JP2009168636A - Inspection apparatus - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide an inspection apparatus that quantitatively determines a detecting object speedily, inexpensively, easily, and accurately, and increases the efficiency of cleaning of a reaction vessel. <P>SOLUTION: This inspection apparatus 10 for inspecting analytes comprises a moving passage 23, where the reaction vessel moves, an analyte introducing section 33 for introducing the analyte into the reaction vessel positioned at an analyte inlet position 231 of the moving passage 23, a first reagent inlet section 43 for introducing a first reagent into the reaction vessel positioned at 233, a cleaning mechanism 50 for removing an object in the reaction vessel positioned in a removing position 235, and a magnet 80 forming a magnetic field. The magnet 80 is disposed in an area that excludes the proximity of the removing position 235, and forms a magnetic field. <P>COPYRIGHT: (C)2009,JPO&INPIT

Description

  The present invention relates to an inspection apparatus for inspecting a biological sample or the like.

  Conventionally, latex agglutination has been performed as a method for analyzing components in a specimen. The latex agglutination method is a method for detecting the antigen in a fluid such as a biological sample by mixing the fluid with a latex carrying an antibody or fragment thereof that specifically binds to the antigen to determine the degree of latex aggregation. This is a method for quantifying an antigen by measuring (see, for example, Patent Document 1).

  According to such a latex agglutination method, an antigen added as a specimen crosslinks a plurality of latex-bound antibodies to promote latex agglutination. Based on the degree of aggregation, the antigen can be quantified.

  Incidentally, magnetic fine particles such as magnetite are used to improve detection accuracy. For example, Patent Document 2 discloses a technique for detecting nucleic acids and proteins using magnetic fine particles on which an antibody is immobilized. According to such a reagent, the magnetic particles are recovered just by bringing a magnet or the like after the antibody is bound to the detection target, and the detection target is separated accordingly. Since the detection target is separated in this way, the detection target can be analyzed with high accuracy.

  On the other hand, analysis devices have also been developed in order to easily use a quantitative system using magnetic fine particles. For example, in the apparatus shown in Patent Document 3, a permanent magnet is embedded in the lower surface of the sample dispensing position of the reaction disk. According to such an apparatus, when the reaction container containing the mixture of the specimen and the reagent rotates for a while and reaches the sample dispensing position, the magnetic fine particles bound to the detection target are captured on the bottom surface in the reaction container under the influence of the permanent magnet. The Thereafter, the capturing body and the supernatant are separated and the quantitative operation is performed.

In the apparatuses shown in Patent Documents 4 and 5, movable magnets are provided over the entire circumference of the reaction disk, and an insertion / removal mechanism for moving these movable magnets closer to and away from the reaction vessel is also provided. These insertion / removal mechanisms are normally controlled so that the movable magnet is separated from the reaction vessel while the magnetic particles are separated from the reaction vessel.
Japanese Patent Publication No.58-ll575 WO2002-16571 pamphlet JP-A-6-213900 JP-A-6-160401 JP 7-318559 A

  However, in the latex agglutination method, when the amount of antigen is very small, the crosslinking is difficult to occur, so that the latex does not aggregate sufficiently. For this reason, it is difficult to detect a trace amount of antigen.

  In order to improve the detection sensitivity, it is possible to adopt a system using an enzyme substrate reaction. However, in this system, special reagents and devices such as secondary antibodies, luminescent reagents, and luminescence detection devices are essential, and the operation cost is high. .

  Moreover, as shown in FIG. 25, this method is composed of multiple steps such as a step of incubating the sample and each reagent (ST110, ST130), a step of washing the system (ST120), and a step of measuring luminescence (ST140). The operation is complicated. In addition, the time required for each stage is extremely long and is not suitable for large-scale processing.

  Thus, the present inventors have found that aggregation of the stimulus-responsive polymer is inhibited when approaching a charged or hydrophilic substance, and have developed a new quantitative method (see WO2008001868 pamphlet).

  FIG. 1 is a schematic configuration diagram of a conjugate 1 used in a certain quantitative method. In one embodiment of such a method, first, a binding substance 1 in which an aggregating substance having a thermoresponsive polymer 2 immobilized on the surface of a magnetic particle 9 and an antibody 3 to the detection target 4 are mixed is mixed with a specimen. Then, when the detection target 4 exists, the charge portion of the detection target 4 approaches the thermoresponsive polymer 2 bonded to the antibody 3.

  Here, a magnet is brought close to the mixture, and in this state, the mixture is heated or cooled to a temperature at which the thermoresponsive polymer 2 aggregates, and the transition of the turbidity of the mixture is measured.

  Then, in the absence of the detection target, the thermoresponsive polymer 2 aggregates and an aggregate 6 is formed. And since the agglomerate 6 contains a large amount of magnetic particles 9, it is adsorbed by the magnet, and the turbidity of the mixture decreases (FIG. 3).

  On the other hand, when the detection target 4 exists, the charge portion is arranged in the vicinity of the thermoresponsive polymer 2, and thus aggregation of the thermoresponsive polymer 2 is inhibited. In the non-aggregated state, the magnetic particles 9 are sparse, so that adsorption to the magnet hardly occurs. As a result, a decrease in turbidity of the mixture is suppressed (FIG. 2).

  Therefore, the amount of the detection target 4 can be calculated according to the degree of the turbidity fluctuation. Moreover, since the turbidity of the mixture varies in response to a slight difference in the detection target 4, the detection target 4 can be quantified with high sensitivity.

  However, when the above detection method is performed by the apparatus shown in Patent Document 3, the agglomerate 6 is not adsorbed because the magnet is not arranged except in the vicinity of the sample dispensing position. For this reason, since the fluctuation range of the turbidity in response to the abundance of the detection target 4 is reduced, the sensitivity of the determination is deteriorated.

  Moreover, in the apparatus shown by patent document 4 and 5, since the magnet is located in the vicinity of the reaction vessel even after measuring the turbidity, the aggregate 6 continues to adhere to the reaction vessel. For this reason, when the cleaning device automatically cleans the reaction container, it is difficult to remove the aggregate 6 from the reaction container. When the target reaction container moves to the cleaning position, it may be possible to control the movable magnet to be separated from the reaction container, but the control becomes complicated.

  The present invention has been made in view of the above circumstances, and an object of the present invention is to provide an inspection apparatus capable of quantifying a detection target quickly, inexpensively, simply and with high accuracy, and improving the efficiency of washing a reaction container.

