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 Art

[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) in the middle of the flow path, and an external electric field or the like is applied to the captured magnetic particles to cause the labeling substance bound to the magnetic particles to emit light. By detecting the luminescence intensity at this time, the amount of the detection substance bound to the magnetic particles can be measured.

[0003] For example, in Patent Document 1, when detecting the luminescence intensity, a sample analyzer is described in which magnetic particles are collected by bringing a magnet closer to the flow path to strengthen the magnetic field, and when cleaning the inside of the flow path, the magnet is moved away from the flow path to weaken the magnetic field and discharge the magnetic particles.

Prior Art Documents

Patent Documents

[0004]

Patent Document 1

Summary of the Invention

Problems to be Solved by the Invention

[0005] However, when using a mechanism in which a magnet as a magnetic field generation source moves, the number of components responsible for its holding and movement increases, so the degree of freedom related to positioning increases, and there is a possibility of causing misalignment when repeatedly used. Even if a mechanism in which the magnet does not move is not used, there is a possibility of misalignment of the magnet when the components are operated due to maintenance or the like. If the magnetic field in the flow path is misaligned due to the misalignment of the magnet, the magnetic particles cannot be reliably captured, and the analysis accuracy will decrease.

[0006] The objective of the present invention is to provide a sample analysis device that makes it difficult for the magnetic field in the flow path to shift even if the magnet shifts, thereby enabling highly accurate analysis. [Means for solving the problem]

[0007] To solve the aforementioned problems, the present invention provides a sample analyzer comprising: a channel for introducing a sample solution containing magnetic particles bound to a labeling substance; a liquid delivery means for supplying and discharging the sample solution into the channel; a magnetic field application means for applying a magnetic field to capture the magnetic particles in the channel; and a detector for detecting the labeling substance bound to the captured magnetic particles, wherein the magnetic field application means is composed of a plurality of members, and at least one member is formed integrally with the channel. [Effects of the Invention]

[0008] According to the present invention, even if the magnet is displaced, the magnetic field in the flow path is less likely to be displaced, and a sample analysis device capable of high-precision analysis can be provided. [Brief explanation of the drawing]

[0009] [Figure 1] Schematic diagram of an immunoassay analyzer. [Figure 2] A diagram showing the configuration of the magnetic field application means and flow cell in Example 1. [Figure 3] A diagram showing the magnetic field source and flow cell when a displacement occurs. [Figure 4] As a comparative example, this figure shows an analytical model when no fixed magnetic material is used. [Figure 5] This figure shows an analysis model for Example 1, where a fixed magnetic material is used. [Figure 6] This figure shows the analysis results of magnetic flux density for the comparative example's analysis model and the analysis model for Example 1. [Figure 7] As Example 2, this figure shows an analytical model for the case where the fixed magnetic material and the core are in contact. [Figure 8] This figure shows the analysis results of magnetic flux density for the comparative example's analysis model and the analysis model for Example 2. [Figure 9] FIG. showing an analysis model when the end face on the flow path side of the fixed magnetic material has a small area as Example 3. [Figure 10] FIG. showing the analysis results of the magnetic flux density for the analysis model of the comparative example and the analysis model of Example 3. [Figure 11] FIG. showing a plurality of modified examples regarding the shape of the fixed magnetic material. [Figure 12] Cross-sectional view showing the distribution of magnetic flux density in a typical shape example of the fixed magnetic material. [Figure 13] FIG. showing the configuration of the magnetic field applying means and the flow cell of Example 4. [Figure 14] FIG. showing an analysis model when the fixed magnetic material is arranged on the top wall of the flow path as Example 4. [Figure 15] FIG. showing the analysis results of the magnetic flux density for the analysis model of the comparative example and the analysis model of Example 4. [Figure 16] FIG. showing the configuration of the magnetic field applying means and the flow cell of Example 5. [Figure 17] FIG. showing the configuration of the magnetic field applying means and the flow cell of Example 6. [Figure 18] FIG. showing the configuration of the magnetic field applying means and the flow cell of Example 7. [Figure 19] FIG. showing the configuration of the magnetic field applying means and the flow cell of Example 8. [Figure 20] FIG. showing the configuration of the magnetic field applying means and the flow cell of Example 9.

BEST MODE FOR CARRYING OUT THE INVENTION

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

[0011] In this embodiment, an immunoassay device will be described as an example of a sample analyzer. However, the present invention is applicable not only to immunoassays but also to any sample analyzer that uses magnetic particles and captures the magnetic particles by switching the magnetic field strength, and can be applied to analyzers for DNA, biochemistry, etc. Also, the embodiments shown below are not limited to the shape, dimensions, number, etc., and can be changed without departing from the gist thereof.

[0012] Fig. 1 shows a schematic configuration diagram of the immunoassay device. The immunoassay device includes a flow path 10, a liquid feeding means, a magnetic field applying means, a photodetector 23, a controller 50, and the like. The flow path 10 is a site for introducing a sample liquid containing magnetic particles 13 bound to a labeling substance, and is formed by a flow path top wall 11 and a flow path bottom wall 12. In this specification, the detection unit including the flow path top wall 11, the flow path bottom wall 12, the reaction field electrode 14, and the counter electrode 15 is referred to as a flow cell as an integral member.

[0013] The flow path top wall 11 is preferably made of a transparent material, for example, preferably made of glass, plastic, or the like. Thereby, the photodetector 23 can detect the wavelength of the light emitted by the labeling 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 the flow path 10, and a counter electrode 15 is installed on the opposite side across the flow path 10, that is, around the upper part of the flow path 10. Further, the reaction field electrode 14 and the counter electrode 15 are connected to a voltage applying means 16 via signal lines 55b and 55c. The voltage applying means 16 is connected to the controller 50 via a signal line 55a.

