magnetic separation device 102 is used as an automated device for separating hematopoietic stem cells from human blood in the process of establishing iPS cells in regenerative medicine, for example.

[0106] The magnet unit 104 includes a first magnet 112 , a second magnet 114 , a third magnet 116 , a first yoke 118 , a second yoke 120 , and a third yoke 122 .

[0107] Each of the first magnet 112, the second magnet 114, and the third magnet 116 is, for example, a permanent magnet, and is formed in a substantially rectangular shape when viewed in the XY plane. The first magnet 112, the second magnet 114, and the third magnet 116 are arranged in this order from the front side to the rear side of the magnetic separation device 102.

[0108] Each of the first yoke 118, the second yoke 120, and the third yoke 122 is formed, for example, in a substantially U-shape when viewed in the XY plane. The first yoke 118, the second yoke 120, and the third yoke 122 are attached to three sides of the first magnet 112, the second magnet 114, and the third magnet 116, respectively, when viewed in the XY plane, and are connected to each other. Specifically, the first yoke 118 and the second yoke 120 are connected to each other, and the second yoke 120 and the third yoke 122 are connected to each other. In other words, the first magnet 112, the second magnet 114, the third magnet 116, the first yoke 118, the second yoke 120, and the third yoke 122 can slide together. The first yoke 118, the second yoke 120, and the third yoke 122 amplify the magnetic attraction forces of the first magnet 112, the second magnet 114, and the third magnet 116, respectively.

[0109] The movement mechanism 106 is an actuator for sliding (an example of displacement) one of the magnet unit 104 and the container 124 (described later) relative to the other in the left-right direction (X-axis direction) of the magnetic separation device 102. The movement mechanism 106 slides one of the magnet unit 104 and the container 124 relative to the other in the left-right direction, thereby changing the magnetic field generated by the magnet unit 104 inside the container 124. In other words, the movement mechanism 106 has the function of adjusting the strength of the magnetic field generated by the magnet unit 104 inside the container 124. In this embodiment, the container 124 is fixed to a housing (not shown) of the magnetic separation device 102, and the magnetic separation device 102 slides the magnet unit 104 relative to the container 124 in the left-right direction.

[0110] Conversely, the magnet unit 104 may be fixed to the housing of the magnetic separation device 102, and the magnetic separation device 102 may be configured to slide the container 124 in the left-right direction relative to the magnet unit 104. Alternatively, both the magnet unit 104 and the container 124 may be configured to be movable with respect to the housing of the magnetic separation device 102. In this case, the movement mechanism 106 may simultaneously slide both the magnet unit 104 and the container 124 in opposite directions to each other in the left-right direction.

[0111] The driving source 108 is a servo motor for driving the moving mechanism 106 .

[0112] The control unit 110 is a controller for controlling the rotation position, rotation direction, rotation speed, etc. of the drive source 108 .

[0113] Furthermore, a container 124 is placed on the magnet unit 104. That is, the magnet unit 104 is disposed near the container 124. In this specification, "disposed near the container 124" means not only that the magnet unit 104 is in contact with the container 124, but also that there is a gap of, for example, several millimeters to several tens of millimeters between the magnet unit 104 and the container 124.

[0114] The container 124 is formed, for example, from a flexible non-magnetic material and is shaped like a bag so that a liquid (described later) can be stored therein. In the XY plane view, the size of the container 124 is larger than the size of the magnet unit 104. An inflow port 128 (an example of a port) is formed in the center in the left-right direction of the rear end 124b of the container 124, allowing liquid supplied from, for example, a syringe (not shown) to flow into the container 124. Furthermore, an outflow port 126 (an example of a port) is formed at one end (left end) in the left-right direction of the front end 124a of the container 124, allowing the liquid inside the container 124 to flow out of the container 124.

[0115] Although not shown, an inlet-side on-off valve and an outlet-side on-off valve (both examples of on-off valves) for switching between flow and blocking of liquid, etc. are disposed in the inlet port 128 and the outlet port 126, respectively. Also, although not shown, an intake / exhaust port for letting air in and out of the container 124 is formed in the rear end 124b (or the front end 124a) of the container 124.

[0116] The container 124 contains a liquid that has flowed in through the inlet port 128. The liquid is, for example, human blood, and is illustrated in FIG. 6 with a dotted pattern. The liquid contains a solvent component such as plasma, a plurality of biological particles 130, a plurality of impurity particles 132, and a plurality of magnetic particles 134. That is, the liquid is produced by mixing a plurality of magnetic particles 134 with human blood that contains a solvent component such as plasma, a plurality of biological particles 130, and a plurality of impurity particles 132. The amount of liquid contained in the container 124 is, for example, approximately 10 ml to several tens of ml.

[0117] For ease of explanation, Fig. 6 shows only a few biological particles 130, impurity particles 132, and magnetic particles 134, but in reality, the liquid contains a large number of biological particles 130, impurity particles 132, and magnetic particles 134. For ease of explanation, Fig. 6 shows the sizes of the biological particles 130, impurity particles 132, and magnetic particles 134 exaggerated.