  The present inventors add magnetic force at the time of measurement by providing magnetic field forming means in an area downstream of the introduction position for introducing the specimen and the test reagent and excluding the vicinity of the removal position for removing the object in the reaction container. As a result, it was found that the agglomerates were adsorbed and that the agglomerates were prevented from adhering to the reaction vessel during washing, and the present invention was completed. Specifically, the present invention provides the following.

[1] An inspection apparatus for inspecting a specimen,
A moving path through which the reaction container moves, an introducing means for introducing a sample and a test reagent into the reaction container positioned at the introduction position of the moving path, and an object in the reaction container positioned at the removal position of the moving path. Removing means for removing, and magnetic field forming means for forming a magnetic field provided in the magnetic field area of the moving path,
The inspection apparatus, wherein the magnetic field area is an area downstream of the introduction position and excluding the vicinity of the removal position.
[2] The inspection apparatus according to [1], wherein the magnetic field forming unit is fixed to the moving path.
[3] The inspection apparatus according to [1] or [2], wherein the magnetic field forming means is provided at a predetermined interval in the magnetic field area.
[4] The inspection apparatus according to [3], wherein the magnetic field forming means adjacent to each other with a predetermined interval have the same magnetic pole arrangement.
[5] The movement path forms a circulation path including the introduction position and the removal position,
The said magnetic field area is an inspection apparatus in any one of [1] to [4] which is substantially all areas except the vicinity of the said removal position of the said circulation path.
[6] The inspection apparatus according to [5], wherein the magnetic field forming units located on both sides of the removal position have opposite magnetic pole arrangements.
[7] It further includes emission detection means for emitting light to the reaction container located at the detection position of the moving path and detecting light transmitted through the reaction container,
The inspection apparatus according to any one of [1] to [6], wherein the magnetic field forming means is provided in an area further excluding the optical path.
[7] The inspection apparatus according to [7], wherein the magnetic field forming unit is located below the optical path.
[8] The inspection apparatus according to [7], wherein the magnetic field forming unit is positioned at substantially the same height as the optical path.
[10] The inspection device according to any one of [7] to [9], wherein the launch detection unit performs detection a plurality of times for each reaction container.

  According to the present invention, the reaction container that has moved to the introduction position moves into the magnetic field area located downstream of the introduction position after the sample and the test reagent are introduced therein. Then, since a magnetic field is formed in the magnetic field area by the magnetic field forming means, a magnetic force is applied to the object (mixture of the specimen and the test reagent) in the reaction container.

  Here, when the atmosphere of the mixture is changed over time to a condition in which the thermoresponsive polymer contained in the test reagent is aggregated, an aggregate is gradually generated depending on the abundance of the detection target. Since such agglomerates contain a large amount of magnetic particles, they are separated from the mixture under the influence of magnetic force. As a result, since the turbidity of the mixture decreases with time, the detection target can be quantified with high sensitivity by detecting a change in a parameter (transmitted light amount, etc.) value based on such turbidity fluctuation.

  After the measurement of the parameter value, when the reaction container moves to the removal position, the removal means removes the object in the reaction container. Since no magnetic field forming means is provided at the removal position, the magnetic force applied to the object in the reaction vessel located at the removal position is reduced. Thereby, since adhesion of the aggregate to the reaction vessel is eased, the aggregate is easily removed from the reaction vessel by the removing means. Therefore, the cleaning of the reaction vessel can be made efficient.

  Hereinafter, embodiments of the present invention will be described with reference to the drawings. In addition, in description of each embodiment other than 1st Embodiment, the same code | symbol is attached | subjected about what is common in 1st Embodiment, and the description is abbreviate | omitted.

<First Embodiment>
FIG. 4 is a schematic configuration diagram of the inspection apparatus 10 according to the first embodiment of the present invention. The inspection apparatus 10 includes a reaction device 20, a sample introduction system 30, a first reagent introduction system 40, a cleaning mechanism 50 as a removal means, a transmitted light measurement system 60 as a firing detection means, a reaction instrument 70, and a magnetic field formation means. A magnet 80 is provided. Hereinafter, each configuration will be described in detail.

  The reaction apparatus 20 includes a rotatable disk-shaped rotary table 25, and a heat insulating tank 21 is provided so as to surround the rotary table 25. The heat retention tank 21 has an annular moving path 23, and the moving path 23 communicates with the fluid supply unit 213. As a result, a fluid having a predetermined temperature is supplied from the fluid supply unit 213 into the movement path 23 and the movement path 23 is filled with the fluid. A reaction vessel 71 (described later) is immersed in this fluid, and the reaction vessel 71 moves in a state where the temperature is maintained.

  FIG. 5 is an overall perspective view of the reaction device 70 in FIG. The reaction device 70 includes a plurality of reaction containers 71. These reaction containers 71 are inserted into the respective insertion holes 73 arranged in an arc shape of the holder 74 and are held by the holder 74, and an extending portion 75 is extended to the holder 74. . Pins 76 are provided in the extending portion 75, and these pins 76 are fitted into fitting holes 253 formed on the outer edge of the rotary table 25. As a result, the reaction vessel 71 moves in the movement path 23 in conjunction with the rotation of the turntable 25.

  Referring back to FIG. 4 again, the sample introduction system 30 includes a rotatable disk-shaped sample table 31, and a sample tube 35 for storing the sample is placed on the sample table 31. The sample introduction system 30 further includes a sample introduction unit 33 that supplies the sample in the sample tube 35 into the reaction container 71. The sample introduction unit 33 has a rotatable sample pipette mechanism 331, and the sample pipette mechanism 331 is provided with a sample nozzle 333.

  When the sample tube 35 moves below the sample pipette mechanism 331 due to the rotation of the sample table 31, the sample nozzle 333 is inserted into the sample tube 35, and the sample is sucked into the sample nozzle 333 by the suction pressure of the sample pipette mechanism 331. The Thereafter, when the sample pipette mechanism 331 rotates to the reaction apparatus 20 side, the sample is supplied into the reaction container 71 located below by the discharge pressure of the sample pipette mechanism 331. The sample pipette mechanism 331 and the sample nozzle 333 have a self-cleaning mechanism (not shown), and the self-cleaning mechanism cleans the sample pipette mechanism 331 and the sample nozzle 333 after the suction and supply of the sample.

  The first reagent introduction system 40 includes a rotatable disk-shaped first reagent table 41, and a first reagent tube 47 and a first cleaning liquid tube 48 are placed on the first reagent table 41. The first reagent table 41 has a temperature adjustment mechanism (not shown), and this temperature adjustment mechanism holds the first reagent tube 47 at a temperature different from the aggregation temperature of the thermoresponsive polymer in the first reagent table 41. And preventing aggregation of the thermoresponsive polymer.

