A magnetic concentration device and method of use

Abstract

The application belongs to the technical field of electrochemical analysis and detection, and discloses a magnetic gathering device and a using method, which comprises a permanent magnet base, positioning columns, permanent magnets, a magnetic guide column fixing base, magnetic guide columns, an electrode alignment base and electrodes. The permanent magnets are arranged on the permanent magnet base. The positioning columns are at least two and arranged on both sides of the permanent magnet base. The magnetic guide columns are at least one. The magnetic guide column fixing base is arranged above the permanent magnets and between the positioning columns. The electrode alignment base is arranged above the magnetic guide column fixing base and detachably connected through the positioning columns. One end of the magnetic guide column is connected with the permanent magnet. The other end of the magnetic guide column passes through the magnetic guide fixing base and the electrode alignment base and corresponds to and abuts against the electrodes. The magnetic gathering device can realize local magnetic gathering within millimeters, and has high magnetic field strength and uniform magnetic distribution.

Description

Technical Field

[0001] This invention belongs to the field of electrochemical analysis and detection technology, specifically relating to a magnetic focusing device and its usage method. Background Technology

[0002] Magnetic beads possess superparamagnetism, exhibiting magnetism under the influence of an external magnetic field. This property allows the magnetic beads and the substances bound to them to be separated together in a suspension. In electrochemical immunoassay and electrochemical molecular detection, by providing an external magnetic field to a designated area, magnetic beads can be efficiently and conveniently separated and enriched for subsequent operations. Therefore, magnetic enrichment technology has been widely used.

[0003] In practice, permanent magnets are typically used to directly provide a magnetic field within a specific working area for magnetic enrichment operations. Permanent magnets are simply magnets, such as neodymium iron boron (NdFeB), samarium cobalt (SMC), AlNiCo, and ferrite permanent magnet materials. NdFeB magnets are currently the strongest magnets, capable of attracting up to 640 times their own weight. Some technology platforms have high requirements for the strength, uniformity, area, and distribution of the applied magnetic field. Larger magnets generally possess stronger magnetism, better stability, and more uniform magnetic field. However, sometimes only a small working area needs to be generated, and millimeter-sized magnets are used to provide this magnetic field. However, due to their inherent properties and manufacturing limitations, such as the fact that neodymium iron boron magnets are mostly sintered and prone to rusting due to the presence of neodymium and iron, requiring protective electroplating, sintering and plating are difficult for small magnets with side lengths and diameters less than 2 mm. Furthermore, millimeter-sized magnets exhibit worse stability, magnetic field strength, and uniformity of magnetic field distribution compared to larger magnets. Therefore, they are not suitable for applications requiring high uniformity and stability of magnetic fields, such as experiments and tests. Due to size limitations, the magnetic field strength of millimeter-sized magnets has an upper limit, while while large magnets possess stronger magnetic fields, their magnetic field range and distribution are difficult to meet requirements.

[0004] Furthermore, the magnetic field lines of commonly axially magnetized cylindrical magnets are distributed from the N pole side through the surrounding space to the S pole side. Due to the characteristics of the magnetic field line distribution, the magnetic field is strongest at the edge of the end face and weakest at the center; the magnetic field is stronger closer to the magnet and weaker farther away. These characteristics can lead to uneven distribution of magnetic beads during magnetic enrichment, thus affecting the detection results.

[0005] Patent document CN213113295U discloses a fully automated cell separation device based on magnetic bead separation, including a base. Two first side plates are vertically connected to one end of the top of the base, and two second side plates are vertically connected to the other end. A top plate is coaxially mounted on the top of the base. Two first connecting plates are vertically connected to one end of the bottom of the top plate, with the bottoms of the two first connecting plates slidably connected within the two first side plates. Two second connecting plates are vertically connected to the other end of the bottom of the top plate, with the bottoms of the two second connecting plates slidably connected within the two second side plates. A plurality of permanent magnets are equidistantly connected to the mounting base. A plurality of through holes are symmetrically arranged on the top plate, and a plurality of placement slots are provided at corresponding positions on the top of the base. However, this technology only addresses the issue of adjusting the number of permanent magnets to accommodate test tube racks of different sizes; it does not solve the problems of weak magnetic field strength, poor uniformity, and poor stability when using millimeter-level permanent magnets in a small working area. Summary of the Invention

[0006] The present invention aims to address the problems of the prior art by providing a magnetic focusing device that can achieve local magnetic focusing within millimeters, and has a strong magnetic field strength and uniform magnetic distribution.

