Antigen detection device and antigen detection method

Abstract

To provide a compact, lightweight and portable novel antigen detection device that can perform magnetic immunity inspection.SOLUTION: An antigen detection device that detects an antigen to be detected in a container containing a sample solution including magnetic particles and the antigen to be detected which can be combined with magnetic particles comprises: a detection coil which detects a signal corresponding to a magnetic field by the sample contained in the container; an excitation coil which applies an AC magnetic field to the sample; and a support part which is arranged concentrically with the center axis of the detection coil with the container put close to the detection coil, wherein the detection coil detects a signal corresponding to a magnetic field by the sample which is applied with the AC magnetic field by the excitation coil and also in a cohesion state in which the antigen to be detected bonded to the magnetic particles coheres in the container arranged concentrically with the detection coil, and the detection coil further detects a magnetic field by the sample which is applied with the AC magnetic field by the excitation coil and also in a dispersion state in which the antigen to be detected bonded to the magnetic particles is dispersed in the container arranged concentrically with the detection coil.SELECTED DRAWING: Figure 1

Description

Technical Field

[0001] The present invention relates to an antigen detection apparatus and an antigen detection method for detecting a target antigen by magnetic immunoassay using a magnetic marker.

Background Art

[0002] Immunoassay for detecting biological substances such as proteins and pathogenic bacteria derived from diseases is used in medical diagnosis. Immunoassay utilizes an antigen-antibody reaction in which an antigen, which is a target substance to be detected, and an antibody specifically bind to each other. The antibody is labeled with a substance called a marker, and by detecting a signal from the marker of the antibody bound to the antigen, it becomes possible to measure the amount of the antigen.

[0003] As one type of immunoassay, an optical immunoassay is performed in which an optical marker such as a fluorescent enzyme is added to and labeled on an antibody whose binding ability to a target substance is known, and the degree of binding to the target substance is optically detected. Here, in many optical immunoassays, there is an aspect that a washing and removing step for separating the optical marker bound to the target substance from the optical marker not bound to it is required, and the inspection process is complicated and time-consuming.

[0004] On the other hand, unlike optical immunoassay, a technique for detecting a substance using a magnetic method is known as magnetic immunoassay (Patent Documents 1 and 2). Magnetic immunoassay is a method for detecting antigen-antibody reactions using magnetic particles and a magnetic sensor. Magnetic particles (hereinafter referred to as magnetic markers) are attached to an antibody to label it, and the degree of binding to the antigen, which is the substance to be detected, is detected by a magnetic signal from the magnetic marker using a magnetic sensor. Specifically, a sample is prepared by binding the substance to be detected and an antibody with a magnetic marker attached in solution, and a DC magnetic field is applied to the sample from the outside to magnetize the magnetic marker. After the application of the DC magnetic field is cut off, the magnetic marker-attached antibody (hereinafter referred to as the bound marker) that is bound to the substance to be detected forms aggregates, and its volume becomes larger than that of the magnetic marker-attached antibody that is not bound to the substance to be detected (unbound marker). As a result, the Brownian rotation motion slows down, and the Brownian relaxation time becomes relatively longer. Consequently, the bound marker retains residual magnetism for a longer period of time.

[0005] On the other hand, antibodies with magnetic markers that did not bind to the substance to be detected (unbound markers) also exist in the solution. Because unbound markers exist individually, they have a small volume and undergo rapid Brownian rotation. Consequently, the direction of the magnetic moment of unbound marker antibodies tends to be random, their Brownian relaxation time is short, and unbound markers have residual magnetism for a short period. By utilizing the difference in Brownian times between bound and unbound markers, it is possible to selectively detect the magnetic signal of only the bound marker.

[0006] Thus, by utilizing the differences in the Brownian relaxation properties of magnetic markers, magnetic immunoassays can measure the degree of binding to the substance to be detected without the need for a washing and removal process of the magnetic marker-added antibody.

[0007] Patent documents 1-5 disclose a configuration for detecting an antigen based on a magnetic signal derived from Brownian relaxation of a magnetic marker, using a SQUID (Superconducting Quantum Interference Device) as a magnetic sensor.