  The first reagent introduction system 40 includes a first reagent introduction unit 43 that supplies the first reagent in the first reagent tube 47 into the reaction container 71, and a first stirring mechanism 45 that stirs an object in the reaction container 71. In addition. The first reagent introduction unit 43 has a rotatable first reagent pipette mechanism 431, and the first reagent pipette mechanism 431 is provided with a first reagent nozzle 433. The first stirring mechanism 45 has a first telescopic shaft 451, and a first stirring rod 453 is provided on the first telescopic shaft 451.

  When the first reagent tube 47 is moved below the first reagent pipette mechanism 431 by the rotation of the first reagent table 41, the first reagent nozzle 433 is inserted into the first reagent tube 47, and the first reagent pipette mechanism 431 The first reagent is sucked into the first reagent nozzle 433 by the suction pressure. Subsequently, when the first reagent pipette mechanism 431 rotates to the reaction apparatus 20 side, the first reagent is supplied into the reaction container 71 positioned below by the discharge pressure of the first reagent pipette mechanism 431. Thereafter, the turntable 25 rotates to position the reaction vessel 71 below the first stirring bar 453. Here, the specimen and the first reagent are mixed by the first stirring bar 453 stirring the inside of the reaction vessel 71. The sample introduction system 30 and the first reagent introduction system 40 described above constitute introduction means.

  The cleaning mechanism 50 sucks and removes the object in the reaction vessel 71 located below. The cleaning mechanism 50 cleans the reaction container 71 by supplying a cleaning liquid into the reaction container 71 after the suction and sucking the cleaning liquid from the reaction container 71.

  The transmitted light measurement system 60 includes a photometry unit 61 and a light source 63, and the photometry unit 61 and the light source 63 are disposed to face each other with the moving path 23 interposed therebetween. When the reaction vessel 71 is positioned between the photometry unit 61 and the light source 63, the light emitted from the light source 63 is applied to the side surface 711 of the reaction vessel 71. The irradiation light reaches the photometry unit 61 after passing through the object in the reaction vessel 71, and the amount of the reached light is measured by the photometry unit 61.

  6 is a partially exploded perspective view of FIG. 4, and FIG. 7 is an overall perspective view of the magnet 80. The magnet 80 is a C-shaped plate body made of a magnetic material and has substantially the same curvature as the movement path 23. The magnet 80 is fixed to the bottom 232 of the moving path 23, and a reaction vessel 71 is provided above the magnet 80. The magnet 80 installed in this way is positioned below the optical path of the light emitted from the photometry unit 61.

  Moreover, it consists of the magnet 80, the 1st magnet part 88, and the 2nd magnet part 89, and the edge part 885 of these 1st magnet parts 88 and the edge part 895 of the 2nd magnet part 89 are arrange | positioned at intervals. The first magnet portion 88 has an N pole 881 on the outer side and an S pole 883 on the inner side, and the second magnet portion 89 has an N pole 891 on the inner side and an S pole 893 on the outer side. The magnetic pole arrangement at 885, end 895 is the opposite. As a result, the magnetic field generated from one end 885 cancels out the magnetic field generated from the other end 895, and the magnetic field between the end portions 885 and 895 is weakened.

  FIG. 8 is a diagram showing the positional relationship of the above configuration. Specifically, (a) is a plan view of the reaction device 20 in use, and (b) is a perspective view of the reaction device 70 in (a). As shown in FIG. 8B, the movement path 23 includes a sample introduction position 231 located below the sample introduction section 33, a first reagent introduction position 233 located below the first reagent introduction section 43, and a cleaning mechanism. 50 is classified into a removal position 235 located below 50 and a detection position 237 located between the photometry unit 61 and the light source 63. Note that the sample introduction position 231 and the first reagent introduction position 233 constitute an introduction position.

  The magnet 80 is provided so that each of the first magnet unit 88 and the second magnet unit 89 is located in an area excluding the vicinity of the removal position 235 in the moving path 23, and forms a magnetic field in the magnetic field area. As a result, the magnetic pole arrangement of the end portions 885 and the end portions 895 located on both sides of the removal position 235 is reversed. The magnetic field area is an area excluding the vicinity of the removal position 235, and magnetic force is applied to the first reagent and the sample in the reaction container 71 located downstream of the first reagent introduction position 233.

  “Near the removal position” refers to a minimum area where the magnetic field forming means need not be provided because the magnetic field at the removal position is weaker than the magnetic field in the magnetic field area. Further, “downstream of the first reagent introduction position 233” includes the first reagent introduction position 233, and the magnetic field area includes not only the downstream of the first reagent introduction position 233 but also the upstream of the first reagent introduction position 233. Also good. As a result, in the present embodiment in which the movement path 23 forms a circulation path, the magnetic field area is the entire area except the vicinity of the removal position 235.

  In the present embodiment, the magnet 80 is fixed to the moving path 23. Thereby, it is suppressed that an installation position shifts unexpectedly by the fluid flow etc. in the movement path 23 accompanying the movement of the reaction vessel 71. Note that the term “fixed” simply means a strong connection and does not mean that it cannot be attached or detached. Therefore, when the magnet 80 or the moving path 23 is consumed, the magnet 80 may be removed from the moving path 23 and only the worn one may be replaced with a new one.

  9 is a cross-sectional view taken along line IX-IX in FIG. The magnet 80 is located below the bottom surface 713 and applies a magnetic force to the object in the reaction vessel 71. Thereby, the object attracted to the magnet 80 side by the magnetic force is deposited on the bottom surface 713. The magnet 80 and the bottom surface 713 may be arranged with a predetermined distance as shown in FIG. 7 or may be in contact with each other.

[Operation]
The operation of the inspection apparatus 10 will be described with reference to FIG.

  First, various samples are introduced into the sample tube 35 and the sample tube 35 is set on the sample table 31. When the sample table 31 is operated here, the sample table 31 rotates, and each of the sample tubes 35 sequentially moves below the sample pipette mechanism 331. Then, the sample nozzle 333 is inserted into the sample tube 35, and the sample is sucked into the sample nozzle 333 by the suction pressure of the sample pipette mechanism 331. Thereafter, the sample pipette mechanism 331 rotates to the reaction apparatus 20 side, and the sample is supplied into the reaction container 71 located at the sample introduction position 231. After the sample is aspirated and supplied, the sample pipette mechanism 331 and the sample nozzle 333 are washed by the self-cleaning mechanism, and the next sample is aspirated and supplied repeatedly.

