Sample analyzer

Abstract

To provide a sample analyzer which does not easily cause a displacement in a magnetic field in a flow passage even if a displacement of a magnet is generated and can make precise analysis.SOLUTION: A sample analyzer includes: a flow passage for introducing sample liquid including magnetic particles connected to a labelled material; liquid sending means for supplying and discharging the sample liquid in the flow passage; magnetic field application means for applying a magnetic field which captures the magnetic particles in the flow passage; and a detector for detecting the labelled material which is joined to the magnetic particles. The magnetic field application means is made of a plurality of members and at least one member is integrally formed with the flow passage.SELECTED DRAWING: Figure 2

Description

[Technical Field]

[0001] The present invention relates to a sample analyzer. [Background technology]

[0002] In a sample analyzer such as an immunoassay analyzer, a sample solution containing magnetic particles bound to a labeling substance is introduced into a flow path such as a flow cell, the magnetic particles are captured (adsorbed) along the way, and an external electric field or the like is applied to the captured magnetic particles, causing the labeling substance bound to the magnetic particles to emit light. The intensity of this light emission can be detected to measure the amount of the detection substance bound to the magnetic particles.

[0003] For example, Patent Document 1 describes a sample analysis device that, when detecting luminescence intensity, brings a magnet closer to a flow path to strengthen the magnetic field and capture magnetic particles, and, when cleaning the flow path, moves the magnet away from the flow path to weaken the magnetic field and discharge the magnetic particles. [Prior art documents] [Patent documents]

[0004] [Patent Document 1] International Publication No. 2011 / 155489 Summary of the Invention [Problem to be solved by the invention]

[0005] However, when a mechanism that moves a magnet, which is the source of the magnetic field, is used, the number of parts that hold and move the magnet increases, which increases the degree of freedom in positioning and may lead to misalignment with repeated use. Even if a mechanism that moves the magnet is not used, there is a possibility that the magnet may become misaligned when parts are manipulated for maintenance, etc. If the magnetic field in the flow channel becomes misaligned due to magnet misalignment, magnetic particles cannot be reliably captured, resulting in reduced analysis accuracy.

[0006] An object of the present invention is to provide a sample analyzer that is capable of performing highly accurate analysis by making it difficult for the magnetic field in the flow channel to shift even if the magnet shifts in position. [Means for solving the problem]

[0007] In order to solve the above-mentioned problems, the present invention provides a sample analysis device comprising a flow path for introducing a sample liquid containing magnetic particles bound to a labeled substance, a liquid delivery means for supplying and discharging the sample liquid into the flow path, a magnetic field application means for applying a magnetic field to capture the magnetic particles in the flow path, and a detector for detecting the labeled substance bound to the captured magnetic particles, wherein the magnetic field application means is composed of multiple components, at least one of which is formed integrally with the flow path. [Effects of the Invention]

[0008] According to the present invention, even if the magnet is displaced, it is difficult for the magnetic field in the flow channel to be displaced, and a sample analyzer capable of performing highly accurate analysis can be provided. [Brief explanation of the drawings]

[0009] [Figure 1] FIG. 1 is a schematic diagram of an immunoassay analyzer. [Figure 2] FIG. 2 is a diagram showing the configuration of a magnetic field application means and a flow cell according to the first embodiment. [Figure 3] FIG. 10 is a diagram showing the magnetic field source and the flow cell when misalignment occurs. [Figure 4] FIG. 10 is a diagram showing an analysis model in which a fixed magnetic material is not used, as a comparative example. [Figure 5] FIG. 2 is a diagram showing an analysis model in the case where a fixed magnetic material is used as the first embodiment. [Figure 6] FIG. 10 is a diagram showing analysis results of magnetic flux density for the analysis model of the comparative example and the analysis model of the first embodiment. [Figure 7] FIG. 10 is a diagram showing an analytical model in the case where the fixed magnetic material and the core are in contact with each other as a second embodiment. [Figure 8] FIG. 10 is a diagram showing analysis results of magnetic flux density for an analysis model of a comparative example and an analysis model of Example 2. [Figure 9] FIG. 11 is a diagram showing an analytical model in a case where the end face of the fixed magnetic material on the flow path side has a small area, as a third embodiment. [Figure 10] FIG. 10 is a diagram showing analysis results of magnetic flux density for an analysis model of a comparative example and an analysis model of Example 3. [Figure 11] 10A and 10B are diagrams showing several modified examples of the shape of the fixed magnetic material. [Figure 12] 1 is a cross-sectional view showing the distribution of magnetic flux density in a typical example shape of a fixed magnetic material; [Figure 13] FIG. 10 is a diagram showing the configuration of a magnetic field application means and a flow cell according to a fourth embodiment. [Figure 14] FIG. 10 is a diagram showing an analytical model in the case where a fixed magnetic material is arranged on the top wall of the flow channel, as a fourth embodiment. [Figure 15] FIG. 10 is a diagram showing analysis results of magnetic flux density for an analysis model of a comparative example and an analysis model of Example 4. [Figure 16] FIG. 10 is a diagram showing the configuration of a magnetic field application means and a flow cell according to a fifth embodiment. [Figure 17] FIG. 13 is a diagram showing the configuration of a magnetic field application means and a flow cell in Example 6. [Figure 18] FIG. 13 is a diagram showing the configuration of a magnetic field application means and a flow cell according to a seventh embodiment. [Figure 19] FIG. 13 is a diagram showing the configuration of a magnetic field application means and a flow cell in Example 8. [Figure 20] FIG. 13 is a diagram showing the configuration of a magnetic field application means and a flow cell in Example 9. DETAILED DESCRIPTION OF THE INVENTION

[0010] Hereinafter, an embodiment of the present invention will be described with reference to the drawings.

[0011] In this embodiment, an immunoassay analyzer will be described as an example of a sample analyzer. However, the present invention is not limited to immunoassays, and can be applied to any sample analyzer that uses magnetic particles to capture magnetic particles by switching the magnetic field strength, and can also be applied to analyzers for DNA, biochemistry, etc. Furthermore, the following embodiments are not limited to shapes, dimensions, numbers, etc., and can be modified within the scope of the spirit of the invention.

[0012] Figure 1 shows a schematic diagram of an immunoassay device. The immunoassay device comprises a flow channel 10, a liquid delivery means, a magnetic field application means, a photodetector 23, a controller 50, and the like. The flow channel 10 is a site into which a sample solution containing magnetic particles 13 bound to a labeling substance is introduced, and is formed by a flow channel top wall 11 and a flow channel bottom wall 12. In this specification, the detection section consisting of the flow channel top wall 11, the flow channel bottom wall 12, the reaction field electrode 14, and the counter electrode 15 is referred to as a flow cell as an integrated component.

[0013] The channel top wall 11 is preferably made of a transparent material, such as glass, plastic, etc. This allows the photodetector 23 to detect the wavelength of light emitted by the labeled substance bound to the magnetic particles 13 around the reaction field electrode 14.

[0014] A reaction field electrode 14 is installed around the bottom of flow channel 10, and a counter electrode 15 is installed on the opposite side of flow channel 10, i.e., around the top of flow channel 10. Furthermore, reaction field electrode 14 and counter electrode 15 are connected to voltage application means 16 via signal lines 55b and 55c. Voltage application means 16 is connected to controller 50 via signal line 55a.

[0015] The materials for reaction field electrode 14 and counter electrode 15 can be, for example, gold, platinum, palladium, tungsten, iridium, nickel, alloys thereof, carbon materials, etc. Alternatively, reaction field electrode 14 and counter electrode 15 can be formed by depositing the above materials on a base material such as titanium by plating, sputtering, etc.