[0015] The materials of the reaction field electrode 14 and the counter electrode 15 can be composed of, for example, gold, platinum, palladium, tungsten, iridium, nickel, their alloys, carbon materials, or the like. Also, the reaction field electrode 14 and the counter electrode 15 can use, for example, those formed by plating or sputtering the above materials on a base material such as titanium.

[0016] The reaction field electrode 14 is basically a planar shape for ease of luminescence measurement, and here it is placed on the bottom surface of the channel 10. However, it may be on other surfaces within the channel 10, or on multiple surfaces arranged in three dimensions, and it does not necessarily have to be a planar shape as long as it is suitable for capturing the magnetic particles 13 or for electrochemiluminescence of the labeled substance bonded to the magnetic particles 13; it may be linear, a combination of linear and planar shapes, etc. The counter electrode 15 may be arranged and shaped in a way that generates a voltage within the channel 10 when combined with the 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 to capture the magnetic particles 13 in the flow channel 10 consists of a magnetic field source and a fixed magnetic material 22 that guides the magnetic field from the magnetic field source to the reaction field electrode 14. The magnetic field source may be an electromagnet or a permanent magnet.

[0018] In Figure 1, an electromagnet consisting of a coil 20 and a core 21 is used as the magnetic field source. The coil 20 can be any general solenoid coil, etc., as long as it is capable of generating a magnetic field as an electromagnet. For example, a solenoid coil made of single or stranded copper wire can be used. The core 21 and the fixed magnetic material 22 can be any general soft magnetic material such as iron, silicon steel, permalloy, permendur, magnetic alloy, or soft ferrite, as long as they are capable of generating or inducing a magnetic field. The core 21 and the fixed magnetic material 22 may be the same soft magnetic material or different soft magnetic materials.

[0019] The electromagnet, consisting of a coil 20 and the like, is connected to the controller 50 via signal lines 56a and 56b and a voltage application means 17. When capturing (attracting) magnetic particles 13, the voltage application means 17 is controlled by the controller 50, and a voltage is applied to the coil 20. This generates a magnetic field around the reaction field electrode 14 and the counter electrode 15 in the flow path 10. The magnetic particles 13 are collected on the reaction field electrode 14 by the magnetic force originating from the generated magnetic field. The voltage application to the coil 20 can be in either DC or AC mode, as long as the electromagnet consisting of the coil 20 and the like is capable of generating a magnetic field. However, when operating with AC, it is preferable to use stranded wire or take other measures to address the skin effect.

[0020] When the magnetic field source is a permanent magnet, as will be described later using Figure 20, for example, a movable arm and a permanent magnet are installed near the reaction field electrode 14, and the distance between the permanent magnet and the reaction field electrode 14 is controlled by moving the arm in response to a signal from the controller 50. In this way, even when a permanent magnet is used as the magnetic field source, the increase or decrease of the magnetic field in the flow path 10 can be controlled in the same way as in the case of an electromagnet.

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

[0022] The photodetector 23 detects a labeled substance bound to magnetic particles 13 captured by the magnetic field applied by the magnetic field application means, and is, for example, a camera or a photomultiplier tube. This photodetector 23 can detect the wavelength of light emitted by the labeled substance around 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 the sample solution into the flow path 10 within the flow cell, and consists of tubes, a pump, and valves. The flow path 10 is connected to a sipper nozzle 30 and a pump 35 through tubes 32 and 33. The sipper nozzle 30 is movably mounted by an arm 31, and a suspension container 40, a washing solution container 42, and a buffer container 43 are installed within its range of movement. A valve 36 is provided in tube 33 between the flow path 10 and the pump 35. The pump 35 and valve 36 are connected to a controller 50 through signal lines 52 and 53, and to a waste container 45 through a 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, respectively. This allows the controller 50 to control each connection point independently.

[0025] The samples to be analyzed are biologically derived substances such as serum and urine. If the sample is serum, the specific components to be analyzed are, for example, tumor markers, antibodies, antigen-antibody complexes, or single proteins. In the following explanation, the specific component will be assumed to be TSH (thyroid-stimulating hormone).

[0026] The suspension container 40 contains a sample to be analyzed that has been mixed with a bead solution and reagents as a pretreatment step, and then reacted at a constant temperature (e.g., 37 degrees Celsius) for a certain period of time. The bead solution is a solution in which magnetic particles 13, in which particulate magnetic material is embedded in a matrix material such as polystyrene, are dispersed in a buffer solution, and streptavidin, which can bind to biotin, is bound to the surface of the matrix material. The reagents contain substances that bind the magnetic particles 13 to specific components TSH in the sample, and these include anti-TSH (Thyroid Stimulating Hormone) antibodies with biotin-treated ends. The reagents vary depending on the type of specific component to be analyzed, and for example, immunoglobulins, antigens, antibodies, or other biological substances may be used.

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

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

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

[0030] The particles used as magnetic particles 13 are preferably as follows: (1) particles exhibiting paramagnetic, superparamagnetic, ferromagnetic, or ferrimagnetic properties; (2) particles in which paramagnetic, superparamagnetic, ferromagnetic, or ferrimagnetic particles are encapsulated in materials such as synthetic polymer compounds (polystyrene, nylon, etc.), natural polymers (cellulose, agarose, etc.), or inorganic compounds (silica, etc.). The particle size is preferably in the range of 0.01 to 200 μm, and more preferably in the range of 1 to 10 μm. The specific gravity is preferably 1.3 to 1.5. With these specifications, the magnetic particles 13 are less likely to settle in liquid and are easily suspended. A substance that has the property of specifically binding to the analyte, for example, an antibody that has the property of specifically binding to an antigen, is attached to the surface of the particles.