  The reaction container 71 into which the sample has been introduced moves in the movement path 23 as the turntable 25 rotates, and eventually reaches the first reagent introduction unit 43. Then, the first reagent nozzle 433 is inserted into the first reagent tube 47 that has been rotated below the first reagent pipette mechanism 431 by the rotation of the first reagent table 41, and the first reagent table 433 containing the conjugate 1 shown in FIG. One reagent is sucked into the first reagent nozzle 433. Subsequently, the first reagent pipette mechanism 431 rotates toward the reaction apparatus 20, and the first reagent is supplied into the reaction container 71 located in the first reagent introduction unit 43. The reaction vessel 71 into which the first reagent has been introduced moves below the first stirring bar 453, where the specimen and the first reagent are mixed by the first stirring bar 453. The fluid supply unit 213 sets the fluid temperature in the movement path 23 to a temperature at which the normal 11 is aggregated. Note that the order of introduction of the specimen and the first reagent is not particularly limited.

  Thereafter, the reaction vessel 71 starts moving again. At this time, as the object in the reaction vessel 71 changes to the temperature of the fluid in the moving path 23, the aggregate 6 is formed at a speed depending on the amount of the detection target. Here, magnetic force is continuously applied to the inside of the reaction vessel 71 from the magnet 80 located below the bottom surface 713, and the formed agglomerates 6 are sequentially deposited on the bottom surface 713, and the reaction is performed according to the amount of deposition. The permeability of the object in the container 71 increases. Then, while the reaction container 71 passes through the detection position 237, the amount of light emitted from the light source 63 and transmitted through the reaction container 71 is measured by the photometry unit 61.

  This measurement is performed a plurality of times for each of the reaction containers 71, and the detection target in the sample is detected or quantified based on the change in the amount of transmitted light over time. In order to make the measurement conditions uniform, it is preferable to unify the time from the mixing of the specimen and the first reagent to each measurement for all the reaction vessels 71. The number of times of measurement may be singular. In this case, it is preferable to unify the time from the mixing of the sample and the first reagent to the measurement for all the reaction vessels 71 in order to make the measurement conditions uniform. .

  The reaction vessel 71 that has finished the measurement moves to the removal position 235. Then, since the magnetic force applied in the reaction vessel 71 is weakened, the adhesion force of the aggregate 6 deposited on the bottom surface 713 to the inner wall of the reaction vessel 71 is also weakened. For this reason, when the cleaning mechanism 50 sucks the object in the reaction vessel 71, a larger amount of avidin 5 is easily removed. The reaction container 71 whose interior has been cleaned in this manner moves again to the sample introduction position 231 and the next sample is introduced.

[First reagent]
The first reagent that can be preferably used in the above-described inspection apparatus 10 contains a bound substance in which an aggregating substance and an affinity substance are bound. Each component will be described.

(Aggregating substance)
The cohesive substance used in the present invention contains a thermoresponsive polymer. This thermoresponsive polymer undergoes a structural change in response to an external stimulus, and is a polymer capable of adjusting aggregation and dispersion.

  In particular, in the present invention, as the heat-responsive polymer, a temperature-responsive polymer that can be aggregated and dispersed by temperature change can be used. Examples of the temperature-responsive polymer include a polymer having a lower critical solution temperature (hereinafter also referred to as LCST) and a polymer having an upper critical solution temperature.

  As the polymer having the lower critical solution temperature used in the present invention, Nn-propylacrylamide, N-isopropylacrylamide, N-ethylacrylamide, N, N-dimethylacrylamide, N-acryloylpyrrolidine, N-acryloylpiperidine, N -N substitution such as acryloylmorpholine, Nn-propylmethacrylamide, N-isopropylmethacrylamide, N-ethylmethacrylamide, N, N-dimethylmethacrylamide, N-methacryloylpyrrolidine, N-methacryloylpiperidine, N-methacryloylmorpholine Polymer consisting of (meth) acrylamide derivative; hydroxypropyl cellulose, polyvinyl alcohol partially acetylated product, polyvinyl methyl ether, (polyoxyethylene-polyoxypropy N) block copolymers, polyoxyethylene alkylamine derivatives such as polyoxyethylene laurylamine; polyoxyethylene sorbitan ester derivatives such as polyoxyethylene sorbitan laurate; (polyoxyethylene nonylphenyl ether) acrylate, (polyoxyethylene octylphenyl) (Polyoxyethylene alkylphenyl ether) (meth) acrylates such as ether) methacrylate; and (polyoxyethylene alkyl ether) (meth) acrylate such as (polyoxyethylene lauryl ether) acrylate and (polyoxyethylene oleyl ether) methacrylate And other polyoxyethylene (meth) acrylic acid ester derivatives. Furthermore, copolymers comprising these polymers and at least two of these monomers can also be used. A copolymer of N-isopropylacrylamide and Nt-butylacrylamide can also be used. When a polymer containing a (meth) acrylamide derivative is used, another copolymerizable monomer may be copolymerized with the polymer within a range having a lower critical solution temperature. In the present invention, among others, Nn-propylacrylamide, N-isopropylacrylamide, N-ethylacrylamide, N, N-dimethylacrylamide, N-acryloylpyrrolidine, N-acryloylpiperidine, N-acryloylmorpholine, Nn- From at least one monomer selected from the group consisting of propylmethacrylamide, N-isopropylmethacrylamide, N-ethylmethacrylamide, N, N-dimethylmethacrylamide, N-methacryloylpyrrolidine, N-methacryloylpiperidine, N-methacryloylmorpholine Or a copolymer of N-isopropylacrylamide and Nt-butylacrylamide can be preferably used.

  As the polymer having the upper critical solution temperature used in the present invention, a polymer comprising at least one monomer selected from the group consisting of acryloylglycinamide, acryloylnipecotamide, acryloyl asparagine amide, acryloyl glutamine amide, etc. is used. it can. Moreover, the copolymer which consists of these at least 2 types of monomers may be sufficient. These polymers include other copolymers such as acrylamide, acetylacrylamide, biotinol acrylate, N-biotinyl-N′-methacryloyl trimethylene amide, acroyl sarcosine amide, methacryl sarcosine amide, acroyl methyl uracil, etc. Possible monomers may be copolymerized in a range having an upper critical solution temperature.

  The aggregating substance preferably further contains a particulate magnetic substance in that detection accuracy can be improved by applying a magnetic force described later. Such a magnetic substance may be composed of a polyhydric alcohol and magnetite.

  The polyhydric alcohol is not particularly limited as long as it is an alcohol structure having at least two hydroxyl groups as a structural unit and capable of binding to iron ions, and examples thereof include dextran, polyvinyl alcohol, mannitol, sorbitol, and cyclodextrin. . For example, Japanese Patent Application Laid-Open No. 2005-82538 discloses a method for producing a particulate magnetic material using dextran. Moreover, the compound which has an epoxy group and forms a polyhydric alcohol structure after ring-opening like a glycidyl methacrylate polymer can also be used.

