Automatic analysis device

Abstract

This automatic analysis device comprises: a flow path (10) for introducing a sample containing magnetic particles (13) bonded to a specific substance into a capture region (14); a supply means for supplying the sample to the flow path (10); a magnet (19) that captures the magnetic particles (13); a slide mechanism (20) that moves the magnet (19) to the vicinity of a projection surface onto which the capture region (14) is projected; a photodetector that detects the specific substance on the magnetic particles (13); a discharge means for discharging the magnetic particles (13) from the flow path (10) after detection by the photodetector; and a magnet guide mechanism (24) that is composed of a magnetic material and moves the magnet (19).

Description

automatic analyzer

[0001] The present invention relates to an automatic analyzer.

[0002] One example of a method for detecting a substance to be measured in an automatic analyzer is to immobilize the substance to be measured on magnetic particles, bind a labeling substance to the substance to be measured, and measure a signal derived from the label (see Patent Document 1).

[0003] International Publication No. 2013 / 099648

[0004] However, the automatic analyzer described in Patent Document 1 does not take into consideration the correction of the magnet position, which affects the reproducibility of magnetic particle capture during magnetic particle capture during measurement. The capture position and capture amount of magnetic particles are affected by the capture operation position of the magnet. To reduce the difference in analytical performance between measurements and between devices, it is necessary to position the magnet for magnetic particle capture in the same location relative to the detection area.

[0005] Therefore, an object of the present invention is to provide an automatic analyzer that reduces the difference between measurements and between devices in magnet position, improves the reproducibility of magnetic particle capture in the detection area, and enables highly accurate measurements.

[0006] The present invention is characterized by comprising a flow path for introducing a sample containing magnetic particles bound to a specific substance into a capture region, a supply means for supplying the sample to the flow path, a magnet for capturing the magnetic particles, a slide mechanism for moving the magnet to the vicinity of a projection surface on which the capture region is projected, a detector for detecting the specific substance on the magnetic particles, a discharge means for discharging the magnetic particles from the flow path after detection by the detector, and a magnet guide mechanism made of a magnetic material for moving the magnet.

[0007] According to the present invention, it is possible to provide an automatic analyzer that reduces the difference in magnet position between measurements and between devices, improves the reproducibility of magnetic particle capture in the detection region, and enables highly accurate measurements.

[0008] 1 is a schematic diagram of an immunoassay analyzer. A schematic diagram of an immunoassay analyzer using laser light. A diagram of the vicinity of a flow path of an immunoassay analyzer. A diagram of the vicinity of a flow path according to the first embodiment. A cross-sectional view taken along an xy plane passing through the magnet guide mechanism according to the first embodiment. A cross-sectional view taken along an xy plane passing through the magnet guide mechanism according to a modified example of the first embodiment. A diagram of the vicinity of a flow path according to the second embodiment. A cross-sectional view taken along an xy plane in which a magnet according to the second embodiment and a flow path wall come into contact. A cross-sectional view taken along an xy plane in which a magnet according to a modified example of the second embodiment and a flow path wall come into contact. A diagram of the vicinity of a flow path according to the third embodiment. A diagram showing the positional relationship between the magnet guide mechanism and the magnet according to the third embodiment. A diagram showing the positional relationship between the magnet guide mechanism and the magnet according to a modified example of the third embodiment. A side view of a slide mechanism according to the fourth embodiment. A top view of a slide mechanism according to the fourth embodiment. A diagram of the vicinity of a flow path according to the fifth embodiment. A diagram of the vicinity of a flow path according to the sixth embodiment.

[0009] Hereinafter, embodiments of the present invention will be described in detail with reference to the drawings. However, the present invention is not limited to the following embodiments, and various modifications and applications within the technical concept of the present invention are also included within its scope. Furthermore, the following will describe an immunoassay device as an example of an automated analyzer. However, the present invention is not limited to immunoassays, and can be applied to any automated analyzer that uses magnetic particles and captures them by switching the magnetic field strength, and the technology can be similarly applied to analyzers for DNA, biochemistry, etc.

[0010] (First embodiment) Fig. 1 is a schematic diagram of an immunoassay apparatus. As shown in Fig. 1, the immunoassay apparatus (automatic analyzer) 1A is configured to include a flow channel 10 that introduces a sample containing magnetic particles 13 bound to a specific substance into a capture region 14, a pump 35 that supplies the sample to the flow channel 10, a magnet 19 that captures the magnetic particles 13, a slide mechanism 20 that moves the magnet 19 to the vicinity of a projection surface 61 (see Fig. 4A ) on which the capture region 14 is projected, a photodetector 21 (detector) that detects the specific substance on the magnetic particles 13, and a pump 35 that discharges the sample containing the magnetic particles 13 from the flow channel 10 after detection by the photodetector 21. The pump 35 serves both the function of supplying the sample to the flow channel 10 and the function of discharging the sample from the flow channel 10.

[0011] A sipper nozzle 33 is connected to the flow path 10 through a tube 30. A pump 35 is also connected to the flow path 10 through a tube 31. An ON / OFF valve 36 is provided in the tube 31 between the flow path 10 and the pump 35. The pump 35 is controlled by a controller 50 through a signal line 52, allowing for accurate suction and discharge of liquid. The pump 35 is also connected to a waste liquid container 45 through a tube 32. The tube 32 is connected to a tube 31 between the valve 36 and the pump 35. An ON / OFF valve 37 is also provided in the tube 32. The valve 37 is controlled by the controller 50 through a signal line 51.