[0031] The labeling substance is preferably one of the following substances. Specifically, the following examples can be given in terms of specifically binding the labeling substance to the analyte by appropriate means and causing it to emit light by appropriate means. (1) Labeling substances used in fluorescence immunoassays. For example, antibodies labeled with fluorescein isothiocyanate. (2) Labeling substances used in chemiluminescence immunoassays. For example, antibodies labeled with acridinium ester. (3) Labeling substances used in chemiluminescent enzyme immunoassays. For example, 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, we will explain the operation of the immunoassay analyzer. In operation, one analysis is considered 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 pre-aspiration period. One cycle begins when the suspension container 40 containing the suspension processed in the reaction unit 41 is set in its designated position.

[0034] During the suspension suction period, valve 36 is set to open and valve 37 is set to closed. A signal from controller 50 causes arm 31 to move and insert the sipper nozzle 30 into the suspension container 40. Subsequently, a signal from controller 50 causes pump 35 to perform a certain amount of suction. The suspension in the suspension container 40 is drawn into tube 32 via the sipper nozzle 30 and enters tube 32. At this point, pump 35 is stopped and arm 31 is moved to insert the sipper nozzle 30 into the cleaning mechanism 44. The sipper nozzle 30 is cleaned as it passes through the cleaning mechanism 44.

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

[0036] During the detection period, the voltage application to the electromagnet is stopped by a signal from the controller 50. Subsequently, the photodetector 23 is activated and voltage is applied to the reaction field electrode 14 and the counter electrode 15 by a signal from the controller 50. This allows measurement to be performed by receiving light emitted from the labeled material bound to the magnetic particles 13 with the photodetector 23 while the magnetic particles 13 are held on the reaction field electrode 14. The intensity of the detected light emission is recovered as a signal by the controller 50. After a certain period of time, the voltage application 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 moved and the sipper nozzle 30 is inserted into the cleaning mechanism 44.

[0037] During the cleaning period, the cleaning solution drawn from the cleaning solution container 42 is passed through the flow path 10 by suction using the pump 35. At this time, the electromagnet is inactive, so the magnetic particles 13 are not retained on the reaction field electrode 14 and are carried away with the cleaning solution.

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

[0039] During the preliminary aspiration period, buffer solution is aspirated from the buffer solution container 43, filling the tube 32 and the flow path 10 with buffer solution. After the preliminary aspiration period, the next cycle becomes ready to run.

[0040] Regarding the sample analysis apparatus of this embodiment described above, the specific structure of the magnetic field application means will be explained below using Examples 1 to 9. [Examples]

[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 source. Due to individual differences in manufacturing, changes in the operating environment, and a decrease in operating current due to heat generation, variations may occur in the magnetic field around the reaction field electrode 14 of the sample analyzer. 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) to the electromagnet, changing the operating time, etc.

[0042] Figure 2 shows the configuration of the magnetic field application means and flow cell of Example 1. It shows a cross-section in the zx plane when a coordinate system is set with the direction of flow in the flow channel 10 as the x-axis, the horizontal direction of the cross-section perpendicular to the flow as the y-axis, and the vertical direction as the z-axis. The magnetic particles 13 flow through the flow channel 10 of the flow cell along the direction of flow 61. Note that the counter electrode 15 is not shown in Figure 2.

[0043] A magnetic field application means is provided below the reaction field electrode 14 of the flow cell. If a mechanism that moves permanent magnets closer together or further apart is used as the magnetic field application means, the number of parts responsible for holding and moving them increases, which increases the degree of freedom related to positioning and may lead 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, so misalignment is relatively unlikely to occur. However, even with an electromagnet, misalignment of the electromagnet may occur when parts are manipulated for maintenance or other reasons.

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

[0045] Furthermore, the fixed magnetic material 22 is installed on the bottom wall 12 of the channel, and the distance between the channel 10 and the fixed magnetic material 22 is minimized on the bottom side of the channel 10. In other words, since the fixed magnetic material 22 is interposed between the magnetic field source and the reaction field electrode 14, the magnetic field generated by the magnetic field 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 fixing it by bonding it to the channel wall with an adhesive after the flow cell is fabricated, or fixing it by embedding it in the channel wall using an insert mold during the flow cell fabrication process. When the fixed magnetic material 22 is bonded to the flow cell in a way that exposes it to the magnetic field source, the fixed magnetic material 22 is brought closer to the magnetic field source, which reduces the magnetic flux leaking from the magnetic field source into the air and suppresses the 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, so although the magnetic field reaching the fixed magnetic material 22 itself is weaker, the fixed magnetic material 22 is closer to the channel 10, making it less likely for the magnetic field to shift relative to the channel space to occur.

[0047] Figure 3 shows the magnetic field source and flow cell when a misalignment occurs. The position of the electromagnet, consisting of a coil 20 and a core 21 placed below the flow cell, moves in the upstream (-x) direction of the flow path, causing a misalignment. The distance between the electromagnet and the upstream (-x) end of the reaction field electrode 14 is shortened, while the distance between the reaction field electrode 14 and the downstream (+x) end of the flow path is increased. As a result, when a fixed magnetic material 22 is not used, the magnetic field generated from the electromagnet when it is operated will be biased on the upstream and downstream sides of the flow path of the reaction field electrode 14.

[0048] When trapping magnetic particles 13 on the reaction field electrode 14, it is preferable to trap the magnetic particles 13 uniformly and in a high proportion on the reaction field electrode 14. However, if there is a bias in the magnetic field around the reaction field electrode 14, the distribution or efficiency of trapping the magnetic particles 13 deteriorates.

[0049] Therefore, in this embodiment, the magnetic field generated from 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 a displacement occurs in the magnet that generates the magnetic field, deterioration of the distribution or efficiency when trapping the magnetic particles 13 on the reaction field electrode 14 can be suppressed.

