KR102437359B1 - Appratuses for seperation using the magnetically driven internal reflux of magnetic particles inside a fluidic channel and methodes using thereof - Google Patents

Abstract

The present invention relates to a separation apparatus using magnetic particles and a separation method using the same, and more particularly, to a separation apparatus and a separation method using circulation of magnetic particles.
A separation device according to the present invention comprises: a fluid channel through which a fluid containing a material to be separated fixed to magnetic particles flows;
a first magnet for fixing magnetic particles upstream of the fluid channel;
a second magnet for moving the magnetic particles downstream of the fluid channel to a region where the fluid drag force is smaller than the magnetic force of the first magnet; and
contains magnetic particles.

Description

A separation apparatus using internal reflux of magnetic particles in a fluid channel and a separation method using the same

The present invention relates to a separation apparatus using magnetic particles and a separation method using the same, and more particularly, to a separation apparatus and a separation method using circulation of magnetic particles.

Testing the concentration of biomarkers, including pathogenic bacteria, viruses, and proteins in samples, is used as an important indicator to determine the condition of patients and samples. . Therefore, it is possible to quickly cope with and prevent diseases through early detection of the substances. However, since these substances exist only in trace amounts in the sample, a technique for rapidly separating and concentrating the target substance in a large-capacity sample is essential.

To this end, a technique for selectively collecting a target material in a composite sample using particles having a magnetic property capable of binding to the target material and then separating and concentrating it using an external magnetic field has been developed.

However, since the process of collecting the target material using magnetic particles is based on the binding reaction between the target material and the collecting material fixed on the surface of a limited amount of magnetic particles, the coupling efficiency between the two materials decreases when applied to a large sample such as water. This causes a decrease in the speed, functionality, and convenience of the technology.

In order to solve this problem, a method of increasing the coupling efficiency by flowing a sample containing a target material through a fluid channel in which magnetic particles are disposed has been developed. However, since the magnetic particles are lost by the drag force of the flowing fluid, there is a problem in that it is difficult to apply a high flow rate. In Korean Patent Application No. 10-2019-0112817, a virtual net made of magnetic particles is formed using a magnetic field in the conductive flow path, so that when the magnetic particles move in the flow direction of the fluid, the force in the opposite direction is generated by Lenz's law. A method of preventing the magnetic particles fixed to the flow path from flowing away is proposed. However, there is a limitation in that a conductive flow path is required, and when the flow rate is increased, the loss amount of the magnetic particles is increased.

Accordingly, a technology has been developed to quickly collect a target material with a small amount of magnetic particles by adding a fluid recirculation structure to the channel, but the size and complexity of the device become larger and complicated because additional channels and mechanical devices are required for recirculation. exist.

Accordingly, there is a continuing demand for an apparatus or method capable of simply restoring the magnetic particles that are fixed by the magnetic field and then drifted away by the fluid to their original positions.

An object to be solved in the present invention is to provide a new method for solving the loss of magnetic particles fixed by a magnetic field by the flow of a fluid.

An object to be solved in the present invention is to provide a new separation device capable of solving the loss of magnetic particles fixed by a magnetic field by the flow of a fluid.

An object to be solved in the present invention is to provide a new method that can reduce the amount of particles outflow and increase the efficiency of collecting pathogens by magnetically circulating magnetic particles that are fixed by a magnetic field by the flow of a fluid and then lost.

In order to solve the above problems,

fluid channels;

a first magnet for fixing magnetic particles upstream of the fluid channel;

a second magnet for moving the magnetic particles downstream of the fluid channel to a region where the fluid drag force is smaller than the magnetic force of the first magnet; and

A separation method comprising magnetic particles reciprocating between a first magnet and a second magnet is provided.

Although not limited in theory, when the magnetic particles fixed upstream by the magnetic field of the first magnet are separated from the center of the large fluid drag force due to the increase of the fluid drag force, the second magnet located downstream separates the separated magnetic particles with a small fluid drag force. The magnetic particles moved to the peripheral region of the flow path and moved to the region having a small fluid drag are again attracted to the first magnet and refluxed upstream, thereby causing the magnetic particles to reciprocate between the first magnet and the second magnet.

In the present invention, the first magnet is to fix the magnetic particles upstream of the fluid channel, and to reflux the magnetic particles lost and moved to a region with low fluid drag by the second magnet in the upstream direction.