[0016] Reaction field electrode 14 is basically planar for ease of luminescence measurement, and here it is provided on the bottom surface of flow channel 10. However, it may be provided on another surface within flow channel 10 or on multiple surfaces arranged three-dimensionally. Furthermore, it does not necessarily have to be planar, and may be linear, a combination of linear and planar shapes, or the like, as long as it is suitable for capturing magnetic particles 13 or for electrochemiluminescence of labeled substances bound to magnetic particles 13. Counter electrode 15 may be arranged or shaped in any way that allows it to generate a voltage within flow channel 10 in combination with reaction field electrode 14, and may be linear, planar, or a combination thereof.

[0017] In this embodiment, the magnetic field applying means for applying a magnetic field that captures the magnetic particles 13 in the flow channel 10 is composed of a magnetic field generating source and a fixed magnetic material 22 that induces a magnetic field from the magnetic field generating source to the reaction field electrode 14. The magnetic field generating source may be an electromagnet or a permanent magnet.

[0018] 1, an electromagnet consisting of a coil 20 and a core 21 is used as the magnetic field generating source. Coil 20 can be a general solenoid coil or the like as long as it is capable of generating a magnetic field as an electromagnet, for example, a solenoid coil made of solid or twisted copper wire. Furthermore, core 21 and fixed magnetic material 22 can be general soft magnetic materials such as iron, silicon steel, permalloy, permendur, magnetic alloys, and soft ferrite as long as they are capable of generating or guiding a magnetic field, and core 21 and fixed magnetic material 22 can be made of the same soft magnetic material or different soft magnetic materials.

[0019] The electromagnet consisting of coil 20 and the like is connected to controller 50 via signal lines 56a, 56b and voltage application means 17. When capturing (attracting) magnetic particles 13, controller 50 controls voltage application means 17 to apply a voltage to coil 20. This generates a magnetic field around reaction field electrode 14 and counter electrode 15 in flow channel 10. Magnetic particles 13 are captured on reaction field electrode 14 by the magnetic force resulting from the generated magnetic field. The voltage application to coil 20 may be operated using either a direct current or an alternating current method, as long as the electromagnet consisting of coil 20 and the like is capable of generating a magnetic field. However, when operating with an alternating current, it is preferable to take general measures to address the skin effect, such as using twisted wire.

[0020] When the magnetic field source is a permanent magnet, as will be described later with reference to Figure 20, for example, a movable arm and permanent magnet are placed near reaction field electrode 14, and the arm is moved by a signal from controller 50 to manipulate the distance between the permanent magnet and reaction field electrode 14. With this method, even when a permanent magnet is used as the magnetic field source, it is possible to control the increase and decrease of the magnetic field in flow channel 10, just as in the case of an electromagnet.

[0021] The voltage application means 16 is controlled by a controller 50. When a voltage is applied between the reaction field electrode 14 and the counter electrode 15 in the flow channel 10 in response to a command from the controller 50 to the voltage application means 16, the labeled substance bound to the magnetic particles 13 captured on the reaction field electrode 14 can be made to electrochemically emit light.

[0022] The photodetector 23 detects the labeled substance bound to the magnetic particles 13 captured by the magnetic field applied by the magnetic field application means, and is, for example, a camera, a photomultiplier tube, etc. The photodetector 23 can detect the wavelength of light emitted by the labeled substance in the vicinity of the reaction field electrode 14, and is operated by a signal from the controller 50.

[0023] The liquid delivery means is a means for supplying and discharging sample liquid into and from flow path 10 in the flow cell, and is composed of tubes, pumps, valves, etc. Flow path 10 is connected to sipper nozzle 30 and pump 35 through tubes 32 and 33. Sipper nozzle 30 is movably attached by arm 31, and suspension container 40, washing solution container 42, and buffer solution container 43 are installed within its range of movement. A valve 36 is provided in tube 33 between flow path 10 and pump 35. Pump 35 and valve 36 are connected to controller 50 through signal lines 52 and 53, and to waste container 45 through valve 37 and tube 34.

[0024] The controller 50 is connected to the valves 36 and 37, the pump 35, the arm 31, the voltage application means 16 and 17, and the photodetector 23 by independent signal lines 51, 52, 53, 54, 55a, 56a, and 57. This allows the controller 50 to control each of the connection points independently.

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

[0026] The suspension container 40 contains a sample to be analyzed, which has been mixed with a bead solution and a reagent as part of a pretreatment process 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, consisting 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, such as an anti-TSH (thyroid stimulating hormone) antibody with a biotin-terminated end. The reagent varies depending on the type of specific component to be analyzed; for example, immunoglobulins, antigens, antibodies, or other biological substances are used.

[0027] The cleaning liquid container 42 contains a cleaning liquid for cleaning the inside of the flow path 10 and the tube 32.

[0028] When the length along the flow (path length) and the thickness (vertical direction) and width (horizontal direction) of the cross section perpendicular to the flow are defined, the shape of the flow channel 10 is desirably formed so that the path length is 2 to 20 times the larger of the thickness and width. This is because ensuring a sufficient path allows the magnetic particles 13 in the fluid to spread within the flow channel 10 and then to be easily captured on the reaction field electrode 14 provided on the bottom surface of the flow channel 10.

[0029] The capture distribution of magnetic particles 13 within flow channel 10 is determined by the magnetic force from a magnet (electromagnet or permanent magnet) installed near flow channel 10 and the drag force due to the fluid flow. The magnetic field within flow channel 10 preferably has a magnetic flux density strength of about 0.1 to 0.5 T. The fluid flow velocity at this time is preferably about 0.05 to 0.10 m / s.

[0030] The particles used as the magnetic particles 13 are preferably the following: (1) particles exhibiting paramagnetic, superparamagnetic, ferromagnetic, or ferrimagnetic properties; (2) particles exhibiting paramagnetic, superparamagnetic, ferromagnetic, or ferrimagnetic properties encapsulated in a material such as a synthetic polymer compound (polystyrene, nylon, etc.), a natural polymer (cellulose, agarose, etc.), or an inorganic compound (silica, etc.). The particle size is preferably in the range of 0.01 to 200 μm, more preferably 1 to 10 μm. The specific gravity is preferably 1.3 to 1.5. These specifications make the magnetic particles 13 less likely to settle in a liquid and easier to suspend. A substance capable of specifically binding to an analyte, such as an antibody capable of specifically binding to an antigen, is bound to the particle surface.

[0031] The labeling substance is preferably a substance as shown below. Specifically, the following examples can be mentioned from the viewpoint of specifically binding the labeling substance to the analyte by an appropriate means and causing it to emit light by an appropriate means. (1) Labeling substances used in fluorescent immunoassays, such as antibodies labeled with fluorescein isothiocyanate. (2) Labeling substances used in chemiluminescent immunoassays, such as antibodies labeled with acridinium esters. (3) Labeling substances used in chemiluminescent enzyme immunoassays, such as antibodies labeled with chemiluminescent enzymes that use luminol or adamantyl derivatives as luminescent substrates.

[0032] The above is a description of the configuration of the immunoassay analyzer. Next, the operation of the immunoassay analyzer will be described. One analysis is considered to be one cycle, and the basic operating state of the device is to perform multiple cycles consecutively.

[0033] One analysis cycle consists of a suspension aspiration period, a magnetic particle capture period, a detection period, a washing period, a reset period, and a preliminary aspiration period. One cycle starts when the suspension container 40 containing the suspension treated in the reaction unit 41 is set in a predetermined position.

[0034] During the suspension suction period, valve 36 is set to an open state and valve 37 is set to a closed state. Arm 31 is operated in response to a signal from controller 50, and sipper nozzle 30 is inserted into suspension container 40. Subsequently, pump 35 is operated in response to a signal from controller 50 to perform a fixed amount of suction. Sucked into the fluid in tube 32, the suspension in suspension container 40 passes through sipper nozzle 30 and enters tube 32. In this state, pump 35 is stopped, and arm 31 is operated to insert sipper nozzle 30 into cleaning mechanism 44. Sipper nozzle 30 is cleaned as it passes through cleaning mechanism 44.