[0050] The effect of this embodiment on suppressing magnetic field displacement will be explained based on the results of magnetic field analysis, as shown in Figures 4, 5, and 6.

[0051] Figure 4 shows an analytical model without a fixed magnetic material as a comparative example. Figure 4(a) shows the case where the electromagnet, consisting of the coil 20 and the core 21, does not experience any displacement, while Figure 4(b) shows the case where the electromagnet experiences a displacement of dimension B1 in the x-direction from the state in Figure 4(a). A position 81 where the magnetic field is to be strengthened is shown as a spatial position assumed to be on the reaction field electrode 14, and adjacent to it are adjacent locations 82 on the upstream side of the flow path and adjacent locations 83 on the downstream side of the flow path. In Figure 4(a), the center position of the position 81 where the magnetic field is to be strengthened in the xy plane and the center position of the core 21 in the xy plane are assumed to be the same. 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, and the core diameter A7. Furthermore, regarding the dimensions of the location 81 where the magnetic field is to be strengthened, the adjacent location 82 on the upstream side of the flow path, and the adjacent location 83 on the downstream side of the flow path, the x-axis dimension L1 of the location 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 are shown.

[0052] Figure 5 shows an analytical model for Example 1, where a fixed magnetic material is used. Figure 5(a) shows the case where the electromagnet, consisting of the coil 20 and the core 21, does not experience any displacement, while Figure 5(b) shows the case where the electromagnet experiences a displacement of dimension B1 in the x-direction from the state in Figure 5(a). A position 81 where the magnetic field is to be strengthened is shown as a spatial position assumed to be on the reaction field electrode 14, and adjacent to it are adjacent locations 82 on the upstream side of the flow path and adjacent locations 83 on the downstream side of the flow path. The shape and dimensions of the analytical model are shown by the horizontal position and dimension A1 of the core, the vertical position and dimension A2 of the core, 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. Furthermore, regarding the dimensions of the position 81 where the magnetic field is to be strengthened, the adjacent location 82 on the upstream side of the flow path, and the adjacent location 83 on the downstream side of the flow path, 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 are shown. Since the fixed magnetic material 22 is fixed to the flow cell, the relative position of the fixed magnetic material 22 and the position 81 where the magnetic field is to be strengthened remains unchanged in Figures 5(a) and (b), and it can be seen that only the coil 20 and the core 21 are moving.

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

[0054] The magnetic field analysis was performed using a general-purpose magnetic field analysis method based on Maxwell's equations and Ampère'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 region approximately five times the length of the electromagnet's major axis (sum of upper core length A3, coil length A4, and lower core length A5). The average magnetic flux density within the following three locations within the air region was determined: location 81 (a square with x and y axis dimensions of 8 mm each) where the magnetic field was to be strengthened, location 82 adjacent to the upstream side of the flow path, and location 83 adjacent to the downstream side of the flow path (a rectangle with x axis dimension of 2 mm and y axis dimension of 8 mm). As for the analysis conditions, the coil 20 was made of copper with 5000 turns. For comparison, the current value was set to a value such that Figures 4(a) and 5(a) would have similar magnetic flux densities, so it was 0.5A in Figure 4 and 1.0A in Figure 5. PB permalloy, a type of general permalloy, was used for the core 21 and the fixed magnetic material 22.

[0055] Figure 6 shows the analysis results of the magnetic flux density, illustrating the magnitude of the magnetic flux density at three target locations for the comparative example analysis model described in Figure 4 and the analysis model for Example 1 described in Figure 5. When there is no positional displacement and B1=0mm, a large magnetic flux density is generated at position 81 where the magnetic field is to be strengthened, regardless of the presence or absence of a fixed magnetic material, while small magnetic flux densities are generated at the adjacent upstream location 82 and the adjacent downstream location 83 of the flow path. In this case, a strong magnetic field can be generated exclusively on the reaction field electrode 14, which can be interpreted as a magnetic field suitable for capturing magnetic particles 13. In the cases of B1=1mm and B1=2mm, where there is positional displacement, the magnetic flux density at position 81 where the magnetic field is to be strengthened was a large value 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 increased particularly at the adjacent upstream location 82 of the flow path. Since a strong magnetic field is generated in locations other than on the reaction field electrode 14, which makes it easy for magnetic particles 13 to be captured in locations that do not contribute to detection, this 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 displacement occurs, the adjacent location 82 on the upstream side of the flow path and the adjacent location 83 on the downstream side of the flow path maintain a smaller magnetic field than the location 81 where the magnetic field is to be strengthened. Therefore, by using the fixed magnetic material 22, a strong magnetic field limited to the reaction field electrode 14 can be maintained, and a magnetic field structure that is less prone to displacement of the magnetic field around the reaction field electrode 14 can be provided.

[0056] Although the analysis results described above only show the x-direction, this embodiment suppresses the bias of the magnetic field around the reaction field electrode 14 by guiding the magnetic field generated from the magnet to the reaction field electrode 14 using the fixed magnetic material 22. Therefore, similar effects can be expected in the y-direction and z-direction as well. In other words, regardless of whether the displacement of the magnet is due to displacement, tilting, or rotation in any direction in the xyz axis space, by adjusting the position, size, shape, number, etc., of the fixed magnetic material 22, the magnetic field can be guided to an appropriate location in the space surrounding 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 prone to misalignment of the magnetic field at a predetermined position in the detection channel and capable of high-precision analysis. [Examples]

[0057] Example 2 will be described using Figures 7 and 8. In the following examples, the same configuration and effects as in Example 1 will not be explained.

