JP2005233931A - Magnetic separator - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a magnetic separator allowing effective magnetic separation, by imparting a high magnetic field gradient over all the wells, in the magnetic separator for generating a high-gradient magnetic field. <P>SOLUTION: In this magnetic separator, wherein an inspection liquid is sampled in the each well 4 of a microwell plate, and wherein a magnet 1a is arranged in a side way of the each well 4 to impress the magnetic field to the inspection liquid, in order to separate magnetic particles in the inspection liquid, four or more of magnetic poles are provided in the outer circumferential side face of the magnet 1a. A polar anisotropic magnet is preferably used as the magnet. <P>COPYRIGHT: (C)2005,JPO&NCIPI

Description

  The present invention relates to separation and purification of magnetic particles, and more particularly to an apparatus for magnetic separation of magnetic particles suitable for biological analysis.

  Magnetic separators used for immunology, histocompatibility testing, cancer research, transplantation medicine, bacteriology, parasitology, DNA technology, clinical chemistry, etc. for specific substances or cell separation and purification technology, etc. Magnetic generation means having a high magnetic flux density and magnetic field gradient are required.

  In this separation and purification method, when the target molecule is present in the liquid of the test solution having a large amount of impurities, the target molecule is adsorbed specifically or non-specifically to the magnetic particle, and further, a magnetic field is applied from the outside by applying a magnetic field After collecting on the wall of the container and removing the supernatant, a new suspension liquid is added, and at the same time, the magnetic field is removed to redisperse the target magnetic particles.

A microwell plate is used for this general separation and purification method. A microwell plate is a plate-like base provided with a number of test tubular recesses called wells. A standard microwell plate has a base size of 85 mm × 127 mm and has 96 wells in the base. The well has a depth of about 15 mm and an outer diameter of about 7 mm. The shape of the well has a bottom portion that looks like a cone upside down, and the measurement solution is concentrated at the bottom portion even if there is little test solution. An example of a magnetic separation apparatus using a microwell plate is disclosed in Patent Document 1. This is because the magnet is magnetized in one direction parallel to the base, and one magnet is arranged for every four wells (4 well type) adjacent to the microwell plate, and the direction of the magnetic poles is repelled. Is to be placed. As a result, when the adjacent magnets are arranged in the horizontal direction and in the repulsion direction, and the four-well application type arrangement is employed, it is easy to increase the applied magnetic force and magnetic field gradient, and quick and reliable magnetic separation is possible. It is explained that the magnetic field can be applied under the same conditions in all wells. In this specification, only the cylindrical shape of the well is described. In the magnetic separation device of Patent Document 2, wells are arranged in a grid, and a magnet is arranged in the center of all grids defined by four wells (full set type). The magnet is prismatic and has two magnets facing each other. The two magnetic poles face the well. It is disclosed that the direction of the magnetic field is such that all the magnets are oriented in the same direction, that the magnet is arranged so that the direction of 180 ° rotates about every 90 ° pitch around the well, and that the latter can apply a stronger magnetic field to the well. Has been.
JP 2000-292426 A ((0012) to (0021), FIG. 1) JP-A-1-201156 (the sixth page, upper right column, line 17 to the lower left column, seventh line, FIGS. 1 and 1A)

  The current inspection apparatus has the ability to measure all the magnetically separated inspection liquids in the above-described 96-well microwell plate (hereinafter referred to as 96 microwell plate) in about several seconds. However, the magnetic separation requires several minutes to several hours, and in a 96 microwell plate or the like, it is difficult to apply a high magnetic field to each well because the well portions are adjacent to each other. In order to shorten the measurement time, it is necessary to reduce the time required for magnetic separation of the test solution.

  SUMMARY OF THE INVENTION An object of the present invention is to provide a magnetic separation apparatus that generates a high gradient magnetic field, which provides a high magnetic field gradient throughout the well and enables more effective magnetic separation. .

