Magnet plate, separation device, and automatic dispenser using magnet plate
The magnetic plate design addresses the issue of magnetic interference between wells by using a magnetic member to isolate the magnetic influence, resulting in precise magnetic bead collection and improved separation accuracy.
Patent Information
- Application Number
- JP2023182829
- Authority / Receiving Office
- JP · JP
- Patent Type
- Applications
- Current Assignee / Owner
- Filing Date
- 2023-10-24
- Publication Date
- 2025-05-09
AI Technical Summary
Existing magnetic plates used for separating specimens in well plates face challenges due to the magnetic influence on adjacent wells, leading to inaccurate collection of magnetic beads.
The magnetic plate design incorporates a magnet located on the sides of each well, with a magnetic member disposed between this magnet and adjacent wells, reducing the magnetic influence on neighboring wells.
This design allows for precise collection of magnetic beads on the sides of each well, reducing the impact of adjacent magnets and enhancing the accuracy of the separation process.
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Figure 2025072225000001_ABST
Abstract
Description
[Technical field]
[0001] The present invention relates to a magnetic plate, a separation device, and an automatic dispenser using the magnetic plate. [Background technology]
[0002] There is a magnet plate that separates samples contained in a well plate by using the magnetic force of a magnet. The samples contained in the multiple wells provided in the well plate include magnetic beads. The magnetic beads are collected at the desired position by the magnetic force of the magnet, and the samples are separated by the magnet plate. In an automatic dispenser that uses a magnet plate, the samples separated in the wells are dispensed by sucking them up using a tip.
[0003] There are types of magnet plates that collect magnetic beads on the sides of wells. Non-Patent Document 1 listed below discloses a magnet plate for a 96-well plate. [Prior art documents] [Non-patent literature]
[0004] [Non-Patent Document 1] Magna Stand, [online], [searched on September 28, 2023], Internet<URL:https: / / n-genetics.com / products / detail / FG-SSMAG96 / > Summary of the Invention [Problem to be solved by the invention]
[0005] In the magnet plate of the type that collects magnetic beads on the side of the well, the magnetic beads are collected at one place on one side of the well in all wells. Therefore, there is an advantage that it is easy to perform the operation of sucking the extraction target while avoiding the magnetic beads. In this type of magnet plate, multiple magnets are arranged in a matrix in one-to-one relationship with multiple wells arranged in a matrix. Therefore, a magnet arranged corresponding to a certain well is arranged relatively close to other adjacent wells. Therefore, if the positional relationship between the well and the magnet is slightly shifted, the magnet will affect the other adjacent wells with its magnetic force. This state prevents the magnetic beads from being collected at one place on one side in the well. Therefore, in this type of magnet plate, it is necessary to improve the accuracy of the magnet arrangement in order to improve the accuracy of sample separation. Alternatively, it is necessary to devise a method such as using a magnet with a weak magnetic force in order to reduce the influence of the magnet on the adjacent wells.
[0006] An object of the present invention is to reduce the influence of magnets on adjacent wells in a magnetic plate. [Means for solving the problem]
[0007] A magnetic plate according to one aspect of the present invention is a magnetic plate on which a well plate having a plurality of wells is placed and which separates samples using magnetic force, and includes magnets arranged on the sides of one or more wells in correspondence with the one or more wells when the well plate is placed, and a magnetic member is arranged between the magnets arranged on the sides of the one or more wells and other wells adjacent to the one or more wells.
[0008] A separation device according to another aspect of the present invention includes a well plate having a plurality of wells, and a magnet plate for separating samples using magnetic force. The magnet plate has magnets arranged on the sides of one or more wells in correspondence with the one or more wells, and a magnetic member is arranged between the magnets arranged on the sides of the one or more wells and other wells adjacent to the one or more wells.
[0009] The present invention is also directed to an automatic dispenser using the above-mentioned magnetic plate. Effect of the Invention
[0010] According to the present invention, the influence of magnets on adjacent wells in a magnet plate can be reduced. [Brief description of the drawings]
[0011] [Figure 1] 1 is a front cross-sectional view of a separation device including a magnet plate according to an embodiment of the present invention. [Diagram 2] FIG. 2 is a plan view of the separation device according to the embodiment. [Diagram 3] FIG. 2 is a plan view of the separation device, in which the structure of the magnet plate below the well plate is drawn with dashed lines. [Figure 4] FIG. [Diagram 5] FIG. [Figure 6] FIG. 2 is a partially enlarged front cross-sectional view of a separation device including a magnet plate. [Figure 7] FIG. 4 is a right side view of the magnet support plate. [Figure 8] 11A and 11B are diagrams showing experimental results of the magnet plate according to the present embodiment. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS
[0012] Next, the configuration of a magnet plate 2 according to an embodiment of the present invention and a separation device 1 equipped with the magnet plate 2 will be described with reference to the accompanying drawings.