[0058] Figure 7 shows an analytical model for Example 2, where the fixed magnetic material and the core are in contact. As shown in Figure 7, in this example, the fixed magnetic material 22 is not only exposed from the bottom surface of the flow cell, but is also in contact with the core 21 of the magnetic field source. Therefore, the magnetic flux leaking from the magnetic field source into the air can be further reduced, and the decrease in the magnetic field on the reaction field electrode 14 can be further suppressed.

[0059] Figure 7 shows a magnetic field application means consisting of a coil 20, a core 21, and a fixed magnetic material 22, where the coil 20 and core 21, which are not fixed to the flow cell, are misaligned. A position 81 where the magnetic field is to be strengthened is shown in a spatial position assumed to be on the reaction field electrode 14, and adjacent to it are adjacent locations 82 on the upstream side of the flow path and adjacent locations 83 on the downstream side of the flow path. The shape and dimensions of the analysis model are shown by the horizontal position and dimension of the core A1, the vertical position and dimension of the core 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. In addition, 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 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 are shown.

[0060] In Figure 7, the following dimensions were used for comparison with Figure 4 (analysis model without fixed magnetic material). Specifically, 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 displacement dimension B1 was 0-2 mm, the fixed magnetic material length A9 was 2 mm, the x-axis dimension L1 of the position where the magnetic field is to be strengthened was 8 mm, and the x-axis dimensions L2 of the adjacent location on the upstream side of the flow path and L3 of the adjacent location on the downstream side of the flow path were 2 mm (the position 81 where the magnetic field is to be strengthened is an 8 mm square, and the adjacent locations on the upstream side of the flow path 82 and the adjacent locations on the downstream side of the flow path 83 are rectangles with an x-axis dimension of 2 mm and a y-axis dimension of 8 mm). Furthermore, in Figure 7, since the core 21 and the fixed magnetic material 22 are arranged without any gaps, the gap A8 between the fixed magnetic material and the core is 0 mm, and therefore its description is omitted.

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

[0062] Figure 8 shows the results of the magnetic flux density analysis, illustrating the magnitude of the magnetic flux density at three locations for the analysis model of the comparative example described in Figure 4 and the analysis model of Example 2 described in Figure 7. In the case where there is no positional displacement and B1=0mm, the core 21 and the fixed magnetic material 22 in Figure 7 are adjacent without displacement, resulting in the same structure as in Figure 4 in the analysis model, and the plot with the fixed magnetic material has been omitted.

[0063] As shown in Figure 8, at B1=1mm and B1=2mm, where there is a misalignment, in the comparative example, i.e., without a fixed magnetic material, the magnetic flux density at the adjacent location 82 on the upstream side of the flow path increases, while in this embodiment, i.e., with a fixed magnetic material, a small magnetic flux density is maintained. Therefore, by using the fixed magnetic material 22 of this embodiment, a magnetic field structure that is less prone to misalignment of the magnetic field around the reaction field electrode 14 can be provided.

[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 has the effect of making it difficult for displacement of the magnetic field around the reaction field electrode 14 to occur, as well as suppressing the decrease in the magnetic field on the reaction field electrode 14. Therefore, in this embodiment, it is not necessary to increase the applied voltage (current) as in Embodiment 1 of Figure 5, and displacement of the magnetic field around the reaction field electrode 14 is less likely 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 fixed magnetic material 22, thereby easing manufacturing and operating conditions and saving energy consumption. [Examples]

[0065] Example 3 will be described with reference to Figures 9 to 12.

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

[0067] Figure 9 shows a magnetic field application means consisting of a coil 20, a core 21, and a fixed magnetic material 22, where the coil 20 and core 21, which are the magnetic field sources, are misaligned. The shape of the fixed magnetic material 22 is such that the cross-section of the end on the reaction field electrode 14 side (upper side) is made up of a circle with a smaller diameter than the cross-section of the end on the coil 20 side (lower side), and it is trapezoidal in the xz cross-section. A position 81 where the magnetic field should be strengthened is shown as a spatial position assumed to be on the reaction field electrode 14, and adjacent to it are adjacent locations 82 on the upstream side of the flow path and adjacent locations 83 on the downstream side of the flow path. The shape and dimensions of the analysis model are shown by the horizontal position and dimension of the core A1, the vertical position and dimension of the core 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 between the fixed magnetic material and the core A8, the length of the fixed magnetic material A9, the upper surface diameter of the fixed magnetic material A10, and the side dimension of the fixed magnetic material A11. Additionally, the displacement dimension B1, the x-axis dimension L1 of the location 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 are shown.

[0068] In Figure 9, the following dimensions were used for comparison with Figure 4 (analysis model without fixed magnetic material). Specifically, the horizontal core position and dimension A1 was set to 0.5 mm, the vertical core position and dimension A2 to 0.5 mm, the upper core length A3 to 3 mm, the coil length A4 to 60 mm, the lower core length A5 to 5 mm, the coil diameter A6 to 17 mm, the core diameter A7 to 7 mm, the misalignment dimension B1 to 0-2 mm, the gap A8 between the fixed magnetic material and the core to 0.5 mm, the fixed magnetic material length A9 to 2 mm, the upper surface diameter A10 of the fixed magnetic material to 5 mm, the side dimension A11 of the fixed magnetic material to 1 mm, the x-axis dimension L1 of the position where the magnetic field is to be strengthened to 8 mm, 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 to 2 mm (the position 81 where the magnetic field is to be strengthened is an 8 mm square, and the adjacent locations 82 on the upstream side of the flow path and 83 on the downstream side of the flow path are 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 shown in Figure 9, the current value of 1.0A was set, the same as in Figure 5. The other analysis conditions are the same as in Example 1.