According to the inventor of the present application, the above object is achieved by the following means.
In the first invention of the present application, a test solution is collected in a well of a microwell plate, a permanent magnet is disposed on the side of each well, a magnetic field is applied to the test solution, and magnetic particles in the test solution are separated. The magnetic separation device is a magnetic separation device in which four or more magnetic poles are provided on the outer peripheral surface of the magnet. With the configuration of the present invention, it is possible to obtain a magnetic separation device that generates a high gradient magnetic field that effectively utilizes attraction and repulsion between magnetic poles. This magnet is preferably an anisotropic magnet. Here, the anisotropic magnet in the present application is not only a magnetic field applied at the time of molding the alloy powder to align the magnetic particles in a specific direction to improve the magnetic properties, but also an isotropic magnet. In addition, a magnet with extremely anisotropic or radial anisotropic magnetization is also used. The polar anisotropic magnet is preferably ring-shaped or cylindrical, but may be, for example, a polygonal cylinder or column.

  In the magnetic separator, polar anisotropy magnets having outer peripheral four poles are arranged in a lattice pattern on a plate-like plate so as to be arranged between the wells of the microwell plate, and the magnetization of each of the polar anisotropic magnets By arranging them in the same direction, a magnetic circuit can be formed by applying a magnetic field from the side to the well and effectively utilizing attraction and repulsion between the magnetic poles by the four magnets surrounding the well. Therefore, a magnetic separation device having a high magnetic separation effect can be obtained.

  When the microwell plate has an inverted conical bottom, the size of the gap is different between the lower end and the upper end of the microwell plate. Therefore, in order to apply a magnetic field from the side to the entire microwell plate, a high magnetic field gradient can be applied to the entire microwell by taking a magnet shape in accordance with this gap. Accordingly, it is preferable to dispose a plurality of anisotropically magnetized magnets and to arrange between the wells a substantially conical polar anisotropic magnet having a trapezoidal cross-sectional shape including the axis along the bottom of the well. Here, the substantially conical shape includes not only the conical shape but also a shape obtained by cutting a part of the apex side of the cone perpendicular to the axis as shown in FIG. In addition, a polygonal pyramid shape such as a quadrangular pyramid or an octagonal pyramid is not a perfect cone, but an equivalent range.

  By applying a strong magnetic field to the microwell plate, a higher magnetic field gradient can be provided in the well. Therefore, a magnetic separation device for a microwell plate having a higher magnetic separation effect can be obtained by making the direction of the magnetic pole closest to each well.

  The magnetic separation device thus obtained is a device that generates a high gradient magnetic field from the center of the well to the outer peripheral surface, and the magnetic particles are collected on the side surface of the well. Usually, an operation of removing the supernatant liquid after magnetic separation occurs. At this time, the supernatant liquid is removed using a pipette. If the tip of the pipette hits the side surface of the well, a part of the magnetic particles is lost along with the removal of the supernatant liquid. For this reason, it is necessary to insert the pipette perpendicularly to the well. By limiting the side of the well where the magnetic particles adsorb, it is possible to prevent the magnetic particles from being lost when the supernatant is removed. In order to generate a high gradient magnetic field, it is preferable to arrange magnets at four locations around the well, but by arranging magnets at only two locations around the well, the range in which magnetic particles are collected can be reduced, and the pipette The supernatant liquid can be easily removed using

On the other hand, a magnetic separation device using an inner circumferential anisotropic magnet can be obtained. The inner circumferential anisotropic magnet is a magnet generally used for a motor or the like, but can form a high gradient magnetic field using magnetic pole attraction / repulsion in a cylindrical inner space. Moreover, since a high gradient magnetic field space can be obtained with one magnet, the structure can be simplified. That is, the magnetic separation device collects the test solution in the wells of the microwell plate, disposes a magnet on the side of each well, applies a magnetic field to the test solution, and separates the magnetic particles in the test solution. Then, a ring magnet having four or more poles on the inner peripheral surface is used as means for applying the magnetic field, and the ring magnet is placed on a plate-like plate so that each bottom of the well is inserted into the inner diameter side of the ring magnet. By using the magnetic separation devices arranged in a grid pattern, a magnetic separation device having a high magnetic separation effect can be obtained.
The ring magnet preferably has a sufficiently large inner diameter compared to the diameter of the bottom of the well, and preferably has an axial length longer than the liquid level height of the collected test liquid. If the size is smaller than this, the magnetic field is not sufficiently applied to the test solution, and the magnetic separation effect becomes insufficient.