  The fine particle magnetic material (magnetic fine particles) prepared using such a polyhydric alcohol preferably has an average particle size of 0.9 nm or more and less than 1000 nm so as to have good dispersibility. The average particle size is preferably 2.9 nm or more and less than 200 nm, in particular, in order to increase the detection sensitivity of the target detection target.

(Affinity substance)
The affinity substance may be, for example, a monoclonal antibody that recognizes different antigenic determinants to be detected. The antibody used herein may be any type of immunoglobulin molecule, and may be an immunoglobulin molecule fragment having an antigen binding site such as Fab. The antibody may be a monoclonal antibody or a polyclonal antibody.

(Production)
The bound substance is prepared by binding an aggregating substance and an affinity substance. The binding method is not particularly limited. For example, both the aggregating substance side (for example, the thermoresponsive polymer moiety) and the affinity substance (for example, antibody) side have substances having affinity for each other (for example, avidin and biotin, Glutathione and glutathione S-transferase) are bound, and the aggregating substance and affinity substance are bound via these substances.

  Specifically, the biotin is bonded to the thermoresponsive polymer by binding biotin or the like to a polymerizable functional group such as a methacryl group or an acrylic group as described in WO 01/09141. An addition-polymerizable monomer can be used by copolymerizing with other monomers. The binding of avidin or the like to the affinity substance can be performed according to a conventional method. Next, when the biotin-binding thermoresponsive polymer and the avidin-binding affinity substance are mixed, the affinity substance and the thermo-responsive polymer are bonded through the binding between avidin and biotin.

  Alternatively, a monomer having a functional group such as a carboxylic acid, an amino group or an epoxy group is copolymerized with another monomer at the time of polymerization of the polymer, and the antibody affinity substance is passed through this functional group according to a method well known in the art. (For example, a method of binding melon gel, protein A, protein G) to a polymer can be used. By binding an antibody to the antibody affinity substance thus obtained, a conjugate of the thermoresponsive polymer and the antibody against the antigen to be detected is produced.

  Alternatively, a monomer having a functional group such as carboxylic acid, amino group or epoxy group may be copolymerized with another monomer at the time of polymerization of the polymer, and an antibody against the antigen to be detected may be directly bonded to these functional groups according to a conventional method. Good.

  Alternatively, an affinity substance and a thermoresponsive polymer may be bound to a fine particle magnetic substance.

  The aggregated substance may be purified by centrifuging after separating the aggregating substance under conditions where the thermoresponsive polymer aggregates. Purification of the bound product may be performed by a method in which a magnetic substance in the form of fine particles is bound to the thermoresponsive polymer, and further an affinity substance is bound, and then the magnetic substance is recovered by applying a magnetic force.

  The fine magnetic substance can be bonded to the thermo-responsive polymer via a reactive functional group, or a polymerizable unsaturated bond is introduced into the active hydrogen or polyhydric alcohol on the polyhydric alcohol in the magnetic substance. The graft polymerization may be carried out by a method known in the art such as graft polymerization (for example, ADV.Polym.Sci., Vol.4, p111, 1965, J. Polymer Sci., Part-A, 3, p1031). 1965).

[Function and effect]
According to 1st Embodiment of this invention, the following effects are obtained.

The reaction container 71 that has moved to the first reagent introduction position 233 has a magnetic field formed by the magnet 80 when the specimen and the first reagent are introduced therein. Magnetic force is applied to the mixture.
Here, since the reaction vessel 71 is immersed in a fluid having a predetermined temperature, the temperature of the mixture in the reaction vessel 71 is changed to a temperature at which the thermoresponsive polymer 2 contained in the first reagent aggregates, and the detection target 4 The agglomerates 6 are gradually generated depending on the abundance of. Since such agglomerates 6 contain a large amount of magnetic particles 9, they are separated from the mixture under the influence of magnetic force. As a result, since the turbidity of the mixture decreases with time, the detection target can be quantified with high sensitivity by detecting a change in the amount of transmitted light based on the turbidity fluctuation.
When the reaction container 71 moves to the removal position 235 after measuring the amount of transmitted light, the cleaning mechanism 50 removes the object in the reaction container 71. Since the magnet 80 is not provided at the removal position 235, the magnetic force applied to the object in the reaction vessel 71 located at the removal position 235 is reduced. As a result, adhesion of the aggregate 6 to the reaction vessel 71 is alleviated, so that the aggregate 6 is easily removed from the reaction vessel 71 by the cleaning mechanism 50. Therefore, the cleaning of the reaction vessel 71 can be made efficient.

  Thus, according to the inspection apparatus according to the present invention, since a magnetic force is not continuously applied at a fixed position but a magnetic force is continuously applied to separate the agglomerates 6 over time, There is no need to control the timing of magnetic field formation. For this reason, it is sufficient to fix the magnet 80 to a position other than the vicinity of the removal position 235, and the configuration and control can be simplified. Moreover, since it is sufficient to install the magnet 80 in the conventional apparatus, the initial cost can be reduced.

  Since the magnet 80 is provided in an area excluding the optical path from the light source 63 to the photometry unit 61, physical shielding of the optical path by the magnet 80 itself is prevented. Thereby, the transmitted light amount detected by the photometry unit 61 becomes a parameter depending on the turbidity fluctuation in the reaction container 71, and the detection target can be quantified with high accuracy.

  In addition, since the magnet 80 is provided below the optical path, the aggregate 6 formed in the reaction vessel 71 is attracted below the optical path. Thereby, the bad influence to the transmitted light amount by the aggregate 6 blocking the light path unexpectedly is suppressed. As a result, the transparency of the mixture increases and decreases and the amount of transmitted light also increases and decreases strongly depending on the increase and decrease of the amount of aggregates produced, so that the detection target can be quantified with higher accuracy.

  By measuring the amount of transmitted light for each reaction vessel 71 a plurality of times, a change in the amount of transmitted light over time is detected. As a result, the detection target can be quantified with much higher accuracy than the single measurement.

When the movement path 23 is a non-circulation path, when the reaction container 71 is moved to various positions on the movement path 23, it is necessary to frequently move the reaction container 71 back and forth over a long distance, and the time spent for the entire measurement process is increased. It is inefficient because it is prolonged.
However, since the moving path 23 is an annular circulation path in the present embodiment, the reaction vessel 71 can be moved to any position in the moving path 23 by simply rotating the rotary table 25 in one direction. Thereby, the time spent for all the measurement steps can be shortened, and the drive control of the rotary table 25 can be simplified. Such an effect is particularly effective when the amount of transmitted light is measured a plurality of times.