[0007] To achieve the above technical objectives, the present invention adopts the following technical solution:

[0008] A magnetic focusing device includes a permanent magnet base, a positioning post, a permanent magnet, a magnetic guide post fixing seat, a magnetic guide post, an electrode alignment seat, and electrodes;

[0009] The permanent magnet is mounted on the permanent magnet base;

[0010] There are at least two positioning posts, which are arranged on both sides of the permanent magnet base;

[0011] There is at least one magnetic guide post, and the magnetic guide post fixing seat is disposed above the permanent magnet and located between the positioning posts;

[0012] The electrode pair seat is positioned above the magnetic post fixing seat and is detachably connected via the positioning post;

[0013] One end of the magnetic column is connected to the permanent magnet, and the other end of the magnetic column passes through the magnetic fixing base and the electrode alignment base, corresponding to and abutting against the electrodes one by one.

[0014] Preferably, the permanent magnet base has a groove, and the permanent magnet is embedded in the groove of the permanent magnet base.

[0015] Preferably, the electrode mounting base has holes on both sides that correspond to and match the positioning post, and the positioning post passes through the holes to detachably connect the electrode mounting base to the upper part of the magnetic fixing base.

[0016] Preferably, the contact method between the magnetic post and the electrode includes single-electrode contact and multi-electrode contact.

[0017] Preferably, the electrode includes an electrode substrate, an insulating layer, and an array of metal electrodes. The array of metal electrodes is arranged on the electrode substrate and includes a counter electrode, a reference electrode, and a working electrode. The insulating layer covers a portion of the array of metal electrodes. The magnetic posts abut against the working electrodes, and each magnetic post corresponds to one working electrode.

[0018] Preferably, the permanent magnet is one of neodymium iron boron magnets, samarium cobalt magnets, alnico magnets, and ferrite magnets.

[0019] Preferably, the material of the magnetic column is one of carbon steel, industrial pure iron, iron-nickel alloy, iron-oxygen-nitrogen, and silicon steel.

[0020] Preferably, the magnetic post is shaped as one of the following: cylindrical, conical, saucer-shaped, disc-shaped, pyramid-shaped, or bowling pin-shaped.

[0021] Preferably, the end of the magnetic post that abuts against the working electrode is one of the following shapes: point, line, triangle, polygon, circle, ellipse, sphere, or ellipsoid.

[0022] The present invention also provides a method of using a magnetic focusing device, applicable to the aforementioned magnetic focusing device, comprising the following steps:

[0023] S1. Specific antibodies are incubated on the electrode. The test sample mixed with magnetic beads is added to the reaction area of ​​the electrode. Then the electrode is placed on the magnetic focusing device for magnetic enrichment. Under the action of the magnetic field of the magnetic focusing device, the magnetic beads in the test sample in the reaction area are enriched in the working electrode area. The magnetic enrichment time is preset to 0.5-10 min.

[0024] S2. After enrichment, remove the magnetic focusing device and incubate the electrodes for a preset time of 5-20 minutes.

[0025] S3. After incubation, use cleaning solution to wash away the sample to be tested in the reaction area and drain the water around the reaction area.

[0026] S4. Add 30-100 μL of reaction solution to the reaction zone of the electrode. After the reaction is allowed to proceed for a preset time of 0.5-5 min, apply a voltage of -0.1 to -0.5 V for electrochemical detection for 40-120 s and record the current signal value.

[0027] Compared with the prior art, the beneficial effects of the present invention are:

[0028] (1) The magnetic focusing device of the present invention obtains a strong magnetic field within a millimeter range by using a magnetic column to guide the magnetic field of a permanent magnet, thereby achieving the effect of local magnetic focusing within a millimeter.

[0029] (2) The magnetic column of the present invention enables the magnetic field of the permanent magnet to be distributed along the set shape of the magnetic column, so that the magnetic field strength within the millimeter range is stronger and the distribution is more uniform, thereby improving the separation efficiency and enrichment efficiency of the magnetic beads.