  Further, this ring magnet is not limited to a polar anisotropic magnet, and the same effect can be obtained even by using a cylindrical magnet having a radial anisotropic magnetization.

  Further, the magnetic separation device using these polar anisotropic magnets or radial anisotropic magnets can provide a magnetic separation device capable of giving a higher magnetic field gradient when the number of magnetic poles is four. it can.

  In the second invention of the present application, a permanent magnet is provided around the well, and four or more magnetic poles are arranged opposite to the well so that magnetic poles having different polarities alternately appear in the circumferential direction around the well. This is a magnetic separation device. Since the space between the wells is wider than the narrow space surrounded by the four wells, a rectangular (plate-shaped) permanent magnet that can be easily manufactured can be used.

The magnetic pole preferably has a width equal to or less than the pitch length of the well and is formed in a rectangular (plate) permanent magnet magnetized in the thickness direction. The permanent magnet may be a rectangular shape having a width equal to or less than the pitch length of the well. In this case, it is magnetized in the thickness direction. The greatest advantage of this rectangular permanent magnet is that it is easy to manufacture and magnetize. The characteristics are stable, and variations in the magnetic field gradient in each well loading space can be suppressed. A sintered magnet can also be adopted for the rectangular permanent magnet. In particular, a high magnetic field gradient can be provided by using a rare earth sintered magnet typified by a neodymium iron boron based sintered magnet.
In the present invention, it is desirable that four or more magnetic poles are disposed to face the well, and it is necessary to increase the magnetic force of the magnet. In the case of a rectangular magnet like this one, increasing the magnet width more than necessary with respect to the magnet thickness leads to an increase in the magnet shape anisotropy, resulting in a decrease in the magnetic force of the magnet. In order to increase the magnetic force, it is desirable that the width of the magnet is equal to or less than the pitch length. In addition, by making the width of the magnet equal to or less than the pitch length, it is possible to easily combine the opposing surfaces of the adjacent four-pole magnets with different polarities. For this reason, it can be said that it is desirable to make the width of the magnet shorter than the pitch length of the well.

The magnetic circuit including the well charging space located on the outer peripheral part of the magnetic separation device and the magnetic circuit located on the inner peripheral part have different magnet permeances, so the magnetic field gradient of each well charging space is different even if magnets with the same characteristics are used. The separation time in each well varies. The work efficiency is lowered because it is necessary to wait for the separation of the wells that require the longest time.
In the present invention, a method of aligning the magnetic field gradient in each well is also possible. In this magnetic separator, since adjacent magnets are combined so as to have different polarities, a magnetic circuit is formed by these magnets, and the magnetic force of the internal magnets can be increased. On the other hand, since the magnetic circuit is not formed on the outer side of the magnet at the outer peripheral portion, the surface magnetic flux density is smaller than that of the inner magnet. As a method of increasing the magnetic force of the outer peripheral magnet, the thickness of the outer peripheral magnet is increased to increase the magnetic force, and a plate-shaped yoke is disposed around the outer peripheral magnet to increase the permeance of the permanent magnet. Two types of enhancement methods are conceivable. Therefore, this time, the magnetic separation device is arranged by adjusting the plate thickness of the plate-like yoke so that the magnetic force generated by the internal permanent magnet and the magnetic force generated by the permanent magnet at the outer peripheral portion are substantially equal to each other. The fluctuation of the magnetic field gradient inside is suppressed. In addition, among the four permanent magnets arranged in each well, two opposing permanent magnets are made longer in the side direction than the other two permanent magnets, so that the magnetic separation device The magnetic circuit can be stable.