[0118] The bioparticles 130 are target cells, such as hematopoietic stem cells, that are to be separated by the magnetic separation device 102. For ease of explanation, the bioparticles 130 are simply illustrated as white circles in Figure 6.

[0119] The impurity particles 132 are all cells other than the bioparticles 130 that are not subject to separation by the magnetic separation device 102. For ease of explanation, the impurity particles 132 are simply illustrated as white triangles in Fig. 6.

[0120] The magnetic particles 134 are artificial particles that have magnetism, and are so-called magnetic beads. A modified shape is formed on the surface of the magnetic particles 134, and they can specifically bind to the bioparticles 130. For ease of explanation, the magnetic particles 134 are simply illustrated as black circles in Figure 6.

[0121] [2-2. Flow of magnetic separation method] The flow of the magnetic separation method using the magnetic separation device 102 according to embodiment 2 will be described with reference to Figures 7 to 12. Figure 7 is a flowchart showing the flow of the magnetic separation method using the magnetic separation device 102 according to embodiment 2. Figures 8 to 12 are schematic diagrams showing the flow of the magnetic separation method using the magnetic separation device 102 according to embodiment 2.

[0122] For convenience of explanation, the moving mechanism 106, the driving source 108, and the control unit 110 are omitted from illustration in Figures 8 to 12. Furthermore, in Figures 8 to 10 and 12, the magnet unit 104 is illustrated so as to be visible through the container 124 in order to explain the positional relationship between the magnet unit 104 and the container 124.

[0123] As a preliminary preparation, a liquid is prepared by mixing a plurality of magnetic particles 134 with human blood containing a solvent component such as plasma, a plurality of biological particles 130, and a plurality of impurity particles 132, and the prepared liquid is left for a certain period of time, whereby the biological particles 130 and the magnetic particles 134 in the liquid are specifically bound to each other.

[0124] 7, with the inlet-side on-off valve open and the outlet-side on-off valve closed, the liquid prepared in advance is poured into the container 124 through the inlet port 128 (S11). As a result, the liquid is contained in the container 124.

[0125] 8, the container 124 is placed on the magnet unit 104 (S12). At this time, the container 124 is placed on the magnet unit 104 so as to completely cover the magnet unit 104 in the XY plane view.

[0126] As a result, a magnetic field is generated by the magnet unit 104 inside the container 124. Therefore, magnetic particles 134 bonded to bioparticles 130 present at any position inside the container 124 are affected by the magnetic field inside the container 124 and move inside the container 124 toward the magnet unit 104. Then, the magnetic particles 134 bonded to the bioparticles 130 are magnetically attracted to each of the first magnet 112, the second magnet 114, and the third magnet 116 of the magnet unit 104, and are fixed directly above the first yoke 118, the second yoke 120, and the third yoke 122 inside the container 124 (i.e., regions inside the container 124 where the magnetic field strength is relatively high).

[0127] 9 and 10 , the movement mechanism 106 (see FIG. 6 ) slides the magnet unit 104 leftward (toward the negative side of the X-axis) relative to the container 124 (S13). At this time, the movement mechanism 106 slides the magnet unit 104 across the left side of the container 124 (i.e., the side where the outflow port 126 is located) so that the container 124 slides on the magnet unit 104.

[0128] While the magnet unit 104 slides relative to the container 124, the magnetic particles 134 coupled to the bioparticles 130 are magnetically attracted to the first magnet 112, the second magnet 114, and the third magnet 116 of the magnet unit 104, respectively, and remain fixed directly above the first yoke 118, the second yoke 120, and the third yoke 122 inside the container 124. Therefore, as the magnet unit 104 slides leftward relative to the container 124, the magnetic particles 134 coupled to the bioparticles 130 are locally collected in a specific region 136 (the region surrounded by a dashed line in FIG. 10 ) near the inlet port 128 inside the container 124. In other words, a high concentration of the bioparticles 130 is trapped in the specific region 136 inside the container 124. Note that the impurity particles 132 are not affected by the magnetic field inside the container 124 and are therefore dispersed throughout the entire interior of the container 124.

[0129] Next, a cleaning liquid such as PBS is injected into the container 124 through the inflow port 128 (S14). As a result, the solvent components such as plasma and impurity particles 132 present in the liquid inside the container 124 are discharged from the outlet port 126 to the outside of the container 124 by the flow of the cleaning liquid.

[0130] 11, the inlet valve is opened and the outlet valve is closed, and the recovery solution is injected into the container 124 from the inlet port 128 (S15). Next, as shown in FIG. 11, the magnet unit 104 is completely separated from the container 124 (S16).

[0131] Next, as shown in Figure 11, with the inlet valve closed and the outlet valve open, a portion of the recovery solution present inside the container 124 (specifically, the recovery solution containing the bioparticles 130 present in the specific region 136) is discharged from the outlet port 126 to the outside of the container 124, thereby recovering the bioparticles 130 that have gathered in the specific region 136 (S17).

[0132] At this time, by squeezing a part of the container 124, a part of the recovery solution present inside the container 124 is discharged from the outlet port 126 to the outside of the container 124. If the container 124 is not flexible, a part of the recovery solution present inside the container 124 may be discharged from the outlet port 126 to the outside of the container 124 by injecting the recovery solution into the inside of the container 124 from the inlet port 128 or by sending gas into the inside of the container 124 from the intake / exhaust port.