[0012] Sipper nozzle 33 is movably attached by arm 34. A suspension container 40, a cleaning solution container 42, and a buffer solution container 43 are installed within the movement range of sipper nozzle 33. Suspension container 40 is provided in reaction unit 41. Reaction unit 41 is a unit for producing immune complexes consisting of magnetic particles 13 and labeled substances, and has a structure for storing suspension container 40. A cleaning mechanism 44 has the function of cleaning sipper nozzle 33.

[0013] The flow channel 10 is configured to include a flow channel wall 11 located at the top, a flow channel wall 12 located at the bottom, a capture region 14 for magnetic particles 13, a reaction field electrode 15, and a counter electrode 16. A member for increasing height is sandwiched between the flow channel wall 11 and the flow channel wall 12. Note that hereinafter, the flow channel walls 11 and 12, the capture region 14, the reaction field electrode 15, and the counter electrode 16 may be collectively referred to as a flow cell. In other words, a flow cell is a structure (mechanism) that allows for observation of flowing matter.

[0014] The flow path wall 11 is made of a transparent material. The flow path walls 11 and 12 can be made of, for example, a planar plate, but are not limited to this. Since the flow path wall 11 is made of a transparent material, it transmits light and allows the internal flow state to be observed. Note that the entire flow path wall 11 does not need to be transparent; only the portion through which light transmits needs to be transparent as a window.

[0015] The flow channel wall 11 is preferably made of a material that is substantially transparent to the wavelength of light emitted by the labeling substance of the magnetic particle complex (a mass of the object to be measured and the labeling substance) adsorbed to the capture region 14 in the flow cell, such as glass or plastic.

[0016] A capture region 14 for capturing magnetic particles 13 is provided within the flow channel 10. A reaction field electrode 15 is provided in this capture region 14. A counter electrode 16 is also provided on the opposite side of the flow channel 10 from the reaction field electrode 15 (capture region 14). Furthermore, the reaction field electrode 15 and the counter electrode 16 are connected to a voltage application means 18 via lead wires 17a and 17b. The voltage application means 18 is connected to a controller 50 via a signal line 58.

[0017] Furthermore, a magnet 19 is used as a magnetic field application means to attract the magnetic particles 13 in the capture region 14. This magnet 19 is a permanent magnet or an electromagnet. When attracting the magnetic particles 13, for example, the magnet 19 is moved directly below the flow channel 10. For example, the magnet 19 is placed on a slide mechanism 20 that can perform circular motion, and when attracting the magnetic particles 13, the magnet 19 is moved directly below the flow channel 10.

[0018] The magnetic particles 13 are attracted (captured) to the capture region 14 in the flow channel 10 by the magnetic force of the magnetic field of the magnet 19. This capture region 14 is easy to measure luminescence if it is formed as a surface with a predetermined area. The capture region 14 may be provided on the bottom surface of the flow channel 10, on another surface within the flow channel 10, or on multiple surfaces arranged three-dimensionally.

[0019] When cleaning the inside of the flow channel 10, for example, the magnet 19 can be moved to a position where the influence of the magnet 19 in the flow channel 10 can be sufficiently reduced, thereby enabling sufficient cleaning.

[0020] The controller 50 is connected to the valves 36, 37, the pump 35, the arm 34, the voltage application means 18, the photodetector 21, and the slide mechanism 20 via signal lines 53, 51, 52, 54, 58, 57, and 56, and can control each of them independently.

[0021] During measurement, the controller 50 controls the voltage application means 18. Accordingly, a voltage is applied between the reaction field electrode 15 and the counter electrode 16 in the flow channel 10. This causes the labeled substance bound to the magnetic particles 13 adsorbed on the reaction field electrode 15 (capture region 14) to electrochemically emit light. As long as the area around the counter electrode 16 is made of a transparent material so as to enable measurement by the photodetector 21, the other parts of the flow channel wall 11 do not need to be made of a transparent material.

[0022] The reaction field electrode 15 and the counter electrode 16 can be made of, for example, gold, platinum, palladium, tungsten, iridium, nickel, alloys thereof, carbon materials, etc. Alternatively, the reaction field electrode 15 and the counter electrode 16 can be made of a base material such as titanium, on which the above-mentioned materials are deposited by plating, sputtering, or the like.

[0023] By adopting a light emission method using a counter electrode 16, the reaction field electrode 15 and the counter electrode 16 can be fixed to the flow cell. Compared to the immunoassay analyzer 1B using laser light described below in Fig. 2, the immunoassay analyzer 1A in Fig. 1 does not require a condenser lens 22 or a laser light source 23, and therefore does not require positioning of the laser light or selection and installation of a transparent material in the capture region 14, which is expected to simplify the device and reduce variations in light emission.

[0024] The photodetector 21 may be, for example, a camera or a photomultiplier tube.

[0025] The sample to be analyzed is a substance derived from a living body, such as serum or urine. When the sample is serum, the specific component to be analyzed is, for example, a tumor marker, an antibody, an antigen-antibody complex, or a single protein. In the following description, the specific component is assumed to be TSH (thyroid stimulating hormone).

[0026] The suspension container 40 contains a suspension obtained by pre-treatment, in which the sample to be analyzed is mixed with a bead solution and a reagent, and then reacted at a constant temperature (e.g., 37°C) for a certain period of time. The bead solution is a solution in which magnetic particles 13, each of which is composed of particulate magnetic material embedded in a matrix material such as polystyrene, are dispersed in a buffer solution. Streptavidin, which can bind to biotin, is bound to the surface of the matrix material. The reagent contains a substance that binds the magnetic particles 13 to the specific component TSH in the sample, including an anti-TSH antibody with a biotin-terminated end. The reagent varies depending on the type of specific component to be analyzed, and may be, for example, an immunoglobulin, an antigen, an antibody, or other biological substance.