The present invention has the following effects.
1) A magnetic separator having a magnetic field gradient with a high magnetic separation effect can be obtained by using polar anisotropic magnets arranged between the wells.
2) Using a ring magnet, forming a magnetic pole on the inner diameter side, and inserting a well of a microwell plate, a magnetic separation device having a magnetic field gradient with a high magnetic separation effect can be obtained.
3) Since it can be easily reduced in size, a magnetic separation apparatus corresponding to an apparatus for performing a plurality of processes using a microwell plate can be produced.
4) The position of collecting magnetic particles can be changed to an arbitrary position by changing the arrangement of the polar anisotropic magnets.

(Example 1)
FIG. 1 is a perspective view showing a magnetic field member 3a which is a main part of the magnetic separation device of the present invention. It comprises a polar anisotropic cylindrical magnet 1a and a base 2a that supports the polar anisotropic cylindrical magnet 1a. By making the base 2a a magnetic body, there is an effect of preventing magnetic coupling to an installation base on which the magnetic field member 3 is installed. At this time, the magnets are arranged so that the magnets are located adjacent to the gaps and the surrounding positions of the wells arranged in a lattice pattern.
FIG. 2A shows a cross-sectional view taken along the line AA ′ when the well in the first embodiment is inserted. A test solution 7 is placed in each well 6 of 96 microwells 5. FIG. 3A shows the direction of magnetization of the polar anisotropic magnet used in the first embodiment. FIG. 4 shows the positions and magnetization directions of magnets arranged around one well in the first embodiment. As shown in FIG. 3A, the polar anisotropic cylindrical magnet 1a is magnetized so as to have four poles of polar anisotropy at the outer peripheral portion. In addition, since this magnet material is desirably a material that generates a larger magnetic field, an Nd—Fe—B sintered magnet material was used. As shown in FIG. 4, the magnets in the well are arranged in a lattice shape so that the magnetic poles of all the magnets are in the same direction, and the direction of the magnetic poles is the direction toward the center where the well 6 is inserted. did.
In this magnetic separation device, polar anisotropic cylindrical magnets 1 a are arranged so as to surround four locations around the well 4. At this time, the magnetic pole adjacent to the magnetic pole having the polar anisotropic cylindrical magnet 1a is arranged so as to be different from each other, and therefore, between the magnetic poles in the same magnet and between the different poles of the adjacent magnets, FIG. A magnetic circuit such as the magnetic field lines shown in FIG. In this magnetic circuit, since the center of the well is farthest from each magnet, the magnetic field is the smallest, and the magnetic field distribution can be increased so that the magnetic field increases as the distance from the outer periphery of the well increases.
At this time, since it is necessary to determine the direction of the magnetic pole in order to arrange the polar anisotropic magnet, a positioning mark such as a notch may be provided in a part of the magnet in order to improve assemblability. FIG. 5 shows the result of magnetic field distribution obtained by magnetic field analysis when a 96 microwell plate having a 5 mm outer diameter polar anisotropic cylindrical magnet and a well 6 having a diameter of 7 mm is used. The center circle shows the space 4 in which the well is inserted, and the magnetic field distribution is shown by a contour map. This shows that the narrower the interval between the contour lines, the higher the magnetic field gradient is obtained. Compared to the comparative example described later, the number of contour lines is larger and the interval is narrower, and a higher magnetic field gradient can be obtained. I understood.

(Reference example)
A magnetic separator similar to that of Example 1 was manufactured. However, the magnetic pole direction of the pole anisotropic pole-shaped magnet 1a having four poles on the outer periphery is arranged in the direction of the adjacent magnet as shown in FIG. 10 and the poles of the adjacent magnets face each other. Magnetic field analysis was performed on this magnetic field member in the same manner as in Example 1, and the magnetic field distribution generated in the well was obtained. However, it was found that the magnetic field gradient as in Example 1 could not be obtained. In this magnetic separator, polar anisotropy magnets having outer peripheral four poles are arranged in a lattice form on a plate-like base so as to be arranged between the wells of the microwell plate, and It arrange | positions so that the direction of magnetization may become the same direction. A magnetic circuit having a certain degree of magnetic separation effect can be formed by applying a magnetic field from the side to the well and effectively using attraction and repulsion between the magnetic poles by the four magnets surrounding the well. Can be obtained.