[0008] Furthermore, Patent Document 6 discloses a magnetic field measuring device that uses a magnetoresistive effect element (MR sensor) to measure the Brownian relaxation characteristics of a magnetic marker as a difference in AC magnetic susceptibility. That is, a coupled marker with a larger volume has lower tracking ability to high-frequency AC magnetic fields than an uncoupled marker with a smaller volume, and the AC magnetic susceptibility depends on the frequency and Brownian relaxation time. From this, the amount of coupled markers can be measured by measuring the AC magnetic susceptibility using a magnetoresistive effect element (MR sensor).

[0009] Furthermore, Patent Document 7 discloses a magnetic foreign matter inspection device that uses a thin-film magnetic sensor (magnetoresistive sensor, magnetic impedance sensor) having directionality in the magnetic field detection direction to detect the presence or absence of magnetic foreign matter in an object to be inspected.

[0010] Furthermore, Patent Documents 8 and 9 disclose a magnetic field measuring device that detects an antigen, which is a substance to be detected, by utilizing Brownian relaxation, which is achieved by rotating a sample containing a magnetic marker (magnetic nanoparticles) using a rotation mechanism and switching the magnetic field at each rotation period, as proposed by the present inventor. [Prior art documents] [Patent Documents]

[0011] [Patent Document 1] Japanese Patent Publication No. 2015-163846 [Patent Document 2] Japanese Patent Publication No. 2007-240349 [Patent Document 3] Japanese Patent Publication No. 2009-115529 [Patent Document 4] Japanese Patent Application Publication No. 1-112161 [Patent Document 5] Japanese Patent Publication No. 2001-033455 [Patent Document 6] Patent No. 5560334 [Patent Document 7] Japanese Patent Publication No. 2014-159984 [Patent Document 8] Japanese Patent Publication No. 2018-194305 [Patent Document 9] Japanese Patent Publication No. 2020-159871 [Overview of the project] [Problems that the invention aims to solve]

[0012] The magnetic field measuring devices proposed in Patent Documents 8 and 9 are equipped with a rotating mechanism that rotates a sample containing a magnetic marker (magnetic nanoparticles) and an antigen, which is the substance to be detected, making the device inevitably large. The inventors of the present invention have continued their research and development efforts and have now developed an improved antigen detection device and antigen detection method that enables a more compact, lighter, and portable highly sensitive magnetic immunoassay.

[0013] The object of the present invention is to provide a novel antigen detection device and antigen detection method that enable the performance of a compact, lightweight, and portable magnetic immunoassay. [Means for solving the problem]

[0014] A first configuration of the antigen detection device of the present invention for achieving the above objective is an antigen detection device for detecting a detectable antigen in a container containing a solution-like sample comprising magnetic particles and a detectable antigen capable of binding to the magnetic particles, comprising: a detection coil for detecting a signal corresponding to a magnetic field generated by the sample contained in the container; an excitation coil for applying an alternating magnetic field to the sample; and a support portion for positioning the container close to the detection coil and concentrically with its central axis, wherein the detection coil detects a signal corresponding to a magnetic field generated by an aggregated sample in which the detectable antigen bound to the magnetic particles has aggregated within the container concentrically positioned with the detection coil, and furthermore, the detection coil detects a signal corresponding to a magnetic field generated by a dispersed sample in which the detectable antigen bound to the magnetic particles has dispersed within the container concentrically positioned with the detection coil, and wherein the sample in which the alternating magnetic field generated by the excitation coil has aggregated

[0015] The present invention provides an antigen detection method for detecting a detectable antigen in a container containing a solution-like sample comprising magnetic particles and a detectable antigen capable of binding to the magnetic particles, comprising the steps of: positioning the container close to a detection coil and concentrically with its central axis; applying an alternating magnetic field to the aggregated sample, in which the detectable antigen bound to the magnetic particles has aggregated in the container concentrically with the detection coil, and detecting a signal corresponding to the magnetic field from the aggregated sample; and applying an alternating magnetic field to the dispersed sample, in which the detectable antigen bound to the magnetic particles has dispersed in the container concentrically with the detection coil, and detecting a signal corresponding to the magnetic field from the dispersed sample.

[0016] A second configuration of the antigen detection device of the present invention is an antigen detection device for detecting a detectable antigen in a container containing a solution-like sample comprising magnetic particles and a detectable antigen capable of binding to the magnetic particles, the device comprising: a bridge circuit having a first detection coil and a second detection coil and outputting a signal corresponding to the magnetic field produced by the sample; a support portion that supports the container, which can be inserted into the central axes of the first detection coil and the second detection coil, at the position of the central axes; and a signal processing unit that measures the amount of the detectable antigen based on the signal from the bridge circuit when the container is inserted into the central axis of one of the first detection coil and the second detection coil.