[0013] (1) Overall configuration of separation device 1 FIG. 1 is a front cross-sectional view showing a separation device 1 according to the present embodiment. The separation device 1 is configured to include a magnet plate 2 and a well plate 3 placed on the magnet plate 2. The separation device 1 including the magnet plate 2 is a device for separating samples, and is used, for example, in an automatic dispenser. The magnet plate 2 separates samples by attracting magnetic beads contained in the samples using magnetic force. The particle size, shape, properties, etc. of the magnetic beads used in the magnet plate 2 of the present embodiment are not particularly limited. For example, nano-sized particles having a magnetic core coated with functional groups and biomolecules are used as the magnetic beads. In the following description, the arrow L in FIG. 1 is the left direction, the arrow R is the right direction, the arrow U is the upward direction, and the arrow D is the downward direction. The same directions R, L, U, and D are defined in other figures 2 to 6.
[0014] Fig. 2 is a plan view of the separation apparatus 1. As shown in Fig. 2, wells 31 are arranged in a matrix on a well plate 3 provided in the separation apparatus 1 of this embodiment. In this embodiment, a well plate 3 having 96 wells 31 arranged with 12 wells in the front-rear direction and 8 wells in the left-right direction is used. In the following description, arrow F in Fig. 2 is taken to indicate the forward direction and arrow B is taken to indicate the rearward direction. Similar directions F and B are defined in other Figs. 3 to 7.
[0015] FIG. 3 is a plan view of the separation device 1, and the structure of the magnet plate 2 below the well plate 3 is drawn with a broken line. FIG. 4 is a plan view of the magnet plate 2. That is, FIG. 4 is a plan view of the separation device 1 with the well plate 3 removed. FIG. 5 is a perspective view of the magnet plate 2. That is, FIG. 5 is a perspective view of the separation device 1 with the well plate 3 removed. As shown in FIG. 1 and FIG. 3 to FIG. 5, the magnet plate 2 is provided with eight magnet support plates 5, 5... Each magnet support plate 5 is a flat plate-shaped member extending in the front-rear direction. For example, an aluminum member can be used as the magnet support plate 5. The eight magnet support plates 5, 5... are arranged at intervals with the eight wells 31 arranged in the horizontal direction of the well plate 3.
[0016] The magnet plate 2 has a base 21, as shown in Figs. 4 and 5. Each component of the magnet plate 2 is placed on the upper part of the base 21. The base 21 is provided with cases 22, 22 that cover the front and rear of the magnet plate 2. The base 21 is also provided with support plates 23, 23 for supporting eight magnet support plates 5. The support plates 23, 23 support the front and rear ends of each magnet support plate 5. As shown in Figs. 1 and 5, each magnet support plate 5 is supported by the support plates 23, 23 in a state inclined with respect to the up-down direction.
[0017] (2) Magnet support structure Next, the support structure of the magnet 6 will be described. As shown in Fig. 4, one magnet support plate 5 is provided with 12 magnet insertion holes 51, 51... at equal intervals in the front-rear direction. Eight magnet support plates 5, 5... are arranged in the horizontal direction, so a total of 12 x 8 = 96 magnet insertion holes 51, 51... are provided in the eight magnet support plates 5, 5.... These 96 magnet insertion holes 51, 51... are provided in correspondence with the 96 wells 31, 31... formed in the well plate 3.
[0018] 1 and 4, a magnet 6 is embedded in each magnet insertion hole 51. That is, 96 magnets 6 are provided corresponding to the 96 magnet insertion holes 51. In this embodiment, the magnet insertion hole 51 is a cylindrical hole, and a cylindrical magnet 6 is embedded in the magnet insertion hole 51. The magnet 6 is fixed to the left end of the magnet insertion hole 51 by, for example, an adhesive member.
[0019] Fig. 6 is a partially enlarged view showing a front cross section of the magnet plate. That is, Fig. 6 is an enlarged view of the structure around the two magnets 6 in Fig. 1. In Fig. 6, the two wells 31 shown in the figure will be described as wells 31A and 31B. Moreover, the magnet support plates 5 arranged corresponding to the wells 31A and 31B will be described as magnet support plates 5A and 5B, respectively. Furthermore, a magnet 6A is embedded in the magnet insertion hole 51A of the magnet support plate 5A, and a magnet 6B is embedded in the magnet insertion hole 51B of the magnet support plate 5B.