[0027] The cleaning liquid container 42 contains a cleaning liquid for cleaning the inside of the flow path 10 and the tube 30 .

[0028] The immunoanalyzer 1A (see FIG. 1) has been described above, but as an example of an apparatus according to a modification with a different mechanism, an immunoanalyzer using an excitation light source will be described with reference to FIG. 2. FIG. 2 is a schematic diagram of an immunoanalyzer using laser light as an example of excitation light.

[0029] 2, the immunoassay analyzer 1B includes a condenser lens 22 and a laser light source 23 instead of the reaction field electrode 15, the counter electrode 16, and the voltage application means 18 provided in the immunoassay analyzer 1A. The laser light source 23 is connected to a controller 50 via a signal line 55. Note that, in the immunoassay analyzer 1B, components similar to those of the immunoassay analyzer 1A shown in FIG. 1 are designated by the same reference numerals, and redundant explanations will be omitted.

[0030] The laser light source 23 and the condenser lens 22 are installed around the lower part of the flow channel 10. The flow channel walls 11 and 12 of the flow cell are formed of a transparent material. The capture region 14 installed within the flow channel walls 11 and 12 of the flow cell collects laser light irradiated from the lower part of the flow channel 10 via the laser light source 23 and the condenser lens 22. In order to enable the laser light to be irradiated onto the capture region 14, the capture region 14 is preferably made of a material that is substantially transparent to the wavelength of light emitted by the labeling substance of the magnetic particle complex adsorbed to the capture region 14 in the flow cell, and is preferably made of, for example, glass, plastic, or the like.

[0031] Furthermore, for example, if the laser light source 23 and the condenser lens 22 are configured by devising an arrangement or the like so that the laser light does not need to pass through the capture region 14, then it is preferable that the capture region 14 be made of a material that has excellent mechanical strength, corrosion resistance, processing efficiency, etc., such as gold, platinum, or carbon, taking into consideration that the magnetic particle composite will be adsorbed onto its upper surface. Furthermore, if the laser light does not need to pass through the capture region 14, the channel wall 12 does not need to be a transparent material, and materials such as ceramics, metals, and plastics can be used.

[0032] When measuring luminescence, the fluid in the flow channel 10 is stopped in advance, and the magnetic force in the flow channel 10 is released by using the slide mechanism 20 to move the magnet 19 away from the position directly below the flow channel 10. Note that releasing the magnetic force also stops the flow, so the magnetic particles 13 are held in the capture region 14. This allows the magnetic particles 13 to emit light by irradiation with laser light while being held in the capture region 14. Measurement can be performed by receiving the luminescence from the labeled substance bound to the magnetic particles 13 with the photodetector 21.

[0033] The labeling substance used in the immunoassay analyzer 1B shown in Fig. 2 may be different from the labeling substance used in Fig. 1. Specific examples of labeling substances can be appropriately designed by those skilled in the art based on known techniques, etc.

[0034] Next, the operation of the automatic analyzer will be explained using the immunoassay analyzer of Figure 1 as an example. One analysis cycle consists of a suspension aspiration period, a magnetic particle adsorption period, a detection period, a washing period, a reset period, and a preliminary aspiration period. One cycle starts when suspension container 40 containing suspension treated in reaction unit 41 is set in a predetermined position.

[0035] During the suspension suction period, valve 36 is opened and valve 37 is closed in response to a signal from controller 50. Then, arm 34 is operated in response to a signal from controller 50, and sipper nozzle 33 is inserted into suspension container 40. Next, pump 35 (supply means) performs a suction operation of a fixed amount in response to a signal from controller 50. As a result, the suspension in suspension container 40 is introduced into tube 30 via sipper nozzle 33. In this state, pump 35 is stopped, and arm 34 is operated to insert sipper nozzle 33 into cleaning mechanism 44. Sipper nozzle 33 is cleaned as it passes through cleaning mechanism 44.

[0036] During the magnetic particle adsorption period, the slide mechanism 20 is operated by a signal from the controller 50, and the magnet 19 moves to the bottom of the flow channel 10. Then, the pump 35 performs suction at a constant speed in response to a signal from the controller 50. During this time, the suspension present in the tube 30 passes through the flow channel 10. Because a magnetic field is generated from the magnet 19 within the flow channel walls 11 and 12, the magnetic particles 13 contained in the suspension are attracted toward the magnet 19 by magnetic force and captured in the capture region 14. After a certain time has passed, the suction of the suspension by the pump 35 is stopped. In other words, the flow in the flow channel 10 (flow cell) is stopped.

[0037] During the detection period, the sliding mechanism 20 is operated by a signal from the controller 50, and the magnet 19 is moved away from the flow channel 10. Then, the voltage application means 18 is controlled by a signal from the controller 50, and a voltage is applied between the reaction field electrode 15 and the counter electrode 16 in the flow channel 10. This causes the labeled substance bound to the magnetic particles 13 adsorbed on the reaction field electrode 15 (capture region 14) to electrochemically emit light. The emitted light is detected by a photodetector 21, such as a camera or photomultiplier tube, with wavelength selection optionally performed using a filter. The intensity of the detected light emission is collected as a signal by the controller 50. After a certain period of time has elapsed, the voltage application is stopped. During the detection period, the arm 34 is operated, and the sipper nozzle 33 is inserted into the cleaning mechanism 44.

[0038] During the washing period, the pump 35 is used to suck the washing solution sucked from the washing solution container 42 and pass it through the flow path 10 in response to a signal from the controller 50. At this time, the magnet 19 is moved away from the flow path 10, so the magnetic particles 13 are not retained in the capture region 14 and are washed away together with the washing solution.