In the present invention, the first magnet may be an array of permanent magnets, and preferably, the magnetic particles may provide a magnetic field including linear magnetic force lines crossing the fluid channel to form a virtual filter shape across the fluid channel, , The permanent magnet arrangement may include a parallel magnet arrangement, a Halbach arrangement, a Halbach ring.

In the practice of the present invention, the permanent magnet arrangement constituting the first magnet is Halbach in which 12 magnets are arranged with a difference in magnetization direction between adjacent magnets of 60 degrees so that the magnetic field can uniformly fill the cross section of the fluid channel therein. It may be a ring. In such a Halbach ring, the magnetic field forms a stronger magnetic force at the center than at the inlet and outlet of the ring, and the magnetic particles are pulled toward the center. , it is possible to prevent the target material from passing through the empty space of the fluid channel without being able to combine with the magnetic particles.

In the present invention, the second magnet moves the magnetic particles drifting away from the magnetic field of the first magnet by the drag force of the fluid to a region with a small drag force, to reflux in the upstream direction by the magnetic force of the first magnet. It may be an arrangement of installed permanent magnets.

In the present invention, since the fluid drag force is weaker at the wall surface than the center of the fluid channel, the second magnet may be an arrangement of permanent magnets that provides a force to pull magnetic particles from the center to the wall surface.

In the present invention, the second magnet may be a reverse propulsion magnet ring that additionally provides a force for pushing the magnetic particles in the upstream direction.

In a preferred embodiment of the present invention, the reverse propulsion magnet ring may be composed of four cube magnets with a difference in magnetization direction between adjacent magnets with respect to a flow path arranged at intervals of 90°.

In the present invention, the second magnet is disposed to be spaced apart from the first magnet by a predetermined distance, and the magnetic force of the first magnet so that the magnetic particles moved to a region with a low drag by the second magnet can be refluxed by the first magnet. It is preferable to be spaced apart within a distance greater than the drag in the region where this drag is small.

In the practice of the present invention, the distance between the first magnet and the second magnet may be determined in consideration of the magnetic force and flow velocity of the first magnet, and when the distance from the first magnet becomes too far, the magnetic particles are dragged by the second magnet Even if it moves to this small wall surface, the magnetic force of the first magnet is weak, so that it is not refluxed and remains fixed to the wall surface.

In the present invention, the fluid channel may be any type of channel through which the fluid can pass, and therefore, the material or shape thereof is not limited.

In an embodiment of the present invention, the fluid channel may be made of ceramic, polymer, metal, or a composite material thereof, and may be, for example, a glass tube or a plastic tube.

In the present invention, the magnetic particles are understood to be magnetic particles that respond to magnetic force.

In one embodiment of the present invention, the magnetic particles may be magnetic nanoparticles, magnetic nanoparticle chains, a composite of magnetic nanoparticles and nonmagnetic nanoparticles, a cluster of magnetic nanoparticles and nonmagnetic nanoparticles, or coated magnetic nanoparticles. can

In the present invention, the magnetic particles may be magnetic particles magnetized by magnetic force, and may be fixed across the channel along a magnetic force line passing through the channel. In the practice of the present invention, the magnetic particles may be fixed in the form of a virtual net along the lines of magnetic force. When the external magnetic force is removed, the magnetic particles may flow together with the fluid and be discharged from the outside of the channel.

In one embodiment of the present invention, the magnetic particles can be manufactured and used by a known method, and can also be purchased and used commercially. For example, the magnetic particles may be fine particles exhibiting magnetism in response to a magnetic force, such as triiron tetraoxide (Fe ₃ O ₄ ).

In the present invention, the material to be separated is not particularly limited as long as it can be separated by magnetic particles fixed to the channel by a magnetic field. For example, the material to be separated is attached to magnetic particles by filtering by a network structure formed by fixed magnetic particles, physical-chemical bonding with magnetic particles, electrostatic bonding with magnetic particles, and biological bonding such as antigen-antibody. can be combined

In one embodiment of the present invention, the material to be separated may be a pathogenic microorganism. The pathogenic microorganism may be food poisoning bacteria that can cause food poisoning by being included in food, for example, enterohemorrhagic E. coli O157:H7, hospital E. coli, Salmonella, Staphylococcus aureus, enteritis vibrio, Listeria, Campylo vector, Bacillus It may be cereus, etc., but is not limited thereto.