[0133] 12 , the moving mechanism 106 may slide the magnet unit 104 relative to the container 124 in a direction from the upstream side to the downstream side of the outlet port 126 (toward the positive side of the Y axis). As a result, the bioparticles 130 collected in a specific region 136 inside the container 124 are discharged from the outlet port 126 to the outside of the container 124 while remaining magnetically attracted to the magnet unit 104 as the magnet unit 104 slides.

[0134] [2-3. Effects] In the present embodiment, as described above, the moving mechanism 106 slides the magnet unit 104 relative to the container 124 so as to collect the magnetic particles 134 bound to the bioparticles 130 in a specific region 136 inside the container 124. As a result, when, for example, a recovery solution is injected into the container 124 to recover the bioparticles 130, the bioparticles 130 collected in the specific region 136 inside the container 124 can be discharged to the outside of the container 124 together with the recovery solution present in the specific region 136 (i.e., a portion of the recovery solution injected into the container 124). As a result, the bioparticles 130 remaining inside the container 124 can be recovered in a state where they are dispersed in a relatively small amount of recovery solution, and the recovery concentration of the bioparticles 130 can be increased.

[0135] (Embodiment 3) The configuration of a magnetic separation device 102A according to embodiment 3 will be described with reference to Fig. 13. Fig. 13 is a schematic diagram showing the configuration of a magnetic separation device 102A according to embodiment 3. In this embodiment, the same components as those in embodiment 2 above are denoted by the same reference numerals, and their description will be omitted.

[0136] 13 , in a magnetic separation device 102A according to the third embodiment, the configuration of a magnet unit 104A is different from that of the magnetic separation device according to the second embodiment. Specifically, the magnet unit 104A has a rotating member 138, a first magnet 140, a second magnet 142, a third magnet 144, and a fourth magnet 146.

[0137] The rotary member 138 is formed in an annular shape and is rotatable in a predetermined direction (counterclockwise in FIG. 13) around a central axis 148 extending in the up-down direction (Z-axis direction).

[0138] Each of the first magnet 140, the second magnet 142, the third magnet 144, and the fourth magnet 146 is, for example, a permanent magnet, and is formed in a substantially rectangular shape when viewed in the XY plane. The first magnet 140, the second magnet 142, the third magnet 144, and the fourth magnet 146 are fixed to the rotating member 138, and are arranged at intervals along the circumferential direction of the rotating member 138.

[0139] Furthermore, the magnetic separation device 102A includes a rotation mechanism 150 (an example of an adjustment unit) instead of the movement mechanism 106 described in the second embodiment. The rotation mechanism 150 is an actuator for rotating (an example of displacement) the magnet unit 104A in a predetermined direction relative to the container 124, and is driven by the drive source 108. The rotation mechanism 150 rotates the magnet unit 104A in a predetermined direction relative to the container 124, thereby changing the magnetic field generated by the magnet unit 104A inside the container 124. In other words, the rotation mechanism 150 has the function of adjusting the magnetic field strength generated by the magnet unit 104A inside the container 124.

[0140] While the magnet unit 104A rotates relative to the container 124, the magnetic particles 134 bound to the bioparticles 130 are magnetically attracted to each of the first magnet 140, the second magnet 142, the third magnet 144, and the fourth magnet 146 of the magnet unit 104A, and are fixed directly above the outer peripheries of the first magnet 140, the second magnet 142, the third magnet 144, and the fourth magnet 146 inside the container 124 (i.e., in regions inside the container 124 where the magnetic field strength is relatively high). Therefore, as the magnet unit 104A rotates relative to the container 124, the magnetic particles 134 bound to the bioparticles 130 are locally collected in a specific region 136 near the outlet port 126 inside the container 124.

[0141] Therefore, in this embodiment as well, the same effects as those in the second embodiment can be obtained.

[0142] (Embodiment 4) The configuration of a magnetic separation device 102B according to embodiment 4 will be described with reference to Fig. 14. Fig. 14 is a schematic diagram showing the configuration of a magnetic separation device 102B according to embodiment 4. In this embodiment, the same components as those in embodiment 2 above are denoted by the same reference numerals, and their description will be omitted.

[0143] As shown in FIG. 14, a magnetic separation device 102B according to the fourth embodiment includes a plurality of electromagnets 152 instead of the magnet unit 104 described in the second embodiment.

[0144] Each of the multiple electromagnets 152 is an example of a magnet and is formed in a substantially rectangular shape when viewed in the XY plane. The multiple electromagnets 152 are arranged two-dimensionally near the container 124, specifically directly below the container 124. More specifically, the multiple electromagnets 152 are arranged two-dimensionally so as to cover the entire area of ​​the container 124 and the outflow port 126. When a current is supplied to one or more of the multiple electromagnets 152, a magnetic force is generated from the one or more electromagnets 152. Note that no magnetic force is generated from the other one or more electromagnets 152 to which no current is supplied.

