JP7161851B2 - Method for confirming state of immunoassay device and immunoassay device - Google Patents

Description

The present invention relates to an immunoassay device for measuring a test substance in a sample.

As a technique for increasing the sensitivity of immunoassay, there is an immunoassay device using an immune complex transfer method (see, for example, Patent Document 1).

As shown in FIG. 23, the immunoassay apparatus disclosed in Patent Document 1 forms an immune complex 913 containing a test substance 911 and a labeling substance 912 on a solid phase carrier 914 in a first container 901. , release the immune complex 913 from the solid phase carrier 914 by the release reagent 915 . Then, the immunoassay apparatus leaves the solid phase carrier 914 in the first container 901 and executes the immune complex transfer method in which the liquid phase containing the released immune complex 913 is transferred to the second container 902. 2. A signal based on labeling substance 912 contained in immune complex 913 in container 902 is detected.

JP 2017-49059 A

By the way, since the measurement results obtained by the immunoassay device are used as a basis for determining disease diagnosis and treatment policy, the reliability of the measurement results is required. As a method to ensure the reliability of measurement results, there is a conventional method of measuring a quality control sample containing a known concentration of the test substance. Used in measuring equipment.

However, in an immunoassay device using the immune complex transfer method, a function not found in conventional immunoassay devices is added in order to execute the immune complex transfer method. For this reason, the conventional method of measuring quality control samples may not be able to confirm the state of normality, abnormality, etc. of the function for performing the immunocomplex transfer method. Even in Patent Document 1 using the immune complex transfer method, there is no disclosure of a method for checking the state of the function for executing the immune complex transfer method, and the function for executing the immune complex transfer method is not disclosed. It is desirable to be able to easily check the status of

The present invention is directed to making it possible to easily check the state of the function for executing the immune complex transfer method in an immunoassay device.

A method for confirming the state of an immunoassay device according to the first aspect of the present invention provides an immune complex (84) containing a test substance (81) in a specimen and a labeling substance (83) and supported on a solid phase carrier (82). ) in a first container (11) containing an immunoconjugate (84) released from a solid phase carrier (82) and transferring the liquid phase in the first container (11) to a second container (12). A method for confirming the state of an immunoassay device (100) for body metastasis processing, comprising: a first container (11 ) in a first container (11), transferring the liquid phase in the first container (11) to a second container (12), and Based on the step of detecting the labeling substance (21) in the transferred second container (12) and comparing the detected value of the labeling substance (21) in the second container (12) with the reference value, the complex and determining the presence or absence or degree of abnormality in the function of collecting the solid phase carriers (82) in the first container (11) in the immunoassay device (100) for performing metastasis treatment.
A method for confirming the state of an immunoassay device according to the second aspect of the present invention provides an immune complex (84) containing a test substance (81) in a sample and a labeling substance (83) and supported on a solid phase carrier (82). ) in a first container (11) containing an immunoconjugate (84) released from a solid phase carrier (82) and transferring the liquid phase in the first container (11) to a second container (12). A method for confirming the state of an immunoassay device (100) that performs body metastasis processing, comprising: a step of transferring to a second container (12); a step of detecting the labeling substance (21) in the second container (12) to which the liquid phase has been transferred; Presence or absence of abnormality in the function of transferring the liquid phase in the first container (11) to the second container (12) in the immunoassay device (100) that performs the complex transfer treatment based on the comparison between the detected value and the reference value. or determining the degree of abnormality .

In the method for confirming the state of an immunoassay device according to the first and second aspects, the first container (11) containing the control sample (20) containing the labeling substance (21) is , a liquid phase transfer operation similar to the complex transfer treatment can be performed to detect the labeling substance (21) in the control sample (20) transferred to the second container (12). If the complex transfer process is not performed normally, an abnormal detection result deviating from the expected detection result will be obtained. This makes it possible to determine the state of the immunoassay device, such as whether or not the complex transfer treatment was performed normally, based on the detection result of the labeling substance (21) in the second container (12). As a result, it is possible to easily check the state of the function for executing the immune complex transfer method in the immunoassay device. Here, in the complex transfer treatment, in order to transfer the liquid phase containing the immune complex (84) to the second container (12) and leave the solid phase carrier (82) in the first container (11), It is important whether the function of collecting the solid support (82) in the first container (11) is normal. A function of transferring the liquid phase in the first container (11) to the second container (12) in order to detect the immune complex (84) transferred to the second container (12) by the complex transfer treatment. is normal or not. According to the first and second aspects, the presence or absence of abnormality in these functions can be determined, which is particularly useful for ensuring the reliability of measurement results.

In the method for confirming the state of the immunoassay device according to the first aspect, preferably, in the step of determining the state of the function of collecting the solid phase carrier (82), the labeling substance (21) is detected in the second container (12). Abnormalities in the function of collecting the solid phase carriers (82) in the first container (11) are determined based on the fact that the value exceeds the reference value (V1).
In the method for confirming the state of an immunoassay device according to the second aspect, preferably, in the step of determining the state of the function of transferring the liquid phase in the first container (11) to the second container (12), the second container Abnormality in the function of transferring the liquid phase in the first container (11) to the second container (12) is judged based on the fact that the detected value of the labeling substance (21) in (12) is below the reference value.
With this configuration, by presetting the reference values (V1, V2) for distinguishing between normality and abnormality based on the detection value obtained by measurement in the normal state, the detection value and the reference value can be obtained. Only by comparing the values (V1, V2), it is possible to easily determine whether the complex transfer processing is abnormal.