  Since the end portion 885 and the end portion 895 located on both sides of the removal position 235 have opposite magnetic pole arrangements, the magnetic field generated from the one end 885 is offset with the magnetic field generated from the other end 895, and the magnetic field at the removal position 235 is weakened. . Thereby, since the adhesion of the agglomerates 6 to the reaction vessel 71 is further eased, the cleaning of the reaction vessel 71 can be made more efficient.

Second Embodiment
FIG. 11 is a diagram showing a magnet 80A constituting an inspection apparatus 10A according to the second embodiment of the present invention. This embodiment differs from the first embodiment in the structure of the magnet 80A.

  That is, the magnet 80A includes a plurality of partial arc-shaped magnet units 87. These magnet units 87 are provided in the moving path 23 with a predetermined gap CL therebetween, and the magnet units 87c other than the magnet units 87a and 87b described later have the same magnetic pole arrangement. As a result, the magnetic field generated from each of the magnet units 87 c is amplified in the gap CL, and the increased magnetic force is added to the object in the reaction vessel 71.

  Specifically, each of the magnet units 87 is provided except for the removal position 235 and the vicinity thereof. Further, the magnet unit 87a opposed across the removal position 235 has an N pole 871a on the outer side and an S pole 873a on the inner side, and the magnet unit 87b has an N pole 871b on the inner side and an S pole 873b on the outer side. The magnet units 87a and 87b have magnetic pole arrangements opposite to each other.

[Function and effect]
According to 2nd Embodiment of this invention, in addition to 1st Embodiment, the following effects are obtained.

  Since the magnet units 87c are provided with a gap CL at a predetermined interval from each other, the magnetic field formed by each of the magnet units 87c wraps around the gap CL, and magnetic force due to a multi-directional magnetic field is added into the reaction vessel 71. Thereby, since the separation capability of the aggregate 6 is improved, the detection target can be quantified with higher sensitivity and higher accuracy.

  In addition, since the magnetic pole arrangements of the adjacent magnet units 87 c are the same, the magnetic force amplified and enhanced in the gap CL is added to the object in the reaction vessel 71. Thereby, since the separation capability of the aggregate 6 is further improved, the detection target can be quantified with higher sensitivity and higher accuracy.

<Third Embodiment>
FIG. 12 is a diagram showing a magnet 80B constituting an inspection apparatus 10B according to the third embodiment of the present invention. 13 is a cross-sectional view taken along line XIII-XIII in FIG. 12, and FIG. 14 is a cross-sectional view taken along line XIV-XIV in FIG. This embodiment is different from the first embodiment in the arrangement of the magnets 80B.

  That is, the magnet 80B is fixed to the side wall 236 of the moving path 23, and the reaction vessel 71 is provided on the side of the magnet 80B. The magnet 80 </ b> B installed in this way is located at the same height as the optical path of the light emitted from the photometry unit 61, and in this embodiment, is located over the optical path. However, as shown in FIG. 14, the magnet 80 </ b> B is provided except for a position where the light path is blocked, and in this embodiment, the light emitting portion of the light source 63 is not covered.

  As shown in FIG. 15, according to the inspection apparatus 10B, the magnetic force is continuously applied to the inside of the reaction vessel 71 from the magnet 80 located on the side of the bottom surface 713, so that the speed depends on the amount of the detection target. The formed agglomerates 6 are sequentially deposited on the side surface 711. Since this deposit significantly impedes the transmission of light emitted from the light source 63, the amount of light reaching the photometry unit 61 is reduced according to the amount of deposit. That is, unlike the embodiment, the amount of transmitted light increases or decreases according to the increase or decrease of the amount of detection target in the sample.

[Function and effect]
According to the third embodiment of the present invention, the following operational effects can be obtained in addition to the first embodiment.

  Since the magnet 80B is provided at the same height as the optical path, the aggregate 6 formed in the reaction vessel 71 is deposited on the side surface 711 so as to block the optical path. As a result, the amount of transmitted light detected by the photometry unit 61 decreases depending on the amount of accumulation of the agglomerates 6, and thus reflects the amount of the detection target 4. Therefore, the detection target can be quantified with high sensitivity.

<Fourth embodiment>
FIG. 16 is a schematic configuration diagram of an inspection apparatus 10C according to the fourth embodiment of the present invention. FIG. 17 is a diagram showing a positional relationship of members constituting the inspection apparatus 10C of FIG. This embodiment is different from the above embodiment in the configuration of the reagent introduction system 40C.

  That is, the reagent introduction system 40C further includes a rotatable disc-shaped second reagent table 41 ′, and the second reagent tube 47 ′ and the second cleaning liquid tube 48 ′ are mounted on the second reagent table 41 ′. Is placed. The reagent introduction system 40C includes a second reagent introduction unit 43 ′ that supplies the second reagent in the second reagent tube 47 ′ to the reaction container 71, and a second stirring mechanism that stirs the object in the reaction container 71. 45 'is further provided. The second reagent introduction part 43 'has a rotatable second reagent pipette mechanism 431', and the second reagent pipette mechanism 431 'is provided with a second reagent nozzle 433'. The second stirring mechanism 45 'has a second telescopic shaft 451', and the second telescopic shaft 451 'is provided with a second stirring rod 453'.

  When the second reagent tube 47 ′ is moved below the second reagent pipette mechanism 431 ′ by the rotation of the second reagent table 41 ′, the second reagent nozzle 433 ′ is inserted into the second reagent tube 47 ′, and the second reagent tube ′ is inserted into the second reagent tube 47 ′. The second reagent is sucked into the second reagent nozzle 433 ′ by the suction pressure of the reagent pipette mechanism 431 ′. Subsequently, when the second reagent pipette mechanism 431 ′ rotates to the reaction apparatus 20 side, the second reagent is supplied into the reaction container 71 positioned below by the discharge pressure of the second reagent pipette mechanism 431 ′. Thereafter, the turntable 25 rotates to position the reaction vessel 71 below the second stirring bar 453 '. Here, the sample, the first reagent, and the second reagent are mixed by the second stirring bar 453 ′ stirring the inside of the reaction vessel 71.

  The order of introduction of the specimen, the first reagent, and the second reagent is not particularly limited.

[Second reagent]
The second reagent accommodated in the second reagent tube 47 ′ contains the second combined substance. This second binding substance is a combination of a charged or hydrophilic second substance and a second affinity substance for the detection target. Each component will be described.