[0039] During the reset period, the controller 50 closes the valve 36, opens the valve 37, and causes the pump 35 (discharge means) to discharge. As a result, the liquid in the pump 35 is discharged into the waste liquid container 45.

[0040] During the preliminary suction period, buffer solution is aspirated from the buffer solution container 43 in response to a signal from the controller 50, filling the tube 30 and the flow path 10 with the buffer solution. After the preliminary suction period, the next cycle can be executed.

[0041] As described above, the immunoassay device (automated analyzer) 1A includes a flow path 10 that introduces a sample liquid (sample) containing magnetic particles 13 bound to a specific substance (analyte) into a capture region 14, a pump 35 (supply means) that supplies the sample liquid to the flow path 10, a magnet 19 (capture means) that has a magnetic field structure that generates a magnetic field and attracts the magnetic particles 13 to the capture region 14 using the magnetic field, a photodetector 21 (detector) that measures the specific substance adsorbed to the capture region 14, and a pump 35 (discharge means) that discharges the magnetic particles 13 from the flow path 10 after measurement by the photodetector 21. Note that both the supply means and the discharge means are not limited to the pump 35, and separate components may be used for these. Here, the sample liquid is a liquid containing the analyte, such as a suspension.

[0042] Furthermore, instead of the configuration described above, a part of a known automatic analyzer may be used.

[0043] The flow cell structure and the surrounding structure of the magnet for the immunoassay analyzer 1A described above will be described with reference to FIGS. 3 and 4. FIG. 3 is a diagram illustrating the configuration of the flow path and its vicinity in the immunoassay analyzer. FIG. 4A is a diagram illustrating the configuration of the flow path and its vicinity in the first embodiment. FIG. 4B is a cross-sectional view taken along the x-y plane passing through the magnet guide mechanism in the first embodiment. FIG. 4C is a cross-sectional view taken along the x-y plane passing through the magnet guide mechanism in a modified version of the first embodiment. The flow direction at the center of the flow cell is the x-axis, the horizontal direction of the cross section perpendicular to the flow is the y-axis, and the vertical direction is the z-axis. Note that in FIG. 4A, the reaction field electrode 15 and counter electrode 16 are omitted, and only the capture region 14 is shown (the same applies to the second and subsequent embodiments).

[0044] 3, the flow channel 10 is configured so that the width of the flow channel in the xy plane gradually increases from the end where the suspension is introduced toward the center, and gradually decreases from the center to the end where the suspension is discharged. A magnet 19 is positioned in the center of the flow channel 10 in the x direction by a sliding mechanism 20. A capture region 14 where the magnetic particles 13 are captured has an area larger than that of the magnet 19, for example.

[0045] As shown in FIG. 4A , the suspension containing magnetic particles 13 travels in the +z direction (upward in the figure) through a path 10a formed by channel walls 11a and 12 and enters the flow cell. The suspension then travels in the +x direction, following the flow direction 60 (see the outline arrow) within channel 10, and reaches the end of channel 10. The suspension then travels in the −z direction (downward in the figure) through a path 10b formed by channel walls 11b and 12 and is discharged from the flow cell. During this time, the suspension is subjected to the magnetic field of magnet 19, and magnetic particles 13 are captured on the surface of capture region 14 by magnetic force. Note that in FIG. 4A , the captured magnetic particles are indicated by the reference numeral 13a.

[0046] The first embodiment of the immunoassay device 1A includes a magnet guide mechanism 24 made of a magnetic material near the flow path 10, a stopper structure 25 that stops the movement of the magnet 19, and a slide mechanism 20 having a deformation portion 29 that can be deformed by the magnetic force received by the magnet 19.

[0047] The slide mechanism 20 has a mechanism for moving the magnet 19 in a direction toward or away from the flow path wall 12, and has an arm 20b formed on a rotating shaft 20a, with the magnet 19 attached via a deformation portion 29. Although not shown, the rotating shaft 20a is configured to move in the direction of arrow 62 in response to a signal from the controller 50. The magnet 19 is attached to the tip of the arm 20b, and is configured so that when the rotating shaft 20a rotates counterclockwise, the magnet 19 moves in a direction away from the flow path wall 12, and when the rotating shaft 20a rotates clockwise, the magnet 19 moves in a direction toward the flow path wall 12.

[0048] 4A , during the magnetic particle adsorption period, when slide mechanism 20 operates and magnet 19 moves to the bottom of flow channel 10, magnet 19 receives magnetic force from magnet guide mechanism 24. At this time, deformation portion 29 of slide mechanism 20 deforms, and magnet 19 moves in a direction approaching magnet guide mechanism 24. The moved magnet 19 hits stopper structure 25 and stops, and the position of magnet 19 is corrected.

[0049] The magnet guide mechanism 24 can be made of a general magnetic material, and may be either a hard magnetic material, a soft magnetic material, or a combination of these. When a hard magnetic material is used, the magnet 19 may be moved by either an attractive force or a repulsive force. However, from the viewpoint of reducing the influence on the capture of magnetic particles by the magnet guide mechanism 24, it is preferable to use a soft magnetic material. An example of a soft magnetic material is soft iron.

[0050] Furthermore, when the magnet guide mechanism 24 is located on the wall (outer periphery) of the flow path wall 12, it may be fixed by adhering it to the flow path wall 12 with an adhesive such as a curable resin, or it may be fixed by having the flow path wall 12 have a structure that holds the magnet guide mechanism 24. Furthermore, when the magnet guide mechanism 24 is located inside the flow path wall 12, it may be fixed inside the flow path wall 12 by insert molding or the like.

