JP7299175B2 - Sample analyzer - Google Patents

Description

The present application relates to sample analyzers.

2. Description of the Related Art Conventionally, techniques using sample analysis substrates are known for analyzing specific components in samples such as urine and blood. For example, in Patent Document 1, a disk-shaped sample analysis substrate formed with channels, chambers, etc. is used, and by rotating the sample analysis substrate, a solution is transported, distributed, mixed, and components in the sample solution are analyzed. It discloses the technology to analyze the A specific component is quantified, for example, by detecting light generated by an immune reaction.

Magnetic particles (also called “magnetic beads”, “magnetic particles” or “magnetic beads”), for example, are used in immunoassays and gene detection methods. US Pat. No. 5,300,004 refers to a sandwich immunoassay method using magnetic particles. In the sandwich immunoassay method, the antigen-antibody reaction causes the antigen contained in the sample to be measured, the primary antibody immobilized on the surface of the magnetic particles, and the secondary antibody bound to the labeled substance to combine to form a complex. obtain.

Japanese Patent Publication No. 7-500910 Japanese Patent Application Laid-Open No. 2018-163102

In order to improve the measurement accuracy of a specific component in a sample, it is preferable to generate as many antigen-antibody reactions as possible with antigens in the sample to obtain a large number of complexes. For this purpose, it is required to effectively mix the antigen in the sample with the primary antibody and the secondary antibody.

One exemplary, non-limiting embodiment of the present application provides a sample analyzer that allows for increased accuracy in measuring specific constituents in a sample.

The sample analyzer of the present disclosure rotates and stops a sample analysis substrate holding a liquid sample to cause a binding reaction between an analyte in the liquid sample and a ligand immobilized on the surface of magnetic particles. An analysis apparatus comprising: a turntable for supporting the loaded sample analysis substrate; a motor for rotating the turntable; a drive circuit for controlling rotation and stoppage of the motor; and rotation of the sample analysis substrate. A first magnet unit arranged on the side of a first surface perpendicular to the axis and generating an attractive force for attracting the magnetic particles; A second magnet unit arranged on the surface side and generating an attractive force for attracting the magnetic particles, and a first magnet unit are moved to change the relative position between the first magnet unit and the substrate for sample analysis. a first actuator, a second actuator that moves the second magnet unit to change the relative position between the second magnet unit and the sample analysis substrate, the motor, the drive circuit, the first actuator, and the and a control circuit for controlling the operation of the second actuator. The sample analysis substrate is a plate-shaped substrate having a predetermined thickness, which can be loaded into and removed from the sample analysis device. and a chamber, which is a space for causing the binding reaction within the base substrate, and when the liquid sample in the chamber is stirred, the first actuator and the second actuator move the chamber The first magnet unit and the second magnet unit are alternately moved to positions where the magnetic particles inside are attracted to the magnet unit.

According to the present disclosure, there is provided a sample analyzer that can improve the measurement accuracy of a specific component in a sample.

FIG. 1 is an example of a schematic diagram illustrating a sandwich immunoassay method using magnetic particles. FIG. 2A is a plan view showing an example of the structure of the substrate for sample analysis. FIG. 2B is an exploded perspective view of the substrate for sample analysis. FIG. 3 is a block diagram showing a hardware configuration example of the sample analyzer 1. As shown in FIG. FIG. 4A is a plan view of the sample analysis substrate 100. FIG. FIG. 4B is an exploded perspective view of the sample analysis substrate 100. FIG. FIG. 5 is a top view showing positions of a plurality of chambers provided on the sample analysis substrate 100. FIG. FIG. 6 is a top view showing the positions of the washing liquid 130, the substrate liquid 132, the primary antibody 134 and the secondary antibody 136 held in advance on the sample analysis substrate 100. FIG. FIG. 7 is a diagram showing a spotting chamber 110 in which blood 190, which is a specimen, is spotted. FIG. 8 is an exploded perspective view of the first magnet unit 16. FIG. FIG. 9 is a plan view of the first magnet unit 16. FIG. FIG. 10A is a diagram illustrating example magnet shapes according to the present disclosure. FIG. 10B is a diagram illustrating example magnet shapes according to the present disclosure. FIG. 10C is a diagram illustrating example magnet shapes according to the present disclosure. FIG. 10D is a diagram illustrating example magnet shapes according to the present disclosure. FIG. 10E is a diagram illustrating example magnet shapes according to the present disclosure. FIG. 10F is a diagram illustrating example magnet shapes according to the present disclosure. FIG. 10G is a diagram illustrating example magnet shapes according to the present disclosure. FIG. 10H is a diagram illustrating example magnet shapes according to the present disclosure. FIG. 11 is a diagram showing an example of the positional relationship between the first magnet unit 16, the second magnet unit 56, and the sample analysis substrate 100. As shown in FIG. FIG. 12 is a diagram showing an example of the positional relationship between the first magnet unit 16, the second magnet unit 56, and the sample analysis substrate 100. As shown in FIG. FIG. 13 is a diagram showing the relationship between the position of the first magnet unit 16 and the position of the measurement chamber 116 after the sample analysis substrate 100 has been rotated about 180 degrees from the state shown in FIG. 14 is an enlarged cross-sectional view taken along line AA in FIG. 13. FIG. FIG. 15 is a plan view showing the configuration of the first magnet unit 16 moved to the retracted position from above the sample analysis substrate 100 and the movement mechanism of the first magnet unit 16 . FIG. 16 is a side view showing the configuration of the first magnet unit 16 moved to the retracted position from above the sample analysis substrate 100 and the movement mechanism of the first magnet unit 16 . FIG. 17 is a plan view showing the configuration of the second magnet unit 56 moved to a position overlapping the sample analysis substrate 100 and the movement mechanism of the second magnet unit 56 . FIG. 18 is a side view showing the configuration of the second magnet unit 56 moved to a position overlapping the sample analysis substrate 100 and the movement mechanism of the second magnet unit 56 . 19 is an enlarged cross-sectional view taken along line CC in FIG. 17. FIG. FIG. 20 is a flow chart showing a procedure of processing of the control circuit 22 that executes a stirring process using magnetic particles. FIG. 21 is a flow chart showing the processing procedure of the control circuit 22 for executing the luminescence measurement processing. FIG. 22 is a diagram showing an example of the positional relationship between the ring-shaped first magnet unit 16 , the semicircular second magnet unit 56 , and the sample analysis substrate 100 . FIG. 23A is a side view of the sample analyzer 1 according to the modification. FIG. 23B is a diagram showing how the south poles of magnets 40 and 80 face each other. FIG. 24 is a side view of the sample analyzer 1 according to a further modified example.

An embodiment of a sample analyzer according to the present invention will be described below with reference to the accompanying drawings. In this specification, more detailed description than necessary may be omitted. For example, detailed descriptions of already well-known matters and redundant descriptions of substantially the same configurations may be omitted. This is to avoid unnecessary verbosity in the following description and to facilitate understanding by those skilled in the art. It should be noted that the present inventors provide the accompanying drawings and the following description for a full understanding of the present disclosure by those skilled in the art and are not intended to limit the claimed subject matter thereby. In the following description, identical or similar components are given the same reference numerals.

2. Description of the Related Art Methods for analyzing components of samples such as urine and blood sometimes use a binding reaction between an analyte, which is an object to be analyzed, and a ligand that specifically binds to the analyte. Such assays include, for example, immunoassays and genetic diagnostics. Samples such as urine and blood are sometimes called specimens in the medical and pharmaceutical fields.

Examples of immunoassays include competitive and non-competitive methods (sandwich immunoassays). Moreover, an example of the genetic diagnosis method is a gene detection method based on hybridization. These immunoassays and gene detection methods use, for example, magnetic particles (also referred to as “magnetic beads”, “magnetic particles” or “magnetic beads”). As an example of these analysis methods, a sandwich immunoassay method using magnetic particles will be specifically described.