[0017] A third configuration of the antigen detection device of the present invention is an antigen detection device that detects a target antigen in a solution sample containing magnetic particles and a target antigen that can bind to the magnetic particles, comprising: a detection coil in which a first coil and a second coil are differentially connected and whose central axes are concentrically arranged, and which outputs a signal corresponding to a magnetic field generated by the sample; a support portion that supports the container, which can be inserted into the central axis of one of the first coil and the second coil, at the position of the central axis; an excitation coil that applies an alternating magnetic field to the sample inserted into the central axis of one of the first coil and the second coil; and a signal processing unit that measures the amount of the target antigen based on the signal from the detection coil while the alternating magnetic field is being applied to the sample by the excitation coil.

Advantages of the Invention

[0018] According to the present invention, a magnetic immunoassay can be carried out by an antigen detection device with a relatively simple configuration. The antigen detection device is small, lightweight, portable, and can be configured at low cost with a simple structure having no moving parts. The antigen detection method can perform a magnetic immunoassay by relatively simple steps using the antigen detection device of the present invention.

Brief Description of the Drawings

[0019] [Figure 1] FIG. showing a first configuration example of the antigen detection device in an embodiment of the present invention. [Figure 2] Flowchart of an antigen detection method using the antigen detection device of the first configuration example. [Figure 3] FIG. showing a measurement example of an antigen detection method in the antigen detection device of the first configuration example. [Figure 4] FIG. showing a second configuration example of the antigen detection device in an embodiment of the present invention. [Figure 5] FIG. showing an external configuration example of the antigen detection device 20 in the second configuration example. [Figure 6] FIG. showing a measurement example of the antigen detection device of the second configuration example. [Figure 7]This figure shows a third configuration example of an antigen detection device according to an embodiment of the present invention. [Figure 8] This figure shows an example of the external configuration of the antigen testing device 30 in the third configuration example. [Modes for carrying out the invention]

[0020] Embodiments of the present invention will be described below with reference to the drawings. However, these embodiments do not limit the technical scope of the present invention.

[0021] Figure 1 shows a first configuration example of an antigen detection device according to an embodiment of the present invention. In Figure 1, the antigen detection device 10 is an antigen detection device that detects an antigen to be detected in a container 50 containing a solution-like sample containing magnetic particles which are magnetic markers and an antigen to be detected that can bind to the magnetic particles, and comprises a detection coil 11 that detects a signal corresponding to a magnetic field emitted from the sample contained in the container 50, an excitation coil 12 that applies an alternating magnetic field to the sample, and a support part 13 that brings the container 50 close to the detection coil 11 and positions it concentrically with its central axis.

[0022] The detection coil 11 detects a signal corresponding to the magnetic field emitted from a sample in an aggregated state, where the material to be detected, coupled with magnetic particles, is aggregated in a container 50 concentrically positioned with the detection coil 11, while an alternating magnetic field is applied to the sample by the excitation coil 12. Furthermore, the detection coil 11 detects a signal corresponding to the magnetic field emitted from a sample in a dispersed state, where the material to be detected, coupled with magnetic particles, is dispersed in a container 50 concentrically positioned with the detection coil 11, while an alternating magnetic field is applied to the sample by the excitation coil 12.

[0023] Container 50 is a cylindrical tube, such as a microtube, and magnetic nanoparticles, which are magnetic markers, and the target substance, the antigen to be detected, are placed in water (physiological saline) inside container 50. In other words, the sample is a mixture of magnetic nanoparticles and the target substance to be detected that can bind to them, and the target antigen is an antigen such as a protein, bacteria, or microorganism to be detected, and the amount of magnetic nanoparticles added is adjusted to be greater than the number of target substances (the maximum expected number). Preferably, sensitivity is increased by adjusting the amount of unbound residual magnetic beads that do not bind to the target substance. Polymer beads can also be used as pseudobacteria when used in experiments.