[0145] Furthermore, the magnetic separation device 102B includes a power supply 154 (an example of an adjustment unit) instead of the moving mechanism 106 described in the second embodiment. The power supply 154 controls the supply of current to each of the plurality of electromagnets 152. The power supply 154 switches on and off the supply of current to each of the plurality of electromagnets 152 based on a control signal from the control unit 110B, thereby changing the magnetic field inside the container 124 generated by the one or more electromagnets 152 to which current is supplied. In other words, the power supply 154 has a function of adjusting the magnetic field strength generated by the one or more electromagnets 152 inside the container 124.

[0146] With the container 124 placed on the plurality of electromagnets 152, the power supply 154 first supplies current to all of the electromagnets 152. Next, the power supply 154 turns off the supply of current to the electromagnet 152 located farthest from the specific region 136 inside the container 124. Next, the power supply 154 turns off the supply of current to the electromagnet 152 located farthest from the specific region 136 among the other plurality of electromagnets 152 to which current is being supplied. By repeating this process, the magnetic particles 134 bound to the bioparticles 130 present inside the container 124 gradually move inside the container 124 toward the specific region 136 while being magnetically attracted to each of the plurality of electromagnets 152 that are closer to the specific region 136.

[0147] The power supply 154 then supplies current only to the multiple electromagnets 152 located directly under the specific region 136. As a result, the magnetic particles 134 bound to the biological particles 130 are locally collected in the specific region 136 near the outlet port 126 inside the container 124.

[0148] Finally, the power supply 154 supplies current only to the multiple electromagnets 152 directly below the outlet port 126, thereby discharging the magnetic particles 134 bound to the biological particles 130 from the outlet port 126 to the outside of the container 124.

[0149] Therefore, in this embodiment as well, the same effects as those in the second embodiment can be obtained.

[0150] <Third Disclosure> Next, as the third disclosure, fifth to seventh embodiments will be described.

[0151] (Fifth Embodiment) [5-1. Configuration of Magnetic Separator] The configuration of a magnetic separation device 202 according to the fifth embodiment will be described with reference to Figs. 15 to 17. Fig. 15 is a schematic diagram showing the configuration of the magnetic separation device 202 according to the fifth embodiment. Fig. 16 is a schematic diagram showing the magnetic separation device 202 according to the fifth embodiment in use. Fig. 17 is a schematic diagram for explaining the angular relationship between the magnet 206 and the inlet port 214 of the magnetic separation device 202 according to the fifth embodiment.

[0152] 15, the left-right direction of the magnetic separation device 202 is the X-axis direction, the front-rear direction of the magnetic separation device 202 is the Y-axis direction, and the up-down direction of the magnetic separation device 202 is the Z-axis direction. The positive side of the X-axis is the "right," the negative side of the X-axis is the "left," the positive side of the Y-axis is the "front," the negative side of the Y-axis is the "rear," the positive side of the Z-axis is the "up," and the negative side of the Z-axis is the "down." That is, FIGS. 15 and 16 are plan views of the magnetic separation device 202 viewed from above.

[0153] 15 and 16 , the magnetic separation device 202 includes a mounting portion 204 and a plurality of magnets 206. The magnetic separation device 202 is used as an automated device for separating hematopoietic stem cells from human blood in the process of establishing iPS cells in regenerative medicine, for example.

[0154] The mounting portion 204 is a mounting table for mounting the container 208. A mounting surface 210 is formed on the upper surface of the mounting portion 204. The mounting surface 210 is a real or virtual flat surface on which the container 208 is mounted.

[0155] Here, the container 208 is formed, for example, from a flexible non-magnetic material and is formed in a bag shape so as to be able to contain a liquid (described later) therein. A cylindrical inlet port 214 (an example of a port) is connected to the center in the left-right direction of a rear end 212 of the container 208, through which a liquid or the like supplied from, for example, a syringe (not shown) flows into the container 208. Furthermore, a cylindrical outlet port 218 is formed at one end (left end) in the left-right direction of a front end 216 of the container 208, through which the liquid or the like inside the container 208 flows out of the container 208. When a liquid or the like flows into the container 208 from the inlet port 214, the container 208 is formed so that the internal volume of the container 208 increases (i.e., the container 208 changes from a deflated state to an expanded state) as the liquid or the like flows in.

[0156] 16 shows the mounting portion 204 and the plurality of magnets 206 as if they are visible through the container 208 in order to explain the positional relationship between the mounting portion 204 and the plurality of magnets 206 and the container 208. Although not shown, an inlet-side on-off valve and an outlet-side on-off valve are disposed in the inlet port 214 and the outlet port 218, respectively, for switching between flow and blocking of a liquid or the like. Although not shown, an intake / exhaust port is formed in the rear end 212 (or the front end 216) of the container 208 for letting air in and out of the container 208.

[0157] The container 208 contains a liquid that has flowed in through the inlet port 214. The liquid is, for example, human blood, and is illustrated in FIG. 15 with a dotted pattern. The liquid contains a solvent component such as plasma, a plurality of biological particles 220, a plurality of impurity particles 222, and a plurality of magnetic particles 224. That is, the liquid is produced by mixing a plurality of magnetic particles 224 with human blood that contains a solvent component such as plasma, a plurality of biological particles 220, and a plurality of impurity particles 222. The amount of liquid contained in the container 208 is, for example, approximately 10 ml to several tens of ml.