[0030] (3) The magnetic focusing device of the present invention can improve the detection performance of electrochemical immunoassay and electrochemical molecular detection, with a lower detection limit, a smaller CV value and a larger signal-to-noise ratio, and the detection results are more stable and reliable. It can be used in working scenarios where nano- and micro-sized magnetic beads need to be precisely positioned and evenly distributed.

[0031] (4) By setting positioning posts, the present invention enables precise connection between the magnetic posts and the electrodes, ensuring the stability of the detection process and improving detection performance;

[0032] (5) The present invention avoids mutual interference of magnetic fields between multiple magnetic points through the design of magnetic pillars. Different working electrodes between multiple electrodes can remain independent of each other, so that multiple electrodes can be used to screen multiple conditions and detect multiple targets at the same time, thereby improving detection efficiency. Attached Figure Description

[0033] Figure 1 This is a schematic view of the structure of a single-electrode contact magnetic focusing device according to an embodiment of the present invention;

[0034] Figure 2 An exploded view of a single-electrode contact magnetic focusing device according to an embodiment of the present invention;

[0035] Figure 3 This is a schematic view of the structure of a multi-electrode contact magnetic focusing device according to an embodiment of the present invention;

[0036] Figure 4 An exploded view of a multi-electrode contact magnetic focusing device according to an embodiment of the present invention;

[0037] Figure 5 This is a schematic diagram of a single-electrode structure according to an embodiment of the present invention;

[0038] Figure 6 This is a schematic diagram of a multi-electrode structure according to an embodiment of the present invention;

[0039] Figure 7A comparison chart showing the test results of electrochemical immunoassay using a magnetic focusing device with different materials as magnetic conductors and electrochemical immunoassay using a certain type of magnet.

[0040] Figure 8 A comparison of the detection results of electrochemical immunoassay with electrodes incubated with different concentrations of specific antibodies under magnetic enrichment and electrochemical immunoassay with magnetic enrichment.

[0041] Figure 9 This is a schematic diagram of the electrochemical immunoassay results of a multi-electrode magnetic focusing device in the same environment.

[0042] The specific meanings of the markings in the attached diagram are as follows:

[0043] 1. Permanent magnet base; 2. Positioning post; 3. Permanent magnet; 4. Magnetic guide post fixing seat; 5. Magnetic guide post; 6. Electrode alignment seat; 7. Electrode; 71. Electrode substrate; 72. Insulating layer; 73. Array metal electrode. Detailed Implementation

[0044] The technical solutions of the embodiments of the present invention will be clearly and completely described below with reference to the accompanying drawings. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention.

[0045] In the description of this invention, it should be understood that the terms "coaxial", "bottom", "one end", "top", "other end", "upper", "side", "top", "inner", etc., indicate the orientation or positional relationship based on the orientation or positional relationship shown in the drawings, and are only for the convenience of describing this invention and simplifying the description, and are not intended to indicate or imply that the device or element referred to must have a specific orientation, or be constructed and operated in a specific orientation, and therefore should not be construed as a limitation of this invention.

[0046] In this invention, unless otherwise explicitly specified and limited, the terms "installation," "setting," "connection," etc., should be interpreted broadly. For example, they can refer to a fixed connection, a detachable connection, or an integral part; they can refer to a mechanical connection or an electrical connection; they can refer to a direct connection or an indirect connection through an intermediate medium; they can refer to the internal connection of two components or the interaction between two components. Unless otherwise explicitly limited, those skilled in the art can understand the specific meaning of the above terms in this invention according to the specific circumstances.