In a preferred embodiment of the present invention, when the material to be separated is a pathogenic microorganism, the magnetic particles may be magnetic particles capable of binding to the pathogenic microorganism contained in the sample. Magnetic particles capable of binding to pathogenic microorganisms may include magnetic particles and antibodies, aptamers or molecularly imprinted polymers disposed on the surface thereof, and the antibody, aptamer or molecularly imprinted polymers may bind to pathogenic microorganisms.

In the present invention, the magnetic particles may selectively bind to some of the substances to be separated, and using this, it is possible to selectively separate the substances included in the sample. For example, when a multi-virtual net is formed in a channel using magnetic particles that selectively collect each microorganism, multiple pathogenic microbes may be captured at separate locations for each species.

In the present invention, the reverse propulsion magnet ring is a magnet ring arranged so that a strong magnetic flux density is formed at the outer edge of the permanent magnet ring, and the magnetic particles in the ring are arranged on the outer tube wall portion of the ring by the magnetic field generated at this time.

Furthermore, when the permanent magnet arrangement and the reverse propulsion magnet ring are arranged at the same time, the magnetic particles passing between the two magnet rings are driven to the wall due to the strong magnetic flux density formed on one wall between the rings. Since a lower drag force is applied to the wall than the center of the channel, internal reflux may occur in which the particles driven to the wall return to the inside of the permanent magnet array by the magnetic field of the permanent magnet array.

In the present invention, the fluid channel is any type of channel through which a fluid can pass, including a glass tube and a plastic channel, and the material or shape is not limited, and the permanent magnet arrangement and the reverse magnet ring are outside the fluid channel, It can be placed inside or on the side, so there is no restriction on its placement.

The present invention in one aspect,

fluid channels;

a first magnet for fixing magnetic particles upstream of the fluid channel;

a second magnet for moving the magnetic particles downstream of the fluid channel to a region where the fluid drag force is smaller than the magnetic force of the first magnet; and

providing a separation device comprising magnetic particles reciprocating between the first magnet and the second magnet; and

It provides a separation method comprising the step of supplying a sample containing a material to be separated bound to the magnetic particles to the fluid channel of the separation device.

The present invention in one aspect,

Provided is a separation device characterized in that by installing a Halbach ring around the fluid channel to fix the magnetic particles, and to separate the sample using the fixed magnetic particles.

The present invention in one aspect,

A first magnet forming a virtual net of magnetic particles is provided upstream of the fluid channel, and a second magnet pushing magnetic particles in an upstream direction is provided downstream of the fluid channel, so that the magnetic particles are disposed between the first magnet and the second magnet. A separation device for circulating the

The present invention in one aspect,

fluid channels;

a first magnet for fixing magnetic particles upstream of the fluid channel;

a second magnet for moving magnetic particles downstream of the fluid channel toward a wall surface of the channel; and

Provided is a separation device comprising magnetic particles reciprocating between a first magnet and a second magnet.

According to the present invention, a virtual filter composed of magnetic particles can be formed using the permanent magnet array constituting the first magnet, and the target material can be efficiently collected through this. In addition, by the first magnet, the magnetic particles of the virtual net resist the drag force caused by the injection of the liquid sample and pass the impurities of a large size, so that a phenomenon may occur in which the virtual net maintains its structure in the fluid channel, and various When a virtual filter is formed using magnetic particles that can bind to a substance, multiple substances can be collected at once, and they can be simply recovered and concentrated in a small volume.

According to the present invention, by arranging a reverse propulsion magnet ring at the rear of the permanent magnet array constituting the first magnet, it is possible to induce the internal circulation of magnetic particles without an additional channel or mechanical device, and through this, the target material can be stably collected even at a high flow rate. have. That is, the present invention can be applied to various situations by quickly collecting target materials using magnetic particles and a simple magnet arrangement and their arrangement without a complicated processing process or bulky equipment, and easily recovering the captured target material. It can provide a method with a wide range of use.