(Second substance)
The charged second substance is, for example, a polymer compound having a charge, and is preferably a polyanion or a polycation. The polyanion means a substance having a plurality of anion groups, and the polycation means a substance having a plurality of cation groups. Examples of polyanions include nucleic acids such as DNA and RNA. These nucleic acids have the properties of polyanions due to the presence of a plurality of phosphodiester groups along the nucleic acid urn. In addition, the polyanion contains, as a polymerization component, a polypeptide having a large number of carboxylic acid functional groups (polypeptide consisting of amino acids such as glutamic acid and aspartic acid), polyacrylic acid, polymethacrylic acid, and acrylic acid or methacrylic acid. Polysaccharides such as polymers, carboxymethylcellulose, hyaluronic acid, and heparin are also included. On the other hand, examples of the polycation include polylysine, polyarginine, polyornithine, polyalkylamine, polyethyleneimine, and polypropylethyleneimine. The number of functional groups of the polyanion (carboxyl group) or polycation (amino group) is preferably 25 or more.

  The hydrophilic second substance is, for example, a water-soluble polymer compound, and contains a polymer containing an ether bond such as polyethylene glycol, polypropylene glycol, polyethylene oxide, or polypropylene oxide, and an alcoholic hydroxyl group such as polyvinyl alcohol. Examples thereof include polymers, water-soluble polysaccharides such as dextran, cyclodextrin, agarose and hydroxypropylcellulose.

  These charged or hydrophilic substances may have a functional group or the like for binding the second affinity substance in the polymer chain or at the terminal.

(Second affinity substance)
The second affinity substance can bind to the detection target at the same time as the first affinity substance at a site different from the first affinity substance. The first affinity substance and the second affinity substance may be, for example, monoclonal antibodies that recognize different antigenic determinants to be detected.

[Production method]
The second binding substance is created by directly or indirectly binding the second substance and the second affinity substance. Although not particularly limited, for example, substances that are compatible with each other (for example, avidin and biotin, glutathione, and glutathione S-transferase) on both the second substance side and the second affinity substance (eg, second antibody) side. And the second substance and the second affinity substance are indirectly bound via these substances.

  When the second substance and the second affinity substance are directly bound, they may be bound via a functional group. For example, when a functional group is used, the method of Gosh et al: Bioconjugate Chem. , 1, 71-76, 1990). Specifically, there are the following two methods.

  In the first method, a mercapto group (also called a sulfhydryl group) is first introduced into the 5 ′ end of a nucleic acid, while a 6-maleimidohexanoic acid succinimide ester (for example, “EMCS (trade name)” (Dojin) is introduced into an antibody. The maleimide group is introduced by reacting Chemical Laboratories). Next, these two substances are bonded through a mercapto group and a maleimide group.

  In the second method, first, a mercapto group is introduced into the 5 ′ end of the nucleic acid in the same manner as in the first method, and N, N-1,2-phenylenedioxide, which is a homobifunctional reagent, is further introduced into this mercapto group. By reacting with maleimide, a maleimide group is introduced at the 5 ′ end of the nucleic acid, while a mercapto group is introduced into the antibody. Next, these two substances are bonded through a mercapto group and a maleimide group.

  In addition, as a method for introducing a nucleic acid into a protein, for example, the methods described in Nucleic Acids Research Vol. 15 5275 (1987) and Nucleic Acids Research Vol. 16 3671 (1988) are known. Yes. These techniques can be applied to the binding of nucleic acids and antibodies.

  According to Nucleic Acids Research 16: 3671 (1988), a mercapto group is first introduced into the 5'-terminal hydroxyl group of an oligonucleotide by reacting the oligonucleotide with cystamine, carbodiimide and 1-methylimidazole. After purifying an oligonucleotide with a mercapto group introduced, it is reduced with dithiothreitol, followed by the addition of 2,2'-dipyridyl disulfide to introduce a pyridyl group via a disulfide bond at the 5 'end of the oligonucleotide. To do. On the other hand, for a protein, a mercapto group is introduced by reacting iminothalylene. The oligonucleotide introduced with the pyridyl disulfide group and the protein introduced with the mercapto group are mixed, and the pyridyl group and the mercapto group are specifically reacted to bind the protein and the oligonucleotide.

  According to Nucleic Acids Research Vol. 15, page 5275 (1987), first, an amino group was introduced into the 3 ′ end of the oligonucleotide, and dithio-bis-propionic acid-N-, which is a homobifunctional reagent. Hydroxysuccinimide ester (abbreviation: dithio-bis-propionyl-NHS) is reacted. After the reaction, dithiothreitol is added to reduce the disulfide bond in the dithio-bis-propionyl-NHS molecule and introduce a mercapto group at the 3 'end of the oligonucleotide. For protein treatment, a heterobifunctional cross-linking agent as shown in JP-A-5-48100 is used. First, it has a first reactive group (succinimide group) that can react with a functional group (for example, an amino group) in a protein, and a second reactive group (for example, a maleimide group) that can react with a mercapto group. By reacting the heterobifunctional cross-linking agent with the protein, a second reactive group is introduced into the protein to obtain a preactivated protein reagent. The protein reagent thus obtained is covalently bound to the mercapto group of the thiolated polynucleotide.

  Even when a polyanion or polycation other than a nucleic acid is used, a second bound product can be produced by the same operation as described above by introducing a mercapto group at the terminal or the like.

  The above second bound substance is mixed with the first bound substance and the specimen, and this mixture is subjected to a condition where the thermoresponsive polymer aggregates. Then, when the detection target is present, the thermoresponsive polymer is dispersed and inhibited by the charge in the second binding substance, whereas when the detection target is not present, the thermoresponsive polymer is not inhibited from aggregation. Aggregate. This phenomenon will be described with reference to FIGS.

  As shown in FIG. 18, the second conjugate 90 includes a second substance 91 having a negative charge, and this second substance 91 is bound to the second antibody 93 against the detection target 4. The first antibody 3 and the second antibody 93 can simultaneously bind to the detection target 4 at different parts of the detection target 4.

  When the mixture of the first binding substance 1, the second binding substance 90 and the specimen is placed under a predetermined condition, when the detection target exists, the thermoresponsive polymer 2 is caused by the charge in the second binding substance 90. Aggregation is inhibited and dispersed (FIG. 19). Here, the degree of aggregation inhibition of the first conjugate 1 is greater than that of the above-described embodiment.

  On the other hand, when the detection target 4 does not exist, the thermoresponsive polymer 2 aggregates without being inhibited from aggregation, and a large amount of aggregate 6 is formed (FIG. 20).

[Function and effect]
According to 4th Embodiment of this invention, in addition to 1st Embodiment, the following effects are obtained.

