JP2002001163A - Magnetic separation device and separation method for fluid - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a separation device and method which are capable of separating the particulate materials contg. in fluid with high accuracy and high resolution. SOLUTION: This magnetic separating device includes a flow passage in which the fluid to be separated containing the particulate materials to be separated flows at a specified viscosity force, a magnetic field generating means which is disposed on the outside of this flow passage and imparts the magnetic field acting on the flow passage and a magnetic force field intensifying body which is disposed between the flow passage and the magnetic field generating means and/or within the flow passage and optimizes the magnetic force field acting on the fluid.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to an apparatus and a method for separating particulate matter contained in a fluid by using a magnetic force, and more particularly, to an apparatus and a method for separating a particulate matter contained in a fluid between a fluid flow path and a magnetism generating member. Alternatively, a separation apparatus and a separation method for particulate matter which enable high-precision and high-resolution selective identification and separation by providing a magnetic force field enhancer in a fluid flow path and applying a magnetic force to a fluid to be separated About.

[0002]

2. Description of the Related Art In transplantation of hematopoietic stem cells, which are performed to replace dysfunctional blood cells with newly functional blood cells in intractable blood diseases such as leukemia at present, they are collected from donors. The main focus is on how to accurately and efficiently separate and purify stem cells from bone marrow fluid and cord blood. On the other hand, in the treatment of cancer, it is extremely important to accurately identify and separate the types of cancer cells, particularly in chemotherapy, in determining the prognosis of a patient and performing appropriate treatment.

[0003] All of these contain a process for quickly identifying and separating a specific cell from other cells or components, and the appearance of a reliable method is awaited. Currently, automated cell identification / separation methods include flow cytometry using fluorescently labeled antibodies. Including the problem that it takes a long time to learn and process, it is not a practical and versatile practical device as expected.

In recent years, high gradient magnetic separation (HGMS) has attracted attention as a technique for separating particulate matter in a fluid containing particulate matter such as a suspension. For example, an apparatus that applies high gradient magnetic separation technology to purify steelmaking wastewater has already been put to practical use. However, a device that has been put into practical use is to install a magnetic filter composed of a ferromagnetic fine wire in a strong magnetic field generated by a superconducting electromagnet, and to allow the suspension to be separated to flow through the magnetic filter. This is a contact method in which the fine particles are separated by attaching the fine particles to a filter material. In this case, there is a drawback that only particles larger than about 100 μm for paramagnetic particles and about 10 μm for ferromagnetic particles can be adsorbed. That is, this method is a technique for collecting a large amount of fine powder at a high speed, and is not suitable for identifying and separating cells while maintaining a physiological environment.

[0005] Japanese Patent Application Laid-Open No. 7-232097 proposes a separation method called magnetic chromatography. In this method, an external magnetic field is applied to a fine particle suspension flowing in a laminar flow state in a channel, and a high gradient magnetic field is formed by a ferromagnetic thin wire arranged near the channel, so that the fine particles in the suspension are magnetized. A concentration distribution is generated in the channel cross section according to the rate, and as a result, fine particles having different magnetic susceptibilities are separated based on a difference in flow velocity in the laminar flow. That is, a non-contact separation method using a high gradient magnetic field. However, since this separation method is based on the concentration distribution and the flow velocity difference in the laminar flow, it is separated as a relatively high-concentration fraction, and in terms of the purity (resolution) of the separated particles. It may not be enough.
Further, theoretical calculations have been performed for various systems, but have not been put to practical use.

Regarding the application of magnetic separation to biological components,
For example, attempts have been made to magnetically separate red blood cells in blood, but these methods apply a magnetic field gradient to red blood cells moving in liquid and separate the red blood cells by bending the course of red blood cells by the paramagnetism of the red blood cells. (Makoto Tak
ayasu, David R. Kelland, "Selective Continuous Sep
aration of Two Component Particulate Suspensions ",
IEEE Transactions on Magnetics, Vol.MAG-22, No.5,
Sep. (1986) pp. 1125-1127), cells have not yet been identified and separated with high precision and high resolution.