[0070] Figure 10 shows the results of the magnetic flux density analysis, illustrating the magnitude of the magnetic flux density at three target locations for the comparative example analysis model described in Figure 4 and the analysis model for Example 3 described in Figure 9. At B1=1mm and B1=2mm, where there is a positional displacement, the magnetic flux density at the adjacent location 82 on the upstream side of the flow path increases in the comparative example, i.e., when there is no fixed magnetic material, while in this example, i.e., when there is a fixed magnetic material, a small magnetic field is maintained. Therefore, by using the fixed magnetic material 22 of this example, it is possible to provide a magnetic field structure in which a positional displacement of the magnetic field around the reaction field electrode 14 is less likely to occur even if a positional displacement occurs in the magnetic field source.

[0071] Furthermore, various modifications to the shape of the fixed magnetic material 22 are possible. Here, we will list several representative shapes for the fixed magnetic material 22 and explain the individual effects obtained for each shape. Figure 11 is a diagram showing several modifications related to the shape of the fixed magnetic material.

[0072] Figures 11(a) and (b) show examples of cylindrical and prismatic fixed magnetic materials 22. By making the end face of the fixed magnetic material 22 on the reaction field electrode 14 side conform to the shape and size of the reaction field electrode 14, the magnetic field on the reaction field electrode 14 can be efficiently increased. For example, if the reaction field electrode 14 is square, a prismatic 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. In addition, the magnetic field bias may be suppressed by making the end face of the fixed magnetic material 22 on the magnetic field source side conform to the shape and size of the core 21 of the magnetic field source.

[0073] Figures 11(c), (d), (e), and (f) show examples where the cross-sectional area of ​​the end of the fixed magnetic material 22 on the channel 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 is passed from one surface to the opposite side. For example, as shown in Figures 11(c), (d), (e), and (f), by having the magnetic flux incident into the fixed magnetic material 22 from a surface with a large cross-sectional area below the z axis and emitted from a surface with a small cross-sectional area above the z axis, the density can be increased, and a strong magnetic field can be generated in a limited area.

[0074] Furthermore, a large amount of magnetic flux that enters the fixed magnetic material 22 from the core 21 through the air region is released into the air region 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 surface 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 Figure 11(d), it is possible to reduce the magnetic flux that is released into the air region from the corners of the side surface and does not contribute to increasing the magnetic field on the reaction field electrode 14. As a means of reducing sharp corners, for example, by making the fixed magnetic material 22 have two or more corners on the side surface, as shown in Figure 11(e), and making each of the angles C1 and C2 on the side surface less than 90 degrees, more preferably 45 degrees or less, and even more preferably 30 degrees or less, a similar effect can be expected. Furthermore, this effect is more pronounced in shapes without corners on the side surface, and can be further enhanced in shapes such as Figure 11(f), where the side surface is a three-dimensional curved surface.

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

[0076] As shown in Figures 11(g), (h), and (i), by providing an uneven surface on the upper end surface of the fixed magnetic material 22, a large amount of magnetic flux incident into the fixed magnetic material 22 is released into the air region from the corners of the upper end surface. This allows for even distribution of areas where a large amount of magnetic flux is released within the plane of the opposing reaction field electrode 14. This suppresses localized magnetic field bias on the reaction field electrode 14 and enables the capture of uniform magnetic particles 13 suitable for light emission detection.

[0077] Figure 11(j) shows an example where the upper surface of the fixed magnetic material 22 has an asymmetrical uneven shape on the upstream and downstream sides in the direction of fluid delivery of the flow path 10. When capturing magnetic particles 13 from a fluid in a sample analyzer, the capture distribution of 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, magnetic particles 13 tend to be captured on the upstream (-x) side of the reaction field electrode 14. In this case, to obtain a capture distribution of magnetic particles 13 suitable for photodetection, the magnetic field is controlled so that it is weaker on the upstream side and stronger on the downstream side of the reaction field electrode 14, by increasing the distance between the fixed magnetic material 22 and the reaction field electrode 14 on the upstream side and decreasing the distance on the downstream (+x) side, as shown in Figure 11(j). This optimizes the capture distribution so as to cancel out the bias in the capture distribution of magnetic particles 13 caused by the flow field.

[0078] As shapes for the fixed magnetic material 22 that have the same effect, for example, a shape in which the length of the side surface of the fixed magnetic material 22 differs depending on the location, as shown in Figure 11(k), and a shape in which the side surface of the fixed magnetic material 22 in a specific direction is cut off, as shown in Figure 11(l), are also effective. In Figure 11(k), by allowing the magnetic flux to pass asymmetrically on the upstream and downstream sides of the flow channel 10 at the surface in which the magnetic flux of the fixed magnetic material 22 is incident or emitted, the capture distribution can be optimized so as to cancel out the bias in the capture distribution of magnetic particles 13 caused by the flow field. Furthermore, in the structure of Figure 11(l), by using a combination of cutting the side surface of the fixed magnetic material 22 in a specific direction and creating an uneven shape on the end face, it is possible to suppress local bias in the magnetic field on the reaction field electrode 14 in addition to generating an asymmetric magnetic field on the upstream and downstream sides of the flow channel 10.

[0079] Figure 12 is a cross-sectional view showing the distribution of magnetic flux density in typical shapes of a fixed magnetic material. Figures 12(a), (b), (c), and (d) show the cases where the fixed magnetic material is cylindrical, has a small cross-sectional area at the upper end, has an uneven upper surface, and has an asymmetrical uneven upper surface, respectively, corresponding to the shapes of (a), (c), (g), and (j) in Figure 11.

[0080] Figures 12(a) and 12(b) are the same analysis examples as Figure 5(a) and Figure 9 when the misalignment dimension B1 = 0 mm, respectively, and the following dimensions were used. Specifically, 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 misalignment dimension B1 was 0-2 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 upper diameter A10 of the fixed magnetic material was 5 mm, and the side dimension A11 of the fixed magnetic material was 1 mm.