[0024] The support portion 13 is a container fixing device that supports the container 50 such that the central axis of the container 50 and the central axis of the detection coil 11 are concentric, and the bottom of the container 50 is positioned directly above the detection coil 11. By attaching the container 50 to the support portion 13, the container 50 is positioned upright directly above the central axis of the detection coil 11. The shape and support method of the support portion 13 are designed appropriately according to the shape and size of the container 50.

[0025] The detection coil 11 is a magnetic field sensor that outputs a voltage signal corresponding to the magnitude of the magnetic field to be detected, and is composed of, for example, two differentially connected coils. These two coils constituting the detection coil 11 are positioned so that their central axes are concentric and overlap in the axial direction, and are differentially connected.

[0026] The excitation coil 12 is positioned around the detection coil 11, preferably concentric with the central axis of the detection coil 11, and applies an alternating magnetic field to the container 50 which is concentric with it. The oscillator 60 energizes the excitation coil 12 to generate an alternating magnetic field of a predetermined frequency, and applies the alternating magnetic field to the sample in the container 50.

[0027] Furthermore, as will be described later, during the measurement process, a probe-shaped yoke 64 magnetized by a magnet is passed through the central axis of the detection coil 11, and its tip is brought close to the bottom of the container 50, so that the magnetic particles in the container and the antigen to be detected bound to them are collected and aggregated at the bottom of the container 50.

[0028] The yoke 64 is magnetized by a magnet, and preferably, its tip is formed to be thin and extend like a probe. The yoke 64 is removably positioned in the hollow portion (central axis) of the detection coil 11 so as to be positioned with a small gap from the bottom surface of the container 50. In the illustration, the yoke 64 is positioned so as to protrude slightly from the top of the detection coil 11 through its central axis and face close to the bottom surface of the container 50. By positioning the yoke 64 close to the bottom surface of the container 50, the sample dispersed in the container 50 can be concentrated at the bottom, creating an aggregated state in which it is aggregated into smaller clumps.

[0029] The signal detected by the detection coil 11 is amplified by an amplifier (not shown) and input to the measuring device 62. The measuring device 62 is, for example, a so-called lock-in amplifier, and by using the frequency signal of the excitation coil 12 as a reference signal, the detection signal of the detection coil 11 can be measured with high sensitivity.

[0030] The signal processing device 63 is a means for processing the output signal of the measuring device 62 based on the detection signal of the detection coil 11. It calculates the magnetic field (specifically, the magnetic susceptibility) from the output signal of the measuring device 62 and calculates calculation results related to the presence or absence and quantity of the object to be detected in the container 50 based on its magnitude. The signal processing device 63 can be implemented using a general-purpose computer or a specific digital arithmetic circuit.

[0031] Depending on the amount of antigen to be detected bound to the magnetic particles, the magnitude of the magnetic field differs between the aggregated and dispersed states of the sample within the container 50. The antigen detection device of the present invention determines the difference in the magnitude of the magnetic field based on the difference in the state of the sample, and determines the presence or absence of the antigen to be detected and its amount (number, concentration). The measurement procedure using the antigen detection device according to the first configuration example is described below.

[0032] Figure 2 is a flowchart of the antigen detection method using the antigen detection device of the first configuration example. First, a container 50 containing a solution-like sample containing magnetic particles and the antigen to be detected is set on the support unit 13. By setting the container 50 on the support unit 13, the container 50 is positioned close to the detection coil 11 and concentric with its central axis. Then, the tip of the magnetic probe yoke 64 is brought close to the bottom of the container 50 fixed to the support unit 13, passing through the central axis of the detection coil 11, and the sample in the container 50 is magnetized (S101). The insertion and removal of the yoke 64 may be done manually or mechanically. Due to magnetization, the magnetic particles and the antigen to be detected bound to them are attracted to the bottom of the container 50 and aggregate, becoming a mass-like state in the solution. After the magnetic particles and the antigen to be detected are aggregated, the yoke 64 is removed from the detection coil 11 (S102).

[0033] When the sample is in an aggregated state, the excitation coil 12 is driven to apply an alternating magnetic field (S103), and the output signal (voltage signal) Vm of the detection coil 11 in the aggregated state is measured (S104). The output signal Vm of the detection coil 11 is the response signal of the magnetic particles bound to the antigen to be detected in the aggregated state to the alternating magnetic field. The frequency of the alternating magnetic field from the excitation coil 12 may be fixed to a single frequency, or the frequency may be changed by frequency sweeping to measure the output signal.