The present inventors have proposed that when a fine particle suspension is caused to flow through a flow path placed in a magnetic field such as a superconducting magnet or the like, the magnetic force acting on the material in the flow path is the product of the magnetic flux density and the magnetic field gradient ( Focusing on the fact that it is proportional to the magnitude of the magnetic force field, the magnetic susceptibility or magnitude of the particulate matter is determined from the value of the viscous force at the point where the magnetic force acting on the particulate matter and the viscous force from the fluid are balanced. The required susceptibility measurement method was proposed (K. Shinohara and R. Aoga
gi, Chemistry Letters, 1027 (1999)). Further, the present inventors dispose a magnetic force field enhancing body made of a ferromagnetic material or the like between the magnetic field generating means such as a superconducting magnet and the flow path and / or in the flow path to reduce the material in the flow path. The inventors have found that such a magnetic force field can be remarkably improved, and have completed the present invention in which even a particulate matter having a small magnetic susceptibility difference, such as a cell, can be accurately separated using a magnetic force field gradient.

[0008]

SUMMARY OF THE INVENTION Accordingly, an object of the present invention is to provide a non-contact separation apparatus and method capable of separating particulate matter contained in a fluid with high precision and high resolution.
In particular, it is an object of the present invention to provide a separation apparatus and a method applicable to separation of biological components such as cells.

[0009]

The object of the present invention is to provide a flow path in which a fluid to be separated containing particulate matter to be separated flows with a predetermined viscous force, and a flow path provided outside the flow path and provided in the flow path. Magnetic field generating means for applying such a magnetic field, and a magnetic force field enhancer disposed between the flow path and the magnetic field generating means and / or inside the flow path to optimize a magnetic force field applied to the fluid. A magnetic separation device, and a fluid to be separated containing particulate matter to be separated is caused to flow through a flow path with a predetermined viscous force, and is disposed outside the flow path and applied to the flow path. A magnetic force corresponding to a magnetic force field formed by a magnetic field generating means for applying a magnetic field and a magnetic force field enhancer disposed between the flow path and the magnetic field generating means and / or inside the flow path and the particles; In a fluid stream to be separated based on magnetic interaction with Separating the child matter can be solved by a magnetic separation wherein the.

[0010]

In the separation apparatus and method of the present invention, a large magnetic field is applied to particulate matter in a fluid, and the magnetic field is generated according to the magnetic force field and the magnetic susceptibility and / or magnitude of the particulate matter. The flow rate of the particulate matter is changed by the suction force or the repulsive force. That is, in the present invention, the concentration distribution of the particulate matter is formed in the cross section of the flow channel as in the above-described magnetic chromatography, and the particulate matter is relatively dispersed depending on the flow velocity distribution originally possessed by the laminar flow. Instead of separating the particles, a magnetic field (magnetic force field) is positively applied to the particles to substantially stop or delay the flow of the particles according to the magnetic susceptibility of each particle.

[0011]

FIG. 1 is a diagram showing an example of an apparatus suitable for magnetic separation according to the present invention. In FIG. 1, a flow path 2 is arranged inside a cylindrical magnetic field generating means 1 along a central axis of the magnetic field generating means 1, and two flat plates are provided in a gap between the magnetic field generating means 1 and the flow path 2. Are provided at opposing positions with the flow path 2 interposed therebetween.

For example, the fluid to be separated introduced into the flow channel 2 from the left side in FIG. 1 flows in the flow channel 2 toward the right side in FIG. 1 with a predetermined viscous force. At this time, the magnetic field generated by the magnetic field generating means 1 is applied to substantially the entire flow channel 2. Assuming that the magnetic flux density at this time is B, when the magnetic force field reinforcing body 3 does not exist, FIG.
As shown by the dotted line in (A), a magnetic flux density distribution having the center of the magnetic field at the top is generated. In the magnetic separation device of the present invention, since the magnetic force field reinforcing body 3 is disposed, a change in the magnetic flux density occurs near the center of the magnetic force field, resulting in a magnetic flux density distribution as shown by the solid line in FIG. .

[0013] Here, the magnetic force F _m of particulate matter placed in a magnetic field having a magnetic field gradient is subjected is expressed by the following equation.