1 is a view showing an outline of a separation device according to the present invention.
2 is a view showing the magnetic field state of the magnet arrangement installed in the separation device according to the present invention.
3 is a view showing a Halbach ring and a virtual filter used in the separation device of the present invention. (a) Photograph (b) magnetic field distribution, (c) image of magnetic particles immobilized on the Halbach ring. Scale bar is 1 mm
4 is a view showing the movement of magnetic particles in the separation device according to the present invention. 4A shows a state in which there is no second magnet, and FIGS. 4B to 4D are views showing the movement of magnetic particles according to the distance between the first magnet and the second magnet. Fig. 3b is 1 cm, Fig. 3c is 2 cm, and Fig. 3d is 3 cm.
5 is a view for explaining the principle of capturing E. coli by a combination of a Halbach ring and a reverse propulsion magnet ring in the separation device according to the present invention.
6 is a graph showing the collection efficiency according to whether a second magnet is installed in the separation device of the present invention.
7 is a graph showing the collection efficiency according to the distance between magnets in the separation device of the present invention.
8 is a schematic diagram showing the synthesis process of the chain-type magnetic nanoparticles.

Hereinafter, preferred embodiments of the present invention will be described with reference to the accompanying drawings. However, the embodiments of the present invention may be modified in various other forms, and the scope of the present invention is not limited to the embodiments described below.

Example 1.

separator

As shown in FIG. 1 , a first magnet 20 is disposed upstream of the fluid channel 10 made of a glass tube to fix the magnetic particles in the form of a filter across the fluid channel 10 , On the downstream side, the second magnet 30 was disposed at a predetermined distance from the first magnet 10 so that the magnetic particles were moved to the wall surface having a small drag and circulated in the upstream direction by the magnetic force of the first magnet 20 .

The first magnet 20 is a Halbach ring composed of 12 trapezoidal magnets, and each magnet has a magnetization direction angle of 60 degrees with respect to adjacent magnets. A trapezoidal magnet was used with a height of 4 cm and a thickness of 2.5 cm. At the center of the array, there is a space through which a fluid channel can pass.

The second magnet 30 was arranged such that the four cube magnets had a magnetization direction angle of 90 degrees with respect to the adjacent magnets. For the cube magnet, a magnet with a size of 1.2×1.2×1.2 cm ³ was used. The distance between the magnet and the opposite magnet is 2.5 cm, and there is a space in the center for the fluid channel to pass through.

The fluid channel 10 places a 3.2 mm diameter glass tube passing through the center of the permanent magnet array. As the magnetic particles, magnetic iron oxide nanoparticles having a polymer fixed on the surface were used.

The fluid channel 10 was fixed to pass through the center of the first magnet 20, the Halbach ring, and the second magnet 30, the reverse propulsion magnet ring, using an acrylic frame. The positions of the first magnet 20 and the second magnet 30 were also fixed using an acrylic frame. A permanent magnet (not shown) was placed at the end of the glass tube and used to collect particles.

As in FIGS. 2 and 3 , when the magnetic field distribution calculated using FEMM and COMSOL is applied, it shows that the internal magnetic field is linearly and uniformly distributed with respect to the cross section of the Halbach ring constituting the first magnet 20 . In addition, as shown in FIG. 2b, observing the magnetic field distribution of the Halbach ring from the side, it can be observed that the strength of the magnetic field decreases as the distance from the magnet ring to both sides increases. Accordingly, if the particle is located on the right side of the Halbach ring, it will receive a magnetic force to the left and become closer to the Halbach ring. Accordingly, the magnetic particles are fixed in the form of one surface in the central cross-section inside the Halbach ring, as shown in FIG. 2c.

Figure 2d shows the second magnet 30 when observing the magnetic field distribution on the cross section of the reversely propelling magnet ring, the magnetization direction of the magnets constituting the reverse thrusting magnet ring has a radial orientation so that the internal magnetic field is offset. Observing the magnetic field distribution of the reverse propulsion magnet ring with respect to the side in FIG. 2e , in contrast to the Halbach ring, the reverse propulsion magnet ring has the highest magnetic field strength around both ends. And at both ends of the reverse propulsion magnet ring, the magnetic field increases as it approaches the channel wall from the channel center. Accordingly, as shown in FIG. 2, the magnetic nanoparticles are concentrated on the fluid channel wall surface at the front end of the reverse propulsion magnet ring.

As shown in Fig. 4a, in the state where the second magnet consisting of the reverse propulsion magnet ring was removed and only the Halbach ring was installed in the fluid channel, 8 mg of magnetic nanoparticles were injected and the particles were arranged using the Halbach ring. Then, when water was injected at a flow rate of 15 mL/min, magnetic nanoparticles flowed out behind the Halbach ring. Most of the magnetic nanoparticles flowed down along the fluid due to the strong drag force of the fluid, while some particles returned to the Halbach ring along the tube wall. This is because the linear velocity of the fluid is highest at the center of the fluid channel and lower as it approaches the fluid channel wall. Therefore, some of the magnetic nanoparticles leaked from the center of the fluid channel, pushed to the wall, receive a weak drag force from the fluid, so they come back again by the magnetic force of the Halbach ring.