[0034] After the signal measurement in the aggregated state in step S104 is completed, the application of the alternating magnetic field by the excitation coil 12 is stopped, and then the aggregated sample in the container 50 is stirred to disperse the sample (S105). For example, the solution is stirred and the sample is dispersed by aspirating and discharging the liquid surface of the container 50 using a pipetting operation. Alternatively, the solution may be stirred and the sample dispersed by moving a permanent magnet or electromagnet closer to and further away from the top of the container 50 to pull up and move the sample aggregated at the bottom of the container 50. Preferably, the stirring in the container 50 is repeated multiple times using pipetting operations or by applying a magnetic field until the aggregated sample is sufficiently dispersed.

[0035] In the dispersed state of the sample, the excitation coil 12 is driven to apply an alternating magnetic field (S106), and the output signal (voltage signal) Vref of the detection coil 11 is measured (S107). The output signal Vref of the detection coil 11 is the response signal of the magnetic particles bound to the antigen to be detected in the dispersed state to the alternating magnetic field. Similar to the measurement in the aggregated state, the frequency of the alternating magnetic field from the excitation coil 12 may be fixed to a single frequency, or the frequency may be changed by frequency sweeping to measure the output signal.

[0036] After the completion of the signal measurement in the dispersed state in step S107, the application of the alternating magnetic field by the excitation coil 12 is stopped, and then the signal processing device 63 performs the following calculation using the signals measured in steps S104 and S107, according to equation (1), to calculate the magnetic susceptibility κ (S108).

[0037] Magnetic susceptibility κ=(Vm-Vref) / Vh (1)

[0038] Vm is the output signal of the detection coil 11 in the aggregated state measured in S104, Vref is the output signal of the detection coil 11 in the dispersed state measured in S107, and Vh is the output signal of the detection coil 11 when the container 50 containing the sample is not placed on the support part 13 (when no sample is placed), and these are measured in advance. If the detection coils 12 are differentially connected, the output signal from one of the coils is taken as Vh. Vh is also determined for frequencies matched to Vm and Vref, or for frequencies changed by frequency sweep. The magnetic susceptibility κ calculated has a correlation with the amount of sample, i.e., the amount (number) of antigen, and the amount of antigen can be measured with high sensitivity based on the value of the magnetic susceptibility κ.

[0039] The antigen detection device in the first configuration example can measure an antigen-containing sample in a stationary state, has a relatively simple configuration that does not require moving parts, and allows for miniaturization and weight reduction of the device. The components necessary for outputting the detection signal can be housed within the casing, making it a portable device. Furthermore, the cost of the antigen detection device can be reduced.

[0040] Figure 3 shows an example of measurement using the antigen detection method in the antigen detection device of the first configuration example described above. The measurement example shown in Figure 3 shows the measurement results using 7 μmφ polymer beads as the antigen, and is a graph showing the value of the magnetic susceptibility κ when the amount of polymer beads contained in the sample is changed. Specifically, the amount of polymer beads was changed to 5 × 10 3 (0.1 μL), 5 × 10 4 (1 μL), 5 × 10 5 (10 μL), 5 × 10 6 In a sample of 100 μL, Figure 3(a) is a graph showing the relationship between the frequency of the alternating magnetic field (horizontal axis) and the magnetic susceptibility κ (vertical axis), and Figure 3(b) is a graph showing the relationship between the magnetic susceptibility κ (vertical axis) and the number of polymer beads as antigen (horizontal axis). From Figure 3, it is clear that there is a correlation between the amount (number) of antigen and the calculated magnetic susceptibility κ, and that the magnetic susceptibility κ tends to increase as the amount (number) of antigen increases. Thus, the amount (number) of antigen can be determined based on the magnetic susceptibility κ.

[0041] Figure 4 shows a second configuration example of an antigen detection device according to an embodiment of the present invention. In Figure 4, the antigen detection device 20 in the second configuration example is an antigen detection device that detects a detectable antigen in a container 50 containing a sample comprising magnetic particles and a detectable antigen capable of binding to the magnetic particles, similar to the first configuration example. The antigen detection device 20 comprises a bridge circuit 23 having a first detection coil 21 and a second detection coil 22, a support part 24 that positions the container 50 close to one of the first detection coil 21 and the second coil 22 and concentric with its central axis, and a signal processing unit 25 that determines the amount of the detectable antigen based on the signal from the bridge circuit 23 when the container 50 is close to one of the first detection coil 21 and the second coil 22.