(Equation 1) In the equation (1), χ is the volume susceptibility of the particulate matter, _{ｍ m} is the volume susceptibility of the fluid, μ ₀ is the vacuum permeability, r is the radius when the particulate matter is assumed to be a sphere, and B is the magnetic flux density And dB / d
x indicates a magnetic field gradient. That is, χ, _ｍm , and r are values specific to the substance and μ ₀ is a constant, and thus the magnetic susceptibility is proportional to the product of magnetic flux density and magnetic field gradient (B (dB / dx)). In this specification, the product of the magnetic flux density and the magnetic field gradient (B (dB /
dx)) is called a magnetic force field.

The values of the magnetic force field are plotted in FIG.
(B). For comparison, the value of the magnetic force field in the case where the magnetic force field reinforcing body 3 is not provided is indicated by a dotted line. Compared to this, by arranging the magnetic field strengthening body 3, a strong magnetic force field generated due to the formation of a steep magnetic field gradient particularly near the center of the magnetic field is formed, and the maximum value of the magnetic field is also increased. This is significantly larger than the case where the field reinforcement 3 is not provided.

On the other hand, the fluid to be separated flows with a predetermined viscous force. This viscous force _Fv is expressed by the following equation.

(Equation 2) In equation (2), η is the fluid viscosity, and ν is the relative velocity of the particulate matter to the fluid.

In the magnetic separation device shown in FIG. 1, the particulate matter contained in the fluid introduced into the flow channel 2 is converted into the flow direction of the fluid (from left to right in FIG. 1) by the formula (2). The viscous force _Fv is received. When such a particulate matter flows and enters a magnetic field, the magnetic force F _m represented by the above equation (1) is obtained.
Will receive. Although the direction in which the magnetic force acts depends on the magnetism of the particulate matter, considering the flow direction of the fluid in FIG. 1, the particulate matter that receives the magnetic force in the flow direction on the left side of the top of the magnetic flux density distribution is the top On the right-hand side, it receives a magnetic force in the opposite direction to the flow, and vice versa. Eventually, any particulate matter will once experience a magnetic force in the magnetic field gradient opposite to the fluid flow. Therefore, unless the viscous force acting on the particulate matter exceeds the magnetic force in the direction opposite to the flow, the particulate matter will not proceed in the flow direction.

That is, a certain viscous force _Fv acts on the particulate matter in the fluid flowing through the flow path 2 at a constant flow rate, and the magnetic force field applied to the particulate matter is equal. beyond the susceptibility and / or size (volume, i.e., the radius) by the difference of the magnetic force F _m that acts in response to the particulate matter and the gradient of further flow beyond the point where the value of the magnetic force field is maximum The particulate matter remaining without being separated is separated.

In the magnetic separation apparatus shown in FIG. 1, a liquid reservoir may be provided on the fluid introduction side (left side in the figure) of the flow channel 2 and means for adjusting the flow velocity between the liquid reservoir and the flow channel may be provided. Good. If the flow velocity (or viscous force) is increased by this means, the amount of particulate matter flowing beyond a certain magnetic field gradient increases, and if the flow velocity (or viscous force) is reduced, the particulate matter remains in the same magnetic force field. Particulate matter increases. Further, a flow locking means (not shown) such as a cock may be provided at the outlet of the flow path 2, and a container for collecting the outflowing fluid or a fraction collector may be provided.

The magnetic field generating means 1 used in the magnetic separation apparatus of the present invention has a sufficient magnetic field of about 0.2 T, preferably 1 T, more preferably 5 T, and still more preferably 10 T.
There is no particular limitation as long as it is an electromagnet or a permanent magnet that can emit a magnetic flux density of T. For example, a superconducting magnet,
High-temperature superconducting magnets, bitter magnets, hybrid magnets and the like are included. The shape is not particularly limited, but generally a cylindrical shape is easily available.
For example, about 430T ² m for a 10T class superconducting magnet
^-1 , about 170T for 20T class hybrid magnet
A magnetic force field value of 0T ² m ⁻¹ is obtained.