[0035] During the magnetic particle capture period, a voltage is applied in response to a signal from the controller 50, which activates an electromagnet consisting of a coil 20 and the like. A signal from the controller 50 causes the pump 35 to suck at a constant speed. During this time, the suspension present in the tube 32 passes through the flow channel 10. Because a magnetic field is generated within the flow channel 10 by the electromagnet, the magnetic particles 13 contained in the suspension are attracted by magnetic force toward the bottom wall 12 of the flow channel and captured on the reaction field electrode 14.

[0036] During the detection period, a signal from the controller 50 stops the application of voltage to the electromagnet. Subsequently, a signal from the controller 50 activates the photodetector 23 and applies voltage to the reaction field electrode 14 and the counter electrode 15. As a result, while the magnetic particles 13 are held on the reaction field electrode 14, the photodetector 23 receives luminescence from the labeled substance bound to the magnetic particles 13, thereby performing measurement. The intensity of the detected luminescence is collected as a signal by the controller 50. After a certain time has elapsed, the application of voltage to the reaction field electrode 14 and the counter electrode 15 and the photodetector 23 are stopped. During the detection period, the arm 31 is operated, and the sipper nozzle 30 is inserted into the cleaning mechanism 44.

[0037] During the cleaning period, the cleaning solution sucked from the cleaning solution container 42 is passed through the flow path 10 by using the pump 35. At this time, the electromagnet is in a non-operating state, so the magnetic particles 13 are not retained on the reaction field electrode 14 and are washed away together with the cleaning solution.

[0038] During the reset period, the valve 36 is closed, the valve 37 is opened, and the pump 35 is operated to discharge the liquid. The liquid in the pump 35 is discharged into the waste container 45.

[0039] During the preliminary suction period, the buffer solution is sucked from the buffer solution container 43 to fill the tube 32 and the flow path 10 with the buffer solution. After the preliminary suction period, the next cycle can be executed.

[0040] With regard to the sample analyzer of this embodiment described above, the specific structure of the magnetic field application means will be described below using Examples 1 to 9. [Example]

[0041] The structure of the sample analyzer according to Example 1 will be described in detail with reference to Figures 2 and 3. In this example, an electromagnet is used as the magnetic field generating source. Sample analyzers may experience variations in the magnetic field around reaction field electrode 14 due to individual differences in manufacturing, changes in the operating environment, a decrease in operating current due to heat generation, and the like. However, in a sample analyzer using an electromagnet as in this example, the desired magnetic field can be obtained without moving the electromagnet by adjusting the load voltage (current) on the electromagnet, changing the operating time, and the like.

[0042] 2 is a diagram showing the configuration of the magnetic field application means and flow cell of Example 1, and shows a cross section of the zx plane in a coordinate system in which the flow direction in flow channel 10 is the x-axis, the horizontal direction of a cross section perpendicular to the flow is the y-axis, and the vertical direction is the z-axis. Magnetic particles 13 flow within flow channel 10 of the flow cell along flow direction 61. Note that the counter electrode 15 is not shown in FIG. 2.

[0043] A magnetic field application means is provided below the reaction field electrode 14 of the flow cell. If a mechanism for moving permanent magnets closer to or further away from each other is used as the magnetic field application means, the number of parts required for holding and moving the magnets will increase, increasing the degree of freedom in positioning and potentially leading to misalignment with repeated use. On the other hand, if an electromagnet is used as the magnetic field application means, as in this embodiment, there is no need to move the magnetic field source, making misalignment relatively unlikely. However, even with an electromagnet, there is still a possibility that the electromagnet may become misaligned when parts are manipulated for maintenance, etc.

[0044] Therefore, in this embodiment, the magnetic field application means is composed of multiple members, of which fixed magnetic material 22 is formed integrally with the flow cell. Therefore, even if the magnetic field generation source (coil 20 and core 21), which are other members constituting the magnetic field application means, is displaced, fixed magnetic material 22 will not be displaced, and bias in the magnetic field around reaction field electrode 14 is suppressed.

[0045] Furthermore, the fixed magnetic material 22 is installed on the bottom wall 12 of the flow channel, and the distance between the flow channel 10 and the fixed magnetic material 22 is smallest on the bottom side of the flow channel 10. In other words, since the fixed magnetic material 22 is interposed between the magnetic field generation source and the reaction field electrode 14, the magnetic field generated by the magnetic field generation source can be effectively guided to the reaction field electrode 14.

[0046] Methods for integrating the fixed magnetic material 22 with the flow cell include a method of bonding the fixed magnetic material 22 to the channel wall with an adhesive or the like after the flow cell is fabricated, and a method of embedding the fixed magnetic material 22 in the channel wall by insert molding during the fabrication process of the flow cell. When the fixed magnetic material 22 is attached to the flow cell in a manner that exposes it toward the magnetic field source, the fixed magnetic material 22 can be brought closer to the magnetic field source, thereby reducing the magnetic flux leaking into the air from the magnetic field source and making it possible to suppress a decrease in the magnetic field on the reaction field electrode 14. On the other hand, when the fixed magnetic material 22 is embedded inside the bottom wall 12 of the channel, the fixed magnetic material 22 is farther from the magnetic field source, and therefore the magnetic field reaching the fixed magnetic material 22 is weaker. However, the fixed magnetic material 22 is closer to the channel 10, making it less likely that the magnetic field will deviate from its position relative to the channel space.

[0047] 3 is a diagram showing the magnetic field source and flow cell when a positional deviation occurs. The position of the electromagnet, consisting of coil 20 and core 21 arranged below the flow cell, has moved in the upstream (-x) direction of the flow channel, causing a positional deviation. The distance between the electromagnet and the upstream (-x) end of reaction field electrode 14 relative to the flow channel has decreased, while the distance between the electromagnet and the downstream (+x) end of reaction field electrode 14 relative to the flow channel has increased. As a result, when fixed magnetic material 22 is not used, the magnetic field generated by the electromagnet when it is operated causes a bias between the upstream and downstream sides of reaction field electrode 14 relative to the flow channel.

[0048] When capturing magnetic particles 13 on the reaction field electrode 14, it is preferable to capture the magnetic particles 13 uniformly and at a high rate on the reaction field electrode 14. However, if the magnetic field around the reaction field electrode 14 is biased, the distribution or efficiency of capturing the magnetic particles 13 deteriorates.

[0049] Therefore, in this embodiment, the magnetic field generated by the electromagnet is guided to the reaction field electrode 14 via the fixed magnetic material 22, thereby suppressing the bias of the magnetic field around the reaction field electrode 14. As a result, even if the magnet that generates the magnetic field is displaced, it is possible to suppress deterioration in the distribution or efficiency when capturing the magnetic particles 13 on the reaction field electrode 14.

[0050] The effect of suppressing the positional deviation of the magnetic field according to this embodiment will be explained with reference to FIGS. 4, 5 and 6, which were confirmed by magnetic field analysis.

[0051] As a comparative example, Figure 4 shows an analytical model without a fixed magnetic material. Figure 4(a) shows the case where the electromagnet consisting of the coil 20 and the core 21 is not displaced, and Figure 4(b) shows the case where the electromagnet is displaced by a dimension B1 in the x direction from the state shown in Figure 4(a). A position 81 where the magnetic field is to be strengthened is shown at an assumed spatial position on the reaction field electrode 14, and adjacent positions 82 and 83 are shown adjacent to the position on the upstream side and downstream side of the flow path, respectively. In Figure 4(a), the center position on the xy plane of the position 81 where the magnetic field is to be strengthened is the same as the center position on the xy plane of the core 21. The shape and dimensions of the analytical model are indicated by the horizontal core position and dimension A1, the vertical core position and dimension A2, the upper core length A3, the coil length A4, the lower core length A5, the coil diameter A6, and the core diameter A7. In addition, with regard to the dimensions of the position 81 where the magnetic field is desired to be strengthened, the adjacent position 82 on the upstream side of the flow path, and the adjacent position 83 on the downstream side of the flow path, the x-axis dimension L1 of the position where the magnetic field is desired to be strengthened, the x-axis dimension L2 of the adjacent position on the upstream side of the flow path, and the x-axis dimension L3 of the adjacent position on the downstream side of the flow path are shown.