As shown in FIG. 1, first, a primary antibody 304 immobilized on the surface of a magnetic particle 302 (hereinafter referred to as "magnetic particle-immobilized antibody 305") and an antigen 306 contained in a sample to be measured are is bound by an antigen-antibody reaction. Next, the secondary antibody (hereinafter referred to as "labeled antibody 308") to which the labeling substance 307 is bound is bound to the antigen 306 by antigen-antibody reaction. As a result, a complex 310 in which the magnetic particle-immobilized antibody 305 and the labeled antibody 308 are bound to the antigen 306 is obtained.

A signal based on the labeled substance 307 of the labeled antibody 308 bound to the complex 310 is detected, and the antigen concentration is measured according to the amount of the detected signal. The labeling substance 307 includes, for example, enzymes (for example, peroxidase, alkaline phosphatase, luciferase, etc.), chemiluminescent substances, electrochemiluminescent substances, fluorescent substances, and the like. A signal such as luminescence or fluorescence is detected. The light to be detected does not originate from the sample itself. However, the analysis of the components of the sample is to measure the concentration of the antigen 306 in the sample, etc., and the complex 310 to which the antigen 306 binds emits light. Therefore, in this specification, for the sake of clarity, the sample may be described as emitting light.

When the sample is transferred between a plurality of chambers provided on the sample analysis substrate by the above-described measurement method and the component analysis of the sample is performed by detecting the luminescence of the sample, the procedure for transferring the sample or the sample analysis Since the sample is transferred or held using the centrifugal force generated by the rotation of the substrate for analysis, the luminescence of the sample may be detected while the substrate for sample analysis is being rotated.

In order to more accurately measure the concentration of the antigen 306 in the sample, it is possible to generate a complex 310 in which as many antigens 306 as possible in the sample, the magnetic particle-immobilized antibody 305 and the labeled antibody 308 are bound. desirable. For this purpose, it is required to generate as many antigen-antibody reactions as possible between the antigen 306 and the magnetic particle-immobilized antibodies 305 and labeled antibodies 308 .

A conventional sample analyzer agitates a solution containing a sample by performing an oscillating motion in which the direction of rotation of the substrate for sample analysis is reversed one after another. However, the conventional method contains a lot of room for improving the measurement accuracy.

For example, in solution, agglutination of magnetic particles and unreacted sample (such as blood) may occur. Since the agglomeration cannot be eliminated by the rocking motion, there are cases where it cannot be said that the solution is sufficiently agitated.

In addition, the above-mentioned measurement of luminescence is performed on the reaction solution after removing the unreacted substances in which the antigen-antibody reaction did not occur. Therefore, a step of removing and separating unreacted substances, that is, a step of B/F separation (Bound/Free Separation) is required. The "reactant" referred to here is the complex, and the "unreacted substance" is, for example, an unreacted substance in the sample, a substance nonspecifically adsorbed to magnetic particles, etc., which did not participate in the formation of the complex. It is a labeling substance.

In the B/F separation step, magnetic particles are captured using a magnet, and the reaction liquid is discharged in this state. A wash solution is then dispensed into the chamber. At this time, even if the sample analysis device rocks the sample analysis substrate for cleaning, the unreacted sample remains captured between the aggregated magnetic particles attracted to the magnet. was there. Therefore, there were cases where it could not be said that the solution was sufficiently washed.

In one embodiment of the sample analysis device according to the present disclosure, the first magnet unit and the second magnet unit are arranged on the first surface side and the second surface side opposite to the first surface of the sample analysis substrate, respectively. there is The sample analyzer alternately moves the first magnet unit and the second magnet unit to a position where the magnetic particles in the chamber are attracted to the magnet unit, for example, when the liquid sample in the chamber is stirred in the B/F separation process. . When the first magnet unit moves closer to the sample analysis substrate, the magnetic particles are attracted to the first surface side, and when the second magnet unit moves closer to the sample analysis substrate, the magnetic particles are attracted to the second surface side. be done. As a result, the magnetic particles are agitated, so that the washing effect can be improved, and the measurement accuracy of the specific component in the sample can be improved. According to the present disclosure, there is provided a sample analyzer that can improve the measurement accuracy of a specific component in a sample. That is, the outline of the sample analyzer of the present disclosure is as follows.
[Item 1]
A sample analysis device for causing a binding reaction between an analyte in the liquid sample and a ligand immobilized on the surface of magnetic particles by rotating and stopping a sample analysis substrate holding a liquid sample, wherein
The sample analysis substrate can be loaded into and removed from the sample analysis device. and a chamber, which is the space in which the
a turntable supporting the loaded sample analysis substrate;
a motor for rotating the turntable;
a driving circuit for controlling rotation and stopping of the motor;
a first magnet unit arranged on the side of the first surface perpendicular to the rotation axis of the sample analysis substrate and generating an attractive force for attracting the magnetic particles;
a second magnet unit arranged on the second surface side opposite to the first surface perpendicular to the rotation axis of the sample analysis substrate and generating an attractive force for attracting the magnetic particles;
a first actuator that moves the first magnet unit to change the relative position between the first magnet unit and the sample analysis substrate;
a second actuator that moves the second magnet unit to change the relative position between the second magnet unit and the sample analysis substrate;
and a control circuit that controls operations of the motor, the drive circuit, the first actuator, and the second actuator, wherein the first actuator and the second actuator move the chamber during stirring of the liquid sample in the chamber. and moving the first magnet unit and the second magnet unit alternately to positions where the magnetic particles inside are attracted to the magnet unit.
[Item 2]
the first surface is a surface opposite to the turntable with respect to the sample analysis substrate;
the first magnet unit has a first shape that is part or all of a circle or a ring;
The sample analyzer according to item 1, wherein the second magnet unit has a second shape that is a partial circular shape or a partial or complete ring shape.
[Item 3]
the first magnet unit includes a single magnet having the first shape or a plurality of magnets arranged along the first shape;
The sample analyzer according to item 2, wherein the second magnet unit includes a single magnet having the second shape, or multiple magnets arranged along the second shape.
[Item 4]
When the sample analysis substrate rotates at a predetermined number of rotations, and when the magnetic particles are attracted at the number of rotations, it takes T seconds for the movement of the magnetic particles,
The first actuator causes the first magnet unit to approach and separate from the sample analysis substrate at a period of 2T seconds, and
4. The sample analyzer according to item 2 or 3, wherein the second actuator separates the second magnet unit from the sample analysis substrate and brings it closer to the sample analysis substrate at a period of 2T seconds.
[Item 5]
When the first shape and the second shape are part or all of a ring,
The first actuator and the second actuator cause the first magnet unit and the second magnet unit to approach the sample analysis substrate, respectively, and move the radial center position of the ring to the sample analysis substrate. 5. The sample analyzer according to any one of items 2 to 4, which is matched to a position in the chamber furthest from the center of rotation.
[Item 6]
6. Any one of items 1 to 5, wherein the first actuator and the second actuator respectively move the first magnet unit and the second magnet unit along a direction parallel to the axis of rotation of the sample analysis substrate. A sample analyzer as described.
[Item 7]
the second shape is the shape of a portion of the ring;
6. Any one of items 1 to 5, wherein the first actuator and the second actuator respectively move the first magnet unit and the second magnet unit along a direction perpendicular to the axis of rotation of the sample analysis substrate. A sample analyzer as described.
[Item 8]
the first actuator separates the first magnet unit to a position where the first magnet unit and the sample analysis substrate do not overlap when viewed in a direction parallel to the rotation axis of the sample analysis substrate;
Item 7, wherein the second actuator separates the second magnet unit to a position where the second magnet unit and the sample analysis substrate do not overlap when viewed in a direction parallel to the rotation axis of the sample analysis substrate. The sample analyzer according to .
[Item 9]
The first magnet unit and the second magnet unit face each other with the sample analysis substrate interposed therebetween,
The sample analyzer according to any one of items 1 to 8, wherein the polarities of the first magnet unit and the second magnet unit on the sample analysis substrate side are opposite to each other.
[Item 10]
Further comprising an optical sensor arranged on the second surface side,
After completion of the binding reaction, during a luminescence reaction performed by allowing a predetermined luminescent substrate to act on the bound complex of the analyte and the ligand,
the second actuator moves the second magnet unit to a position where the magnetic particles in the chamber are attracted to the magnet unit;
10. The sample analyzer according to any one of items 1 to 9, wherein the optical sensor detects light generated by the luminescent reaction.
[Item 11]
11. A sample analyzer according to item 10, wherein the optical sensor is a photomultiplier tube.
[Item 12]
12. The sample analyzer according to any one of items 1 to 11, wherein the first actuator and the second actuator are stepping motors or linear motors.