The magnetic force field enhancer 3 generally means an object which is magnetized by a magnetic field generated by the magnetic field generating means and changes the magnetic flux density distribution by the magnetic field generating means.
This change in the magnetic flux density distribution includes one in which the magnitude of the magnetic force field defined by the product of the magnetic flux density and the magnetic field gradient increases or decreases, and the magnetic force on the particulate matter to be separated is optimal for separation. It is such a change. In general, it is preferable that a change larger than a magnetic force field obtained by only the magnetic field generating means be obtained. It should be noted that the gradient used in the present specification is a degree of change in a value depending on a position.

This magnetic force field enhancer is made of a material capable of giving the above-mentioned change, and is generally made of a diamagnetic material, a paramagnetic material, a ferromagnetic material, an antiferromagnetic material, a superconductor, a high-temperature superconductor. Conductor or composite. However, from the viewpoint that a large magnetic force field can be given, a material having a high magnetic permeability and a high saturation magnetization is preferable.
G or more, more preferably relative permeability 200 or more, saturation magnetization 0.5T or more, still more preferably relative permeability 1000 or more,
A material having a saturation magnetization of 1.5 T or more is preferably used.
Such materials include, for example, ferromagnetic substances, among them iron, cobalt, corrosion-resistant metals such as stainless steel, nickel,
Examples include metals such as gadolinium, Nd-Fe-B magnets, yttrium iron garnet, permendur, and the like.

It is preferable that the magnetic field strengthening member 3 is arranged near the center of the magnetic field. As described above, since the magnetic force field enhancer has a steep magnetic field gradient, if the magnetic field generating means gives a change near the maximum value of the magnetic flux density (that is, the center of the magnetic field), the result is as follows. As a result, the value of the magnetic force field, which is the product of the magnetic flux density and the magnetic field gradient, also increases. In addition,
By arranging the magnetic force field enhancer near the center of the magnetic field,
There is also the advantage that the magnetic force field strengthening body itself receives the smallest magnetic force in the direction of the center of the magnetic field and can be stably fixed. The vicinity of the center of the magnetic field means a position coincident with the center of the magnetic field and a position arranged as close as possible to the center of the magnetic field.

The magnetic field strengthening body 3 according to the present invention can be provided outside and / or inside the fluid flow path 2. When the magnetic field enhancer is disposed outside the flow path as shown in FIG. 1, the shape thereof is not particularly limited as long as the flow path can be disposed inside the flow path reinforcement. The thing etc. are used. For example, in the case of a ring shape, the flow path passes through the inside of the ring. The shape of the inner and outer diameters of the ring may be any shape, and examples thereof include a cylindrical shape, a cylindrical shape having a polygonal hole, and a polygonal shape having an annular or polygonal hole. be able to. Also, as shown in FIG. 1, two magnetic plates may be arranged so as to sandwich the flow path between the two flat magnetic force field strengthening members. Also, the cross sections of the ring and the flat plate may have various shapes.

In the case of a magnetic field strengthening member provided outside, for example, when a flow path is arranged in a ring shape, the inner diameter is set to two sheets when the flow path is sandwiched between two flat plates. It is desirable to make the gap between the flat plates as small as possible. The present inventors use a superconducting magnet with an output of 10 T as the magnetic field generating means and use cylindrical iron magnetic force field reinforcements having various inner diameters, for example, 1280 T for an inner diameter of 6.5 mm.
² m ⁻¹ , about 5300 T ² m ⁻¹ at an inner diameter of 3.5 mm,
Approximately 30,000 to 50,000 T ² m for an inner diameter of 1.0 mm
^-1 and 100,000 T ² m for an inner diameter of 100 μm
It was experimentally confirmed that a magnetic force field of ^-1 or more could be obtained. Similar results were obtained when the gap was changed using two flat magnetic force field enhancers.

The length and thickness of the ring in the case of using the ring-shaped magnetic field strengthening body, and the length, width and thickness of each flat plate in the case of using two flat plates are determined by the inner diameter and the inner diameter with respect to the obtained magnetic force field. It does not have the same effect as the gap, but the maximum is about 2 times the inner diameter in the case of a ring, and about 2 times the width of the gap and about 3 times the width in the case of a flat plate. It is preferable because the effect is obtained. These are appropriately selected in consideration of various conditions. A cutout may be provided in a part of the ring so that the inside of the flow path can be observed.