[0052] Figure 5 shows an analytical model for Example 1 using a fixed magnetic material. Figure 5(a) shows the case where the electromagnet consisting of coil 20 and core 21 is not displaced, and Figure 5(b) shows the case where the electromagnet is displaced by a dimension B1 in the x direction from the state shown in Figure 5(a). A position 81 where the magnetic field is to be strengthened is shown at an assumed spatial position on reaction field electrode 14, and adjacent positions 82 and 83 are shown adjacent to the position on the upstream side and downstream side of the flow path, respectively. The shape and dimensions of the analytical model are shown by the horizontal core position and dimension A1, the vertical core position and dimension A2, the upper core length A3, the coil length A4, the lower core length A5, the coil diameter A6, the core diameter A7, the gap A8 between the fixed magnetic material and the core, and the fixed magnetic material length A9. 5(a) and 5(b), the dimensions of the position 81 where the magnetic field is to be strengthened, the adjacent position 82 on the upstream side of the flow path, and the adjacent position 83 on the downstream side of the flow path are shown as x-axis dimension L1 of the position where the magnetic field is to be strengthened, x-axis dimension L2 of the adjacent position on the upstream side of the flow path, and x-axis dimension L3 of the adjacent position on the downstream side of the flow path. Since the fixed magnetic material 22 is fixed to the flow cell, it can be seen that the relative positions of the fixed magnetic material 22 and the position 81 where the magnetic field is to be strengthened remain unchanged, and only the coil 20 and the core 21 move.

[0053] 4 and 5, the horizontal core position and dimension A1 are 0.5 mm, the vertical core position and dimension A2 are 0.5 mm, the upper core length A3 in Fig. 4 is 5 mm, the upper core length A3 in Fig. 5 is 3 mm, the coil length A4 is 60 mm, the lower core length A5 is 5 mm, the coil diameter A6 is 17 mm, the core diameter A7 is 7 mm, the positional offset dimension B1 is 0 to 2 mm, the gap A8 between the fixed magnetic material and the core is 0.5 mm, and the fixed magnetic material length A9 is 2 mm. In addition, the x-axis dimension L1 of the position where the magnetic field is to be strengthened is 8 mm, the x-axis dimension L2 of the adjacent location upstream of the flow path and the x-axis dimension L3 of the adjacent location downstream of the flow path are 2 mm, and the y-axis dimension in the depth direction of the paper in Figs. 4 and 5 is 8 mm. Therefore, the position 81 where the magnetic field is to be strengthened is an 8 mm square, and the upstream adjacent portion 82 of the flow path and the downstream adjacent portion 83 of the flow path are rectangles with an x-axis dimension of 2 mm and a y-axis dimension of 8 mm.

[0054] The magnetic field analysis was performed using a general-purpose magnetic field analysis method based on Maxwell's equations and Ampere's law. Based on the electromagnet analysis model shown in Figures 4 and 5, the magnetic field analysis was performed in a system with an air space approximately five times the longitudinal axis of the electromagnet (the sum of the upper core length A3, coil length A4, and lower core length A5). The average magnetic flux density was calculated for three locations within the air space: the location 81 where the magnetic field was to be strengthened (a square with 8 mm x- and y-axes), the location 82 adjacent to the upstream side of the flow path, and the location 83 adjacent to the downstream side of the flow path (a rectangle with 2 mm x- and 8 mm y-axes). The analysis conditions included a copper coil 20 with 5,000 turns. For comparison, the current values ​​were set to 0.5 A in Figure 4 and 1.0 A in Figure 5 so that the magnetic flux densities in Figures 4(a) and 5(a) were similar. PB permalloy, a common type of permalloy, was used for the core 21 and fixed magnetic material 22.

[0055] FIG. 6 shows the results of magnetic flux density analysis, showing the magnitude of magnetic flux density at three target locations for the analytical model of the comparative example described in FIG. 4 and the analytical model of Example 1 described in FIG. 5. When there is no positional misalignment (B1 = 0 mm), a large magnetic flux density is generated at position 81 where the magnetic field is to be strengthened, and a small magnetic flux density is generated at adjacent positions 82 on the upstream side of the flow path and adjacent positions 83 on the downstream side of the flow path, regardless of the presence or absence of a fixed magnetic material. In this case, a strong magnetic field can be generated only above reaction field electrode 14, which can be interpreted as a magnetic field suitable for capturing magnetic particles 13. When there is a positional misalignment (B1 = 1 mm or B1 = 2 mm), the magnetic flux density at position 81 where the magnetic field is to be strengthened is large regardless of the presence or absence of a fixed magnetic material. In the comparative example, i.e., when there is no fixed magnetic material, the magnetic flux density is particularly increased at adjacent position 82 on the upstream side of the flow path. If a strong magnetic field is generated at locations other than reaction field electrode 14, magnetic particles 13 are likely to be captured in locations that do not contribute to detection, which can be interpreted as an inappropriate magnetic field. On the other hand, in this embodiment, i.e., when a fixed magnetic material is present, even if a positional displacement occurs, the magnetic field maintained at upstream adjacent portion 82 and downstream adjacent portion 83 of the flow path is weaker than that at position 81 where the magnetic field is desired to be strengthened. Therefore, by using fixed magnetic material 22, a strong magnetic field can be maintained limited to reaction field electrode 14, and a magnetic field structure can be provided in which the magnetic field around reaction field electrode 14 is less likely to be displaced.

[0056] Although the above analysis results only show the x-direction, in this embodiment, the magnetic field generated by the magnet is guided to the reaction field electrode 14 by the fixed magnetic material 22, thereby suppressing the bias of the magnetic field around the reaction field electrode 14. Therefore, similar effects can be expected in the y- and z-directions. In other words, even if the magnet is misaligned due to displacement in any direction in the x-, y-, and z-axis space, or due to tilt or rotation, by adjusting the position, size, shape, number, etc. of the fixed magnetic material 22, the magnetic field can be guided to the appropriate location in the space around the flow cell, thereby suppressing the bias of the magnetic field. As a result, it is possible to provide a sample analyzer that is less likely to cause the magnetic field to be misaligned at a predetermined position in the detection flow channel, and that enables high-precision analysis. [Example]

[0057] Second Embodiment A second embodiment will be described with reference to Figures 7 and 8. In the following embodiments, the description of the same configurations and effects as those of the first embodiment will be omitted.

[0058] Figure 7 shows an analytical model of Example 2 in which the fixed magnetic material and the core are in contact. As shown in Figure 7, fixed magnetic material 22 in this example is not only exposed from the bottom surface of the flow cell, but also in contact with core 21 of the magnetic field generation source. This makes it possible to further reduce the magnetic flux leaking into the air from the magnetic field generation source, and further suppress the reduction of the magnetic field on reaction field electrode 14.

[0059] Figure 7 shows a state in which the coil 20 and core 21, which are not fixed to the flow cell, are misaligned, among the magnetic field application means consisting of the coil 20, core 21, and fixed magnetic material 22. A position 81 where the magnetic field is to be strengthened is shown at an assumed spatial position on the reaction field electrode 14, along with adjacent upstream and downstream positions 82 and 83. The shape and dimensions of the analytical model are shown by the horizontal core position and dimension A1, the vertical core position and dimension A2, the upper core length A3, the coil length A4, the lower core length A5, the coil diameter A6, the core diameter A7, and the fixed magnetic material length A9. Also shown are the misalignment dimension B1, the x-axis dimension L1 of the position where the magnetic field is to be strengthened, the x-axis dimension L2 of the upstream adjacent position, and the x-axis dimension L3 of the downstream adjacent position.