According to the exemplary aspect described above, the first magnet unit and the second magnet unit are respectively arranged on the first surface side and the second surface side opposite to the first surface of the substrate for sample analysis. The sample analyzer alternately moves the first magnet unit and the second magnet unit to positions where the magnetic particles in the chamber are attracted to the magnet unit when the liquid sample in the chamber of the sample analysis substrate is stirred. When the first magnet unit moves closer to the sample analysis substrate, the magnetic particles are attracted to the first surface side, and when the second magnet unit moves closer to the sample analysis substrate, the magnetic particles are attracted to the second surface side. be done. Since the liquid sample is agitated by the movement of the magnetic particles within the chamber, the antigen-antibody reaction can be caused while suppressing reaction unevenness. This makes it possible to improve the measurement accuracy of the specific component in the sample. For example, when an antigen-antibody reaction is to occur between a sample and a reagent, the reaction can be promoted by performing the above operation to stir the inside of the chamber. Also, by performing the above operation in the B/F separation step, for example, washing of the solution can be achieved.

A sample analyzer according to an exemplary embodiment of the present disclosure will now be described.

2A and 2B are perspective views showing an example of the appearance of the sample analyzer 1 according to the exemplary embodiment of the present disclosure. FIG. 3 is a block diagram showing a hardware configuration example of the sample analyzer 1. As shown in FIG.

The sample analysis device 1 rotates and stops the sample analysis substrate 100 holding the liquid sample to cause binding reactions between analytes in the liquid sample and ligands immobilized on the surfaces of the magnetic particles.

A sample analyzer 1 includes a housing 2 having a door 3 that can be opened and closed. The housing 2 has a storage chamber 2a for rotatably storing the substrate for sample analysis 100, and a motor 12 having a turntable 10 is arranged in the storage chamber 2a. With the door 3 open, the sample analysis substrate 100 can be attached to and detached from the turntable 10 in the storage chamber 2a. By closing the door 3, the door 3 blocks light from entering the storage room 2a from outside. The housing 2 is provided with a display device 5 for displaying analysis results.

First, the configuration of the sample analysis substrate 100 will be described below. In this embodiment, it is assumed that the object to be analyzed using the sample analysis substrate 100 is blood. The sample analysis substrate 100 also has chambers and reagents suitable for blood analysis. Note that the sample analysis substrate 100 in this embodiment does not have a magnet and a balancer. The magnet is provided on the sample analyzer 1 side.

4A and 4B are a plan view and an exploded perspective view of the sample analysis substrate 100. FIG. The sample analysis substrate 100 includes a light shielding cap 101 , a rotation axis 102 and a plate-shaped substrate 103 having a predetermined thickness in a direction parallel to the rotation axis 102 . In this embodiment, the substrate 103 of the sample analysis substrate 100 has a circular shape, but may have a polygonal shape, an elliptical shape, a sector shape, or the like. The substrate 103 has two principal surfaces 103c and 103d. In this embodiment, the main surface 103c and the main surface 103d are parallel to each other, and the thickness of the substrate 103 defined by the distance between the main surface 103c and the main surface 103d is the same at any position on the substrate 103. FIG. However, the main surfaces 103c, 103d do not have to be parallel. For example, the two major surfaces may be partially non-parallel, parallel, or entirely non-parallel. Moreover, at least one of the main surfaces 103c and 103d of the substrate 103 may have a structure having a concave portion or a convex portion.

The light-shielding cap 101 includes a pair of light-shielding portions 101a and connecting portions 101b, and is attached to the substrate 103 so that the light-shielding portions 101a partially cover the main surfaces 103c and 103d of the substrate 103. As shown in FIG. In this embodiment, the light shielding portion 101a has a substantially sector shape. The light shielding portion 101a is made of a material that does not transmit light emitted from the composite 310 . The light shielding portion 101a is preferably provided at a position facing the light receiving surface 30a of the photodetector 30 on the main surfaces 103c and 103d of the substrate 103. As shown in FIG. The photodetector 30 is used to detect the luminescence of the sample in the measurement chamber 116, and the light receiving surface 30a is the area that receives the light. In addition, it is preferable that the central angle α of the area where the light shielding portion 101a is located on the main surface 103c or the main surface 103d be larger than the central angle β of the area where the measurement chamber 116 is located.

The substrate 103 of the sample analysis substrate 100 is composed of a base substrate 103a and a cover substrate 103b.

The substrate for sample analysis 100 has a plurality of chambers located within the substrate 100 and channels connecting the chambers. The multiple chambers are, for example, reaction chambers, measurement chambers, substrate holding chambers, and collection chambers.

Each space of the plurality of chambers is formed within the base substrate 103a, and the top and bottom of each space are formed by covering the base substrate 103a with the cover substrate 103b. That is, each space of the plurality of chambers is defined by at least one inner surface of the sample analysis substrate 100 . The channel is also formed in the base substrate 103a, and the upper and lower spaces of the channel are formed by covering the base substrate 103a with the cover substrate 103b. Thus, each chamber and channel is confined to substrate 103 .

FIG. 5 is a top view showing positions of a plurality of chambers provided on the sample analysis substrate 100. FIG. The sample analysis substrate 100 has, for example, a spotting chamber 110, a plasma quantification chamber 112, a reaction chamber 114, a measurement chamber 116, a substrate holding chamber 118, and a collection chamber 120. FIG. 5 also shows the position of the light receiving surface 30a of the photodetector 30. As shown in FIG.

FIG. 6 is a top view showing the positions of the washing liquid 130, the substrate liquid 132, the primary antibody 134 and the secondary antibody 136 held in advance on the sample analysis substrate 100. FIG. Primary antibody 134 is magnetic particle-immobilized antibody 305 . Secondary antibody 136 is labeled antibody 308 . Magnetic particle-immobilized antibody 305 and labeled antibody 308 are carried in reaction chamber 114 in a dried state. These may also be referred to as "dried reagents".

FIG. 7 shows a spotting chamber 110 spotted with blood 190, which is a specimen. When spotting, the user rotates the light shielding cap 101 clockwise around the fulcrum 103 to expose the spotting portion 192 . The user uses the syringe 194, for example, to apply blood from the application portion.

Blood 190 is centrifuged by high-speed rotation of sample analysis substrate 100 by sample analyzer 1 . The centrifuged plasma is transferred from plasma quantification chamber 112 shown in FIG. do. Plasma is a sample solution containing antigens 306 . In the reaction chamber 114, the sample solution dissolves the dried reagent, causing an antigen-antibody reaction (immune reaction). A composite 310 is thereby formed.

As explained in the background art section, when an antigen-antibody reaction occurs, a B/F separation step is required to separate reactants and unreacted substances. The “reactant” referred to here is the complex, and the “unreacted substance” is, for example, an unreacted substance in the sample, a labeling substance that did not participate in the formation of the complex.

In one embodiment according to the present disclosure, the magnet is provided in the sample analysis device 1 and the sample analysis substrate 100 does not require a magnet and a balancer. The sample analyzer 1 controls the magnet to approach the sample analysis substrate 100 to trap magnetic particles and remove unreacted substances.