When the magnetic field strengthening member is disposed inside the flow channel, the material is made of a diamagnetic material, paramagnetic material, ferromagnetic material, antiferromagnetic material, It can be appropriately selected from a conductor, a high-temperature superconductor, or a composite thereof.
The shape and size are not particularly limited as long as they can be arranged in the flow channel, but it is preferable that the flow and the fluid are not hindered. For example, a magnetic field strengthening member made of stainless steel or the like may be filled in a fine tubular channel in the form of fine particles (eg, beads) or fibers, or a member having a plurality of holes in the flow direction of a fluid may be flowed. It may be arranged in the road.

In the present invention, the magnetic force field enhancing body may be provided either outside or inside the flow path, or may be provided both outside and inside. In any case, a person skilled in the art can select the shape of the magnetic force field enhancer to be used without undue experimentation according to the characteristics required according to the purpose and application.

The flow path 2 in the magnetic separation device of the present invention comprises:
As long as the fluid to be separated can flow with a predetermined viscous force, its material, shape, size, etc. are not particularly limited.
However, since a large magnetic force field can be obtained when the inner diameter or gap of the magnetic field strengthening body is made as small as possible, it is preferable that the flow path provided therein is also small. If the flow path is reduced in size, the member of the magnetic force field strengthening member provided on the outside may be reduced in size, which may be advantageous in cost. Generally, the inner diameter is about 10 μm to 2 cm, preferably about 30 μm to 10 mm, more preferably about 50 μm.
A glass or plastic thin tube or slit type flow path of about 150 μm is used.

Alternatively, the magnetic field strengthening body and the flow path can be integrally formed so that the magnetic force field reinforcing body forms a part of the flow path. For example, it is preferable to use a connecting pipe in which two glass tubes or plastic tubes are connected with a stainless steel tube or the like so as to have a single flow path. However, when a magnetic field enhancement body such as a metal is arranged in the flow path or is a part of the flow path,
For example, when a liquid to be separated containing a biological component such as blood or body fluid is passed through a flow path, it is coated with heparin or the like to impart antithrombotic properties, or when corrosion resistance of metals or the like or toxicity to cells becomes a problem. It is preferable to coat with plastic or the like.

Further, by providing a plurality of flow paths in one magnetic field generating means, the amount of fluid that can be processed at one time, that is, the processing efficiency can be improved. At this time, the magnetic field strengthening body may be provided for each flow path, or one magnetic force field reinforcing body may be provided for a bundle of a plurality of flow paths. Is appropriately selected according to the conditions of the above.

The fluid to be treated in the magnetic separation apparatus of the present invention may be a liquid or gas containing particulate matter and flowing with a predetermined viscous force. For example, it may be an aqueous suspension containing a biological substance such as cells, or a body fluid itself such as blood, serum, or cerebrospinal fluid. When it is deemed appropriate for separation, the mixture is appropriately diluted with a medium such as water or physiological saline and then introduced into a magnetic separation device.

In the example of the magnetic separation device shown in FIG. 1, a set of magnetic force field reinforcements is provided. However, in the magnetic separation device of the present invention, a plurality of magnetic force field reinforcements are arranged in the flow direction of the fluid. May be provided. FIG. 3 shows an example of such a device. In FIG. 3, around the flow path 2 provided along the central axis of the cylindrical magnetism generating means 1, five flow paths 2 are arranged along the longitudinal direction of the flow path 2 (that is, the flow direction of the fluid). A cylindrical magnetic field enhancer 3 is provided.

In the magnetic separation device shown in FIG. 3, a magnetic force field as shown schematically in the lower part of FIG. 3 is generated. Therefore, the same magnetic force field (that is, the magnetic force) peaks a plurality of times (five times in FIG. 3) on the particulate matter flowing through the flow path. As a result, the particulate matter that could not be separated at one magnetic force field peak can be separated at the next magnetic force field peak, and the separation accuracy can be improved.