[0047] Example 1

[0048] Combination Figure 1-4As shown, this embodiment of the invention provides a magnetic focusing device, including a permanent magnet base 1, positioning posts 2, a permanent magnet 3, a magnetic guide post fixing seat 4, a magnetic guide post 5, an electrode alignment seat 6, and an electrode 7. The permanent magnet base 1 has a groove, and the permanent magnet 3 is embedded in the groove of the permanent magnet base 1. There are at least two positioning posts 2, which are located on both sides of the permanent magnet base 1. The magnetic guide post fixing seat 4 is located above the permanent magnet 3 and between the positioning posts 2. The electrode alignment seat 6 has holes on both sides that match the positioning posts 2, and the positioning posts 2 pass through the holes, detachably connecting the electrode alignment seat 6 above the magnetic guide post fixing seat. There is at least one magnetic post 5. One end of the magnetic post 5 is connected to the permanent magnet 3, and the other end of the magnetic post 5 passes through the magnetic fixing base and the electrode alignment base 6, and corresponds to and abuts against the electrodes 7 one by one. The electrode 7 includes an electrode substrate 71, an insulating layer 72 and an array of metal electrodes 73. The array of metal electrodes 73 is arranged on the electrode substrate 71. The array of metal electrodes 73 includes a counter electrode (not shown in the figure), a reference electrode (not shown in the figure) and a working electrode (not shown in the figure). The insulating layer 72 covers part of the array of metal electrodes 73. The magnetic post 5 abuts against the working electrode in the array of metal electrodes 73, and the magnetic post 5 corresponds to the working electrode one by one.

[0049] A strong magnetic field within a millimeter range is obtained by guiding the magnetic field of the permanent magnet 3 through the magnetic guide post 5, achieving the effect of local magnetic concentration within a millimeter. The magnetic guide post 5 allows the magnetic field of the permanent magnet 3 to be distributed along the pre-set shape of the magnetic guide post 5, making the magnetic field strength within a millimeter range stronger and more uniformly distributed, thereby improving the separation efficiency and enrichment efficiency of the magnetic beads. This is used to improve the detection performance of electrochemical immunoassay and electrochemical molecular detection, and the detection results are more stable and reliable. It can be used in working scenarios that require precise positioning and uniform distribution of nano- and micro-sized magnetic beads.

[0050] Example 2

[0051] Unlike Embodiment 1, in this embodiment, the contact method between the magnetic post 5 and the electrode includes single-electrode contact and multi-electrode contact. When the magnetic post 5 and the electrode are in contact via a single electrode, each working electrode forms a circuit, and each magnetic post 5 is in contact with the working electrode on each electrode. When the magnetic post 5 and the electrode are in contact via multiple electrodes, multiple working electrodes form a circuit, and each magnetic post is in contact with the working electrode on each of the multiple electrodes in the same circuit.

[0052] The design of the magnetic column 5 avoids mutual interference of magnetic fields between multiple magnetic points, and the different working electrodes between the multiple electrodes can remain independent of each other, so that the multiple electrodes can be used to screen multiple conditions and detect multiple targets at the same time, thus improving detection efficiency.

[0053] Example 3

[0054] Unlike Embodiments 1 and 2, in this embodiment, the permanent magnet 3 is one of neodymium iron boron magnets, samarium cobalt magnets, alnico magnets, and ferrite magnets, or other strong magnets are also applicable.

[0055] Example 4

[0056] Unlike Embodiments 1, 2, and 3, in this embodiment, there is at least one magnetic guide post 5. The material of the magnetic guide post 5 is one of carbon steel, industrial pure iron, iron-nickel alloy, iron-oxygen-nitrogen, and silicon steel, or other materials with high magnetic permeability. The magnetic guide material utilizes the principle of the magnetic field loop preferentially selecting the path with the least magnetic resistance, thereby guiding the magnetic field direction in the magnetic circuit by using a high magnetic permeability material to achieve the effect of local magnetic concentration.

[0057] Example 5

[0058] Unlike Embodiments 1, 2, 3 and 4, in this embodiment, the magnetic guide post 5 is shaped as one of the following: cylindrical, conical, flying saucer, disc, pyramid, or bowling pin.

[0059] Example 6

[0060] Unlike Embodiments 1, 2, 3, 4, and 5, in this embodiment, the end of the magnetic post 5 that abuts against the working electrode is one of the following shapes: point, line, triangle, polygon, circle, ellipse, sphere, or ellipsoid.