(Example 2)
As in Example 1, the magnetic field analysis was performed assuming magnetic field members having polar anisotropy arranged in a lattice on the base 2a, and the magnetic field distribution generated in the well was obtained. However, as the polar anisotropic magnet 1b, a substantially conical Nd—Fe—B bond magnet shown in FIG. 3B was used. FIG. 2B shows a cross-sectional view thereof. Since the tip of the well 6 has a tapered shape, the upper part is narrow and the lower part is wide between the wells. As shown in FIG. 2 (b), the gap between the well and the magnet is arranged at any portion in the vertical direction by using a substantially conical polar anisotropic magnet 1b having a wide lower portion and a narrow upper portion in accordance with the gap of the well. However, the structure is narrow. The outer diameter at the upper end of the polar anisotropic magnet 1b is Φ5 mm, and the outer diameter at the lower end is Φ10 mm. As a result of the magnetic field analysis, a magnetic field distribution almost equal to that in FIG. 5 was obtained. Moreover, when the magnetic field analysis of the lower part was conducted, it was found that a higher magnetic field distribution was obtained.

(Example 3)
FIG. 11 is a perspective view showing a magnetic field member 3c, which is a main part of the magnetic separation device according to the third embodiment of the present invention. It comprises a polar anisotropic cylindrical magnet 1a and a base 2a that supports the polar anisotropic cylindrical magnet 1a. At this time, the magnet is disposed adjacent to one of the opposed positions centering on the gaps of the wells arranged in a lattice pattern and the surrounding wells, and the magnets at the other positions are removed. As shown in FIG. 3, the polar anisotropic cylindrical magnet 1 a is magnetized so as to have a 4-pole polar anisotropy at the outer peripheral portion. In addition, since this magnet material is desirably a material that generates a larger magnetic field, an Nd—Fe—B sintered magnet material was used. FIG. 12 shows the magnet arrangement of the BB ′ cross section of FIG. As shown in FIGS. 11 and 12, the number of magnets in the wells is half that in the first embodiment, and every other well is disposed between the wells. All the magnets were arranged so as to be in the same direction, and the direction of the magnetic poles was the direction toward the center of the well loading space 4 in which the well 5 was loaded. FIG. 13 shows the results of magnetic field distribution obtained by magnetic field analysis when a 96 microwell plate having a 6 mm outer diameter and a 6 microwell plate with a well 6 diameter of 7 mm is used. The center circle shows the space 4 in which the well is inserted, and the magnetic field distribution is shown by a contour map. Compared to Example 1, the interval between the contour lines in the part where the magnet is not arranged is wider, and it can be seen that magnetic particles do not collect in this part. Magnetic particles are collected only in two places, and it is easy to collect the test solution with a pipette.
FIG. 13 shows the magnetization direction of the magnet of this magnetic separation apparatus, the magnetic field lines generated from each magnetic pole, and the magnetic field gradient contour map of each well. In this magnetic separation apparatus, the polar anisotropic cylindrical magnet 1a is arranged at two positions facing each other with respect to the well. At this time, the different polarity at the closest distance to the magnetic pole with the polar anisotropic cylindrical magnet 1a becomes an adjacent different polarity in the same magnet. For this reason, since the main magnetic circuit is formed between adjacent different poles in the same magnet, it looks like the lines of magnetic force shown in FIG. Since the magnetic poles at positions facing each other across the well are arranged so as to have the same polarity, the magnets repel each other, resulting in a small magnetic force at the center of the well. For this reason, a high magnetic field gradient is generated in the vicinity of each magnetic pole as shown in the contour diagram inside the well shown in the figure, resulting in the magnetic particles being collected only in two places.