Further, as shown in FIG. 4, the shape and size of a plurality of magnetic force field reinforcing bodies provided can be changed. In such a magnetic separation device, for example, in the device shown in FIG. 4, it is considered that a magnetic force field shown in the lower side of FIG. 4 is generated. In this case, the size and / or magnetic susceptibility of the particulate matter separated at the peak of one magnetic force field is different from that of the particulate matter separated at the peak of the other magnetic force field. That is,
By adjusting the magnitude of the magnetic force field generated in each magnetic field enhancer, particulate matter having different properties can be separately separated in one channel. As shown in FIG. 4, it is also possible to provide a switching valve 4 in the flow path on the inlet side and the outlet side of each magnetic force field strengthening body 3 to separately collect different separated particulate matter.

Even when a plurality of magnetic field strengthening members are provided, the magnetic force field reinforcing members can be a part of the flow path. For example, if a plastic plate and a stainless steel plate having a predetermined thickness are alternately laminated, a plurality of through holes are opened in parallel with the laminating direction, and the through holes are used as a flow path (and a magnetic field strengthening body), thereby further improving the processing efficiency. Can be achieved.

Further, in the magnetic separation device of the present invention, a member that interacts with the particulate matter contained in the fluid to be separated may be arranged inside the flow path. This member preferably interacts specifically with the particulate matter to be separated. For example, one of the combinations having specific binding properties such as antigen-antibody, ligand-receptor, sugar-lectin, etc. When it is present or expected to be present, it is conceivable to use a member having the other binding partner on the surface. Specifically, when separating a fluid containing biological components such as cells, beads or the like whose surface has been modified with a substance (enzyme, antibody, etc.) that specifically interacts with proteins present on the cell surface are placed in the flow channel. By arranging the cells, the separation efficiency of the cells is improved.

[0037]

The present invention will be described more specifically with reference to the following examples. (Embodiment 1) In the magnetic separation apparatus of the present invention shown in FIG. 1, the magnetic flux density at the time of generating a magnetic field is reduced by using iron rings of various sizes in place of the two flat magnetic force field enhancers. The measurement was performed to calculate the value of the magnetic force field. As a magnetic field generation means, a refrigerator cooled superconducting magnet (HF-10-
100VHT), insert an iron ring (magnetic field strengthening material) in the center of the magnetic field, and use a Gauss meter to measure the magnetic flux density distribution along the zet axis (the center axis of the ring and superconducting magnet) inside the ring. Was measured by FIG. 5A shows the magnetic flux density distribution near the center of the magnetic field by the superconducting magnet alone when the magnetic force field enhancer is not provided when the central magnetic field 10T is output. The maximum value of the magnetic force field at this time is 43 at a position ± 11 cm from the center of the magnetic field.
0T ² m ^{- 1.}

Here, at the center of the magnetic field of the superconducting magnet,
When a steel ring-shaped structure having a length of 1.6 mm, an outer diameter of 22 mm, and an inner diameter of 6.5 mm was inserted, the magnetic flux density distribution on the z-axis changed as shown in FIG. At this time, the maximum value of the magnitude of the magnetic force field was ± 1280 T ² m ^{−1 at} a position of ± about 2 mm from the center of the magnetic field. Next, the length was set to 7.9 mm without changing the inner and outer diameters of the ring.
In the case of 9 mm, the magnetic flux distribution changes as shown in FIGS. 5C and 5D, and the maximum value of the magnetic force field at this time is:
± 2200 T ² m ⁻¹ .

Next, the same measurement was performed while keeping the outer diameter of the ring at 22 mm, the inner diameter at 3.5 mm, and the length at 14.35 mm. The magnetic flux density distribution at this time showed a shape similar to that of FIG. 5D having substantially the same length, and the maximum value of the magnitude of the magnetic force field reached ± about 5300 T ² m ⁻¹ . That is, in a ring having substantially the same length and the same outer diameter, the value of the magnetic force field was more than doubled by reducing the inner diameter from 6.6 mm to 3.5 mm. This is an unreachable value even with the largest hybrid type magnet.

Further, when an iron ring having an inner diameter of 1 mm is used
The maximum value of the magnetic force field is the mobility of the latex sphere.
Calculated as ± 30,000-50,000T
²m ^-1Value. (In this experiment, Gauss
Measurement because the meter probe cannot be inserted into the ring
I changed the way). Finally, insert an iron ring with an inner diameter of 100 μm
The maximum value of the magnetic force field when used is at least
± 100,000T²m^-1The value above
It became clear from the mobility of the tex ball.