[0061] Example 7

[0062] The present invention also provides a method of using a magnetic focusing device, applicable to the magnetic focusing device as described above, comprising the following steps:

[0063] S1. Specific antibodies are incubated on the electrode. The test sample mixed with magnetic beads is added to the reaction area of ​​the electrode. Then the electrode is placed on the magnetic focusing device for magnetic enrichment. Under the action of the magnetic field of the magnetic focusing device, the magnetic beads in the test sample in the reaction area are enriched in the working electrode area. The preset magnetic enrichment time can be 0.5-10 min.

[0064] S2. After enrichment, remove the magnetic focusing device and incubate the electrodes for a preset time, which can be 5-20 minutes.

[0065] S3. After incubation, use cleaning solution to wash away the sample to be tested in the reaction area and drain the water around the working area.

[0066] S4. Add a preset amount of reaction solution to the working area of ​​the electrode. The preset amount can be 30-100 μL. Specifically, it is a TMB solution (TMB is 3,3',5,5'-tetramethylbenzidine). After reacting for 0.5-5 min, apply a voltage of -0.1 to -0.5 V for electrochemical detection for 40-120 s and record the current signal value.

[0067] Electrochemical immunoassay uses electrodes and magnetic beads to perform qualitative and / or quantitative analysis of target substances. The electrodes consist of an electrode substrate, an insulating layer, and an array of metal electrodes, and are manufactured using one or more methods including CNC machining, laser processing, injection molding, 3D printing, casting, die cutting, and soft etching. The electrode surface has a self-assembled layer incubated with specific antibodies or other biomolecules. The magnetic beads include amino-modified, carboxyl-modified, and streptavidin-modified beads, with a particle size between 0.1 and 3 μm. Their surfaces are assembled with specific antibodies or other biomolecules, which may be one or more of the relevant immunoglobulins, relevant antigens, DNA, RNA, enzymes, or aptamers. The electrode surface used for electrochemical immunoassay is pre-treated with a self-assembled layer, and corresponding specific antibodies are incubated on the surface. Similarly, corresponding secondary antibodies are assembled on the surface of the magnetic beads.

[0068] Using the method provided in this embodiment, taking electrochemical immunoassay under the same environment as an example, the magnetic focusing device using the single-electrode contact method of the present invention and the cylindrical magnets with different diameters axially magnetized are compared in electrochemical immunoassay. The specific operation steps are as follows:

[0069] S1. The sample to be tested mixed with magnetic beads is added to the reaction area of ​​the electrode. Then the electrode is placed on a magnetic focusing device or a magnet for magnetic enrichment. Under the action of the magnetic field of the magnetic focusing device or magnet, the magnetic beads in the sample to be tested are enriched in the working electrode area for 1 minute.

[0070] S2. After enrichment, remove the magnetic field of the magnetic focusing device or magnet, and incubate the electrodes for 10 minutes.

[0071] S3. After incubation, use cleaning solution to wash away the sample in the reaction area and drain the water around the reaction area.

[0072] S4. Add 50 μL of TMB solution to the reaction zone. After reacting for 1 min, apply a voltage of -0.2 V for electrochemical detection for 80 s and record the current signal value.

[0073] Cardiac troponin I (cTnI) is a regulatory protein specific to myocardial tissue. It inhibits the binding of myosin to actin and plays an important role in myocardial contraction. Numerous studies have shown that cTnI levels fluctuate significantly in the early stages of acute myocardial infarction, exhibiting high sensitivity. Furthermore, cTnI is not expressed in any type of skeletal muscle, demonstrating high cardiomyocyte specificity. Therefore, cTnI is one of the most sensitive and specific serum biomarkers for cardiomyocyte injury. In addition, cTnI has the advantages of a well-defined diagnostic threshold, a wide window period, and rapid detection, and has gradually become a major biochemical indicator for assessing cardiomyocyte injury in patients with acute myocardial infarction.

[0074] The results of electrochemical immunoassay tests when using materials A, B, and C as the magnetic conductors of the magnetic focusing device, and the results of electrochemical immunoassay tests when using a specific type of magnet, are shown in the attached figures. Figure 7 As shown, when the sample contains 10 ng / mL and 1 ng / mL cTnI antigen, the positive signal values ​​detected by the magnetic focusing device using materials A, B, and C as magnetic columns are all higher than the positive signal values ​​using a single type of magnet. Furthermore, there are differences in the positive signal values ​​between different materials. This indicates that using a suitable material as the magnetic column of the magnetic focusing device can significantly improve the analytical performance of the electrochemical immunoassay.