[0158] For ease of explanation, Fig. 15 shows only a few biological particles 220, impurity particles 222, and magnetic particles 224, but in reality, the liquid contains a large number of biological particles 220, impurity particles 222, and magnetic particles 224. For ease of explanation, the sizes of the biological particles 220, impurity particles 222, and magnetic particles 224 are exaggerated in Fig. 15.

[0159] The bioparticles 220 are target cells, such as hematopoietic stem cells, that are to be separated by the magnetic separation device 202. For ease of explanation, the bioparticles 220 are simply illustrated as white circles in Figure 15.

[0160] The impurity particles 222 are all cells other than the bioparticles 220 that are not subject to separation by the magnetic separation device 202. For ease of explanation, the impurity particles 222 are simply illustrated as white triangles in FIG.

[0161] The magnetic particles 224 are artificial particles that have magnetism, and are so-called magnetic beads. A modified shape is formed on the surface of the magnetic particles 224, and they can specifically bind to the biological particles 220. For ease of explanation, the magnetic particles 224 are simply illustrated as black circles in Figure 15.

[0162] Returning to the description of the mounting unit 204, the mounting surface 210 of the mounting unit 204 has an adsorption region 226 and a non-adsorption region 228. The adsorption region 226 is a region in which a plurality of magnets 206 are arranged, and is a region that magnetically attracts magnetic particles 224 bound to bioparticles 220 inside the container 208. The non-adsorption region 228 is a region formed between the adsorption region 226 and a position directly below a connection portion 230 (or its vicinity) between the inflow port 214 connected to the container 208 and the container 208, and is a region that does not magnetically attract magnetic particles 224 bound to bioparticles 220 inside the container 208. The non-adsorption region 228 is formed so as to expand in a substantially fan shape (e.g., a semicircular shape) from a position directly below the connection portion 230 (or its vicinity) toward the adsorption region 226. Furthermore, in the XY plane view (i.e., when the mounting surface 210 is viewed in plan), the radius R1 (e.g., approximately 2 cm) of the non-suction region 228 is longer than the diameter D1 (e.g., approximately 5 to 8 mm) of the inlet port 214, and is 1 to 5 times the length of the diameter D1. Note that the non-suction region 228 may be a substantial (physical) plane on which a non-magnetic material is arranged, or may be an immaterial virtual plane formed, for example, by a cutout or the like.

[0163] Each of the plurality of magnets 206 is, for example, a permanent magnet, and is formed in a substantially rectangular shape (e.g., a rectangular shape) in an XY plane view. The plurality of magnets 206 are arranged in an attraction region 226 on the mounting surface 210 of the mounting unit 204. The upper surfaces of the plurality of magnets 206 are arranged on substantially the same plane as the mounting surface 210 of the mounting unit 204. More specifically, the plurality of magnets 206 are arranged in multiple rows (two rows in this embodiment) in an arc shape centered at a position directly below a connection portion 230 between the inlet port 214 and the container 208, and are also arranged radially from the position directly below the connection portion 230.

[0164] 17 , the angular relationship between any one of the magnets 206 and the inflow port 214 will be described. As shown in FIG. 17 , in an XY plane view, the magnet 206 is rectangular having a pair of long sides 232 a, 232 b and a pair of short sides 234 a, 234 b, and one long side 232 a of the magnet 206 is disposed substantially parallel to a radial line 236 that extends radially from a position directly below the connection portion 230 along the mounting surface 210. In addition, in an XY plane view, an angle θ formed between a line 242 connecting a radial center 240 at the downstream opening end 238 of the inflow port 214 and the center of the other long side 232 b (an example of the other side) of the magnet 206 that faces the one long side 232 a (an example of one side) of the magnet 206 and the long side 232 b of the magnet 206 is 30° or less.

[0165] As shown in Figure 17, when viewed in the XY plane, for example, if the length of each of the pair of short sides 234a, 234b of the magnet 206 is 20 mm, the length of each of the pair of long sides 232a, 232b is 30 mm, and the distance between the radial center 240 at the downstream opening end 238 of the inlet port 214 and the short side 234a of the magnet 206 (the short side closer to the inlet port 214) is 30 mm, then the angle θ = arctan(20 / 45) = approximately 24°.

[0166] The angular relationship between the inflow port 214 and the other magnets 206 other than the arbitrary one magnet 206 among the plurality of magnets 206 is the same as the angular relationship described above.

[0167] 16, 18, and 19, a method of using the magnetic separation device 202 according to the fifth embodiment will be described. Fig. 18 is a schematic diagram showing the magnetic separation device 202 according to the fifth embodiment in use. Fig. 19 is a schematic cross-sectional view of the magnetic separation device 202 according to the fifth embodiment taken along line XIX-XIX in Fig. 18.

[0168] For ease of explanation, Figure 18 illustrates the mounting portion 204 and the multiple magnets 206 as being visible through the container 208 in order to explain the positional relationship between the mounting portion 204 and the multiple magnets 206 and the container 208.