[0042] The first detection coil 21 and the second detection coil 22 are coils wound around a cylindrical support portion 24, and are arranged spaced apart from each other.

[0043] The support portion 24 consists of a first cylindrical body 24a around which the first detection coil 21 is wound, and a second cylindrical body 24b around which the second detection coil 22 is wound. The container 50 is inserted into and fixed in the hollow portion of either the first cylindrical body 24a or the second cylindrical body 24b. The first cylindrical body 24a and the second cylindrical body 24b are arranged at a predetermined distance apart, and by inserting and fixing the container 50 into one of them, the container 50 is positioned closer to either the first detection coil 21 or the second detection coil 22 than to the other. When the container 50 is inserted into the hollow portion of the first cylindrical body 24a, the container 50 is inserted concentrically with the central axis of the first detection coil 21 and positioned closer to the first detection coil 22. When the container 50 is inserted into the hollow portion of the second cylindrical body 24b, the container 50 is inserted concentrically with the central axis of the second detection coil 22 and positioned closer to the first detection coil 21. The shape and support method of the support portion 24 are not limited to a cylindrical shape; any shape that can be positioned at the center of the coil is designed as appropriate.

[0044] For example, in the water (physiological saline solution) in container 50, magnetic nanoparticles, which are magnetic markers, and the antigen to be detected, which is the substance to be detected, are placed, similar to the first configuration example described above. The magnetic field generated by the magnetic nanoparticles bound to the antigen to be detected in container 50 changes the inductance of one of the coils of either the first detection coil 21 or the second detection coil 22, in which container 50 is inserted on the central axis. The change in inductance correlates with the amount (number, concentration) of the antigen to be detected. The bridge circuit 23 detects the change in inductance of one of the detection coils as an output signal, and the signal processing unit 25 performs predetermined signal processing to measure the amount (number, concentration) of the antigen to be detected.

[0045] Figure 5 shows an example of the external configuration of the antigen test device 20 in the second configuration example. The antigen test device 20 in the second configuration example is housed in a small, portable box-shaped housing 29. The box-shaped housing 29 has holes 28a and 28b through which the container 50 communicates with the hollow portions of the first cylindrical body 24a and the second cylindrical body 24b of the support part 24. The container 50 can be inserted into either the first cylindrical body 24a or the second cylindrical body 24b through the holes 28a and 28b. The box-shaped housing 29 is provided with a display unit 27, such as a liquid crystal display, which can display measurement results from the signal processing unit 25. The signal processing unit 25 can determine measurement results according to various conditions, such as threshold determination, as well as the amount of antigen.

[0046] Figure 6 shows an example of measurement using the antigen detection device of the second configuration example described above. Figure 6(a) shows the specifications of the sample used in the measurement experiment. A certain amount of magnetic nanoparticles were contained in physiological saline (PBS-T), and several samples were prepared with different amounts of polymer beads as pseudo-antigens.

[0047] The measurement is performed by inserting a sample containing magnetic nanoparticles and a pseudo-antigen into either hole 28a or 28b of the box-shaped housing 29, acquiring the output signal of the bridge circuit 23 in that state, and obtaining a measured value through signal processing. Subsequently, a sample without magnetic nanoparticles and a pseudo-antigen (a sample containing only physiological saline) is inserted into the same hole into which the sample containing magnetic nanoparticles and a pseudo-antigen was inserted, acquiring the output signal of the bridge circuit 23 in that state, and obtaining a measured value through signal processing. The reason for measuring the sample containing only physiological saline is to use the output signal between physiological saline and the container 50 as a reference and subtract it from the measurement signal containing magnetic nanoparticles and a pseudo-antigen to extract only the signal of the substance being measured. In other words, the order of measurement of the former and the latter does not matter, and the measurement result is obtained from the difference between the measured values ​​of the former and the latter. Figure 6(b) shows an example of measurement results and is a graph showing the relationship between the measurement result (in arbitrary units) and the number of polymer beads as antigen. Figure 6(b) shows a correlation between the measurement results and the amount (number, concentration) of antigen, with a tendency for the measurement results to decrease as the amount (number, concentration) of antigen increases. Thus, the amount (number, concentration) of antigen can be determined based on the change in coil inductance. The numbers on the horizontal axis of the graph correspond to conditions 1 to 4 in Figure 6(a).