[0060] In Figure 7, for comparison with Figure 4 (analysis model without a fixed magnetic material), the following dimensions were used: the horizontal core position and dimension A1 was 0.5 mm, the vertical core position and dimension A2 was 0.5 mm, the upper core length A3 was 3 mm, the coil length A4 was 60 mm, the lower core length A5 was 5 mm, the coil diameter A6 was 17 mm, the core diameter A7 was 7 mm, the positional offset dimension B1 was 0 to 2 mm, the fixed magnetic material length A9 was 2 mm, the x-axis dimension L1 of the position where the magnetic field was to be strengthened was 8 mm, and the x-axis dimension L2 of the adjacent location on the upstream side of the flow path and the x-axis dimension L3 of the adjacent location on the downstream side of the flow path were 2 mm (the position 81 where the magnetic field was to be strengthened was an 8 mm square, and the upstream adjacent location 82 and the downstream adjacent location 83 were rectangles with an x-axis dimension of 2 mm and a y-axis dimension of 8 mm). In addition, in FIG. 7, since the core 21 and the fixed magnetic material 22 are arranged with no gap therebetween, the gap A8 between the fixed magnetic material and the core is 0 mm and is not shown.

[0061] The magnetic field analysis method is the same as in Example 1. Among the various analysis conditions, in this example of FIG. 7, the current value is 0.5 A, the same as in FIG. 4. The other analysis conditions are the same as in Example 1.

[0062] Fig. 8 is a diagram showing the analysis results of magnetic flux density, and shows the magnitude of magnetic flux density at three target locations for the analytical model of the comparative example described in Fig. 4 and the analytical model of Example 2 described in Fig. 7. When there is no positional misalignment, that is, B1 = 0 mm, the core 21 and the fixed magnetic material 22 in Fig. 7 are adjacent to each other without any misalignment, so the analytical model has the same structure as Fig. 4, and the plot with the fixed magnetic material is omitted.

[0063] 8, when there is a positional deviation of B1 = 1 mm or B1 = 2 mm, the magnetic flux density at upstream adjacent portion 82 of the flow path increases in the comparative example, i.e., when there is no fixed magnetic material, whereas in this embodiment, i.e., when there is a fixed magnetic material, the magnetic flux density remains small. Therefore, by using fixed magnetic material 22 of this embodiment, it is possible to provide a magnetic field structure in which positional deviation of the magnetic field around reaction field electrode 14 is unlikely to occur.

[0064] Furthermore, in this embodiment, by eliminating (or reducing) the gap A8 between the fixed magnetic material and the core, it is possible to reduce the magnetic flux leaking into the air from the gap. This not only reduces the likelihood of misalignment of the magnetic field around the reaction field electrode 14, but also suppresses the reduction of the magnetic field on the reaction field electrode 14. Therefore, in this embodiment, there is no need to increase the applied voltage (current) as in Example 1 of FIG. 5, and misalignment of the magnetic field around the reaction field electrode 14 is unlikely to occur. As a result, it is possible to reduce the number of turns of the coil 20, operate the coil 20 at a low voltage (low current), and use materials with low magnetic susceptibility for the core 21 and the fixed magnetic material 22, thereby easing manufacturing and operating conditions and realizing energy savings. [Example]

[0065] The third embodiment will be described with reference to FIGS.

[0066] Figure 9 shows an analytical model of Example 3 in which the end face of the fixed magnetic material on the flow path side is small. As shown in Figure 9, the cross-sectional area of ​​fixed magnetic material 22 in this example is smaller on the reaction field electrode side than on the magnetic field generation source side. Therefore, the magnetic field generated by the magnetic field generation source has a magnetic flux density that increases as it approaches the flow path side within fixed magnetic material 22, and the force that captures magnetic particles 13 increases.

[0067] Figure 9 shows a state in which the coil 20 and core 21, which are the magnetic field generating sources of the magnetic field application means consisting of the coil 20, core 21, and fixed magnetic material 22, are misaligned. The shape of the fixed magnetic material 22 is a trapezoid in the x-z cross section, with the cross section of the end on the reaction field electrode 14 side (upper side) consisting of a circle with a smaller diameter than the cross section of the end on the coil 20 side (lower side). A position 81 where the magnetic field is to be strengthened is shown at an assumed spatial position on the reaction field electrode 14, and adjacent locations 82 and 83 on the upstream and downstream sides of the flow path are shown. The shape and dimensions of the analytical model are represented by the horizontal core position and dimension A1, the vertical core position and dimension A2, the upper core length A3, the coil length A4, the lower core length A5, the coil diameter A6, the core diameter A7, the gap A8 between the fixed magnetic material and the core, the fixed magnetic material length A9, the fixed magnetic material top diameter A10, and the fixed magnetic material side dimension A11. Also shown are the positional deviation dimension B1, the x-axis dimension L1 of the position where the magnetic field is to be strengthened, the x-axis dimension L2 of the adjacent location on the upstream side of the flow path, and the x-axis dimension L3 of the adjacent location on the downstream side of the flow path.

[0068] In FIG. 9, the following dimensions were used for comparison with FIG. 4 (analysis model without fixed magnetic material). That is, the horizontal core position and dimension A1 was 0.5 mm, the vertical core position and dimension A2 was 0.5 mm, the upper core length A3 was 3 mm, the coil length A4 was 60 mm, the lower core length A5 was 5 mm, the coil diameter A6 was 17 mm, the core diameter A7 was 7 mm, the positional offset dimension B1 was 0 to 2 mm, the gap A8 between the fixed magnetic material and the core was 0.5 mm, the fixed magnetic material length A9 was 2 mm, the fixed magnetic material top surface diameter A10 was 5 mm, the fixed magnetic material side dimension A11 was 1 mm, the x-axis dimension L1 of the position where the magnetic field was to be strengthened was 8 mm, the x-axis dimension L2 of the adjacent point upstream of the flow path and the x-axis dimension L3 of the adjacent point downstream of the flow path were 2 mm (the position 81 where the magnetic field was to be strengthened was an 8 mm square, the adjacent point upstream of the flow path 82 and the adjacent point downstream of the flow path 83 were rectangles with an x-axis dimension of 2 mm and a y-axis dimension of 8 mm).

[0069] The magnetic field analysis method is the same as in Example 1. Among the various analysis conditions, in this example of Figure 9, the current value is 1.0 A, the same as in Figure 5. The other analysis conditions are the same as in Example 1.

[0070] Figure 10 shows the results of magnetic flux density analysis, showing the magnitude of magnetic flux density at three target locations for the analytical model of the comparative example described in Figure 4 and the analytical model of Example 3 described in Figure 9. When there is a misalignment, such as B1 = 1 mm or B1 = 2 mm, the magnetic flux density at upstream adjacent location 82 of the flow path increases in the comparative example, i.e., when there is no fixed magnetic material, whereas in this example, when there is a fixed magnetic material, a small magnetic field is maintained. Therefore, by using fixed magnetic material 22 in this example, a magnetic field structure can be provided in which the magnetic field around reaction field electrode 14 is less likely to be misaligned, even if the magnetic field source is misaligned.

[0071] It should be noted that various modifications can be made to the shape of the fixed magnetic material 22. Here, several representative shapes of the fixed magnetic material 22 are listed, and the individual effects obtained with each shape are explained. Fig. 11 is a diagram showing several modifications of the shape of the fixed magnetic material.