The hardware configuration of the sample analyzer 1 will be described with reference to FIG. 3 again.

The sample analyzer 1 includes an open/close detection switch 4, a display device 5, a motor 12, drive circuits 14, 20 and 60, a first magnet unit 16, a first actuator 18, a control circuit 22, and a photodetector. It has an instrument 30 , an encoder 34 , a communication circuit 36 , a second magnet unit 56 and a second actuator 58 .

The open/close detection switch 4 is, for example, a momentary switch that detects opening/closing of the door 3, but any other switch may be employed.

The motor 12 has a turntable 10 that supports the loaded sample analysis substrate 100 and rotates the sample analysis substrate 100 around a rotation axis 102 . The rotating shaft 102 may be inclined with respect to the direction of gravity at an angle of 0° or more and 90° or less. The motor 12 can, for example, rotate the sample analysis substrate 100 in the range of 100 rpm to 8000 rpm. The rotation speed is determined according to the shape of each chamber and channel, the physical properties of the liquid, the timing of transfer and treatment of the liquid, and the like. Motor 12 may be, for example, a DC motor, a brushless motor, an ultrasonic motor, or the like.

A drive circuit 14 controls rotation and stopping of the motor 12 . Specifically, the drive circuit 14 rotates the substrate for sample analysis 100 clockwise or counterclockwise based on a command from the control circuit 22, rocks it, and controls the stop of rotation and rocking.

The first magnet unit 16 has one or more magnets, and the one or more magnets generate a force (magnetic force) that attracts magnetic particles. The first magnet unit 16 has a “partial or whole” shape of a “circle or ring”. A "partial or full" shape of a "circle or ring" can be realized by the shape of one magnet or by an arrangement of multiple magnets. A specific configuration of the first magnet unit 16 will be described later. A first rack 44 provided with teeth is attached to the first magnet unit 16 .

The first actuator 18 moves the first magnet unit 16 by moving the first rack 44 in the longitudinal direction, thereby changing the relative position between the first magnet unit 16 and the sample analysis substrate 100 . The operation of first actuator 18 is controlled by drive circuit 20 . An example of the first actuator 18 is an electric motor that performs rotary motion. The first actuator 18 is, for example, a stepping motor or a linear motor. Details of the configuration and operation of the first actuator 18 will be described later with reference to FIGS. 11 and 12 and the like.

Control circuit 22 controls the operation of motor 12 , first actuator 18 , and drive circuits 14 and 20 .

The photodetector 30 detects luminescence generated from the labeled substance 307 of the labeled antibody 308 bound to the complex 310 (FIG. 1) held in the measurement chamber 116 (FIG. 5) of the sample analysis substrate 100 . Here, luminescence means emission of photons regardless of the principle of luminescence such as fluorescence or phosphorescence. That is, the photodetector 30 measures the number of luminescence photons generated from the labeling substance 307 and incident on the light receiving surface 30a.

With the sample analysis substrate 100 attached to the turntable 10, the light receiving surface 30a of the photodetector 30 is located below the concentric circle where the measurement chamber 116 is positioned, that is, on the same side as the turntable 10 with respect to the sample analysis substrate 100. placed.

Photodetector 30 is, for example, a photomultiplier tube with a lens shutter and a photon counter (both not shown). The lens shutter is provided between the light receiving surface 30a of the photodetector 30 and the sample analysis substrate 100, and controls opening and closing of the light receiving surface 30a. When the shutter is open, light emitted from the composite 310 held in the measurement chamber 116 of the rotating substrate for sample analysis 100 is incident on the light receiving surface 30a. Also, when the shutter is closed, light emission is cut off. The shutter may have a mechanical structure, or may be a liquid crystal shutter or the like. The photomultiplier tube receives photons emitted from the labeling substance 307 on the light receiving surface 30a, counts the number of pulses corresponding to the number of photons, and outputs the count number.

The control circuit 22 associates the photon count number with the rotation angle of the sample analysis substrate 100 to generate a photon count distribution signal.

The encoder 34 is a so-called rotary encoder that is attached to the rotating shaft of the motor 12 and detects the rotation angle of the motor 12 . When the sample analysis substrate 100 is attached to the turntable 10, the sample analysis substrate 100 rotates around the rotation shaft 102. Therefore, the output of the encoder 34 detects the rotation angle of the sample analysis substrate 100, and the rotation angle signal is Available. The rotation angle signal is, for example, a pulse signal including pulses output at predetermined angles. When the motor 12 is a brushless motor, instead of the encoder 34, a Hall element provided in the brushless motor and a detection circuit that receives an output signal from the Hall element and outputs a rotation angle signal indicating the angle of the rotation shaft 201a. can be adopted. The control circuit 22 can utilize the rotation angle signal to generate a photon count distribution signal and utilize the photon count distribution signal to measure the number of photons from the measurement chamber 116 .

The display device 5 displays the photon measurements. The display device 5 is a display panel such as a liquid crystal display panel or an organic EL panel, and displays measured values of photons output from the control circuit 22 and/or information based on the measured values and past measured values. Note that the display device 5 displays other information such as an operation method of the sample analyzer 1, information prompting an input for operation, and the like.

The photon measurement value may be transmitted to the outside of the sample analyzer 1 via the communication circuit 36 . The communication circuit 36 may be, for example, a circuit that performs wired communication according to the Ethernet (registered trademark) standard, or a circuit that performs wireless communication according to, for example, the Wi-Fi (registered trademark) standard.

The second magnet unit 56 has one or more magnets, and the one or more magnets generate a force (magnetic force) that attracts magnetic particles. The second magnet unit 56 has a “partial or whole” shape of a “circle or ring”. A "partial or full" shape of a "circle or ring" can be realized by the shape of one magnet or by an arrangement of multiple magnets. A specific configuration of the second magnet unit 56 will be described later. A toothed first rack 44 is attached to the second magnet unit 56 .

The second actuator 58 moves the second magnet unit 56 by moving the second rack 84 in the longitudinal direction, thereby changing the relative position between the second magnet unit 56 and the sample analysis substrate 100 . Operation of the second actuator 58 is controlled by a drive circuit 60 . An example of the second actuator 58 is an electric motor that performs rotary motion. The second actuator 58 is, for example, a stepping motor or linear motor. Details of the configuration and operation of the second actuator 58 will also be described later with reference to FIGS. 11 and 12 and the like.

The control circuit 22 implements the operation of the sample analyzer 1 described above by executing a computer program stored in an internal memory 22a, and controls the drive circuit 20 to operate the first magnet unit 16 and the magnet unit 16, which will be described later. The relative position with respect to the sample analysis substrate 100 and the relative position between the second magnet unit 56 and the sample analysis substrate 100 are changed.

The memory 22a loaded with the computer program, eg, the RAM storing the computer program, may be volatile or non-volatile. Volatile RAM is RAM that cannot retain stored information without power. For example, dynamic random access memory (DRAM) is a typical volatile RAM. Non-volatile RAM is RAM that can retain information without being powered. For example, magnetoresistive RAM (MRAM), resistance change memory (ReRAM), and ferroelectric memory (FeRAM) are examples of non-volatile RAM. Both volatile RAM and non-volatile RAM are examples of non-transitory, computer-readable storage media. Magnetic recording media such as hard disks and optical recording media such as optical discs are also examples of non-transitory computer-readable recording media. That is, the computer program according to the present disclosure can be recorded on various non-transitory computer-readable media other than media such as the atmosphere (transitory media) that propagate the computer program as radio signals.

Next, the configuration of the magnet unit 16 and the second magnet unit 56 and the operation of the sample analyzer 1 for changing the relative position between each magnet unit and the sample analysis substrate 100 will be described.