Apart from the above, an outer diameter of 22 mm and an inner diameter of 6.5
An apparatus was assembled in which iron rings having a length of 6.3 mm and a length of 6.3 mm were arranged in series in the longitudinal direction of the flow path at intervals of 4.5 mm, and the same measurement was performed. As a result, the magnetic flux density distribution on the z-axis is shown in FIG.
It became like. A steep magnetic field gradient was obtained corresponding to each iron ring (magnetic field enhanced body). The peak of the magnetic force field at this time is ± about 3000 T ² in the outer gradient.
m ⁻¹ , ± 2500 T ² for the gradient inside
The value of m ^-1 was taken.

In a device in which two flat ferromagnetic materials (iron) are installed facing each other as shown in FIG. 1, almost the same effect as the iron ring is exerted on the magnetic flux density distribution on the z-axis. It was confirmed to give. In this case, the distance between the ferromagnetic materials corresponds to the inner diameter of the ring, and the thickness of the ferromagnetic material corresponds to the difference between the inner and outer diameters of the ring.

(Example 2) Separation experiments were performed using a magnetic separation apparatus as shown in FIG. Specifically, the center of the magnetic field of the same superconducting magnet as in the first embodiment is 2 mm × 2 mm × 2 m
m pieces of iron (strengthened magnetic force field) were arranged in parallel at 0.5 mm intervals, and between them, a Pyrex (registered trademark) glass tube having an outer diameter of 0.5 mm and an inner diameter of 0.2 mm was used. The inside of the tube near the iron piece was observed with a microscope from the gap between the iron pieces.

After exciting the superconducting magnet to 10T, 0.3 moldm was added as a buffer solution in the tube.
^-3 copper sulfate solution was flowed at an average flow rate of 0.1 mm / sec. After the solution flow is formed stably in the tube,
About 300 latex spheres having diameters of 10 μm and 5 μm /
The dispersion at a concentration of μL was injected into the flow of the buffer solution, and the behavior was observed.

When passing near the ferromagnetic material, about 15% of 5 μm particles were collected. Also, 10 μm particles are 70
%. In addition, the flow velocity is 0.3 mm / s
When the particle size was raised to ec, all of the particles of 5 μm passed through the measurement point except for about 1%, but the collection rate of the particles of 10 μm also decreased to about 40%.

Next, the outer diameter of the magnetic force field strengthening body was 2 mm, and the inner diameter was 0.
A similar experiment was conducted with a 5 mm, 2 mm long iron ring, and almost the same results were obtained.

Further, 25 iron rings having an outer diameter of 2 mm, an inner diameter of 0.5 mm, and a length of 2 mm were arranged at intervals of 2 mm, and a tube was passed through the ring, and the average solution speed was 0.3 m.
The same experiment was performed at m / sec. As a result, particles of 5 μm were collected at about 22%, and particles of 10 μm were collected at a rate of about 98%. As described above, it was confirmed that by arranging a plurality of magnetic field enhancers in succession, the particle separation efficiency was significantly increased. Similar results were obtained when a stainless steel bead-like magnetic force field enhancer was placed in the channel.

Example 3 In the same manner as in the latter half of Example 2, 20 iron rings (inner diameter 100 μm, outer diameter 500 μm)
m, 500 μm in length). A physiological saline solution was used as a fluid to be flown, and sheep blood micro-little order was injected into the flow. The red blood cells in the blood were subjected to a strong magnetic force, and the flow velocity was delayed. As a result, the time required for the red blood cells to flow out of the sample outlet was up to about 5 minutes different from other cells. Therefore, red blood cells were collected at a separation rate of about 80% from other cells by separating the cells into different containers every time.