[0072] 11(a) and 11(b) show examples of cylindrical and rectangular prism-shaped fixed magnetic materials 22. The end face of the fixed magnetic material 22 on the reaction field electrode 14 side can be made to conform to the shape and size of the reaction field electrode 14, thereby efficiently increasing the magnetic field on the reaction field electrode 14. For example, if the reaction field electrode 14 is square, a rectangular prism-shaped fixed magnetic material 22 with a square end face on the reaction field electrode 14 side is used, and if the reaction field electrode 14 is circular, a cylindrical fixed magnetic material 22 with a circular end face on the reaction field electrode 14 side is used. Note that the end face of the fixed magnetic material 22 on the magnetic field generation source side may be made to conform to the shape and size of the core 21 of the magnetic field generation source to suppress bias in the magnetic field.

[0073] 11(c), (d), (e), and (f) show examples in which the cross-sectional area of ​​the end of the fixed magnetic material 22 on the flow path side (reaction field electrode 14 side) is smaller than the maximum cross-sectional area of ​​the fixed magnetic material 22. When the fixed magnetic material 22 induces a magnetic field, magnetic flux passes from any one surface to the opposite side. For example, as shown in FIG. 11(c), (d), (e), and (f), magnetic flux that enters the fixed magnetic material 22 from a surface with a large cross-sectional area below the z axis can be emitted from a surface with a small cross-sectional area above the z axis, thereby increasing its density and generating a strong magnetic field in a limited range.

[0074] Furthermore, much of the magnetic flux entering the fixed magnetic material 22 from the core 21 through the air space is released into the air space from the sharp corners of the fixed magnetic material 22. Therefore, for example, by using a shape in which the angle C1 on the side of the fixed magnetic material 22 is less than 90 degrees, more preferably 45 degrees or less, and even more preferably 30 degrees or less, as shown in FIG. 11(d), the magnetic flux that is released into the air space from the side corners and does not contribute to increasing the magnetic field on the reaction field electrode 14 can be reduced. To reduce the number of sharp corners, for example, as shown in FIG. 11(e), the fixed magnetic material 22 can be configured with two or more corners on the side, with each of the corners C1 and C2 on the side being less than 90 degrees, more preferably 45 degrees or less, and even more preferably 30 degrees or less, thereby achieving a similar effect. Furthermore, this effect is more pronounced when the side surfaces are not cornered, and can be further enhanced by a shape in which the side surfaces are three-dimensionally curved, such as shown in FIG. 11(f).

[0075] (g), (h), (i), (j) and (l) of FIG. 11 are examples of fixed magnetic material 22 in which at least one end surface of the fixed magnetic material 22 has an uneven shape or a hole.

[0076] 11(g), (h), and (i), by providing an uneven shape on the upper end surface of the fixed magnetic material 22, it is possible to utilize the fact that the magnetic flux incident on the fixed magnetic material 22 is largely emitted from the corners of the upper end surface into the air space, and to provide areas from which a large amount of magnetic flux is emitted evenly across the surface of the opposing reaction field electrode 14. This makes it possible to suppress localized bias in the magnetic field on the reaction field electrode 14 and achieve uniform capture of magnetic particles 13 suitable for luminescence detection.

[0077] Figure 11(j) shows an example in which the upper end surface of the fixed magnetic material 22 has an asymmetrical uneven shape on the upstream and downstream sides of the flow path 10 in the liquid flow direction. When capturing magnetic particles 13 from a fluid in a sample analyzer, the capture distribution of the magnetic particles 13 on the reaction field electrode 14 can change depending on the flow speed and magnetic field strength. For example, under relatively slow flow conditions, the magnetic particles 13 are more likely to be captured on the upstream (-x) side of the reaction field electrode 14. In this case, to obtain a capture distribution of the magnetic particles 13 suitable for optical detection, as shown in Figure 11(j), the distance from the reaction field electrode 14 is increased on the upstream side of the fixed magnetic material 22 and decreased on the downstream (+x) side. This controls the magnetic field so that it is weaker on the upstream side of the reaction field electrode 14 and stronger on the downstream side. This allows the capture distribution to be optimized to offset the bias in the capture distribution of the magnetic particles 13 caused by the flow field.

[0078] Other effective shapes of the fixed magnetic material 22 that achieve the same effect include a shape in which the side length of the fixed magnetic material 22 varies depending on the location, as shown in (k) of Figure 11, and a shape in which the side of the fixed magnetic material 22 is cut away in a specific direction, as shown in (l) of Figure 11. In (k) of Figure 11, the magnetic flux passes asymmetrically between the upstream and downstream sides of the flow channel 10 at the surface of the fixed magnetic material 22 where the magnetic flux is incident or the surface from which the magnetic flux is emitted, thereby optimizing the capture distribution so as to offset the bias in the capture distribution of magnetic particles 13 caused by the flow field. Furthermore, in the structure of (l) of Figure 11, by combining the cutting of the side of the fixed magnetic material 22 in a specific direction with an uneven shape on the end surface, in addition to generating an asymmetric magnetic field between the upstream and downstream sides of the flow channel 10, it is possible to suppress the local bias in the magnetic field on the reaction field electrode 14.

[0079] Fig. 12 is a cross-sectional view showing the distribution of magnetic flux density in a typical example of the shape of the fixed magnetic material. (a), (b), (c), and (d) in Fig. 12 show the cases where the shape of the fixed magnetic material is cylindrical, has a small cross-sectional area at the top end, has an uneven top end surface, and has an asymmetric uneven top end surface, respectively, which correspond to the shapes (a), (c), (g), and (j) in Fig. 11.

[0080] Figures 12(a) and (b) show the same analytical examples as Figure 5(a) and Figure 9 (where misalignment dimension B1 = 0 mm), respectively, and the following dimensions were used: horizontal core position and dimension A1 was 0.5 mm, vertical core position and dimension A2 was 0.5 mm, upper core length A3 was 3 mm, coil length A4 was 60 mm, lower core length A5 was 5 mm, coil diameter A6 was 17 mm, core diameter A7 was 7 mm, misalignment dimension B1 was 0 to 2 mm, gap A8 between the fixed magnetic material and the core was 0.5 mm, fixed magnetic material length A9 was 2 mm, fixed magnetic material top surface diameter A10 was 5 mm, and fixed magnetic material side dimension A11 was 1 mm.

[0081] In Figure 12(c), the fixed magnetic material length A9 is 1.7 mm, the fixed magnetic material top surface diameter A10 is 5 mm, the fixed magnetic material side dimension A11 is 1 mm, and the fixed magnetic material groove dimension A12 is 0.3 mm, and the other dimensions are the same as Figures 12(a) and (b).

[0082] In Figure 12 (d), the fixed magnetic material length A9 is 1.7 mm, the fixed magnetic material top surface diameter A10 is 3.5 mm, the fixed magnetic material side dimension A11 is 3.5 mm, and the fixed magnetic material groove dimension A12 is 0.3 mm, and the other dimensions are the same as Figures 12 (a) and (b).

[0083] The magnetic field analysis method is the same as in Example 1. Among the various analysis conditions, in this example of Figure 12, the current value is 1.0 A, the same as in Figure 5. The other analysis conditions are the same as in Example 1.

[0084] 12, the effects of (b) a small cross-sectional area of ​​the top end surface, (c) a textured top end surface, and (d) an asymmetric textured top end surface are explained in comparison with (a) a cylindrical shape. For (b) a small cross-sectional area of ​​the top end surface, the magnetic flux density generated from the center of the top end surface of the fixed magnetic material 22 is larger than for (a) a cylindrical shape, and the magnetic field is locally concentrated. This allows for increased magnetic flux density limited to the reaction field electrode 14. For (c) a textured top end surface, the magnetic flux density generated from the top of the fixed magnetic material 22 is concentrated at the corners in (a) a cylindrical shape, but with (c) a textured top end surface, the concentration at the corners is alleviated and tends to spread across the entire top surface of the fixed magnetic material 22. This suppresses localized magnetic field bias within the surface of the reaction field electrode 14, enabling uniform capture of magnetic particles 13 suitable for luminescence detection. (d) For an asymmetrical concave-convex shape on the upper end surface, the magnetic flux density generated from the upper part of the fixed magnetic material 22 differs in magnitude between the -x side and the +x side. This allows, for example, to accommodate conditions where the flow is relatively slow, by making the magnetic field on the downstream side of the reaction field electrode 14 stronger than on the upstream side, and thereby controlling the bias in the capture distribution of the magnetic particles 13 to be offset.