[0075] The magnetic separation efficiency of the magnetic focusing device using material A as the magnetic conductor column was compared with that of three N52 magnets of different diameters, as shown in Table 1. The magnetic focusing device can more effectively separate and enrich the magnetic beads in the sample, thereby improving the utilization efficiency of the magnetic beads.

[0076] Table 1. Comparison of magnetic separation efficiency between the magnetic focusing device and N52 magnets of different diameters.

[0077] N52 1.0mm magnet N52 1.5mm magnet N52 2.0mm magnet magnetic focusing device Magnetic separation efficiency 39.69％ 70.61％ 72.85％ 76.61％

[0078] In this embodiment, cTnI was used as the analyte antigen for detection. When the test samples contained cTnI antigen at concentrations of 10 ng / mL, 1 ng / mL, 0.1 ng / mL, 0.01 ng / mL, and 0 ng / mL, the electrochemical immunoassay results were compared between a magnetic focusing device using material A as the magnetic column and an N52 magnet with a diameter and thickness of 1.5 mm, as shown in Table 2. Figure 8 As shown, the use of a magnetic focusing device enables electrochemical immunoassay to have a lower detection limit, a smaller CV value (CV value is the coefficient of variation), and a larger positive signal value, resulting in more stable and reliable test results.

[0079] Table 2 Comparison of CV values ​​detected by the magnetic focusing device and the CV values ​​detected by the magnet.

[0080] cTnI antigen concentration CV value detected by magnetic focusing device Magnet detection (N52 1.5mm) CV value 10 ng / mL 3.69％ 6.81％ 1ng / mL 1.99％ 12.18％ 0.1 ng / mL 3.28％ 30.40％ 0.01 ng / mL 6.87％ 20.84％ 0 ng / mL 9.13％ 15.35％

[0081] Furthermore, using the method provided in this embodiment, taking electrochemical immunoassay in the same environment as an example, the multi-electrode contact magnetic focusing device of the present invention is used to perform electrochemical immunoassay. The multi-electrode contact magnetic focusing device can generate multiple magnetic focusing points simultaneously, thereby realizing multi-electrode detection in the same environment on the electrodes. The specific operation steps are as follows:

[0082] P1. The surfaces of the six working electrodes on the electrode were incubated with cTnI-specific antibodies at concentrations of 1000 ng / mL, 500 ng / mL, 250 ng / mL, 100 ng / mL, 50 ng / mL, and 25 ng / mL, respectively.

[0083] P2. Mix 50 μL of sample containing different concentrations of cTnI antigen with 10 μg of antibody-labeled magnetic bead complex and 2.5 μg of antibody-HRP complex and add it to the reaction area of ​​the electrode. Then place the electrode above the magnetic concentrator and stop when the magnetic column is 0 mm away from the electrode. The magnetic beads in the sample are enriched in the working electrode area under the action of the magnetic field and the magnetic enrichment lasts for 1 min.

[0084] P3. After magnetic enrichment is completed, remove the magnetic focusing device and let the electrode stand for 10 minutes.

[0085] P4. After incubation, use cleaning solution to wash away the sample in the reaction area and drain the water around the reaction area.

[0086] P5. Add 50 μL of TMB solution to the reaction zone. After reacting for 1 min, apply a voltage of -0.2 V for electrochemical detection for 80 s and record the current signal value.

[0087] When a sandwich complex of antibody-labeled magnetic beads-antigen-antibody-HRP complex is formed on the electrode surface, the active ingredient in the TMB solution is oxidized under the catalysis of HRP. When a negative voltage is applied, the oxide is reduced and a current is generated. The absolute value of the generated current is proportional to the number of sandwich complexes formed.

[0088] The detection results of six working electrode sites under incubation with different concentrations of cTnI specific antibody are as follows: Figure 9 As shown, as the concentration of cTnI-specific antibody incubated in the self-assembled layer on the electrode surface gradually increases, the positive signal value also increases significantly. This shows that the magnetic enrichment process among the six working electrode sites under the magnetic enrichment device does not affect each other and can remain independent. It can screen multiple conditions and detect multiple targets at the same time, thus improving the detection efficiency.