4b to 4d, a second magnet 30 made of a reverse propulsion magnet ring was installed downstream of the first magnet 20 made of a Halbach ring, and the movement of particles according to the interval was observed.

4b and 4c show the behavior of the flowed out magnetic nanoparticles under a flow rate of 15 mL/min when the distance between the first magnet 20 and the second magnet 30 is changed. FIG. 4b shows a case where they are spaced 1 cm apart, FIG. 4c shows a case where they are spaced 2 cm apart, and FIG. 4d shows a case where they are spaced 3 cm apart.

As shown in FIGS. 4b and 4c , when the gap between the first magnet 20 and the second magnet 30 is narrow, the particles flowing out from the Halbach ring, which is the first magnet 20 , are the second magnet 30 . After being pushed to the wall of the glass channel 10 with a small drag by the reverse propulsion magnet ring, internal reflux was formed to return to the first magnet 20, the Halbach ring, and the first magnet 20 and the second magnet 30 Active internal reflux occurred in Fig. 4b, where the distance between the livers was appropriately wider.

On the other hand, as shown in FIG. 4d, when the distance between the first magnet 20 and the second magnet 30 is widened, the particles flowing out from the Halbach ring, which is the first magnet 20, are transferred to the second magnet ( 30) was pushed to the wall of the glass channel 10 with a small drag by the reverse propulsion magnet ring, and was then fixed to the wall without being able to return to the first magnet 20, the Halbach ring. This is the distance between the first magnet 20 and the Halbach ring, which is the first magnet 20, even if the discharged particles are pushed to the wall by the second magnet 30 when the distance between the first magnet 20 and the second magnet 30 becomes 3 cm. It was observed that accumulating on the tube wall rather than circulating because it did not receive enough magnetic force pulling away from it.

Example: Collecting pathogenic E. coli

This experiment was conducted on pathogenic E. coli [ Escherichia coli O157:H7] that causes food poisoning. A distilled water sample containing E. coli was flowed into the glass tube of the separation device to form an E. coli-magnetic nanoparticle complex. Such a process is schematically shown in FIG. 5 . The first magnet 20 of FIG. 5 is a simplified illustration of a Halbach ring.

At this time, in order to determine the E. coli collection efficiency of the internal circulation virtual net, the E. coli sample solution and the E. coli solution that escaped without being captured in the virtual net were collected, spread on a solid medium, and cultured for 16 hours to measure the number of uncollected E. coli. . The collection efficiency of the virtual net according to the arrangement of magnets is shown in FIG. 6 . In addition, as shown in FIG. 7, when the distance between magnets is a certain distance, the maximum collection efficiency is shown due to an increase in effective collision between magnetic particles and pathogens due to internal reflux, and as it increases beyond that, the collection efficiency of the virtual net tends to decrease. It was found that the collection efficiency of more than 90% was found at a distance between arrays of permanent magnets of 2 cm.

comparative example

After forming a virtual net using only the first magnet 20, the collection efficiency was compared at a flow rate of 15 mL per minute. The E. coli sample solution and the E. coli solution that escaped without being collected were collected, spread on a solid medium, and cultured for 16 hours to measure the collection efficiency. As a result, as shown in FIG. 6, when there is only the virtual net by the first magnet 20, the collection efficiency was 41%, and when the internal circulation structure by the second magnet 30 was together, the collection was 92%. showed efficiency.

This is because, due to the internal circulation structure, particles flowing out from the virtual network structure at high flow rates return to the virtual network structure and maintain the dense network structure for a long time.

Synthesis of MNC.