[0085] 12, it can be seen that in both shapes, the magnetic flux density increases from the corners of the upper end surface of the fixed magnetic material 22 to a certain region. Therefore, even if the area of ​​the reaction field electrode 14 located above the fixed magnetic material 22 is somewhat larger than the cross-sectional area of ​​the upper end surface of the fixed magnetic material 22, a large amount of magnetic flux can be induced over the entire reaction field electrode 14 by utilizing the magnetic flux that reaches the reaction field electrode 14 from the fixed magnetic material 22 via the air region. [Example]

[0086] The fourth embodiment will be described with reference to FIGS. 13, 14 and 15. FIG.

[0087] Figure 13 is a diagram showing the configuration of the magnetic field application means and flow cell of Example 4, and shows a cross section of the zx plane when a coordinate system is placed in which the flow direction in the flow channel 10 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.

[0088] In this embodiment, fixed magnetic material 22 is installed on channel top wall 11, and the distance between channel 10 and fixed magnetic material 22 is smallest on the top side of channel 10. However, even in this embodiment, fixed magnetic material 22 is formed integrally with the flow cell, which has the effect of making it difficult for the magnetic field around reaction field electrode 14 to shift position. Although counter electrode 15 is omitted in FIG. 13 , it can be installed above channel 10 without interfering with fixed magnetic material 22 by, for example, arranging multiple linear electrodes in channel 10 in the x or y direction.

[0089] The effect of suppressing the positional deviation of the magnetic field according to this embodiment will be explained with reference to FIGS. 14 and 15, which were confirmed by magnetic field analysis.

[0090] FIG. 14 shows an analytical model for Example 4 in which a fixed magnetic material is placed on the ceiling wall of the flow channel. In FIG. 14, a reaction field electrode 14 is assumed to be located in the space between the core 21 and the fixed magnetic material 22, and a position 81 where the magnetic field is to be strengthened is shown. Also shown are adjacent positions, an upstream adjacent position 82 on the flow channel and an adjacent position 83 on the flow channel downstream. The coil 20 and the core 21 are shown as being misaligned by a misalignment dimension B1. The shape and dimensions of the analytical model are shown by the horizontal core position and dimension A1, the vertical core position and dimension A2, the upper core length A3, the coil length A4, the lower core length A5, the coil diameter A6, the core diameter A7, the gap A8 between the fixed magnetic material and the core, and the fixed magnetic material length A9. Also shown are the misalignment dimension B1, the x-axis dimension L1 of the position where the magnetic field is to be strengthened, the x-axis dimension L2 of the adjacent position upstream on the flow channel, and the x-axis dimension L3 of the adjacent position downstream on the flow channel.

[0091] In Figure 14, the gap A8 between the fixed magnetic material and the core is set to 3 mm, and the position 81 where the magnetic field is to be strengthened is located in the center of this gap; therefore, the vertical core position and dimension A2 are set to 1.5 mm. In Figure 15, the analysis results when the vertical core position and dimension A2 are set to 1.5 mm are obtained and quoted for comparison with the case in Figure 4 (analysis model without a fixed magnetic material) where the position 81 where the magnetic field is to be strengthened is located in the same position. In Figure 14, the fixed magnetic material length A9 is set to 5 mm, and the other dimensions are the same as in Figure 4.

[0092] The magnetic field analysis method was the same as in Example 1, and the current value was set to 0.5 A in Figure 4 and 0.35 A in Figure 14 so that the magnetic flux densities in Figure 4(a) and Figure 14 were similar. Other analysis conditions were the same as in Example 1.

[0093] 15 is a diagram showing the results of magnetic flux density analysis, illustrating the magnitude of magnetic flux density at three target locations for the analytical model of the comparative example described in FIG. 4 and the analytical model of Example 4 described in FIG. 14. When there is no positional misalignment (B1 = 0 mm), the magnetic flux density at position 81 where the magnetic field is desired to be strengthened is approximately the same in both the comparative example, i.e., the case where there is no fixed magnetic material, and this example, i.e., the case where the fixed magnetic material is arranged on the ceiling wall of the flow channel. However, the values ​​in this example are smaller at location 82 adjacent to the upstream side of the flow channel and location 83 adjacent to the downstream side of the flow channel. Therefore, in this example, a strong magnetic field can be obtained limited to reaction field electrode 14.

[0094] Furthermore, when there is a positional misalignment of B1 = 1 mm or B1 = 2 mm, comparing the comparative example, i.e., the case where there is no fixed magnetic material, with this embodiment, i.e., the case where a fixed magnetic material is arranged on the ceiling wall of the flow channel, the difference between position 81 where the magnetic field is to be strengthened and adjacent position 82 on the upstream side of the flow channel, and the difference between position 81 where the magnetic field is to be strengthened and adjacent position 83 on the downstream side of the flow channel are larger in this embodiment. Therefore, this embodiment is more effective in generating a magnetic field limited to reaction field electrode 14, and can ensure a magnetic field suitable for capturing magnetic particles 13. This embodiment also provides a magnetic field structure that is less likely to cause misalignment of the magnetic field around reaction field electrode 14, even if the magnetic field generation source is misaligned.

[0095] When the fixed magnetic material 22 is arranged on the ceiling wall of the flow path, magnetic flux easily passes through the space between the core 21 and the fixed magnetic material 22, making it easier to obtain a higher magnetic flux density than when there is no fixed magnetic material. This is advantageous for capturing the magnetic particles 13, and makes it possible to achieve magnetic particle capture suitable for optical detection. Alternatively, the load voltage (current) on the coil 20 required to obtain the same magnetic flux density can be reduced, allowing for operation with reduced energy consumption.

[0096] When the fixed magnetic material is placed on top as in this embodiment, the fixed magnetic material 22 may interfere with the optical path when observing the luminescence in the flow cell with the photodetector 23. In this case, the optical path can be secured by providing a hole in the fixed magnetic material 22, for example, as shown in (i) and (l) of Figure 11. [Example]

[0097] Example 5 will be described with reference to Fig. 16. Fig. 16 is a diagram showing the configuration of a magnetic field application means and a flow cell of Example 5. In a coordinate system in which the flow direction in the flow channel 10 is the x-axis, the horizontal direction of a cross section perpendicular to the flow is the y-axis, and the vertical direction is the z-axis, Fig. 16(a) shows a cross section in the zx plane, and Fig. 16(b) shows a cross section in the xy plane.

[0098] In this embodiment, the fixed magnetic material 22 is disposed on the side of the flow channel 10, i.e., on the flow channel side wall 18. Even with such an arrangement, it is possible to obtain a magnetic field structure in which the magnetic field around the reaction field electrode 14 is less likely to shift position. When the fixed magnetic material 22 is disposed on the flow channel side wall 18, it may be disposed on one or both of the opposing flow channel side walls 18. [Example]

[0099] Example 6 will be described with reference to Figure 17. Figure 17 is a diagram showing the configuration of the magnetic field application means and flow cell of Example 6. In this example, multiple fixed magnetic members 22 are arranged. Even with this arrangement, a magnetic field structure can be obtained in which the magnetic field around reaction field electrode 14 is less likely to shift position.