[0051] Furthermore, there are no restrictions on the size of the magnet guide mechanism 24 as long as it can move the magnet 19 by magnetic force. However, from the viewpoint of reducing the consumption of the magnetic flux of the magnet 19 used by the magnet guide mechanism 24 to capture the magnetic particles, it is preferable to make the magnet guide mechanism 24 as small as possible.

[0052] Furthermore, the magnet guide mechanism 24 may be an additional member with a simple structure such as a cube or sphere added to the flow cell or its peripheral members, or may have a structure obtained by machining. From the viewpoint of reducing the consumption of magnetic flux of the magnet 19 used to capture magnetic particles by the magnet guide mechanism 24, it is preferable to correct the position of the magnet 19 with as few numbers or locations as possible.

[0053] 4B, stopper structure 25 is formed in a substantially L-shape and is configured to contact surface 19a facing the y-axis direction and surface 19b facing the x-axis direction of magnet 19. In this way, stopper structure 25 is configured to simultaneously contact two surfaces of magnet 19, the x-axis direction and the y-axis direction (simultaneous contact at two or more locations).

[0054] The stopper structure 25 only needs to be able to stop the magnet 19 moving by the magnet guide mechanism 24, and its shape may be rectangular or cylindrical, or it may have any shape that allows it to contact the magnet 19 at two or more points simultaneously.

[0055] Furthermore, stopper structure 25 does not necessarily have to be a continuous structure (see FIG. 4B ), and as shown in FIG. 4C , stopper structures 25 present in two or more locations may contact magnet 19 at two or more locations. However, from the perspective of correcting the position of magnet 19, if magnet 19 is a polyhedron, stopper structure 25 preferably contacts magnet 19 at points, lines, or faces included in two different faces. Furthermore, if magnet 19 is a cylinder and stopper structure 25 contacts a curved surface, stopper structure 25 preferably contacts magnet 19 at a position where it can stop the movement of magnet 19 in the x-axis and y-axis directions.

[0056] The magnet guide mechanism 24 may be configured to move the magnet 19 by magnetic force. The magnet guide mechanism 24 is not limited to being located inside or on the flow path wall 12, but may also be fixed externally, without contacting other flow path components such as the flow path wall 11 or the flow cell. However, with regard to the position in the z-axis direction, from the viewpoint of reducing consumption of magnetic flux from the magnet 19 used to capture magnetic particles by the magnet guide mechanism 24, it is preferable that the magnet guide mechanism 24 be located in the −z direction relative to the center O of the magnet 19 in the z-axis direction when the magnet 19 is in contact with the projection plane 61 on which the capture region 14 is projected. The −z direction refers to the direction away from the projection plane 61. Furthermore, when the magnet guide mechanism 24 is formed from a single additional member, it is preferable that the magnet guide mechanism 24 be located in the x-axis and y-axis directions such that, when a magnetic force acts between the magnet guide mechanism 24 and the magnet 19, the magnet 19 moves in a direction such that the magnetic force contacts the stopper structure 25 at two or more locations.

[0057] The stopper structure 25 may be made of any material that does not deform when it comes into contact with the magnet 19, and may be the same as the material that constitutes the flow path wall 12, or may be made of a different material such as ceramic, metal, or plastic. In addition, the stopper structure 25 may be a separate member that is fixed to the flow path wall 12, or may be part of the structure of the flow path wall 12.

[0058] There are no limitations on the form of motion of the slide mechanism 20, and it is possible to adopt forms such as linear motion in the horizontal or vertical direction or circular motion. However, it is preferable that the magnet 19 be movable in all directions of the x, y, and z axes by both the movement of the slide mechanism 20 in the vicinity of the projection surface 61 on which the capture area 14 is projected and the movement of the magnet 19 by the magnet guide mechanism 24.

[0059] The deformation portion 29 of the slide mechanism 20 may deform when the magnet 19 receives a magnetic force from the magnet guide mechanism 24. For example, the deformation portion 29 may be made of a rod-shaped material such as a general elastic material, such as elastomer, rubber, or resin, or the slide mechanism 20 may be made of an elastomer, rubber, resin, or metal, and have a spring-like structure. Furthermore, the deformation portion 29 made of an elastic material may be a part of the slide mechanism 20 (see FIG. 4A ) or the entire slide mechanism 20.

[0060] The shape of magnet 19 is not limited, and may be a rectangular parallelepiped (see FIG. 4A) or a sphere. The direction of magnetization of magnet 19 is also not limited, and may be, for example, parallel to the z-axis or perpendicular to it.

[0061] The immunoassay device 1A of the first embodiment described above includes a flow path 10 that introduces a sample containing magnetic particles 13 bound to a specific substance (analyte) into a capture region 14, a pump 35 (supply means) that supplies the sample to the flow path 10, a magnet 19 that captures the magnetic particles 13, a slide mechanism 20 that moves the magnet 19 to the vicinity of a projection surface 61 on which the capture region 14 is projected, a photodetector 21 (detector) that detects the specific substance on the magnetic particles 13, a discharge means that discharges the magnetic particles 13 from the flow path 10 after detection by the photodetector 21, and a magnet guide mechanism 24 made of a magnetic material that moves the magnet 19 (see FIGS. 1 and 4A ). This reduces measurement-to-measurement and device-to-device differences in the position of the magnet 19, improves the reproducibility of capture of the magnetic particles 13 in the detection region (capture region 14), and provides an immunoassay device 1A that enables high-precision measurements. Furthermore, in the immunoassay device 1B shown in FIG. 2 that uses excitation light, the irradiation range of the excitation light can be narrowed by improving the reproducibility of capturing the magnetic particles 13, and the laser output can be reduced.