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

[0082] In Figure 12(d), the fixed magnetic material length A9 was set to 1.7 mm, the fixed magnetic material top surface diameter A10 to 3.5 mm, the fixed magnetic material side dimension A11 to 3.5 mm, and the fixed magnetic material groove dimension A12 to 0.3 mm, while the other dimensions were the same as in 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 shown in Figure 12, the current value of 1.0A was set, the same as in Figure 5. The other analysis conditions are the same as in Example 1.

[0084] Regarding Figure 12, the effects of (b) a small cross-sectional area of ​​the upper surface, (c) an uneven shape of the upper surface, and (d) an asymmetric uneven shape of the upper surface will be explained by comparing them with (a) a cylindrical shape. In the case of (b) a small cross-sectional area of ​​the upper surface, the magnetic flux density generated from the center of the upper surface of the fixed magnetic material 22 is larger than in the case of (a) a cylindrical shape, and the magnetic field is locally concentrated. This makes it possible to increase the magnetic flux density specifically on the reaction field electrode 14. In the case of (c) an uneven shape of the upper surface, the magnetic flux density generated from the upper part of the fixed magnetic material 22 is concentrated at the corners in the case of (a) a cylindrical shape, but in the case of (c) an uneven shape of the upper surface, the concentration at the corners is mitigated and tends to spread over the entire upper surface of the fixed magnetic material 22. This suppresses localized magnetic field bias within the plane of the reaction field electrode 14 and enables the capture of uniform magnetic particles 13 suitable for light emission detection. (d) For the upper surface with an asymmetrical uneven shape, the magnetic flux density generated from the upper part of the fixed magnetic material 22 is different in magnitude on the -x side and the +x side. This allows for control to compensate for the bias in the trapping distribution of magnetic particles 13 by making the magnetic field downstream of the reaction field electrode 14 larger than that upstream, for example, in response to relatively slow flow conditions.

[0085] Furthermore, as shown in Figure 12, in all shapes, the magnetic flux density is high in a certain region from the corner of the upper surface of the fixed magnetic material 22. Therefore, even if the area of ​​the reaction field electrode 14 located above the fixed magnetic material 22 is larger than the cross-sectional area of ​​the upper surface of the fixed magnetic material 22, a large amount of magnetic flux can be induced across the entire surface of the reaction field electrode 14 by utilizing the magnetic flux that reaches the reaction field electrode 14 from the fixed magnetic material 22 through the air region. [Examples]

[0086] Example 4 will be explained using Figures 13, 14, and 15.

[0087] Figure 13 shows the configuration of the magnetic field application means and flow cell of Example 4, and shows a cross-section in the zx plane when a coordinate system is set with the direction of flow propagation in the flow channel 10 as the x-axis, the horizontal direction of the cross-section perpendicular to the flow as the y-axis, and the vertical direction as the z-axis.

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

[0089] The effect of this embodiment on suppressing magnetic field displacement will be explained based on the results of magnetic field analysis, as shown in Figures 14 and 15.

[0090] Figure 14 shows an analysis model for Example 4, where a fixed magnetic material is placed on the top wall of the flow channel. In Figure 14, it is assumed that the reaction field electrode 14 is located in the space between the core 21 and the fixed magnetic material 22, and the position 81 where the magnetic field is to be strengthened is shown. Adjacent positions are shown as the upstream adjacent location 82 and the downstream adjacent location 83 of the flow channel. The coil 20 and core 21 are shown assuming a positional displacement of displacement dimension B1. The shape and dimensions of the analysis model are shown by the horizontal position and dimension of the core A1, the vertical position and dimension of the core 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 between the fixed magnetic material and the core A8, and the length of the fixed magnetic material A9. The positional displacement 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 location of the flow channel, and the x-axis dimension L3 of the downstream adjacent location of the flow channel are also shown.

[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 placed in the center of this gap. Therefore, the position and dimension A2 of the vertical core are set to 1.5 mm. In Figure 15, the analysis results obtained when the position and dimension A2 of the vertical core are set to 1.5 mm are cited as a comparison with the case in Figure 4 (analysis model without fixed magnetic material) where the position 81 where the magnetic field is to be strengthened is placed in the same position. In Figure 14, the length A9 of the fixed magnetic material 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 values ​​were set to 0.5A in Figure 4 and 0.35A in Figure 14 so that the magnetic flux density in Figures 4(a) and 14 would be approximately the same. Other analysis conditions were the same as in Example 1.

[0093] Figure 15 shows the results of the magnetic flux density analysis, illustrating the magnitude of the magnetic flux density at three target locations for the comparative example analysis model described in Figure 4 and the example model for Example 4 described in Figure 14. In the case of B1=0mm with no positional displacement, the magnetic flux density at the location 81 where the magnetic field is to be strengthened is approximately the same for both the comparative example (i.e., without fixed magnetic material) and this example (i.e., with fixed magnetic material placed on the top wall of the flow path). However, at the adjacent location 82 on the upstream side of the flow path and the adjacent location 83 on the downstream side of the flow path, the values ​​are smaller in this example. Therefore, in this example, a strong magnetic field can be obtained specifically on the reaction field electrode 14.

[0094] Furthermore, when comparing the comparative example, i.e., the case without a fixed magnetic material, with this embodiment, i.e., the case where a fixed magnetic material is placed on the top wall of the flow channel, at B1=1mm and B1=2mm where there is a misalignment, the difference between the position 81 where the magnetic field is to be strengthened and the adjacent upstream location 82 of the flow channel, and the difference between the position 81 where the magnetic field is to be strengthened and the adjacent downstream location 83 of the flow channel are larger in this embodiment. Therefore, this embodiment is more effective for generating a magnetic field limited to the reaction field electrode 14 and can secure a magnetic field suitable for capturing magnetic particles 13. This embodiment also provides a magnetic field structure in which misalignment of the magnetic field around the reaction field electrode 14 is less likely to occur even if a misalignment occurs in the magnetic field source.