[0100] Furthermore, as in this embodiment, by using multiple fixed magnetic materials 22 and varying the size, shape, material, etc. of each fixed magnetic material 22, the magnetic field on the reaction-field electrode 14 can be appropriately controlled. For example, by arranging fixed magnetic materials 22 with low magnetic susceptibility or saturation magnetic flux density near the upstream side of the reaction-field electrode 14 and arranging fixed magnetic materials 22 with high magnetic susceptibility or saturation magnetic flux density near the downstream side of the reaction-field electrode 14, the magnetic field can be controlled asymmetrically. This makes it possible to offset, for example, the bias in the capture distribution of magnetic particles 13 caused by the flow field. Furthermore, the magnetic field upstream and downstream of the reaction-field electrode 14 can also be controlled by the specifications or operating conditions of the coils 20 and cores 21 of the multiple electromagnets. For example, by applying a higher voltage (current) to the electromagnet coils 20 near the downstream side of the reaction-field electrode 14 than to the electromagnet coils 20 near the upstream side of the reaction-field electrode 14, the magnetic field near the downstream side can be strengthened.

[0101] Therefore, it is not necessary to divide both the fixed magnetic material 22 and the magnetic field generation source, that is, the coil 20 and the core 21, into multiple pieces, and it is also possible to have multiple fixed magnetic materials 22 alone or multiple magnetic field generation sources alone. When using only one fixed magnetic material 22, it may have a shape such as that shown in (j) or (k) of Figure 11. [Example]

[0102] Example 7 will be described with reference to FIG. 18. FIG. 18 is a diagram showing the configuration of the magnetic field application means and flow cell of Example 7. In this example, a fixed magnetic material is used but the core is eliminated; that is, the fixed magnetic material 22 integrated with the flow cell is configured to be insertable into the internal space of the coil 20. Therefore, the fixed magnetic material 22 of this example is responsible for generating a magnetic field in addition to inducing a magnetic field. Furthermore, this example also makes it possible to obtain a magnetic field structure in which the magnetic field around the reaction field electrode 14 is less likely to shift position. [Example]

[0103] Example 8 will be described with reference to Figure 19. Figure 19 is a diagram showing the configuration of the magnetic field application means and flow cell of Example 8. In this example, a curved electromagnet is used, both ends of core 21 face the flow cell, and fixed magnetic material 22 is installed so as to face both ends of core 21. This makes it possible to obtain a magnetic field structure in which the magnetic field around reaction field electrode 14 is less likely to shift position.

[0104] Furthermore, by using a curved electromagnet as in this embodiment, a magnetic circuit with fewer intervening air spaces can be created around the flow cell, thereby increasing the magnetic flux density generated from the end of the core 21. Having the fixed magnetic material 22 facing both ends of the core 21 allows for a large amount of magnetic flux to be diverted, resulting in a large magnetic flux density at the reaction field electrode 14. In this embodiment, even if the reaction field electrode 14 is located on the bottom wall 12 of the flow channel, the placement of the electromagnet is not limited to below the flow cell. That is, the curved electromagnet may be placed, for example, from the bottom to the side of the flow cell, from one side to the opposite side, or from bottom to top. [Example]

[0105] Example 9 will be described with reference to Figure 20. Figure 20 is a diagram showing the configuration of the magnetic field application means and flow cell of Example 9. In this example, a permanent magnet 70 is used as a magnetic field generation source. Specifically, the magnetic field on reaction field electrode 14 is increased or decreased by rotating a movable arm 71 to which the permanent magnet 70 is fixed and moving the permanent magnet 70 closer to or further away from the flow cell.

[0106] 20(a) shows a state in which the permanent magnet 70 is close to the flow cell, and this state is reached when the magnetic particles 13 are captured on the reaction field electrode 14. On the other hand, FIG. 20(b) shows a state in which the permanent magnet 70 is separated from the flow cell, and this state is reached when the magnetic particles 13 are removed from the reaction field electrode 14.

[0107] Furthermore, in this embodiment, fixed magnetic material 22 is formed integrally with the flow cell, so a magnetic field structure can be obtained that is less likely to cause displacement of the magnetic field around reaction field electrode 14. Movable arm 71 in this embodiment is not limited to a rotational motion mechanism with a single fulcrum, and the number, position, and direction of fulcrums during motion can be set based on any position or plane in three-dimensional space. Furthermore, other motion mechanisms other than rotation, such as one-axis movement using rails, may also be used.

[0108] The present invention is not limited to the above-described embodiments, and various modifications are possible. For example, the above-described embodiments have been described in detail to clearly explain the present invention, and the present invention is not necessarily limited to those including all of the described configurations. Furthermore, it is possible to replace part of the configuration of one embodiment with or add to the configuration of another embodiment. [Explanation of symbols]

[0109] 10...flow path, 11...flow path top wall, 12...flow path bottom wall, 13...magnetic particles, 14...reaction field electrode, 15...counter electrode, 16, 17...voltage application means, 18...flow path side wall, 20...coil, 21...core, 22...fixed magnetic material, 23...photodetector, 30...sipper nozzle, 31...arm, 32, 33, 34...tube, 35...pump, 36, 37...valve, 40...suspension container, 41...reaction unit, 42...washing solution container, 43...buffer solution container, 44...washing mechanism, 45...waste container, 50...controller, 51, 52, 53, 54, 55a, 55b, 55c, 56a, 56b, 57...signal line, 61...flow direction, 70...permanent magnet, 71...movable arm, 81...position where magnetic field is to be strengthened, 82...adjacent area on upstream side of flow path, 83...adjacent area on downstream side of flow path

Claims

1. a flow channel for introducing a sample solution containing magnetic particles bound to a labeling substance; a liquid delivery means for supplying and discharging the sample liquid into and from the flow channel; a magnetic field applying means for applying a magnetic field that captures the magnetic particles in the flow channel; a detector for detecting the labeled substance bound to the captured magnetic particles; A sample analyzer comprising: the flow channel is provided with electrodes for applying a voltage that causes the labeling substance to emit light; A sample analysis device characterized in that the magnetic field application means is composed of a magnetic field generating source and a magnetic material that induces a magnetic field from the magnetic field generating source to the electrode, and the magnetic material is formed integrally with the flow path.

2. The sample analyzer according to claim 1, The sample analyzer according to claim 1, wherein the magnetic field source is an electromagnet including a coil.

3. The sample analyzer according to claim 1, A sample analyzer characterized in that the magnetic field source is a permanent magnet.

4. The sample analyzer according to claim 1, A sample analyzer, wherein the magnetic material is embedded inside the wall of the flow channel.

5. The sample analyzer according to claim 1, A sample analyzer, characterized in that the magnetic material is exposed from the flow channel toward the magnetic field source.

6. 6. The sample analyzer according to claim 5, A sample analyzer, wherein the magnetic material is in contact with the magnetic field source.

7. The sample analyzer according to claim 1, The electrodes include a reaction field electrode installed at the bottom of the flow channel and a counter electrode installed at the top of the flow channel; A sample analyzer, characterized in that the magnetic field source is located below the reaction field electrode.

8. The sample analyzer according to claim 7, A sample analyzer characterized in that the magnetic material is installed on a bottom wall of the flow channel.

9. The sample analyzer according to claim 8, A sample analysis device characterized in that the end face of the magnetic material on the reaction field electrode side is shaped to conform to the shape of the reaction field electrode, or the end face on the magnetic field source side is shaped to conform to the shape of the magnetic field source.

10. The sample analyzer according to claim 8, A sample analyzer according to claim 1, wherein the cross-sectional area of ​​the magnetic material on the reaction field electrode side is smaller than the cross-sectional area on the magnetic field source side.

11. The sample analyzer according to claim 8, A sample analyzer according to claim 1, wherein the end surface of the magnetic material on the reaction field electrode side is smaller than the reaction field electrode.

12. The sample analyzer according to claim 7, A sample analyzer characterized in that the magnetic material is installed on a top wall of the flow channel.

13. The sample analyzer according to claim 1, A sample analyzer according to claim 1, wherein the magnetic material has an asymmetric shape between the upstream side and the downstream side in the liquid transport direction of the flow channel.

14. The sample analyzer according to claim 1, A sample analyzer characterized in that different magnetic materials are installed on the upstream and downstream sides of the flow path in the liquid transport direction.

Images