[0062] In the first embodiment, the magnetic material is a soft magnetic material, which can reduce the influence on the capture of magnetic particles by the magnet guide mechanism 24.

[0063] In the first embodiment, the deformation portion 29, which is at least a part of the slide mechanism 20, is made of an elastic material (see FIG. 4A). This allows the deformation of the deformation portion 29 to correct the position of the magnet 19.

[0064] In the first embodiment, the magnet guide mechanism 24 is positioned below the center O of the magnet 19 when the magnet 19 is located at the capture operation position P (see FIGS. 4A and 4B ). This allows the magnet guide mechanism 24 to reduce consumption of the magnetic flux of the magnet 19 used to capture magnetic particles.

[0065] The first embodiment also includes a stopper structure 25 (see FIG. 4B ) that stops the magnet 19 moved by the magnet guide mechanism 24. This allows the magnet 19 to be corrected to the same location, improving the repeatability of capturing the magnetic particles 13.

[0066] In a modification of the first embodiment, stopper structure 25 has a shape that allows it to contact magnet 19 at two or more locations simultaneously (see FIG. 4C ). This makes it easier to correct magnet 19 in the same location (correct its position) than when correcting magnet 19 in one location.

[0067] Second Embodiment Fig. 5A is a configuration diagram of the vicinity of a flow channel according to a second embodiment, Fig. 5B is a cross-sectional view taken along the xy plane where the magnet according to the second embodiment and the flow channel wall meet, and Fig. 5C is a cross-sectional view taken along the xy plane where the magnet according to a modified example of the second embodiment meets the flow channel wall. In the structure shown in Fig. 5A, during the magnetic particle adsorption period, when the slide mechanism 20 operates and the magnet 19 moves to the bottom of the flow channel 10, the magnet 19 receives a magnetic force from the magnet guide mechanism 24A. At this time, the deformation portion 29 of the slide mechanism 20 deforms, causing the magnet 19 to move. The moved magnet 19 hits the magnet guide mechanism 24A and stops, and the position of the magnet 19 is corrected. In the second embodiment, the flow cell does not include the stopper structure 25 shown in the first embodiment, and the magnet guide mechanism 24A is configured to both stop the movement of the magnet 19 and correct the position of the magnet 19.

[0068] 5B, the magnet guide mechanism 24A is made of a magnetic material and is generally L-shaped, and is formed so as to protrude from the flow path wall 12 near the projection surface 61 on which the capture area 14 is projected. Note that, when a hard magnetic material is used as the magnetic material in the second embodiment, it is necessary to use an attractive force to move the magnet 19.

[0069] Furthermore, the magnet guide mechanism 24A only needs to be able to stop the moving magnet 19, and its shape may be a rectangular parallelepiped or cylindrical, or may be shaped so as to contact the magnet 19 at two or more points simultaneously. Furthermore, the magnet guide mechanism 24A does not necessarily have to be a continuous structure; as shown in FIG. 5C , two or more magnet guide mechanisms 24A may be present in two or more locations to contact the magnet 19 at two or more points. However, from the perspective of correcting the position of the magnet 19, if the magnet 19 is a polyhedron, it is preferable that the magnet guide mechanism 24A contact the magnet 19 at points, lines, or faces included in two different faces. Furthermore, if the magnet 19 is cylindrical and the magnet guide mechanism 24A contacts a curved surface, it is preferable that the magnet guide mechanism 24A contact the magnet 19 at a position where the movement of the magnet 19 in the x-axis and y-axis directions can be stopped.

[0070] The second embodiment described above can achieve the same effects as the first embodiment. Furthermore, in the second embodiment, the magnet guide mechanism 24A and the magnet 19 contact each other at least at two or more locations simultaneously (see FIG. 5C ). This allows the stopper structure 25 to be omitted.

[0071] (Third embodiment) Figure 6A is a diagram showing the configuration of the vicinity of the flow path according to the third embodiment, Figure 6B is a diagram showing the positional relationship between the magnet guide mechanism and the magnet according to the third embodiment, and Figure 6C is a diagram showing the positional relationship between the magnet guide mechanism and the magnet according to a modified example of the third embodiment.

[0072] 6A , during the magnetic particle adsorption period, when slide mechanism 20 operates and magnet 19 moves to the bottom of flow channel 10, magnet 19 receives magnetic force from magnet guide mechanism 24B. At this time, deformation portion 29 of slide mechanism 20 deforms, causing magnet 19 to move. The moved magnet 19 is attracted to magnet guide mechanism 24B and stops, and the position of magnet 19 is corrected.

[0073] The magnet guide mechanism 24B is configured to be located inside the flow path wall 12. In this case, the magnet guide mechanism 24B is fixed inside (inside) the flow path wall 12 by insert molding or the like.

[0074] As shown in Figure 6B, magnet guide mechanism 24B is made of a magnetic material and is located between reaction field electrode 15 and projection surface 61 onto which capture region 14 is projected. In the third embodiment, if a hard magnetic material is used as the magnetic material, it is necessary to use attractive force to move magnet 19. Furthermore, in order to ensure the strength of the magnetic force acting between magnet guide mechanism 24B and magnet 19 while not weakening the magnetic field that captures magnetic particles 13, it is preferable that magnet guide mechanism 24B be located inside flow path wall 12 and be exposed from flow path wall 12 so as to coincide with projection surface 61 onto which capture region 14 is projected.