Iron oxide (Fe ₃ O ₄ ) MNPs were synthesized by hydrothermal reaction of iron chloride, sodium citrate, urea and polyacrylamide in a Teflon-lined autoclave at 200 °C for 15 hours. After dispersing 48 mg of MNP in 120 mL of ethanol, 4 mL of APTES was added to the solution. The solution was kept overnight to generate amine groups on the particle surface. Amine-functionalized MNPs (amine-MNPs) were collected with a permanent magnet, washed with ethanol three times, and dispersed in deionized water. To synthesize alginate-coated MNPs (Alg-MNPs), the EDC-NHS coupling reaction was performed by adding 700 μl of 3 wt% sodium alginate solution to 2 mL of DI water containing 80 mg of EDC and 0.4 g of NHS for 15 min. was held for a while. The solution was then mixed with the amine-MNP, and the solution was maintained with shaking overnight. Alg-MNPs were collected using a permanent magnet and washed three times with deionized water. A linear magnetic field was applied to Alg-MNP at 0.1 mg/mL immediately with the addition of citric acid (final concentration 0.1M), and held for 1 hour, to generate MNCs through electrostatic interaction between alginic acid and citric acid. It is worth noting that the magnetic particle size affects the stability of the virtual net and the binding efficiency to bacteria. Larger MNPs can be retained inside the flow channel at higher flow rates, however, as the particle size increases, the surface area of the MNPs decreases and the binding efficiency to bacteria decreases. After washing the MNC three times with DI water, 200 μL of a 0.1 g/mL PEI solution was added to 40 mL of 0.5 mg/mL MNC, and the MNP solution was maintained for 1 hour after vortex mixing. The residual PEI was washed with DI water to obtain PEI coated MNC (PEI-MNC) or PEI coated MNP (PEI-MNP). Figure 8 shows the manufacturing process of PEK-MNCs.

Although the embodiments of the present invention have been described in detail above, the scope of the present invention is not limited thereto, and various modifications and variations are possible within the scope without departing from the technical spirit of the present invention described in the claims. It will be apparent to those of ordinary skill in the art.

10: fluid channel
20: first magnet
30: second magnet

Claims (12)

a fluid channel through which a fluid containing a material to be separated fixed to the magnetic particles flows;
a first magnet for fixing magnetic particles upstream of the fluid channel;
a second magnet for moving the magnetic particles downstream of the fluid channel to a region where the fluid drag force is smaller than the magnetic force of the first magnet; and
Separation device comprising magnetic particles. According to claim 1,
wherein the first magnet is an arrangement of permanent magnets that provides a magnetic field comprising linear magnetic lines of force traversing the fluid channel. 3. The method of claim 2,
The permanent magnet arrangement comprises a parallel magnet arrangement, a Halbach arrangement, and a Halbach ring. 4. The method according to any one of claims 1 to 3,
The first magnet is a separation device, characterized in that the magnet arrangement is arranged to form a magnetic field of uniform strength between the permanent magnets. According to claim 1,
The second magnet is an arrangement of permanent magnets that provides a force to pull the magnetic particles from the center to the wall surface. According to claim 1,
Separation device, characterized in that the second magnet is a permanent magnet arrangement that additionally provides a force to push the magnetic particles in the upstream direction while pulling to the wall surface. According to claim 1,
and the fluid channel is selected from the group consisting of ceramics, polymers, metals, and composite materials thereof. According to claim 1,
The magnetic particles are at least one selected from the group consisting of magnetic nanoparticles, magnetic nanoparticle chains, complexes of magnetic nanoparticles and nonmagnetic nanoparticles, clusters of magnetic nanoparticles and nonmagnetic nanoparticles, or coated magnetic nanoparticles separation device with According to claim 1,
The material to be separated is magnetic particles by at least one of filtering by the network structure formed by the fixed magnetic particles, physical-chemical bonding with magnetic particles, electrostatic bonding with magnetic particles, and biological bonding such as antigen-antibody. Separation device, characterized in that coupled to. According to claim 1,
The material to be separated is a separation device, characterized in that at least one selected from the group consisting of proteins, chemicals, pathogens, and viruses. fluid channel,
a first magnet for fixing magnetic particles upstream of the fluid channel;
a second magnet downstream of the fluid channel for moving the magnetic particles to a region where the fluid drag force is less than the magnetic force of the first magnet; and
providing a separation device comprising magnetic particles reciprocating between the first magnet and the second magnet; and
and supplying a sample containing a material to be separated bound to the magnetic particles to a fluid channel of the separation device. a fluid channel through which a fluid containing a material to be separated fixed to the magnetic particles flows;
a first magnet for fixing magnetic particles upstream of the fluid channel;
a second magnet for moving magnetic particles downstream of the fluid channel toward a wall surface of the channel; and
Separation device comprising magnetic particles reciprocating between the first magnet and the second magnet.

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