[0049]

The device according to the invention is characterized in that a strong magnetic field magnetizes the magnetic field enhancers arranged inside and / or outside the passage,
Similarly, a phenomenon is utilized in which the mobility of the particulate matter, such as magnetized cells, differs depending on the type of the particulate matter due to being attracted or repelled by the magnetic force. The gradient of the magnetic field generated by the magnetic separation device of the present invention is extremely steep,
Since the generated magnetic force field is extremely strong, it can be accurately distinguished and separated due to a slight difference in magnetic properties and a difference in surface state of particulate matter such as cells.
In addition, by arranging a plurality of magnetic force field enhancers, the accuracy of separation can be further improved, and by changing the shape and size of each magnetic force field enhancer, a plurality of particulate matter can be separated. Can also be separated. Since the magnetic separation device of the present invention uses magnetic force that does not involve chemical or physical adsorption, which is basically called magnetic separation technology,
Biological substances such as cells can be collected without breaking them without contact.

[Brief description of the drawings]

FIG. 1 is a schematic sectional view showing an example of a magnetic separation device of the present invention.

FIG. 2 (A) in the magnetic separation device shown in FIG.
It is a figure which shows the change of magnetic flux density and (B) magnetic force field.

FIG. 3 is a cross-sectional view illustrating an example of a magnetic separation device of the present invention including a plurality of magnetic field strengtheners, and a diagram illustrating a change in a magnetic force field generated by the device.

FIG. 4 is a cross-sectional view illustrating another example of the magnetic separation device of the present invention including a plurality of magnetic force field enhancers, and a diagram illustrating a change in the magnetic force field generated by the device.

FIG. 5 is a graph showing a change in magnetic flux density according to the length of the iron ring (magnetic field strengthening body) in Example 1.

FIG. 6 is a graph showing a change in magnetic flux density when a plurality (two) of magnetic field enhancers are provided.

[Explanation of symbols]

1: magnetic field generating means, 2: flow path, 3: magnetic field enhanced body,
4: Valve

 ──────────────────────────────────────────────────続 き Continuation of the front page (72) Inventor Hirofumi Yura 3-12-20-702 Hisamoto, Takatsu-ku, Kawasaki-shi, Kanagawa Prefecture (72) Inventor Yoshio Saito 2-6-1 Nagahama, Kanazawa-ku, Yokohama-shi, Kanagawa Prefecture 19F Term (reference) 4C077 AA12 BB10 DD30 KK11 NN02

Claims (11)

[Claims] 1. A flow path through which a fluid to be separated containing a particulate matter to be separated flows with a predetermined viscous force, and a magnetic field generating means disposed outside the flow path and applying a magnetic field to the flow path A magnetic force field enhancer disposed between the flow path and the magnetic field generating means and / or inside the flow path for optimizing a magnetic force field applied to the fluid. apparatus. 2. The magnetic separation device according to claim 1, wherein the magnetic force field enhancer is arranged near a center of the magnetic field. 3. The magnetic separation device according to claim 1, wherein at least two magnetic force field strengthening members are provided apart from each other along a flow direction of the fluid to be separated in the flow path. . 4. The magnetic separation device according to claim 1, wherein said magnetic field generating means is a superconducting magnet. 5. The magnetic separation device according to claim 1, wherein the magnetic force field enhancer is made of a ferromagnetic material. 6. The magnetic separation device according to claim 5, wherein the ferromagnetic material is iron or stainless steel. 7. The magnetic separation device according to claim 1, wherein the magnetic force field enhancer forms a part of the flow path. 8. The magnet according to claim 1, wherein a member that interacts with particulate matter contained in the fluid to be separated is arranged inside the flow path. Separation device. 9. A magnetic field generating means for causing a fluid to be separated containing particulate matter to be separated to flow through a flow path with a predetermined viscous force, and provided outside the flow path and applying a magnetic field to the flow path; Magnetic interaction between the magnetic force according to the magnetic force field formed between the flow path and the magnetic field generating means and / or the magnetic force field enhancer disposed inside the flow path and the particulate matter A magnetic separation method for separating particulate matter in a fluid stream to be separated based on the following. 10. The magnetic separation method according to claim 9, wherein the magnetic force field enhancer is arranged near the center of the magnetic field. 11. The magnetic separation method according to claim 9, wherein at least two of the magnetic force field enhancing bodies are arranged apart from each other along a flow direction of the fluid to be separated. .