[0075] The number of points where the magnet guide mechanism 24B comes into contact with the magnet 19 is not limited, and the magnet guide mechanism 24B may be attached at one point as shown in Fig. 6B, or discontinuous magnet guide mechanisms 24B may be attached at two or more points as shown in Fig. 6C. However, from the viewpoint of correcting the position of the magnet 19, in the case of one point as shown in Fig. 6B, it is preferable that the dimensions of the members of the magnet guide mechanism 24B and the dimensions of the magnet 19 match at least partially. Furthermore, in the case of two or more points as shown in Fig. 6C, it is preferable that the dimensions of the members of the magnet guide mechanism 24B or the dimensions of the spacing between the members match at least partially.

[0076] Furthermore, the magnet 19 does not necessarily have to stop when the resistance and magnetic force balance when it comes into contact with the magnet guide mechanism 24B or the stopper structure 25, but may stop when the magnetic forces between the magnet guide mechanisms 24B and the magnet 19 at multiple locations balance each other, as shown in Figure 6C.

[0077] The third embodiment described above can achieve the same effects as the second embodiment. Furthermore, in the third embodiment, the magnet guide mechanism 24B is fixed by insert molding within the flow path wall 12 of the flow path 10 (see FIG. 6A). This can reduce variation in the position of the magnet guide mechanism 24B compared to when the magnet guide mechanism 24B is attached to the flow path wall 12 by a separate member.

[0078] In the third embodiment, the magnet guide mechanism 24B shares a shape with at least one or more sides of the magnet 19 in at least one direction of the projection plane 61 (see FIG. 6B ). This allows the position of the magnet 19 to be corrected.

[0079] In the third embodiment, the magnet guide mechanism 24B is a member fixed near the flow path 10, and there are magnet guide mechanisms 24B in two locations (see FIG. 6C). Note that there may be magnet guide mechanisms 24B in three or more locations. This allows the position of the magnet 19 to be corrected.

[0080] (Fourth Embodiment) FIG. 7A is a side view of a sliding mechanism according to a fourth embodiment, and FIG. 7B is a top view of the sliding mechanism according to the fourth embodiment. As shown in FIGS. 7A and 7B, a sliding mechanism 20A according to the fourth embodiment includes a movable structure 26 that is movable in the x-axis and y-axis directions in a drive unit. This movable structure 26 includes an arm 20c having a magnet 19 fixed to the tip thereof and a shaft 26a at its base end. Guide members 26b are provided on both sides of the arm 20c to guide the shaft 26a so that it can slide in the direction of arrow 27a (x-axis direction). The arm 20c is also configured to move in the direction of arrow 27b (y-axis direction). Note that the sliding mechanism 20A according to the fourth embodiment does not include the deformation portion 29 of the first embodiment.

[0081] 7A and 7B , during the magnetic particle adsorption period, when the slide mechanism 20A operates and the magnet 19 moves to the bottom of the flow channel 10, the magnet 19 receives a magnetic force from the magnet guide mechanism 24. At this time, the slide mechanism 20A moves in the x-axis direction or the y-axis direction within the movable structure 26, thereby moving the magnet 19.

[0082] The movable structure 26 does not have to have a structure as shown in Figures 7A and 7B, but rather has a structure that allows the sliding mechanism 20A to move in the x-, y-, or z-axis direction by complementing the direction in which the magnet 19 cannot move due to the movement of the sliding mechanism 20A.

[0083] The fourth embodiment described above can also achieve the same effects as the first embodiment. Furthermore, in the fourth embodiment, a part of the slide mechanism 20A has a movable structure 26 that allows the slide mechanism 20A to move in the x-axis direction and the y-axis direction (at least one or more axes). This allows the position of the magnet 19 to be corrected.

[0084] Fifth Embodiment Fig. 8 is a configuration diagram of the vicinity of a flow path according to a fifth embodiment. As shown in Fig. 8, a slide mechanism 20B used in the fifth embodiment includes an outer shell 28 that surrounds the periphery of a magnet 19. This outer shell 28 is configured to have a gap S between it and the magnet 19. By providing the gap S, the magnet 19 is configured to be movable in the x-axis direction and the z-axis direction within the outer shell 28. That is, in the fifth embodiment, the magnet 19 is not fixed to the slide mechanism 20B.

[0085] 8, during the magnetic particle adsorption period, when slide mechanism 20B is operated and magnet 19 moves to the bottom of flow channel 10, magnet 19 receives magnetic force from magnet guide mechanism 24, and only magnet 19 moves in the space within outer shell 28. Furthermore, during the detection period, when slide mechanism 20B is operated and magnet 19 is moved away from flow channel 10, magnet 19 does not continue to be attracted to magnet guide mechanism 24 by outer shell 28, but is instead pulled away.

[0086] The outer shell 28 may completely surround the magnet 19, or may have a shape that exposes part of the magnet 19 as long as the magnet 19 does not come off from inside the outer shell 28.

[0087] The fifth embodiment described above can also achieve the same effects as the first embodiment. Furthermore, in the fifth embodiment, the slide mechanism 20B includes an outer shell 28 that at least partially contains the magnet 19, and a gap S is formed between the magnet 19 and the outer shell 28, allowing the magnet 19 to move within the outer shell 28. This allows the position of the magnet 19 to be corrected.

[0088] 9 is a configuration diagram of the vicinity of the flow path according to the sixth embodiment. As shown in FIG. 9, in the sixth embodiment, a magnet guide mechanism 24C is a member fixed on the flow path wall 12.

[0089] 9, during the magnetic particle adsorption period, the slide mechanism 20C operates as indicated by the arrow 62. When the magnet 19 approaches the lower part of the flow channel 10, the magnet 19 is pressed against the magnet guide mechanism 24, and the operation of the magnet 19 and the slide mechanism 20C stops.