To simplify the explanation, the first magnet unit 16 will be described as an example, but the second magnet unit 56 is the same. In the following description, "first magnet unit 16" should be replaced with "second magnet unit 56", "magnet 40" should be replaced with "magnet 80", and "case 42" should be replaced with "case 82". Similarly, the "first actuator 18" is replaced with the "second actuator 58", the "drive circuit 20" is replaced with the "drive circuit 60", the "first rack 44" is replaced with the "second rack 84", and the "pinion gear 18a" is replaced. ' is replaced with 'pinion gear 58a', and 'guide 50' is replaced with 'guide 90'. The configuration and operation of the second magnet unit 56 will be described as necessary.

Note that the first magnet unit 16 and the second magnet unit 56 are independent of each other and do not need to have the same configuration. For example, the shape of the magnet 80 of the second magnet unit 56 may be different from the shape of the magnet 40 of the first magnet unit 16 described below. The shape of the case 82 that accommodates the magnet 80 is the same.

FIG. 8 is an exploded perspective view of the first magnet unit 16. FIG. 9 is a plan view of the first magnet unit 16. FIG. As shown in FIGS. 8 and 9, the first magnet unit 16 has magnets 40 and a case 42 . The case 42 accommodates the magnet 40 and fixes it within the case 42 .

The magnet 40 is, for example, a magnet commonly used in competitive immunoassays using magnetic particles. Specifically, a ferrite magnet, a neodymium magnet, or the like can be used as the magnet 40 . In particular, a neodymium magnet is suitable for the magnet 40 because of its strong magnetic force.

8 and 9, the magnet 40 has a semicircular ring shape, but this is an example. Other shapes may be used. 10A-10D show examples of shapes of magnets 40 that can be employed in this embodiment. FIG. 10A shows the semicircular ring-shaped magnet 40a previously described. FIG. 10B shows a ring shaped magnet 40b with an opening in the circular central portion. FIG. 10C shows a fan-shaped magnet 40c. FIG. 10D shows a circular magnet 40d. The shape of the case 42 may be adapted to the shape of any one of the magnets 40a to 40d to be employed.

Although FIGS. 10A-10D were examples of shapes for one magnet, multiple magnets may be utilized. FIGS. 10E-10H show examples of using multiple magnets to achieve shapes equivalent to the magnets 40a-40d shown in FIGS. 10A-10D. FIG. 10E shows a plurality of magnet groups 40e arranged in a semicircular ring shape. FIG. 10F shows a magnet group 40f arranged in a ring shape with an opening in the central part of the circle. FIG. 10G shows a magnet group 40g arranged in a fan shape. FIG. 10H shows a magnet group 40h arranged in a circle. The shape of the case 42 may be adapted to the shape of any one of the magnet groups 40e to 40h to be employed.

Although FIGS. 10A-10H show a single magnet or group of magnets grouped together, the magnets may be separated from each other. In that case, for example, a semicircular ring shape and a fan shape can be combined. In the examples of FIGS. 10A-10H, none of the ring shape (semicircle or circle), sector shape, and circular shape need to be based on a perfect circle, and may be based on an ellipse. In this embodiment, the magnet or magnet group may have a shape of a part or the whole of a circle or a ring in which the sum of central angles of circles or ellipses is 90 degrees or more and 360 degrees or less.

Next, the details of the mechanism and operation for driving each magnet unit will be described. The mechanism is provided inside the housing 2 of the sample analyzer 1 . In the following, only necessary constituent elements are shown and explained, and illustration and explanation of unnecessary constituent elements such as the housing 2 and the door 3 are omitted.

11 and 12 show examples of the positional relationship between the first magnet unit 16, the second magnet unit 56, and the sample analysis substrate 100. FIG. In this embodiment, the first magnet unit 16 is located on the opposite side of the sample analysis substrate 100 from the turntable 10 , and the second magnet unit 56 is located on the same side of the sample analysis substrate 100 as the turntable 10 . Further, in this embodiment, during B/F separation and/or during luminescence measurement, the first magnet unit 16 and the second magnet unit 56 are At the same time, it is driven so as not to overlap the sample analysis substrate 100 . Therefore, only the first magnet unit 16 overlaps the sample analysis substrate 100, only the second magnet unit 56 overlaps the sample analysis substrate 100, or both the first magnet unit 16 and the second magnet unit 56 overlap the sample analysis substrate 100. The control circuit 22 controls the operation of the first magnet unit 16 and the second magnet unit 56 so that the first magnet unit 16 and the second magnet unit 56 do not overlap with the substrate 100 for the magnetic tape. 11 and 12, only the first magnet unit 16 overlaps the sample analysis substrate 100, and the second magnet unit 56 is retracted to a position where it does not overlap the sample analysis substrate 100. FIG.

As described above, the number and shape of magnets used in the first magnet unit 16 and the second magnet unit 56 are arbitrary and can be determined independently.

The details of the method for driving the first magnet unit 16 will be described below.

The first magnet unit 16 is driven by a first actuator 18 . Assume that the first actuator 18 is an electric motor that performs rotary motion. A pinion gear 18 a is attached to the rotating shaft of the electric motor and meshes with the first rack 44 . The drive circuit 20 rotates the first actuator 18 clockwise or counterclockwise or stops the rotation based on the command from the control circuit 22 . By rotating the first actuator 18 clockwise or counterclockwise, the pinion gear 18a feeds the first rack 44 downward or upward in the drawing. Then, the first magnet unit 16 attached to the first rack 44 approaches the sample analysis substrate 100 or moves away from the sample analysis substrate 100 .

The first actuator 18 moves the first magnet unit 16 along a direction perpendicular to the rotation axis 102 of the sample analysis substrate 100 , in other words, along a direction parallel to the circular surface of the sample analysis substrate 100 . To achieve movement of the first magnet unit 16, a pair of guides 50 are provided in FIG. For example, the guide 50 has a substantially U-shaped cross section, and the groove portion sandwiches the upper and lower surfaces of the first magnet unit 16 . Thereby, the movement of the substrate for sample analysis 100 is restricted only in the longitudinal direction of the guide 50 .

During B/F separation for separating reactants and unreacted substances in the chamber, the first actuator 18 moves the magnet unit to a position where the magnetic particles in the measurement chamber 116 are attracted to the first magnet unit 16 . Specifically, the first actuator 18 moves the first magnet unit 16 to the position shown in FIGS. 11 and 12 and fixes it at that position.

Unreacted substances that did not participate in the antigen-antibody reaction in the reaction chamber 114 are then transferred to the measurement chamber 116 together with the reactants. Since the B/F separation is performed to remove unreacted substances (non-magnetic components) present in the measurement chamber 116 , the magnetic force of the magnets of the first magnet unit 16 effectively removes the magnetic particles present in the measurement chamber 116 . must be aspirated to Therefore, the size of the radius of the ring of the first magnet unit 16 is determined according to the position of the measurement chamber 116 of the substrate for sample analysis 100 when fixed at that position. That is, the radius of the ring of the first magnet unit 16 is determined according to the distance from the rotation axis 102 (rotation center) of the sample analysis substrate 100 to the measurement chamber 116 .

More specifically, the center position of the ring of the first magnet unit 16 in the radial direction is aligned with the position in the measurement chamber 116 that is farthest from the center of rotation of the sample analysis substrate 100 . FIG. 11 includes two circles indicated by dashed lines. The inner circle follows the innermost circumference of the first magnet unit 16 and passes through the approximate center position of the measurement chamber 116 in the radial direction. On the other hand, the outer circle is along the radially central position of the ring of the first magnet units 16 and passes through the radially outermost position of the measurement chamber 116 .

FIG. 13 shows the relationship between the position of the first magnet unit 16 and the position of the measurement chamber 116 after the sample analysis substrate 100 has been rotated about 180 degrees from the state shown in FIG. FIG. 13 shows only the outer circle (dashed line) in FIG. 14 is a sectional view taken along the line AA in FIG. 13. FIG. For convenience of explanation, FIG. 14 shows an enlarged cross section around the measurement chamber 116 .