[0020] As shown in Fig. 6, the magnets 6A and 6B are embedded in the left ends of the magnet insertion holes 51A and 51B, respectively. The left side surface of the magnet support plate 5A is disposed adjacent to the right side surface of the well 31A. Therefore, the magnet 6A embedded in the left end of the magnet insertion hole 51A is in a state adjacent to the right side surface of the well 31A. Similarly, the left side surface of the magnet support plate 5B is disposed adjacent to the right side surface of the well 31B, and the magnet 6B embedded in the left end of the magnet insertion hole 51B is in a state adjacent to the right side surface of the well 31B.
[0021] (3) Support structure of magnetic plate Next, the configuration of the magnetic material plate 7 will be described. As shown in Fig. 1, the magnetic material plate 7 is provided so as to cover the right end of the magnet insertion hole 51. Fig. 7 is a right side view of the magnet support plate 5. As shown in Fig. 7, the magnet support plate 5 is provided with a long magnetic material plate 7 extending in the front-rear direction. The magnetic material plate 7 is provided so as to cover the twelve magnet insertion holes 51, 51 ... lined up in the front-rear direction. The magnetic material plate 7 is attached to the magnet support plate 5 by bolts 52, 52 at two points in the front-rear direction.
[0022] In the present embodiment, the magnetic plate 7 is made of a stainless steel member. For example, stainless steel such as SUS430 can be used as the magnetic plate 7.
[0023] 6, the two magnetic plates 7 shown in the figure will be described as magnetic plates 7A and 7B. The magnetic plate 7A is provided so as to cover the right end of the magnet insertion hole 51A of the magnet support plate 5A, and the magnetic plate 7B is provided so as to cover the right end of the magnet insertion hole 51B of the magnet support plate 5B.
[0024] (4) Sample separation A method for separating a sample using the separation device 1 configured as above will be described. First, a sample is placed in each well 31 of the well plate 3. As shown in FIG. 6, magnets 6A and 6B are arranged in close contact with the right side surfaces of wells 31A and 31B. As a result, the magnetic beads contained in the sample placed in well 31A are collected on the right side surface of well 31A by the magnetic force of magnet 6A. The magnetic beads contained in the sample placed in well 31B are collected on the right side surface of well 31B by the magnetic force of magnet 6B. Specifically, the magnetic beads contained in the sample are collected on the side surface of each well 31 at a position slightly above the bottom surface of each well 31.
[0025] Here, as shown in FIG. 6, in the separation device 1, the well 31A, the magnet 6A, the well 31B, and the magnet 6B are arranged in this order from the left. Therefore, the magnet 6B is located adjacent to the right side of the well 31B, and the magnet 6A is located on the left side of the well 31B with a small gap therebetween. Therefore, the sample contained in the well 31B may be influenced by the magnetic force of not only the right magnet 6B but also the left magnet 6A. However, since the magnetic plate 7A is arranged between the well 31B and the left magnet 6A, it is possible to reduce the influence of the magnetic force of the left magnet 6A on the sample contained in the well 31B. As a result, the sample contained in each well 31 is accurately collected on the right side surface of the well 31 by the magnet 6 arranged adjacent to the right side of the well 31 without being influenced by the magnetic force of the magnet 6 arranged for the adjacent well 31.
[0026] With the magnetic beads in each well 31 collected on the right side surface of the well 31 by each magnet 6, the sample is aspirated by the tip of an automatic dispenser (not shown) so as to avoid the magnetic beads. As described above, the magnetic beads are collected on the right side surface of the well 31 at a position slightly above the bottom surface of the well 31. This allows the aspirating operation to be performed while the tip of the tip of the automatic dispenser is in contact with the bottom surface of the well 31. This allows the use of the magnet plate 2 of this embodiment to perform a highly accurate dispensing process.
[0027] There is also a type of magnet plate that collects magnetic beads in a ring shape on the outer periphery of the well 31. When using this type of magnet plate, the automatic dispenser needs to be accurately positioned at the center of the ring to perform the suction operation. When the amount of sample liquid is small, the diameter of the ring becomes small, making the suction operation particularly difficult. According to the magnet plate 2 of this embodiment, the magnetic beads are collected at one point on the side of the well 31, making it easy to perform the suction operation by the automatic dispenser. Even when the amount of sample liquid is small, by using the magnet plate 2 of this embodiment, it is possible for the automatic dispenser to perform the suction operation with high accuracy.