[0048] In the second configuration example, permanent magnets are arranged at a predetermined distance from the central axes of the first detection coil 21 and the second detection coil 22, which are arranged in parallel, and a DC magnetic field may be applied to the first detection coil 21 and the second detection coil 22 when measuring the sample. By applying a DC magnetic field, fluctuations in the signals from the first detection coil 21 and the second detection coil 22 are reduced, and the signal-to-noise ratio of the signals is improved.

[0049] The antigen detection device in the second configuration example can also measure an antigen-containing sample in a stationary state, has a relatively simple configuration that does not require moving parts, and allows for miniaturization, weight reduction, and cost reduction of the device. The components necessary for outputting the detection signal can be housed within the casing, making it a portable device.

[0050] Figure 7 shows a third configuration example of an antigen detection device according to an embodiment of the present invention. In Figure 7, the antigen detection device 30 in the third configuration example is an antigen detection device that detects the antigen to be detected in a container 50 containing a sample that includes magnetic particles and the antigen to be detected that can bind to the magnetic particles, similar to the first and second configuration examples. The antigen detection device 30 is an antigen detection device that detects a detectable antigen in a container containing a sample comprising magnetic particles and a detectable antigen capable of binding to the magnetic particles. The device comprises a detection coil 31 in which a first coil 31a and a second coil 31b are differentially connected and whose central axes are arranged concentrically; a support part 32 that brings the container 50 closer to one of the first coil 31a and the second coil 31b and is arranged concentrically to its central axis; an excitation coil 33 that applies an alternating magnetic field to the sample; and a signal processing unit 34 that determines the amount of the detectable antigen based on a signal from the detection coil 31 when the container 50 is brought closer to one of the first coil 31a and the second coil 31b while the alternating magnetic field is applied to the sample by the excitation coil 33. In the illustration, the signal processing unit 34 is an integrated circuit unit that oscillates the excitation coil 33, but the oscillator may be provided as a separate element.

[0051] The detection coil 31 is composed of a first coil 31a and a second coil 31b that are differentially connected and whose central axes are concentrically arranged, and the excitation coil 33 is arranged around the outside of the detection coil 31.

[0052] The support section 32 is a cylindrical body in which the first coil 31a and the second coil 31b are wound axially, separated into upper and lower sections. In the illustration, the first coil 31a is positioned on the upper side and the second coil 31b on the lower side of the cylindrical body. The container 50 is then inserted and fixed into the hollow portion of the cylindrical body. The container 50 is inserted in a position closer to the first coil 31a, that is, the bottom of the inserted container 50 is positioned so that it does not fall below the lower end of the upper first coil 31a. The shape and support method of the support section 32 are not limited to a cylindrical body; any shape that can be positioned at the center of the coils can be designed as appropriate.

[0053] For example, in the water (physiological saline solution) in container 50, magnetic nanoparticles, which are magnetic markers, and the antigen to be detected, which is the substance to be detected, are placed, similar to the first and second configuration examples described above. The magnetic field created by the magnetic nanoparticles bound to the antigen to be detected in container 50 is changed by the excitation coil 33 as an alternating magnetic field, and this change in the magnetic field changes the inductance of one of the detection coils (in this case, the first coil 31a) in which container 50 is inserted on its central axis. The change in inductance is correlated with the amount (number, concentration) of the antigen to be detected, and the change in the inductance of the detection coil 31, in which two coils are differentially connected, is detected as an output signal, and the amount (number, concentration) of the antigen to be detected can be measured by performing predetermined signal processing by the signal processing unit 34.

[0054] Figure 8 shows an example of the external configuration of the antigen test device 30 in the third configuration example. Similar to the second configuration example, the antigen test device 30 in the third configuration example is housed in a small, portable box-shaped housing 39. The box-shaped housing 39 has a hole 38 through which the container 50 communicates with the hollow portion of the cylindrical body of the support part 32, and the container 50 can be inserted into the support part 32 through the hole 38. The box-shaped housing 39 is provided with a display unit 37, such as a liquid crystal display, which can display measurement results from the signal processing unit 34. The signal processing unit 34 can calculate measurement results according to various conditions, such as threshold determination, as well as the amount of antigen.