Example 4
FIG. 14 is a perspective view showing a magnetic field member 3d which is a main part of a magnetic separation device according to the fourth embodiment of the present invention, and a polar anisotropic cylindrical magnet 1a, a polar anisotropic cylindrical magnet 1a and a support. It consists of a base 2a. At this time, the magnetic field distribution in the well shown by the contour map is shown in FIG. 15 as in the first embodiment in which the magnets are arranged in every other row with respect to the gaps of the wells arranged in a lattice pattern. From this result, it can be seen that the magnetic particles are collected in the vicinity of the magnet.
In the case of such a magnetic circuit, a magnetic circuit is hardly formed between magnets separated by one row, and a magnetic circuit can be formed between adjacent different poles in the same magnet and between different poles of adjacent magnets. . FIG. 15 shows the magnetization direction of the magnet of this magnetic separation apparatus, the lines of magnetic force generated from each magnetic pole, and the magnetic field gradient contour map of each well. In this magnetic separation apparatus, polar anisotropic cylindrical magnets 1a are arranged in a row between wells. The polar anisotropic columnar magnets 1a are arranged so that the magnetization directions are all the same. At this time, the different polarity at a short distance from the magnetic pole having the polar anisotropic cylindrical magnet 1a becomes the adjacent different polarity in the same magnet and the different polarity of the adjacent magnet. For this reason, the main magnetic circuit is formed between adjacent different poles in the same magnet and between different poles of adjacent magnets. Since each polar anisotropic cylindrical magnet 1a is arranged in a line, the opposite side of the well without the magnet is a place where the magnetic field is small, and the magnetic force increases as the magnet is approached. Therefore, a high magnetic field gradient is generated in the vicinity of each magnetic pole as shown in the contour diagram inside the well shown in the figure, resulting in the magnetic particles being collected at two locations on the side where the magnet is arranged.

(Comparative Example 1)
As shown in FIG. 20, a magnetic field analysis was performed on a conventional magnetic separation method in which a magnetic field was applied by a magnet from the side of a well, and a magnetic field distribution generated in the well was obtained. It was assumed that the same 96 microwell plate as in Example 1 was used. The outer diameter of the magnet is 5 mm, the same as in Example 1, and is magnetized only in one direction. The result is shown in FIG. FIG. 19 shows the magnetic field distribution in the space in which the well in the vicinity of the magnet is inserted by a contour map, and shows that the magnetic field gradient is higher as the interval between the contour lines is closer. In FIG. 16, there is a magnetic field gradient in the vicinity of the magnet, but it can be seen that the magnetic field gradient is very small and only lower than the magnetic field gradient of the present invention is obtained when moving away from the magnet.

(Example 5)
FIG. 6 is a perspective view showing a fifth embodiment of the present invention. FIG. 7 shows a perspective view of a polar anisotropic ring magnet 1c used in the fifth embodiment. FIG. 8 is a cross-sectional view when the well 6 is inserted into the polar anisotropic magnet 1c. The magnetic field member 3b in FIG. 6 includes 96 polar anisotropic ring magnets 1c arranged for a 96-well microwell plate and a base 2b that supports the polar anisotropic magnets. The microwell plate is used while being superimposed on the magnetic field member 3b. At this time, the wells 6 arranged in a lattice form fit in the space inside the polar anisotropic ring magnet. The base 2b is preferably made of a magnetic material in order to prevent magnetic coupling to an installation base on which the magnetic separation device is installed by using a magnetic material. As shown in FIG. 7, the polar anisotropic ring magnet 1c is magnetized so as to have a polar anisotropy of four poles in the inner peripheral portion. Further, a Nd—Fe—B based sintered magnet was used as the magnet material. The polar anisotropic ring magnet 1c has a cylindrical shape with an inner diameter of 4 mm, an outer diameter of 6 mm, and a length of 10 mm. Magnetic fields are applied from four locations in the internal space of the polar anisotropic ring magnet, and the polar anisotropic ring magnet 1c is independently formed as one magnetic separation device. In addition, as shown in FIG. 8, the diameter of the magnet and the amount of the sample solution should be selected so that the test solution 7 in the well 6 is almost the same height as or below the upper surface of the polar anisotropic magnet. Is desirable. FIG. 9 shows the magnetic field distribution in the space inside the magnet obtained by magnetic field analysis of the polar anisotropic magnet by contour lines. The space inside this magnet has concentric contour lines, the result is that the outer periphery is strong and the magnetic field weakens as it approaches the center, and the contour interval is narrow, that is, a high magnetic field gradient is obtained. I understood.