As is particularly clear from FIG. 14, it is understood that the center position L in the radial direction of the ring of the first magnet unit 16 coincides with the position 116a in the measurement chamber 116, which is the farthest from the center of rotation. With respect to the radial direction of the sample analysis substrate 100, the magnetic particles 142 are gathered at the position 116a in the measurement chamber 116 farthest from the center of rotation due to centrifugal force while the sample analysis substrate 100 is rotating. The magnetic particles 142 are magnetic particles 302 to which the magnetic particles 302 contained in the complex 310 and the primary antibody 304 are immobilized on the surface. The latter includes magnetic particles in which an antigen-antibody reaction has occurred between the primary antibody 304 and the antigen 306 and magnetic particles in which an antigen-antibody reaction has not occurred.

On the other hand, with respect to the rotation axis direction of the sample analysis substrate 100 , the magnetic particles 142 stick to the position 116 b side in the measurement chamber 116 due to the attractive force of the magnets 40 of the first magnet unit 16 . That is, the magnetic particles 142 can be effectively attracted. By appropriately rotating the sample analysis substrate 100 in this state, it becomes possible to transfer the reaction liquid from the measurement chamber 116 to another chamber while leaving the magnetic particles 142 in the measurement chamber 116 . After this, the washing liquid/substrate liquid, for example, may be transferred to the measurement chamber 116 and discharged while the magnetic particles 142 are magnetically attracted.

Also, as shown in FIG. 13 , the circumferential length of the first magnet unit 16 is longer than the circumferential length of the measurement chamber 116 . Thereby, an attractive force can be applied to all the magnetic particles within the measurement chamber 116 .

15 and 16 are a plan view and a side view showing the configuration of the first magnet unit 16 moved to the retracted position from above the sample analysis substrate 100 and the movement mechanism of the first magnet unit 16. FIG. The position of the second magnet unit 56 remains the same.

The first actuator 18 moves the first magnet unit 16 to a position where the first magnet unit 16 and the sample analysis substrate 100 do not overlap when viewed from the direction parallel to the rotation axis of the sample analysis substrate 100 .

Specifically, in the state shown in FIG. 13 , the drive circuit 20 rotates the first actuator 18 counterclockwise based on a command from the control circuit 22 . By rotating the first actuator 18 counterclockwise, the pinion gear 18a feeds the first rack 44 upward in the drawing. Then, the first magnet unit 16 attached to the first rack 44 moves along the direction parallel to the circular surface of the sample analysis substrate 100 and moves away from the sample analysis substrate 100 .

16 is a cross-sectional view taken along the line BB in FIG. 15. FIG. For convenience of explanation, FIG. 16 shows an enlarged cross section around the measurement chamber 116 .

As is clear from FIG. 16, the magnetic force of the magnet 40 of the first magnet unit 16 is weakened when the first magnet unit 16 is separated from the sample analysis substrate 100 . As a result, the magnetic particles 142 are released from the attractive force of the magnet 40, and the magnetic particles 142 spread toward the position 116a in the measurement chamber 116, which is the farthest from the center of rotation. The B/F separation removes non-magnetic components including uncaptured impurities, enhances the effect of washing reaction products, and provides more accurate analytical results.

17 and 18 are a plan view and a side view showing the configuration of the second magnet unit 56 moved to a position overlapping the sample analysis substrate 100 and the movement mechanism of the second magnet unit 56. FIG. The first magnet unit 16 still remains in the position shown in FIG.

The second actuator 58 moves the second magnet unit 56 to a position where the second magnet unit 56 and the sample analysis substrate 100 overlap when viewed in a direction parallel to the rotation axis 102 of the sample analysis substrate 100 .

Specifically, in the state shown in FIG. 15 , the drive circuit 60 rotates the second actuator 58 clockwise based on a command from the control circuit 22 . As the first actuator 18 rotates clockwise, the pinion gear 58a feeds the second rack 84 upward in the drawing. Then, the second magnet unit 56 attached to the second rack 84 moves along the direction parallel to the circular surface of the sample analysis substrate 100 and approaches the sample analysis substrate 100 . When the second magnet unit 56 reaches the position shown in FIG. 18, the second actuator 58 stops rotating. As a result, the second magnet unit 56 stops at the position shown in FIG. 18 and is fixed at that position.

19 is a cross-sectional view taken along line CC in FIG. 17. FIG. For convenience of explanation, FIG. 19 shows an enlarged cross section around the measurement chamber 116 .

The center position M in the radial direction of the ring of the second magnet unit 56 coincides with the position 116a in the measurement chamber 116 farthest from the center of rotation described above. With respect to the radial direction of the sample analysis substrate 100, the magnetic particles 142 are gathered at the position 116a in the measurement chamber 116 farthest from the center of rotation due to centrifugal force while the sample analysis substrate 100 is rotating.

The radial center position L ( FIG. 14 ) of the ring of the first magnet unit 16 and the radial center position M of the ring of the second magnet unit 56 both coincide with the position 116 a in the measurement chamber 116 . Therefore, the distance from the rotation axis 102 to the center position L and the distance to the center position M are equal.

Thereafter, if necessary, the second magnet unit 56 is retracted, the first magnet unit 16 is moved upward from the sample analysis substrate 100, the first magnet unit 16 is retracted, and the sample analysis substrate 100 is moved downward. The 2-magnet unit 56 is moved. The first actuator 18 and the second actuator 58 alternately move the first magnet unit 16 and the second magnet unit 56 such that the magnetic particles 142 in the measurement chamber 116 are positioned to be attracted to the first magnet unit 16 or the second magnet unit 56 . Move the magnet unit 56 . Magnetic particles 142 transition between the attracted state shown in FIG. 14 and the released state shown in FIG. 16, and between the released state shown in FIG. 16 and the attracted state shown in FIG. Repeated attraction and release of magnetic particles 142 agitates the solution in measurement chamber 116 . Even if an unreacted sample is captured between the magnetic particles 142 in the aggregated state, the stirring makes it easier to release the unreacted sample from the aggregation of the magnetic particles 142 . As a result, promotion of further antigen-antibody reaction and/or washing of the solution can be achieved.

Regarding the first magnet unit 16 and the second magnet unit 56 described above, the period when the approach to the sample analysis substrate 100 and the withdrawal from the sample analysis substrate 100 are alternately performed is, for example, the magnetic particles 142 can be determined in consideration of the movement speed of Assume that it takes about 5 seconds to move the sample analysis substrate 100 from the position 116b to the position 116c of the measurement chamber 116 depending on the components of the solution, the viscosity, the rotation speed of the sample analysis substrate 100, and the like. Magnetic particles 142 of measurement chamber 116 then move from position 116b shown in FIG. 14 through the open state (FIG. 16) to position 116c shown in FIG. 19 and vice versa. It takes about 10 seconds at the fastest to return to . Therefore, one cycle from the start of approach to the substrate for sample analysis 100 to the retreat and return to the same position may be set to 10 seconds. A person skilled in the art can appropriately determine the movement speed/acceleration from start to stop of movement. For example, acceleration may be maximized immediately after the start of retraction in order for one magnet unit to quickly release the magnetic particles 142 . Also, in order for the other magnet unit to quickly attract the magnetic particles 142, the acceleration just before stopping when the substrate for sample analysis 100 approaches may be minimized.

In this way, the first magnet unit 16 and the second magnet unit 56 are respectively moved to change the relative position between the first magnet unit 16 and the sample analysis substrate 100, and the second magnet unit 56 and the sample analysis substrate 100 are moved. By changing the relative position with the substrate 100, the magnetic particles are effectively attracted and released.