[0095] When the fixed magnetic material 22 is placed on the top wall of the flow path, magnetic flux can easily pass through the space between the core 21 and the fixed magnetic material 22, making it easier to obtain a larger magnetic flux density than when there is no fixed magnetic material. This is advantageous for capturing magnetic particles 13, enabling magnetic particle capture suitable for optical detection. Alternatively, the load voltage (current) to the coil 20 required to obtain an equivalent magnetic flux density can be reduced, enabling energy-saving operation.

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

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

[0098] In this embodiment, the fixed magnetic material 22 is placed on the side of the flow channel 10, that is, on the flow channel side wall 18. Even with this arrangement, a magnetic field structure that is less prone to displacement of the magnetic field around the reaction field electrode 14 can be obtained. When installing the fixed magnetic material 22 on the flow channel side wall 18, it may be installed on one or both of the opposing flow channel side walls 18. [Examples]

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

[0100] Furthermore, as in this embodiment, by using multiple fixed magnetic materials 22 and varying the size, shape, and material of each fixed magnetic material 22, the magnetic field on the reaction field electrode 14 can be appropriately controlled. For example, by placing a fixed magnetic material 22 with a low magnetic susceptibility or saturation magnetic flux density near the upstream side of the reaction field electrode 14, and a fixed magnetic material 22 with a 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 can, for example, offset the bias in the capture distribution of magnetic particles 13 caused by the flow field. In addition, the control of the magnetic fields on the upstream and downstream sides of the reaction field electrode 14 can also be performed by the specifications or operating conditions of the coils 20 and cores 21 of multiple electromagnets. For example, by loading a larger voltage (current) onto the coil 20 of the electromagnet near the downstream side of the reaction field electrode 14 than onto the coil 20 of the electromagnet near the upstream side of the reaction field electrode 14, the magnetic field near the downstream side can be increased.

[0101] Therefore, it is not necessary to divide both the fixed magnetic material 22 and the magnetic field source, the coil 20 and core 21, into multiple parts; either the fixed magnetic material 22 or the magnetic field source may be made into multiple parts. If only one fixed magnetic material 22 is used, it may be in a shape like (j) or (k) in Figure 11, for example. [Examples]

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

[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 in Example 8. In this example, an electromagnet with a curved shape is used, with both ends of the core 21 facing the flow cell, and the fixed magnetic material 22 is installed so as to face both ends of the core 21. This makes it possible to obtain a magnetic field structure in which displacement of the magnetic field around the reaction field electrode 14 is less likely to occur.

[0104] Furthermore, as in this embodiment, by using an electromagnet with a curved shape, a magnetic circuit with less air interference can be created around the flow cell, and the magnetic flux density generated from the end of the core 21 can be increased. By having the fixed magnetic material 22 face both ends of the core 21, a large magnetic flux density can be obtained on the reaction field electrode 14 via a large amount of magnetic flux. In this embodiment, even when the reaction field electrode 14 is located on the bottom wall 12 of the flow path, the arrangement of the electromagnet is not limited to below the flow cell. That is, the electromagnet with a curved shape may be arranged, for example, from below to the side of the flow cell, from one side to the opposite side, or from below to above. [Examples]

[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 in Example 9. In this example, a permanent magnet 70 is used as the magnetic field source. Specifically, by rotating a movable arm 71 to which the permanent magnet 70 is fixed, the magnetic field on the reaction field electrode 14 is increased or decreased by moving the permanent magnet 70 closer to or further away from the flow cell.

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

[0107] Furthermore, in this embodiment as well, since the fixed magnetic material 22 is formed integrally with the flow cell, a magnetic field structure that is less prone to displacement of the magnetic field around the reaction field electrode 14 can be obtained. Note that the movable arm 71 in this embodiment is not limited to a rotational motion mechanism based on a single pivot point; the number, position, and direction of the pivot points during motion can be set based on any position or plane in three-dimensional space. Also, other motion mechanisms besides rotation may be employed, such as movement along a single axis using rails.

[0108] The present invention is not limited to the embodiments described above, and various modifications are possible. For example, the embodiments described above are described in detail to make the present invention easier to understand, and are not necessarily limited to those having all the configurations described. Furthermore, it is possible to replace or add to the configurations of one embodiment with those of another embodiment. [Explanation of Symbols]

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

Claims

1. a flow path for introducing a sample liquid 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 to capture 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; 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, characterized in that the sample analysis device.

2. 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. 2. The sample analyzer according to claim 1, The sample analyzer according to claim 1, wherein the magnetic field source is a permanent magnet.

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

5. 2. The sample analyzer according to claim 1, A sample analyzer according to claim 1, wherein the magnetic material is exposed from the flow path toward the magnetic field source.

6. 6. The sample analyzer according to claim 5, The sample analyzer according to claim 1, wherein the magnetic material is in contact with the magnetic field source.

7. 2. 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 upper part of the flow channel, A sample analyzer, characterized in that the magnetic field source is located below the reaction field electrode.

8. 8. The sample analyzer according to claim 7, A sample analyzer according to claim 1, wherein the magnetic material is disposed on a bottom wall of the flow channel.

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

10. 9. 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 of ​​the magnetic field source side.

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

12. 8. The sample analyzer according to claim 7, A sample analyzer according to claim 1, wherein the magnetic material is disposed on a top wall of the flow path.

13. 2. The sample analyzer according to claim 1, The 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. 2. The sample analyzer according to claim 1, A sample analyzer comprising: different magnetic materials disposed on the upstream and downstream sides of the flow path in the liquid transport direction.

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