[0055] The antigen detection device in the third configuration example can measure an antigen-containing sample in a stationary state, has a relatively simple configuration that does not require moving parts, and allows for miniaturization, weight reduction, and cost reduction of the device. The components necessary for outputting the detection signal can be housed within the casing, making it a portable device.

[0056] In embodiments of the present invention, a liquid sample containing magnetic particles and a substance to be detected that can bind to them is placed in close proximity to a detection coil, and the amount of the antigen to be detected is measured based on the output signal of the detection coil. With the above-described configuration, highly sensitive magnetic immunoassay can be performed with a small and lightweight device.

[0057] The present invention is not limited to the embodiments described above, and of course, design changes that do not depart from the spirit of the invention, including various modifications and alterations that can be conceived by a person with ordinary skill in the art of the invention, are also included in the present invention. [Explanation of Symbols]

[0058] 10: Antigen detection device, 11: Detection coil, 12: Excitation coil, 13: Support part, 20: Antigen detection device, 21: First detection coil, 22: Second detection coil, 23: Bridge circuit, 24: Support part, 24a: First cylindrical body, 24b: Second cylindrical body, 25: Signal processing device, 27: Display unit, 28: Hole, 29: Box-shaped housing, 30: Antigen detection device, 31: Detection coil, 31a: First coil, 31b: Second coil, 32: Support part, 33: Excitation coil, 34: Signal processing unit, 37: Display unit, 38: Hole, 39: Box-shaped housing, 50: Container, 60: Oscillator, 62: Measuring device, 63: Signal processing device, 64: Yoke

Claims

1. An antigen detection device for detecting a detectable antigen in a container containing a solution-like sample comprising magnetic particles and an antigen to be detected that can bind to the magnetic particles, A detection coil for detecting a signal corresponding to the magnetic field generated by the sample contained in the container, An excitation coil for applying an alternating magnetic field to the aforementioned sample, The container comprises a support portion positioned close to the detection coil and concentric with its central axis, The detection coil detects a signal corresponding to the magnetic field of the sample, which is subjected to an alternating magnetic field by the excitation coil and is in an aggregated state in which the antigen to be detected is aggregated in a container concentrically arranged with the detection coil and bound to the magnetic particles. The detection coil detects a signal corresponding to the magnetic field of the sample, which is subjected to an alternating magnetic field by the excitation coil and is in a dispersed state in which the antigen to be detected is dispersed in a container concentrically arranged with the detection coil and bound to the magnetic particles. Furthermore, the antigen detection device is characterized by comprising a signal processing unit that determines the amount of the antigen to be detected based on a signal corresponding to the magnetic field produced by the sample in an aggregated state and a signal corresponding to the magnetic field produced by the sample in a dispersed state.

2. The antigen detection device according to claim 1, characterized in that the support portion supports the container such that the bottom of the container is positioned near the upper end of the central axis of the detection coil.

3. An antigen detection method for detecting a detectable antigen in a container containing a solution-like sample comprising magnetic particles and an antigen to be detected that can bind to the magnetic particles, The process of bringing the container close to the detection coil and positioning it concentrically with its central axis, The process involves applying an alternating magnetic field to the aggregated sample, in which the antigen to be detected is aggregated with the magnetic particles in the container concentrically arranged with the detection coil, and detecting a signal corresponding to the magnetic field produced by the aggregated sample. A step of detecting a signal corresponding to the magnetic field of the dispersed sample while applying an alternating magnetic field to the dispersed sample, in which the antigen to be detected is dispersed in the container concentrically arranged with the detection coil and bound to the magnetic particles; An antigen detection method characterized by comprising the step of determining the amount of the antigen to be detected based on a signal corresponding to a magnetic field from the sample in an aggregated state and a signal corresponding to a magnetic field from the sample in a dispersed state.

4. The antigen detection method according to claim 3, characterized in that the bottom of the container is positioned near the upper end of the central axis of the detection coil.

5. The antigen detection method according to claim 4, characterized in that a yoke is passed through the central axis of the detection coil, the yoke is brought closer to the bottom of the container, and the antigen to be detected, which is bound to the magnetic particles in the container, is aggregated.

6. The antigen detection method according to claim 4 or 5, characterized in that a magnetic material is brought close to the top of the container and the aggregated sample is dispersed.

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