(Example 6)
FIG. 16 is a perspective view showing the main part of the magnetic separation device according to the sixth embodiment of the present invention. In FIG. 16, the plate magnet 111 includes two types of lengths, a plate magnet 112, a yoke 221 serving as a base, and a yoke 222 provided on the side of the magnet. The magnet 111 has a thickness of 2 mm, a length of 9 mm, and a height of 20 mm. The magnet 112 has a shape of a thickness of 2 mm, a length of 7 mm, and a height of 20 mm. The magnet material is an NdFeB-based sintered magnet. It was. The yoke 221 is provided with grooves of 2 mm width and 2 mm depth for fixing the plate magnet 111 and the plate magnet 112 in a grid shape at intervals of 9 mm. Since the base yoke 221 is made of a magnetic material, it is possible to prevent magnetic coupling to the installation base on which the magnetic separation device is installed and to fix the magnet. The long magnet 111 is inserted into the groove first, and then the short magnet 112 is inserted. Since the magnets are attracted to the yoke and adjacent magnets, the magnets can be easily aligned and assembled. After the magnet 111 and the magnet 112 are thus placed in predetermined positions, the yoke 222 is attached to the side surface of the magnet.

  The magnetic separation device assembled in this manner is a combination of magnets having magnetization directions as shown in FIG. 17, and the space inside the magnetic separation device has a distribution of magnetic lines shown in the figure. Corresponding to this magnetic field line distribution, a substantially uniform magnetic field gradient can be obtained as shown in the magnetic field contour map inside the well 4. As in the lines of magnetic force shown in FIG. 17, in the internal magnets 111 and 112, a magnetic circuit is formed around four intersections. Since such a magnetic circuit can be formed, the magnetic force generated from each magnet is increased as compared with the case where the magnet exists alone. On the other hand, the outer peripheral magnet lacks one magnet for forming a magnetic circuit. Therefore, a 222 yoke is arranged outside the outer peripheral portion instead of the magnet so as to compensate for the insufficient magnet. If the yoke is thin, its role as a yoke is insufficient, and the magnetic force is not so high. On the contrary, if the plate thickness is too thick, an excessive effect is obtained, and the magnetic force of the magnet on the outer peripheral portion becomes higher than the magnetic force of the internal magnet. This time, in order to set the yoke thickness to an optimum value, the optimum value was obtained using magnetic field analysis by a finite element method and set to 0.5 mm.

  In the magnetic separation apparatus shown in the present embodiment, the magnet 111 uses two types of magnets having different magnet 112 widths. The reason for this is that a similar magnetic separation device can be obtained by combining magnets 112 having the same width as shown in FIG. 18A, but the upper magnet 112 is attracted to both the right and left magnets. At first glance, there seems to be a place to balance. However, in fact, even if it is slightly swung from side to side, it will be attracted to one of the magnets, and the shape will collapse. In order to avoid this problem, when the long magnet 111 is arranged so as to abut as in the present embodiment, the magnet 112 arranged on the left and right works toward this boundary, and the magnet is easily attached. It can be arranged at a predetermined position.

  The present invention relates to a magnetic separation apparatus used for specific substance or cell separation and purification techniques in fields such as immunology, histocompatibility testing, cancer research, transplantation medicine, bacteriology, parasitology, DNA technology, clinical chemistry, etc. Can be used for