[0089] The magnetic focusing device of the present invention can be applied not only to the in vitro diagnostic field of detecting antigens, antibodies, DNA, RNA, exosomes, etc. in electrochemical immunoassay and electrochemical molecular technology, but also to cell sorting, high-throughput sequencing and other technologies; the detection method can be electrochemical immunoassay or other technologies that require the application of immunomagnetic beads and magnetic enrichment.

[0090] The above description is merely an embodiment of the present invention and is not intended to limit the present invention. Any modifications, equivalent substitutions, and improvements made within the scope of the present invention should be included within the protection scope of the present invention.

Claims

1. A magnetic focusing device, characterized in that, Includes permanent magnet base, positioning post, permanent magnet, magnetic guide post fixing seat, magnetic guide post, electrode alignment seat, and electrode; The permanent magnet is mounted on the permanent magnet base; There are at least two positioning posts, which are arranged on both sides of the permanent magnet base; There is at least one magnetic guide post, and the magnetic guide post fixing seat is disposed above the permanent magnet and located between the positioning posts; The electrode pair seat is positioned above the magnetic post fixing seat and is detachably connected via the positioning post; One end of the magnetic column is connected to the permanent magnet, and the other end of the magnetic column passes through the magnetic fixing base and the electrode alignment base, corresponding to and abutting against the electrodes one by one.

2. The magnetic focusing device according to claim 1, characterized in that, The permanent magnet base has a groove, and the permanent magnet is embedded in the groove of the permanent magnet base.

3. The magnetic focusing device according to claim 2, characterized in that, The electrode mounting base has holes on both sides that correspond to and match the positioning post. The positioning post passes through the holes to detachably connect the electrode mounting base to the magnetic fixing base above.

4. The magnetic focusing device according to claim 1, characterized in that, The magnetic post and the electrode are connected in two ways: single-electrode contact and multi-electrode contact.

5. The magnetic focusing device according to claim 3, characterized in that, The electrode includes an electrode substrate, an insulating layer, and an array of metal electrodes. The array of metal electrodes is arranged on the electrode substrate and includes a counter electrode, a reference electrode, and a working electrode. The insulating layer covers a portion of the array of metal electrodes. The magnetic posts abut against the working electrodes, and each magnetic post corresponds to one working electrode.

6. The magnetic focusing device according to any one of claims 1-5, characterized in that, The permanent magnet is one of neodymium iron boron magnets, samarium cobalt magnets, alnico magnets, and ferrite magnets.

7. The magnetic focusing device according to any one of claims 1-5, characterized in that, The magnetic guide post is made of one of the following materials: carbon steel, industrial pure iron, iron-nickel alloy, iron-oxygen-nitrogen, and silicon steel.

8. The magnetic focusing device according to any one of claims 1-5, characterized in that, The magnetic guide post is shaped like one of the following: cylindrical, conical, saucer-shaped, disc-shaped, pyramid-shaped, or bowling pin-shaped.

9. The magnetic focusing device according to any one of claims 1-5, characterized in that, The end of the magnetic post that abuts against the working electrode is one of the following shapes: point, line, triangle, polygon, circle, ellipse, sphere, or ellipsoid.

10. A method of using a magnetic focusing device, applicable to the magnetic focusing device as described in claim 1, characterized in that, Includes the following steps: S1. Specific antibodies are incubated on the electrode. The test sample mixed with magnetic beads is added to the reaction area of ​​the electrode. Then the electrode is placed on the magnetic focusing device for magnetic enrichment. Under the action of the magnetic field of the magnetic focusing device, the magnetic beads in the test sample in the reaction area are enriched in the working electrode area for a preset time. S2. After enrichment is completed, remove the magnetic focusing device and incubate the electrodes for the preset time. S3. After incubation, use cleaning solution to wash away the sample to be tested in the reaction area and drain the water around the reaction area. S4. Add a preset amount of reaction solution to the reaction zone of the electrode, react for a preset time, apply a preset voltage for electrochemical detection, continue for a preset time, and record the current signal value.

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