[0169] As a preliminary preparation, a liquid is prepared by mixing a plurality of magnetic particles 224 with human blood containing a solvent component such as plasma, a plurality of biological particles 220, and a plurality of impurity particles 222, and the prepared liquid is left for a certain period of time, whereby the biological particles 220 and the magnetic particles 224 in the liquid are specifically bound to each other.

[0170] Then, with the inlet valve open and the outlet valve closed, the liquid prepared in advance is poured into the container 208 through the inlet port 214. At this time, as the liquid is poured (flows in), the volume of the interior of the container 208 increases (i.e., the container 208 changes from a deflated state to an expanded state). As a result, the liquid is contained within the container 208.

[0171] 16, the container 208 is placed on the placement surface 210 of the placement unit 204. At this time, the container 208 is placed on the placement surface 210 so as to cover the entire placement surface 210 in the XY plane view.

[0172] As a result, a magnetic field is generated inside the container 208 by the plurality of magnets 206 arranged in the adsorption region 226. Therefore, magnetic particles 224 bound to bioparticles 220 present at any position inside the container 208 are affected by the magnetic field inside the container 208 and move inside the container 208 toward the adsorption region 226. The magnetic particles 224 bound to the bioparticles 220 are then magnetically attracted to each of the plurality of magnets 206 arranged in the adsorption region 226 and fixed directly above each side of the plurality of magnets 206 (i.e., in a region inside the container 208 where the magnetic field strength is relatively high). Note that the impurity particles 222 are not affected by the magnetic field inside the container 208 and are therefore dispersed throughout the entire interior of the container 208.

[0173] 18 and 19 , with both the inlet-side on-off valve and the outlet-side on-off valve open, a cleaning liquid such as PBS is injected into the container 208 through the inlet port 214. At this time, the cleaning liquid from the inlet port 214 flows radially into the container 208. As a result, solvent components such as plasma and impurity particles 222 present in the liquid inside the container 208 are discharged from the outlet port 218 to the outside of the container 208 by the flow of the cleaning liquid.

[0174] Next, although not shown, with the inlet valve open and the outlet valve closed, the recovery solution is injected into the container 208 through the inlet port 214, and the container 208 is removed from the mounting surface 210 of the mounting section 204.

[0175] Next, with the inlet valve closed and the outlet valve open, the recovery solution present inside the container 208 is discharged from the outlet port 218 to the outside of the container 208, thereby recovering the bioparticles 220.

[0176] [5-3. Effects] Here, the configuration of a magnetic separation device 2100 according to a comparative example will be described with reference to Fig. 20. Fig. 20 is a schematic cross-sectional view of the magnetic separation device 2100 according to the comparative example. Note that in Fig. 20, the same components as those in the magnetic separation device 202 according to embodiment 5 are denoted by the same reference numerals, and their description will be omitted.

[0177] 20 , in a magnetic separation device 2100 according to the comparative example, the mounting surface 210 of the mounting portion 204 has only an attraction region 244 and does not have the non-attraction region described above. The attraction region 244 is formed to extend forward (toward the positive side of the Y axis) from a position directly below the connection portion 230. A plurality of magnets 206 are arranged in the attraction region 244.

[0178] When the cleaning solution is injected into the container 208 from the inflow port 214, the cleaning solution flows into the container 208 through the inflow port 214, which has a cross-sectional area smaller than that of the container 208, and therefore the flow rate of the cleaning solution near the connection part 230 is relatively fast. Therefore, as shown in Fig. 20 , when the cleaning solution is flowed into the container 208, the flow of the cleaning solution unintentionally releases the magnetic attraction between the magnetic particles 224 present near the connection part 230 and the magnet 206. As a result, the recovery efficiency of the bioparticles 220 decreases.

[0179] In contrast, in the magnetic separation device 202 according to the fifth embodiment, the mounting surface 210 of the mounting unit 204 has a non-adsorption region 228 formed so as to expand in a generally fan-like shape from a position directly below the connection portion 230 toward the adsorption region 226 (i.e., across the region where the flow rate of the cleaning solution is relatively high). As a result, the magnetic particles 224 bound to the bioparticles 220 inside the container 208 are not magnetically attracted to the non-adsorption region 228. Therefore, as shown in FIG. 19 , even when the flow rate of the cleaning solution flowing near the connection portion 230 is relatively high, it is possible to prevent the magnetic attraction between the magnet 206 and the magnetic particles 224 from being unintentionally released by the flow of the cleaning solution. As a result, it is possible to improve the recovery efficiency of the bioparticles 220.

[0180] (Embodiment 6) The configuration of a magnetic separation device 202A according to embodiment 6 will be described with reference to Fig. 21. Fig. 21 is a schematic diagram showing the configuration of magnetic separation device 202A according to embodiment 6. Note that in this embodiment, the same components as those in magnetic separation device 202 according to embodiment 5 above are denoted by the same reference numerals, and their description will be omitted.

[0181] 21 , in a magnetic separation device 202A according to the sixth embodiment, the arrangement of the magnets 206 in the adsorption area 226 differs from that of the fifth embodiment. Specifically, the magnets 206 are arranged in only one row in an arc shape centered directly below the connection 230 between the inlet port 214 and the container 208. In addition, each long side of the magnets 206 is approximately parallel to the axial direction of the inlet port 214 (the Y-axis direction).