[0090] Furthermore, the magnet guide mechanism 24C is made of a material other than a magnetic material that does not deform when the magnet 19 is stopped. The magnet guide mechanism 24C may be made of the same material as the flow path wall 12, or may be made of a different material such as ceramic, metal, or plastic. Furthermore, the constraints and preferred forms regarding the shape of the magnet guide mechanism 24 are the same as those in the second embodiment.

[0091] Furthermore, in the sixth embodiment, the movement of the arrow 62 of the slide mechanism 20C is described as a circular movement, but it may be combined with a horizontal movement or a vertical movement.

[0092] The sixth embodiment described above includes a flow channel 10 that introduces a sample containing magnetic particles 13 bound to a specific substance into a capture region 14, a pump 35 (supply means) that supplies the sample to the flow channel 10, a magnet 19 that captures the magnetic particles 13, a slide mechanism 20C that moves the magnet 19 to the vicinity of a projection surface 61 on which the capture region 14 is projected, a photodetector 21 that detects the specific substance on the magnetic particles 13a captured on the surface of the capture region 14, and a pump 35 (discharge means) that discharges the magnetic particles 13 from the flow channel 10 after detection by the photodetector 21. The magnet 19, moved by driving the slide mechanism 20C, is pressed against a magnet guide mechanism 24C that is located in the vicinity of the projection surface 61 on which the capture region 14 is projected, and stops (see FIG. 9 ). In this way, by using a configuration different from the first embodiment, the magnetic flux of the magnet 19 used to capture magnetic particles is not consumed, and the differences in the position of the magnet 19 between measurements and between devices are reduced, improving the reproducibility of the capture of magnetic particles 13 in the detection area, thereby providing an immunoassay device 1A capable of high-precision measurements.

[0093] As described above, the embodiments and modifications of the present invention have been specifically described. However, the present invention is not limited to the above-described embodiments and modifications, and can be modified within the scope of the gist of the present invention.

[0094] 1A Immunoassay apparatus (automatic analyzer) 10 Flow path 11, 11a, 11b, 12 Flow path wall 13 Magnetic particles 14 Capture area 15 Reaction field electrode 16 Counter electrode 17a, 17b Lead wire 18 Voltage application means 19 Magnet 20, 20A, 20B, 20C Slide mechanism 21 Photodetector 22 Condenser lens 23 Laser light source 24, 24A, 24B, 24C Magnet guide mechanism 25 Stopper structure 26 Movable structure 26a Shaft portion 26b Guide member 28 Outer shell 29 Deformable portion 30, 31, 32 Tube 33 Sipper nozzle 34 Arm 35 Pump (supply means, discharge means) 36, 37 Valve 40 Suspension container 41 Reaction unit 42 Washing liquid container 43 Buffer solution container 44 Cleaning mechanism 45 Waste liquid container 50 Controller 51, 52, 53, 54, 55, 56, 57, 58 Signal line 61 Projection surface (projection surface on which the capture area is projected) O Center (center of magnet) P Capture operation position

Claims

1. An automatic analyzer comprising: a flow path for introducing a sample containing magnetic particles bound to a specific substance into a capture region; supply means for supplying the sample to the flow path; a magnet for capturing the magnetic particles; a slide mechanism for moving the magnet to the vicinity of a projection plane on which the capture region is projected; a detector for detecting the specific substance on the magnetic particles; discharge means for discharging the magnetic particles from the flow path after detection by the detector; and a magnet guide mechanism made of a magnetic material for moving the magnet.

2. The automatic analyzer according to claim 1, wherein the magnetic material is a soft magnetic material.

3. The automatic analyzer according to claim 1, wherein at least a part of the slide mechanism is made of an elastic material.

4. The automatic analyzer according to claim 1, wherein the magnet guide mechanism is located below the center of the magnet when the magnet is in the capture operation position.

5. The automatic analyzer according to claim 1, further comprising a stopper structure for stopping the magnet moved by the magnet guide mechanism.

6. The automatic analyzer according to claim 5, wherein the stopper structure has a shape that contacts the magnet at at least two or more locations simultaneously.

7. The automatic analyzer according to claim 1, wherein the magnet guide mechanism and the magnet contact at at least two or more locations simultaneously.

8. The automatic analyzer according to claim 7, wherein the magnet guide mechanism is fixed in the wall of the flow path by insert molding.

9. The automatic analyzer according to claim 1, wherein the magnet guide mechanism shares a shape with at least one side of the magnet in at least one projection plane in at least one direction.

10. The automatic analyzer according to claim 9, wherein the magnet guide mechanism is a member fixed near the flow path, and the magnet guide mechanism exists at at least two or more locations.

11. The automatic analyzer according to claim 1, wherein a part of the slide mechanism has a movable structure in which the slide mechanism is movable in at least one axial direction or more.

12. The automatic analyzer according to claim 1, wherein the slide mechanism includes an outer shell that at least partially encloses the magnet, a gap is formed between the magnet and the outer shell, and the magnet moves within the outer shell.

13. A flow path for introducing a sample containing magnetic particles bound to a specific substance into a capture region, supply means for supplying the sample to the flow path, a magnet for capturing the magnetic particles, a slide mechanism for moving the magnet to the vicinity of a projection plane on which the capture region is projected, a detector for detecting a specific substance on the magnetic particles, and discharging means for discharging the magnetic particles from the flow path after detection by the detector. The automatic analyzer is characterized in that the magnet moved by driving the slide mechanism is pressed against a magnet guide mechanism in the vicinity of the projection plane on which the capture region is projected and stops.

Images