The process described above can be performed in any situation where magnetic particles are present in the chamber. For example, the above-described treatment may be performed in a step of causing an antigen-antibody reaction using a sample and a dried reagent, or in a B/F separation step after causing an antigen-antibody reaction. . The measurement accuracy of the specific component in the sample can be maximized when the above-described processing is performed in all the steps exemplified. However, even if at least one of the above-described processes is performed, it is possible to improve the measurement accuracy as compared with the case where the solution is agitated only by shaking the sample analysis substrate 100 .

FIG. 20 is a flow chart showing a procedure of processing of the control circuit 22 that executes a stirring process using magnetic particles. The control circuit 22 executes a computer program including instructions for executing the processes described in the flowchart. It is assumed that the first magnet unit 16 and the second magnet unit 56 have retreated to the positions shown in FIG. 15 when the process shown in FIG. 20 is executed. For example, the time immediately after the sample analysis substrate 100 is loaded into the sample analysis apparatus 1 and the sample is spotted may be assumed.

In step S<b>10 , the control circuit 22 rotates/swings/stops the substrate for sample analysis 100 .

In step S<b>12 , the control circuit 22 moves the first magnet unit 16 to bring the first magnet unit 16 closer to the sample analysis substrate 100 .

In step S<b>14 , the control circuit 22 stops the movement of the first magnet unit 16 at the first predetermined position, and rotates/swings/stops the substrate for sample analysis 100 . The "first predetermined position" is the position of the first magnet unit 16 when the center position L of the ring of the first magnet unit 16 in the radial direction reaches the position 116a in the measurement chamber 116 farthest from the center of rotation. is. At this time, the control circuit 22 may swing the sample analysis substrate 100 .

Then, in step S16, the control circuit 22 causes the first magnet unit 16 to retreat.

In step S<b>18 , the control circuit 22 next moves the second magnet unit 56 to bring the second magnet unit 56 closer to the sample analysis substrate 100 .

In step S<b>20 , the control circuit 22 stops the movement of the second magnet unit 56 at the second predetermined position, and rotates/swings/stops the substrate for sample analysis 100 . "Second predetermined position" is the position of the second magnet unit 56 shown in FIG. That is, the center position M in the radial direction of the ring of the second magnet unit 56 is the position of the second magnet unit 56 when it reaches the position 116a in the measurement chamber 116 farthest from the center of rotation. At this time, the control circuit 22 may swing the sample analysis substrate 100 .

In step S22, the control circuit 22 determines whether or not the termination condition is satisfied. "Termination condition" means that the operation of alternately moving the first magnet unit 16 and the second magnet unit 56 has been completed a predetermined number of times, for example, in order to mix the sample and the dried reagent to cause an antigen-antibody reaction. (a predetermined number of times of agitation has been completed), a predetermined period of time has elapsed, and a predetermined number of operations of transferring the washing liquid/substrate liquid to the measurement chamber 116 and discharging it have been completed (the B/F separation process has been completed). or that the open/close detection switch 4 detects that the door 3 is open during analysis of the sample. If the condition is satisfied, the process ends, and if the condition is not satisfied, the process proceeds to step S24.

At step S24, the control circuit 22 causes the first magnet unit 16 to retreat. After that, the process returns to step S12, and the processes after step S12 are repeated.

Thus, the stirring using movement of the magnetic particles is completed.

FIG. 21 is a flow chart showing the processing procedure of the control circuit 22 for executing the luminescence measurement processing. As in the previous example of FIG. 21, the control circuit 22 executes a computer program containing instructions for executing the processing described in the flowchart. It is assumed that cleaning of the measurement chamber 116 is completed and the first magnet unit 16 and the second magnet unit 56 have retreated to the positions shown in FIG. 15 again when the process shown in FIG. 20 is executed.

In step S<b>30 , the control circuit 22 rotates/rocks/stops the substrate for sample analysis 100 .

In step S<b>32 , the control circuit 22 moves the second magnet unit 56 to bring the second magnet unit 56 closer to the sample analysis substrate 100 .

In step S<b>34 , the control circuit 22 stops the movement of the second magnet unit 56 at the second predetermined position, and rotates/swings/stops the substrate for sample analysis 100 . The second predetermined position is as described with regard to step S20 in FIG.

In step S36, the control circuit 22 measures the number of photons associated with the luminescence reaction.

In step S38, the control circuit 22 outputs (displays) information on the measured number of photons to the display device 5, for example.

Steps S34 and S36 will be described in more detail. As shown in FIG. 18, the second magnet unit 56 is positioned on the same side of the sample analysis substrate 100 as the photodetector 30 . When the sample analysis substrate 100 rotates while the magnetic particles 142 are attracted by the second magnet unit 56 , the magnetic particles 142 pass the position closest to the photodetector 30 . Since the luminescence center when the luminescence reaction occurs is in the vicinity of the magnetic particles 142, the amount of light received by the photodetector 30 can be increased by moving the luminescence center toward the photodetector 30 side. That is, it is possible to improve the measurement accuracy of the number of photons associated with the luminescence reaction. This makes it possible to improve the measurement accuracy of the specific component in the sample.

Next, a modified example of the sample analyzer 1 will be described.

The first magnet unit 16 in the conventional sample analyzer 1 has a semicircular shape. The first magnet unit 16 of the sample analyzer 1 according to the modification has a perfect ring shape (hereinafter simply referred to as "ring shape").

FIG. 22 shows an example of the positional relationship between the ring-shaped first magnet unit 16 , the semicircular second magnet unit 56 , and the sample analysis substrate 100 . The ring of the first magnet unit 16 differs from the semicircular first magnet unit 16 (FIG. 11) only in that it is circular. Others are the same as the example of FIG. Therefore, also in the modified example, the innermost circumference of the first magnet unit 16 passes through the approximate center position of the measurement chamber 116 in the radial direction. Also, the radial center position of the ring of the first magnet unit 16 coincides with the radially outermost position of the measurement chamber 116 . As a result, while the sample analysis substrate 100 is rotating, the magnetic force (attractive force) of the first magnet unit 16 is always applied to the position in the measurement chamber 116 where the magnetic particles are most concentrated. It is understood that the magnitude of the suction force per rotation of the substrate for sample analysis 100 is doubled compared to the example of FIG. This allows more magnetic particles to be adsorbed more quickly.

When the second magnet unit 56 moves under the sample analysis substrate 100 for stirring, the first magnet unit 16 moves parallel to the axis of rotation of the sample analysis substrate 100 and moves from the sample analysis substrate 100. Leave.

FIG. 23A is a side view of the sample analyzer 1 according to the modification. Compared to the example of FIG. 12, the positions of the first actuator 18 and the first rack 44 have been changed to achieve movement of the first magnet unit 16 in a direction parallel to the axis of rotation 102 . Since the principle of moving the first magnet unit 16 is the same as in the example of FIG. 12, the description is omitted.

By adopting the ring-shaped first magnet unit 16, a portion of the first magnet unit 16 (a semicircular portion on the lower side of FIG. 22) and the second magnet unit 56 sandwich the substrate 100 for sample analysis. opposite. The magnetic particles 142 are attracted to both the first magnet unit 16 and the second magnet unit 56 regardless of the polarity of the magnets 40 of the first magnet unit 16 and the polarity of the magnets 80 of the second magnet unit 56 . Therefore, the polarity of the magnet 40 of the first magnet unit 16 and the polarity of the magnet 80 of the second magnet unit 56 can be arbitrarily selected. However, the inventors have found that it is more preferable for the magnets 40 and 80 to have the same polarity on the sides facing each other. This will be explained below.

FIG. 23B is a schematic diagram for explaining the polar relationship between magnet 40 and magnet 80 in FIG. 23A. For reference, the position of the sample analysis substrate 100 is shown.

In this embodiment, as an example, the S pole 40 a of the magnet 40 is arranged facing the sample analysis substrate 100 . The north pole 40b of the magnet 40 is located opposite the south pole 40a. On the other hand, the south pole 80 a of the magnet 80 is arranged facing the sample analysis substrate 100 . The north pole 80b of magnet 80 is located opposite the south pole 80a. That is, the inventor arranged the S pole 40a of the magnet 40 and the S pole 80a of the magnet 80 so as to face each other. The reason is that it is possible to make the density of the lines of magnetic force, that is, the magnitude of the magnetic field, substantially zero.