[0182] Even with the configuration of this embodiment, the same effects as those of the fifth embodiment can be obtained.

[0183] (Seventh embodiment) The configuration of a magnetic separation device 202B according to a seventh embodiment will be described with reference to Fig. 22. Fig. 22 is a schematic diagram showing the configuration of a magnetic separation device 202B according to the seventh embodiment. In this embodiment, the same components as those in the magnetic separation device 202 according to the fifth embodiment are denoted by the same reference numerals, and their description will be omitted.

[0184] As shown in FIG. 22, in a magnetic separation device 202B according to the seventh embodiment, the arrangement of a pair of attraction region 226B and non-attraction region 228B on the mounting surface 210 of the mounting portion 204 differs from that in the fifth embodiment.

[0185] Specifically, the non-suction region 228B is formed to extend linearly forward from a position directly below the connection portion 230 along the axial direction (Y-axis direction) of the inflow port 214. In addition, in the XY plane view, the length D2 (e.g., approximately 2 cm) in the short direction of the non-suction region 228B is longer than the diameter D1 (e.g., approximately 5 to 8 mm) of the inflow port 214, and is 1 to 5 times the length of the diameter D1.

[0186] The pair of attraction regions 226B are disposed on both the left and right sides of the non-attraction region 228B. In each attraction region 226B, the plurality of magnets 206 are disposed at intervals along the axial direction of the inflow port 214. The long sides of the plurality of magnets 206 are substantially parallel to the axial direction of the inflow port 214 (the Y-axis direction).

[0187] In this embodiment, container 208B is made of a non-magnetic material (such as hard plastic) that is not flexible. That is, container 208B is formed so that when a liquid or the like flows into container 208B from inlet port 214, the volume of the interior of container 208B does not change in accordance with the flow of the liquid or the like.

[0188] In this embodiment, when the volume of container 208B is not variable, the cleaning liquid from inflow port 214 flows linearly into container 208B along the axial direction of inflow port 214, and the volume inside container 208B does not change as the cleaning liquid flows in, as shown in Fig. 22. At this time, non-adsorption region 228B is formed so as to extend linearly from a position directly below connection portion 230 along the axial direction of inflow port 214 (i.e., across the region where the flow rate of the cleaning liquid is relatively high), and therefore, it is possible to prevent the magnetic attraction between magnet 206 and magnetic particles 224 from being unintentionally released by the linear flow of the cleaning liquid.

[0189] (Other Embodiments) While the magnetic separation device and the like according to one or more aspects of the present disclosure have been described above based on the embodiments and modifications thereof, the present disclosure is not limited to these embodiments and modifications. As long as they do not deviate from the spirit of the present disclosure, various modifications conceivable by a person skilled in the art to the embodiments and modifications may also be included within the scope of one or more aspects of the present disclosure.

[0190] In the above embodiment 1, the moving mechanism 12 moves one of the first support plate 4 and the second support plate 8 relative to the other, but this is not limited to this, and the user may manually move one of the first support plate 4 and the second support plate 8 relative to the other.

[0191] Furthermore, in the first embodiment, the container 26 is made of a flexible non-magnetic material, but the container 26 may be made of a flexible and stretchable non-magnetic material.

[0192] Furthermore, in the first embodiment, the first magnet 6 contacts the lower end of the container 26 via the first support plate 4, and the second magnet 10 contacts the upper end of the container 26 via the second support plate 8, but this is not limiting. For example, the first support plate 4 and the second support plate 8 may be omitted, and the first magnet 6 may directly contact the lower end of the container 26, and the second magnet 10 may directly contact the upper end of the container 26.

[0193] Furthermore, in the first embodiment, the N magnetic pole portion 20n of the first magnet 6 and the S magnetic pole portion 24s of the second magnet 10 are arranged to face each other, but this is not limited thereto, and the N magnetic pole portion 20n of the first magnet 6 and the N magnetic pole portion 24n of the second magnet 10 may be arranged to face each other. Alternatively, the S magnetic pole portion 20s of the first magnet 6 and the S magnetic pole portion 24s of the second magnet 10 may be arranged to face each other.

[0194] Furthermore, in the above-mentioned embodiment 1, the magnetic separation device 2 is provided with a moving mechanism 12, but this is not limited to this, and for example, the moving mechanism 12 may be omitted and the relative positional relationship between the first support plate 4 and the second support plate 8 may be fixed.

[0195] Furthermore, in the above-mentioned second embodiment, the moving mechanism 106 slides one of the magnet unit 104 and the container 124 relative to the other, but this is not limited to this, and the user may manually slide one of the magnet unit 104 and the container 124 relative to the other.

[0196] Similarly, in the above-mentioned third embodiment, the rotation mechanism 150 slides one of the magnet unit 104A and the container 124 relative to the other, but this is not limited to this, and the user may manually slide one of the magnet unit 104A and the container 124 relative to the other.

[0197] Furthermore, in the above-described second to fourth embodiments, the container 124 is made of a flexible non-magnetic material, but the container 124 may be made of a flexible and stretchable non-magnetic material. Alternatively, the container 124 may be configured not to have flexibility.