[0028] As described above, in the separation device 1 of this embodiment, one magnet 6 is provided on the side of one well 31 corresponding to one well 31, and the magnetic plate 7 is arranged between the one magnet 6 and another well 31 adjacent to the one well 31. This reduces the influence of the magnetic force of the magnet 6 provided for the other adjacent well 31, and allows the magnetic beads to be collected on the side of the well 31 with high accuracy. This does not require high accuracy in the arrangement of the magnet 6, and therefore the cost of constructing the device can be reduced. In addition, it is possible to use a material with strong magnetic force for the magnet 6, and it is possible to adopt a configuration that efficiently collects the magnetic beads.
[0029] (5) Experimental results FIG. 9 is a diagram showing the results of an experiment using the magnet plate 2 of this embodiment. In FIG. 8, condition 1 shows the configuration of a conventional magnet plate in which no magnetic material is arranged between the well and the magnet. Condition 2 shows the configuration of the magnet plate 2 of this embodiment in which a magnetic material is arranged between the well and the magnet. In addition, in FIG. 8, the "distance between the magnet and the well surface" indicates the distance at which the magnetic beads can be gathered at one point on the side of the well with good accuracy. The "distance between the magnet and the well surface" corresponds to the distance between the magnet 6 and the side of the well 31 in this embodiment. For example, in the example shown in FIG. 6, it is the distance between the left end surface of the magnet 6A and the right side surface of the well 31A. Note that neodymium magnets of the same size and quality were used in condition 1 and condition 2.
[0030] As shown in FIG. 8, in condition 1 where no magnetic member is arranged, the magnetic beads can be collected with high precision by bringing the "distance between the magnet and the well surface" closer to 0.3 mm. In contrast, in condition 2 where the magnetic member is arranged, the magnetic beads can be collected with high precision at one location on the side of the well even when the "distance between the magnet and the well surface" is increased to 0.9 mm. In other words, by arranging the magnetic member, it is not necessary to increase the precision of the magnet arrangement. Due to this advantage, the magnet plate 2 of this embodiment can reduce the number of high-precision parts compared to the conventional condition 1, and it can be seen that the device can be manufactured more inexpensively. Furthermore, it is possible to stably adsorb the magnetic beads even when the shape of the well plate (PCR plate) and the well changes.
[0031] Furthermore, the magnet plate 2 of this embodiment can use a magnet with a stronger magnetic force than that of the conventional condition 1. When a magnet with a stronger magnetic force is used, the speed at which the magnetic beads are adsorbed increases. Alternatively, when a magnet with a stronger magnetic force is used, the magnetic beads can be adsorbed even when the amount of sample liquid contained in the well plate (PCR plate) increases.
[0032] (6) Other embodiments In the above embodiment, a case has been described in which the same number of magnets 6 are provided corresponding to a plurality of wells 31. In the above example, a case has been described in which 96 magnets 6 are provided corresponding to 96 wells 31. In another embodiment, one magnet may be provided for a plurality of wells 31. In the above embodiment, for example, a long magnet extending in the front-rear direction may be provided corresponding to two or more wells 31 lined up in the front-rear direction.
[0033] In the above embodiment, an example has been described in which the magnet plate 2 corresponds to a well plate 3 (96-well plate) having 96 wells 31. The configuration of the magnet plate 2 of the present invention can also be adapted to correspond to well plates having a number of wells other than 96.
[0034] The magnet plate 2 of the present embodiment can be applied to, for example, a PCR well plate for carrying out a PCR test. By using the magnet plate 2 of the present embodiment, the accuracy of dispensing in a PCR test can be improved.
[0035] (7) Correspondence between each component of the claims and each element of the embodiment Below, examples of the correspondence between each component of the claims and each element of the embodiments will be described, but the present invention is not limited to the following examples. In the above embodiments, the left-right direction is an example of the first direction, and the front-rear direction is an example of the second direction. In addition, in the above embodiments, the magnet support plate is an example of the support member. In addition, in the above embodiments, the magnetic plate is an example of the magnetic member.
[0036] (8) Description It will be appreciated by those skilled in the art that the exemplary embodiments described above are examples of the following aspects.
[0037] (Section 1) The magnet plate according to one aspect of the present invention comprises: A magnetic plate on which a well plate having a plurality of wells is placed and which separates samples using magnetic force, a magnet disposed on a side of one or more wells in correspondence with the one or more wells when the well plate is placed; Equipped with A magnetic member is disposed between the magnet disposed on the side of the one or more wells and another well adjacent to the one or more wells.
[0038] In the magnet plate, the influence of adjacent magnets can be reduced.
[0039] (Section 2) In the magnet plate according to claim 1, A plurality of magnets corresponding to the plurality of wells are provided; The magnetic member may be disposed between a magnet provided on a side of a well in correspondence with the well and another well adjacent to the well.