More details are provided below. The lines of magnetic force of the magnet 40 and the lines of magnetic force of the magnet 80 are not connected. Therefore, when the S pole 40a of the magnet 40 and the S pole 80a of the magnet 80 face each other, even if the distance between the two is not sufficiently far, that is, even if the distance between the two is relatively close, the line of magnetic force will be at the midpoint between the two magnets. The density becomes 0 and the strength of the magnetic field can be 0. It may be required that no magnetic field be applied to a particular or any chamber. Such a requirement can be met by allowing the magnetic field strength to be zero at the midpoint between the two magnets 40 and 80 . Furthermore, since the distance between the two magnets 40 and the magnet 80 can be made relatively short, the size of the sample analyzer 1 can be kept compact. From the viewpoint of making the strength of the magnetic field between the two magnets 40 and 80 substantially zero, the north pole 40b of the magnet 40 and the north pole 80b of the magnet 80 may be arranged to face each other.

When the S pole of the magnet 40 and the N pole of the magnet 80 face each other, or when the N pole of the magnet 40 and the S pole of the magnet 80 face each other, the lines of magnetic force pass through the midpoint between the two magnets. pass. If the distance between the two magnets is sufficiently long, the strength of the magnetic field can be made substantially zero. Therefore, as described above, it is preferable to arrange the magnets 40 and 80 such that the S poles or the N poles of the magnets 40 and 80 face each other with the sample analysis substrate 100 interposed therebetween.

The second magnet unit 56 may also be moved in a direction parallel to the rotation axis 102 .

FIG. 24 is a side view of the sample analyzer 1 according to a further modified example. Compared to the example of FIG. 23A, the positions of the second actuator 58 and the second rack 84 are changed to achieve movement of the second magnet unit 56 in a direction parallel to the axis of rotation 102 . The principle of moving the second magnet unit 56 is the same as in the examples of FIGS. 12 and 23, so the explanation is omitted.

In the description of the above-mentioned embodiment and its modification example, a mode using a pinion gear and a rack for driving each magnet unit was given. However, this aspect is only an example, and other mechanisms can be used. For example, the magnet unit and the motor are mechanically connected, and the position of the magnet unit is changed according to the rotational position of the motor to achieve withdrawal from the sample analysis substrate 100 and approach to the sample analysis substrate 100. may As another example, the first magnet unit 16 and the second magnet unit 56 may be mechanically coupled so that they alternately retreat from the sample analysis substrate 100 and approach each other. A single actuator is provided instead of the first actuator 18 and the second actuator 58, and the actuator is used to cause one magnet unit to retreat from the sample analysis substrate 100 and the other magnet unit to approach the sample analysis substrate 100. may be configured to allow A structure for moving one or more magnet units may be generically read as a "magnet moving mechanism".

The sample analysis device according to the present disclosure can be suitably used for stirring the magnetic particles and the sample in the sample analysis substrate 100 . Alternatively, the sample analyzer according to the present disclosure can be suitably used for luminescence measurement.

1: sample analyzer, 2: housing, 10: turntable, 12: motor, 14: drive circuit, 16: first magnet unit, 18: first actuator, 20: drive circuit, 22: control circuit, 30: Photodetector, 40, 40a-40d: magnet, 40e-40h: magnet group, 42: case, 56: second magnet unit, 58: second actuator, 60: drive circuit, 100: substrate for sample analysis, 114: Reaction chamber, 116: measurement chamber, 142: magnetic particles

Claims (12)

A sample analysis device for causing a binding reaction between an analyte in the liquid sample and a ligand immobilized on the surface of magnetic particles by rotating and stopping a sample analysis substrate holding a liquid sample, wherein
The sample analysis substrate can be loaded into and removed from the sample analysis device. and a chamber, which is the space in which the
a turntable supporting the loaded sample analysis substrate;
a motor for rotating the turntable;
a driving circuit for controlling rotation and stopping of the motor;
a first magnet unit arranged on the side of the first surface perpendicular to the rotation axis of the sample analysis substrate and generating an attractive force for attracting the magnetic particles;
a second magnet unit arranged on the second surface side opposite to the first surface perpendicular to the rotation axis of the sample analysis substrate and generating an attractive force for attracting the magnetic particles;
a first actuator that moves the first magnet unit to change the relative position between the first magnet unit and the sample analysis substrate;
a second actuator that moves the second magnet unit to change the relative position between the second magnet unit and the sample analysis substrate;
and a control circuit that controls operations of the motor, the drive circuit, the first actuator, and the second actuator, wherein the first actuator and the second actuator move the chamber during stirring of the liquid sample in the chamber. and moving the first magnet unit and the second magnet unit alternately to positions where the magnetic particles inside are attracted to the magnet unit. the first surface is a surface opposite to the turntable with respect to the sample analysis substrate;
the first magnet unit has a first shape that is part or all of a circle or a ring;
2. The sample analyzer according to claim 1, wherein the second magnet unit has a second shape that is part of a circle or part or all of a ring. the first magnet unit includes a single magnet having the first shape or a plurality of magnets arranged along the first shape;
3. The sample analyzer according to claim 2, wherein said second magnet unit includes a single magnet having said second shape, or a plurality of magnets arranged along said second shape. When the sample analysis substrate rotates at a predetermined number of rotations, and when the magnetic particles are attracted at the number of rotations, it takes T seconds for the movement of the magnetic particles,
The first actuator causes the first magnet unit to approach and separate from the sample analysis substrate at a period of 2T seconds, and
4. The sample analyzer according to claim 2, wherein said second actuator separates said second magnet unit from said sample analysis substrate and brings it closer to said sample analysis substrate at a period of 2T seconds. When the first shape and the second shape are part or all of a ring,
The first actuator and the second actuator cause the first magnet unit and the second magnet unit to approach the sample analysis substrate, respectively, and move the radial center position of the ring to the sample analysis substrate. 5. The sample analyzer according to any one of claims 2 to 4, wherein the position inside the chamber that is the furthest from the center of rotation is matched. 6. The first actuator and the second actuator respectively move the first magnet unit and the second magnet unit along a direction parallel to the axis of rotation of the sample analysis substrate. The sample analyzer according to . the second shape is the shape of a portion of the ring;
6. The first actuator and the second actuator respectively move the first magnet unit and the second magnet unit along a direction perpendicular to the axis of rotation of the sample analysis substrate. The sample analyzer according to . the first actuator separates the first magnet unit to a position where the first magnet unit and the sample analysis substrate do not overlap when viewed in a direction parallel to the rotation axis of the sample analysis substrate;
The second actuator separates the second magnet unit to a position where the second magnet unit and the sample analysis substrate do not overlap when viewed in a direction parallel to the rotation axis of the sample analysis substrate. 8. The sample analyzer according to 7. The first magnet unit and the second magnet unit face each other with the sample analysis substrate interposed therebetween,
The sample analyzer according to any one of claims 1 to 8, wherein the north poles or the south poles of the first magnet unit and the second magnet unit face each other. Further comprising an optical sensor arranged on the second surface side,
After completion of the binding reaction, during a luminescence reaction performed by allowing a predetermined luminescent substrate to act on the bound complex of the analyte and the ligand,
the second actuator moves the second magnet unit to a position where the magnetic particles in the chamber are attracted to the magnet unit;
10. The sample analyzer according to any one of claims 1 to 9, wherein said optical sensor detects light generated by said luminescent reaction. 11. The sample analyzer of claim 10, wherein said optical sensor is a photomultiplier tube. The sample analyzer according to any one of claims 1 to 11, wherein said first actuator and said second actuator are stepping motors or linear motors.

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