When the detection target 4 is present, the first antibody 3 and the second antibody 93 are bound to the detection target 4, so that the thermoresponsive polymer 2 bound to the first antibody 3 is bound to the second antibody. The second substance 91 approaches. Thereby, since a charged part or a hydrophilic part is arrange | positioned in the vicinity of the thermoresponsive polymer 2, aggregation of the thermoresponsive polymer 2 in response to heat is inhibited. Therefore, the detection target 4 can be quantified by measuring the change in the amount of transmitted light due to the aggregate 6.
In addition, aggregation inhibition depends on the charged part or hydrophilic part of the second substance 91, and the degree of dependence on the detection target species is greatly reduced. For this reason, detection or quantification of any detection target can be performed, and certainty and versatility can be improved.

<Modification>
The present invention is not limited to the above-described embodiment, and modifications, improvements, and the like within the scope that can achieve the object of the present invention are included in the present invention.

  For example, as shown in FIGS. 21 to 23, the magnets may be configured with an arbitrary magnetic pole arrangement and number. However, in any configuration, it is preferable that the magnetic pole arrangements at both ends are opposite to each other.

  Also, the shape of the magnet is not particularly limited, and in the above-described embodiment, it has a flat plate shape in cross section. However, as shown in FIG. However, regardless of the cross-sectional shape, the magnet should be provided except for the position where the light path of the light emitted from the light source 63 is blocked.

  In the embodiment, the permanent magnet is used as the magnetic field forming means. However, the permanent magnet is not limited to this as long as the magnetic field can be formed, and may be an electromagnet or the like. Moreover, in the said embodiment, although the permanent magnet was fixed to the moving path, you may comprise so that it can move to a various direction.

  In the above embodiment, the thermoresponsive polymer is used. However, the present invention is not limited to this, and the stimuli-responsive polymer that aggregates according to various physical or chemical signals such as light, acid, base, pH, and electricity is used. May be used. When a stimulus other than heat is employed, it is necessary to provide a stimulus applying device that replaces the fluid supply unit 213 used in the embodiment.

  In the above-described embodiment, the moving path 23 is an annular circulation path. However, the movement path 23 is not limited to this, and may be an arbitrarily shaped circulation path or a non-circulation path.

  In the above embodiment, only the inspection procedure using the reagent shown in FIG. 1 is described. However, the present invention is not limited to this, and the inspection may be performed using any system.

It is a schematic block diagram of the reagent used in the test | inspection apparatus which concerns on one Embodiment of this invention. It is a schematic diagram which shows the use condition of the reagent of FIG. It is a schematic diagram which shows the use condition of the reagent of FIG. 1 is a schematic configuration diagram of an inspection apparatus according to a first embodiment of the present invention. It is the whole reaction container perspective view in FIG. FIG. 5 is a partially exploded perspective view of FIG. 4. It is a whole perspective view of the magnetic field formation means which comprises the inspection apparatus which concerns on the said embodiment. It is a figure which shows the positional relationship of the member which comprises the inspection apparatus which concerns on the said embodiment. It is the IX-IX sectional view taken on the line of FIG. It is a figure which shows the use condition of the inspection apparatus which concerns on the said embodiment. It is a figure which shows the magnetic field formation means which comprises the inspection apparatus which concerns on 2nd Embodiment of this invention. It is a figure which shows the magnetic field formation means which comprises the inspection apparatus which concerns on 3rd Embodiment of this invention. It is the XIII-XIII sectional view taken on the line of FIG. It is the XIV-XIV sectional view taken on the line of FIG. It is a figure which shows the use condition of the inspection apparatus which concerns on the said embodiment. It is a schematic block diagram of the test | inspection apparatus 10C which concerns on 4th Embodiment of this invention. It is a figure which shows the positional relationship of the member which comprises the inspection apparatus which concerns on the said embodiment. It is a schematic block diagram of the reagent used in the test | inspection apparatus which concerns on the said embodiment. It is a schematic diagram which shows the use condition of the reagent of FIG. It is a schematic diagram which shows the use condition of the reagent of FIG. It is a figure which shows the modification of the magnetic field formation means which comprises the inspection apparatus which concerns on this invention. It is a figure which shows another modification of the magnetic field formation means which comprises the inspection apparatus which concerns on this invention. It is a figure which shows another modification of the magnetic field formation means which comprises the inspection apparatus which concerns on this invention. It is a figure which shows another modification of the magnetic field formation means which comprises the inspection apparatus which concerns on this invention. It is a flowchart of the inspection method which concerns on a prior art example.

Explanation of symbols

10, 10A, 10B, 10C Inspection device 20 Reaction device 23 Moving path 231 Sample introduction position (introduction position)
233 First reagent introduction position (introduction position)
235 Removal position 237 Detection position 30 Sample introduction system (introduction means)
40 First reagent introduction system (introduction means)
40 'second reagent introduction system (introduction means)
50 Cleaning mechanism (cleaning means)
60 Transmitted light measurement system (fire detection means)
71 Reaction vessel 80, 80A, 80B Magnet (magnetic field forming means)

Claims (10)

An inspection device for inspecting a specimen,
A moving path through which the reaction container moves, an introducing means for introducing a sample and a test reagent into the reaction container positioned at the introduction position of the moving path, and an object in the reaction container positioned at the removal position of the moving path. Removing means for removing, and magnetic field forming means for forming a magnetic field in the magnetic field area of the moving path,
The inspection apparatus, wherein the magnetic field area is an area downstream of the introduction position and excluding the vicinity of the removal position.   The inspection apparatus according to claim 1, wherein the magnetic field forming unit is fixed to the moving path.   The inspection apparatus according to claim 1, wherein the magnetic field forming means is provided at a predetermined interval in the magnetic field area.   4. The inspection apparatus according to claim 3, wherein the magnetic field forming means adjacent to each other with a predetermined interval have the same magnetic pole arrangement. The movement path forms a circulation path including the introduction position and the removal position,
5. The inspection apparatus according to claim 1, wherein the magnetic field area is substantially all areas except for the vicinity of the removal position of the circulation path.   6. The inspection apparatus according to claim 5, wherein the magnetic field forming means located on both sides of the removal position have opposite magnetic pole arrangements. It further comprises emission detection means for emitting light to the reaction container located at the detection position of the movement path and detecting light transmitted through the reaction container,
The inspection apparatus according to claim 1, wherein the magnetic field forming unit is provided in an area further excluding the optical path.   The inspection apparatus according to claim 7, wherein the magnetic field forming unit is located below the optical path.   The inspection apparatus according to claim 7, wherein the magnetic field forming unit is positioned at substantially the same height as the optical path.   The inspection device according to any one of claims 7 to 9, wherein the firing detection means performs detection a plurality of times for each reaction container.

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