[0040] In the magnet plate, the influence of adjacent magnets can be reduced.
[0041] (Section 3) In the magnet plate according to claim 2, The plurality of wells are spaced apart in a first direction (LR direction), The one magnet may be disposed between the one well and the other well in the first direction (LR direction), and the magnetic member may be disposed between the one magnet and the other well in the first direction (LR direction).
[0042] In magnet plates having multiple spaced wells, the effect of adjacent magnets can be reduced.
[0043] (Section 4) In the magnet plate according to claim 1, The magnetic member may be attached to a support member that supports the magnet.
[0044] The member supporting the magnet and the member supporting the magnetic member can be the same, and the configuration of the device can be simplified.
[0045] (Section 5) In the magnet plate according to claim 1, The magnetic member may include a stainless steel member.
[0046] The influence of adjacent magnets can be effectively reduced.
[0047] (Section 6) 4. The magnet plate according to claim 3, The plurality of wells are arranged in a matrix at intervals in the first direction (LR direction) and in a second direction (UD direction) perpendicular to the first direction (LR direction), A plurality of magnets provided corresponding to a plurality of wells aligned in the second direction (UD direction) may be supported by the support member extending in the second direction (UD direction).
[0048] The number of members supporting the magnet can be reduced.
[0049] (Section 7) 7. The magnet plate according to claim 6, The magnetic material member may extend in the second direction (UD direction), and may be disposed between a plurality of magnets arranged in the second direction (UD direction) and a plurality of other wells arranged in the second direction (UD direction).
[0050] The magnetic members corresponding to the plurality of magnets can be made common, and the structure of the magnet plate can be simplified.
[0051] (Section 8) 8. The magnet plate according to claim 7, The magnetic member extending in the second direction (UD direction) may be supported by the support member extending in the second direction (UD direction).
[0052] The member supporting the magnet and the member supporting the magnetic member can be the same, and the configuration of the device can be simplified.
[0053] (Section 9) A separation device according to another aspect of the present invention comprises: A well plate having a plurality of wells; A magnetic plate that separates samples using magnetic force; Equipped with The magnet plate is a magnet disposed on a side of one or more wells in correspondence with said one or more wells; having A magnetic member is disposed between the magnet disposed on the side of the one or more wells and another well adjacent to the one or more wells.
[0054] (Section 10) An automatic dispenser according to another aspect of the present invention uses the magnet plate according to any one of items 1 to 8. [Explanation of symbols]
[0055] 1: Separation device 2:Magnetic plate 3: Well plate 5:Magnetic support plate 6: Magnet 7: Magnetic plate 31: Well 51: Magnet insertion hole
Claims
1. A magnetic plate on which a well plate having a plurality of wells is placed and which separates samples using magnetic force, a magnet disposed on a side of one or more wells in correspondence with the one or more wells when the well plate is placed; Equipped with A magnet plate, in which a magnetic member is arranged between the magnet arranged on the side of the one or more wells and another well adjacent to the one or more wells.
2. A plurality of magnets corresponding to the plurality of wells are provided; The magnet plate according to claim 1 , wherein the magnetic member is disposed between a magnet provided on a side of a well corresponding to the well and another well adjacent to the well.
3. the plurality of wells are spaced apart in a first direction; The magnet plate of claim 2, wherein the one magnet is disposed between the one well and the other well in relation to the first direction, and the magnetic member is disposed between the one magnet and the other well in relation to the first direction.
4. The magnet plate according to claim 1 , wherein the magnetic member is attached to a support member that supports the magnet.
5. The magnet plate according to claim 1 , wherein the magnetic member includes a stainless steel member.
6. The plurality of wells are arranged in a matrix at intervals in the first direction and in a second direction perpendicular to the first direction; The magnet plate according to claim 3 , wherein a plurality of magnets provided corresponding to a plurality of wells aligned in the second direction are supported by the support member extending in the second direction.
7. 7. The magnet plate according to claim 6, wherein the magnetic material member extends in the second direction, and the magnetic material member is disposed between a plurality of magnets aligned in the second direction and a plurality of other wells aligned in the second direction.
8. The magnet plate according to claim 7 , wherein the magnetic member extending in the second direction is supported by the support member extending in the second direction.
9. A well plate having a plurality of wells; A magnetic plate that separates samples using magnetic force; Equipped with The magnet plate is a magnet disposed on a side of one or more wells in correspondence with said one or more wells; having A separation device, wherein a magnetic member is disposed between the magnet disposed on the side of the one or more wells and another well adjacent to the one or more wells.
10. An automatic dispenser using the magnetic plate according to any one of claims 1 to 8.