[0198] Furthermore, in the second embodiment, the first magnet 112, the second magnet 114, and the third magnet 116 are each configured as a permanent magnet, but this is not limited thereto, and they may also be configured as electromagnets.

[0199] Furthermore, in the above-described third embodiment, the first magnet 140, the second magnet 142, the third magnet 144, and the fourth magnet 146 are each made up of a permanent magnet, but this is not limited to this, and they may also be made up of electromagnets.

[0200] Furthermore, in the fifth to seventh embodiments, each of the plurality of magnets 206 is configured as a permanent magnet, but this is not limitative, and each may be configured as an electromagnet.

[0201] The disclosure of this specification also includes any combination of the first, second, and third disclosures. The disclosure of this specification may include forms obtained by applying various modifications to each embodiment that a person skilled in the art would conceive, and forms realized by any combination of the components and functions of each embodiment within the scope of the present disclosure.

[0202] The magnetic separation device according to the present disclosure is applicable to automated devices for separating hematopoietic stem cells from human blood in the process of establishing iPS cells in regenerative medicine, for example.

[0203] DESCRIPTION OF SYMBOLS 2, 2A, 2B Magnetic separation device 4 First support plate 6, 6B First magnet 8 Second support plate 10, 10B Second magnet 12 Moving mechanism 14 Driving source 16 Control unit 18 First recess 20n, 24n North magnetic pole portion 20s, 24s South magnetic pole portion 22 Second recess 26 Container 28 Space 30 Inlet port 32 Outlet port 34 Intake / exhaust port 36 Biological particle 38 Impurity particle 40 Magnetic particle 42 Spacer 44 First non-magnetic plate 46 Second non-magnetic plate 102, 102A, 102B Magnetic separation device 104, 104A Magnet unit 106 Moving mechanism 108 Driving source 110, 110B Control unit 112, 140 First magnet 114, 142 Second magnet 116, 144 Third magnet 118 First yoke 120 Second yoke 122 Third yoke 124 Container 124a Front end 124b Rear end 126 Outlet port 128 Inlet port 130 Biological particle 132 Impurity particle 134 Magnetic particle 136 Specific region 138 Rotating member 146 Fourth magnet 148 Central axis 150 Rotating mechanism 152 Electromagnet 154 Power supply 202, 202A, 202B, 2100 Magnetic separation device 204 Placement section 206 Magnet 208, 208B Container 210 Placement surface 212 Rear end 214 Inlet port 216 Front end 218 Outlet port 220 Biological particle 222 Impurity particle 224 Magnetic particle 226, 226B Attraction region 228, 228B Non-attraction region 230 Connection portion 232a, 232b Long side 234a, 234b Short side 236 Radial line 238 Downstream opening end 240 Radial center 242 Straight line 244 Attraction region

Claims

1. A magnetic separation device for separating biological particles from a liquid containing the biological particles and magnetic particles capable of binding to the biological particles, comprising: a first magnet; and a second magnet arranged to face the first magnet; a space for accommodating the liquid and for placing a flexible container is formed between the first magnet and the second magnet; at least one of the first magnet and the second magnet is movable relative to the other in directions toward and away from the other; and each of the first magnet and the second magnet magnetically attracts the magnetic particles bound to the biological particles in the container.

2. A magnetic separation device as described in claim 1, wherein when one of the first magnet and the second magnet moves relatively toward the other, the container is compressed between the first magnet and the second magnet, and when one of the first magnet and the second magnet moves relatively away from the other, the container is expanded between the first magnet and the second magnet.

3. The magnetic separation device according to claim 2, wherein the first magnet and the second magnet have a first magnetic pole portion and a second magnetic pole portion that are magnetized to different magnetic poles, respectively, and the first magnetic pole portion of the first magnet and the second magnetic pole portion of the second magnet are arranged to face each other.

4. The magnetic separation device according to claim 3, further comprising: a first support plate that supports the first magnet; a second support plate that is arranged opposite the first support plate and that supports the second magnet; and a spacer that is arranged between the first support plate and the second support plate, wherein when one of the first magnet and the second magnet moves relatively in a direction approaching the other, the spacer is clamped between the first support plate and the second support plate.

5. The magnetic separation device according to any one of claims 1 to 4, further comprising: a first non-magnetic plate disposed between the first magnet and the container; and a second non-magnetic plate disposed opposite the first non-magnetic plate and between the second magnet and the container.

6. A magnetic separation method for separating biological particles from a liquid containing the biological particles and magnetic particles that can bind to the biological particles, the magnetic separation method comprising: (a) a step of placing a flexible container that holds the liquid in a space between a first magnet and a second magnet that are arranged facing each other; (b) a step of moving one of the first magnet and the second magnet relatively toward the other to compress the container between the first magnet and the second magnet, thereby magnetically attracting the magnetic particles that have been bound to the biological particles in the container to each of the first magnet and the second magnet; (c) a step of moving one of the first magnet and the second magnet relatively away from the other to expand the container between the first magnet and the second magnet; and (d) a step of discharging particles other than the biological particles that are contained in the liquid and that are not bound to the magnetic particles from the container.

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