It is a perspective view which shows the 1st Example of this invention. It is sectional drawing which shows a mode that the well in the 1st Example was inserted. It is a figure which shows the shape and magnetization direction of the polar anisotropic magnet in a 1st Example. It is a figure which shows the position and magnetization direction of the magnet which are arrange | positioned around one well in a 1st Example. It is a figure which shows the magnetic field distribution by the magnetic field analysis in a 1st Example. It is a perspective view which shows the 5th Example of this invention. It is a perspective view of the polar anisotropic ring magnet used for the 5th example. It is sectional drawing which shows a mode that the well was inserted in the polar anisotropic ring magnet in a 5th Example. It is a figure which shows the magnetic field distribution by the magnetic field analysis in a 5th Example. It is a figure which shows the position and magnetization direction of the magnet arrange | positioned around one well in a reference example. It is a perspective view which shows the 3rd Example of this invention. It is sectional drawing which shows a mode that the well in the 3rd Example was inserted. It is a figure which shows the magnetic field distribution by the magnetic field analysis in a 3rd Example. It is a perspective view which shows the 4th Example of this invention. It is a figure which shows the magnetic field distribution by the magnetic field analysis in a 4th Example. It is a perspective view which shows the magnetic separation apparatus of 2nd invention. It is a top view which expands and shows the corner | angular part of FIG. It is a top view which expands and shows the permanent magnet part of FIG. It is a figure which shows the magnetic field distribution calculated | required from the magnetic field analysis of the well charging space in the conventional magnetic separation apparatus. It is a top view which shows the conventional magnetic separation apparatus.

Explanation of symbols

1a, 1b, 1c: Polar anisotropic magnets 2a, 2b: Bases 3a, 3b, 3c, 3d: Magnetic field member 4: Well loading space 5: Microwell plate 6: Well 7: Test solution 8: Cylindrical magnet ( (Dipole magnetization)
9a, 9b, 9c: Magnetic separators 111, 112: Plate magnets 221, 222: Yoke

Claims (11)

A magnetic separation apparatus for collecting a test solution in a well of a microwell plate, disposing a magnet on a side of each well, applying a magnetic field to the test solution, and separating magnetic particles in the test solution, A magnetic separation device, wherein four or more magnetic poles are provided on the outer peripheral side surface of the magnet. The magnetic separation device according to claim 1, wherein a polar anisotropic magnet is used as the magnet. In the magnetic separation device, polar anisotropic magnets are arranged in a lattice pattern on a plate-like plate such that polar anisotropic magnets having four outer circumferences are arranged between the wells of the microwell plate, and The magnetic separation device according to claim 1 or 2, wherein the magnetization directions of the polar anisotropic magnets are arranged in the same direction. 4. The magnetic separation according to claim 3, wherein the four poles of the outer periphery are arranged such that each magnetic pole faces a direction of each well when the microwell plate is attached. apparatus. The magnetic separation apparatus according to claim 1, wherein the polar anisotropic magnet has a substantially conical shape. A magnetic separation apparatus for collecting a test solution in a well of a microwell plate, disposing a magnet on a side of each well, applying a magnetic field to the test solution, and separating magnetic particles in the test solution, A ring magnet having four or more magnetic poles on the inner peripheral surface is used as means for applying a magnetic field, and the ring magnet is latticed on a plate-like plate so that each bottom of the well is inserted into the inner diameter side of the ring magnet. Magnetic separation device characterized by being arranged in a shape. The magnetic separation device according to claim 6, wherein the ring magnet is anisotropically or radially magnetized with four poles on the inner peripheral side. A magnetic separation apparatus, wherein a permanent magnet is provided around a well, and four or more magnetic poles are arranged opposite to the well so that magnetic poles having different polarities alternately appear in the circumferential direction around the well. 9. The magnetic separation device according to claim 8, wherein the magnetic pole has a width equal to or less than the pitch length of the well and is formed by a plurality of rectangular permanent magnets magnetized in the thickness direction. 9. A plate-like yoke having a plate thickness adjusted so that the surface magnetic flux density of the permanent magnet facing the outermost peripheral surface of the magnetic separation device and the surface magnetic flux inside the opposing permanent magnet are substantially equal is disposed on the outer peripheral portion. Or 9. The magnetic separation device according to 9. 11. The magnetic separation device according to claim 8, wherein a permanent magnet that forms two opposite sides of four sides is longer in a side direction than a permanent magnet that forms the other two sides.

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