In the method for confirming the state of an immunoassay device according to the first or second aspect, preferably, before the step of transferring the liquid phase in the first container (11) to the second container (12), the immunoassay device (100 ) to dispense the control sample (20) into the first container (11). With this configuration, even if the user of the immunoassay device (100) or the service staff who performs the maintenance service of the device does not prepare the control sample (20) in the first container (11) in advance, the immunoassay can be performed. The control sample (20) can be easily accommodated in the first container (11) by the device (100).

In the method for confirming the state of an immunoassay device according to the first aspect , the solid phase carriers (22) are preferably magnetic particles, and the process of collecting the solid phase carriers (22) is preferably performed by moving the magnetic particles by the magnetic force source (52). The step of determining the state of the function of collecting the solid phase carrier (82) , including the process of collecting magnetism, is based on comparison between the detected value of the labeling substance (21) in the second container (12) and the reference value , It includes a step of judging an abnormality in the magnetic collecting function of the magnetic force source (52). In this specification, the term "magnetism collection function" means the function of collecting magnetic particles, and a normal magnetism collection function means that the magnetism cannot be fully collected and ) is kept within an acceptable range. With this configuration, the magnetic particles to which the labeling substance (21) is bound are magnetically collected. It can be easily determined whether the magnetic function is normal or abnormal.

When determining an abnormality in the magnetic collection function of the magnetic force source (52), preferably, when the detected value of the labeling substance (21) exceeds the reference value (V1), the magnetic force source (52) detects an abnormality in the magnetic collection function. Determine that there is. With this configuration, when the detected value of the labeling substance (21) exceeds the reference value (V1), the magnetic particles are not sufficiently collected when the liquid phase is transferred to the second container (12). Since the possibility is high, the magnetic collecting function of the magnetic force source (52) can be easily determined by comparing the detected value and the reference value (V1).

In this case, preferably, the reference value (V1) is an expected detection value of the labeling substance (21) corresponding to the allowable upper limit amount of the magnetic particles transferred to the second container (12) without magnetization. With this configuration, when the amount of magnetic particles exceeding the allowable upper limit amount is transferred to the second container (12), it can be easily determined that the magnetic force collection function of the magnetic force source (52) is abnormal. . Therefore, by confirming that the allowable upper limit amount is not exceeded, the reliability of the measurement result can be ensured.

In the configuration for performing the process of collecting the solid phase carriers, preferably, before the step of transferring the liquid phase in the first container (11) to the second container (12), in the first container (11), a sample containing a test substance (81) of, a labeling substance (83) that binds to the test substance (81), a capture substance (86) that binds to the test substance (81), and a capture substance (86) that binds to Further comprising the step of preparing a control sample (20) in the first container (11) by contacting it with a solid phase support (82). With this configuration, the solid phase carrier (82) bound with the labeling substance (83) is transferred to the first container (11) by the same processing steps as in the actual measurement of the sample containing the test substance (81). can be formed in

In this case, preferably, the control sample (20) contains the first solid phase carrier (82a) dispensed into the first container (11) prior to the complex transfer treatment during sample measurement. With this configuration, the first solid phase carrier (82a) dispensed when actually measuring the specimen containing the test substance (81) is used to bind the labeling substance (21) to the solid phase carrier. (22) can be formed in the first container (11). That is, since it is not necessary to separately prepare a dedicated solid phase carrier (22) for checking the state of the immunoassay device (100), the convenience of the immunoassay device (100) can be improved.

When the step of contacting the sample containing the test substance (81), the labeling substance (83), the capture substance (86), and the solid phase carrier (82) is provided, preferably the control sample (20) is It includes a second solid phase carrier (82b) that is dispensed into the second container (12) after complex transfer treatment at the time of measurement. With this configuration, the solid phase carrier to which the labeling substance (21) is bound is obtained using the second solid phase carrier (82b) that is dispensed when actually measuring the sample containing the test substance (81). (22) can be formed in the first container (11). That is, since it is not necessary to separately prepare a dedicated solid phase carrier (22) for checking the state of the immunoassay device (100), the convenience of the immunoassay device (100) can be improved.

When the step of contacting the sample containing the test substance (81), the labeling substance (83), the capture substance (86), and the solid phase carrier (82) is preferably performed, the liquid in the first container (11) A solid phase carrier (82) bound with an immune complex (84) containing a test substance (81), a labeling substance (83) and a capture substance (86) before the step of transferring the phase to the second container (12). and a step of performing BF separation for separating the liquid phase. With this configuration, the labeling substance (83) in the liquid phase that has not bound to the solid phase carrier (82) can be removed from the first container (11) by BF separation. Therefore, in the step of transferring the liquid phase in the first container (11) to the second container (12), it is possible to suppress the labeling substance (83) from being mixed in the liquid phase. The detection accuracy of the labeling substance (83) for the can be improved.

In this case, preferably, in the complex transfer treatment, the immune complex (84) is released from the solid phase carrier (82) by dispensing the free reagent (85) into the first container (11), and the BF After the step of separating, the liquid phase free of free reagents (85) is divided into the first container (11) before the step of transferring the liquid phase in the first container (11) to the second container (12). The step of pouring is further provided. With this configuration, the liquid phase (25) not containing the free reagent (85) is used instead of the free reagent (85) dispensed when actually measuring the specimen containing the test substance (81). Since the sample is dispensed, the status of the immunoassay device (100) can be confirmed by the same operation as dispensing the free reagent (85) during actual sample measurement. Even in that case, the binding between the labeling substance (83) and the solid phase carrier (82) is not eliminated, so the function of collecting the solid phase carrier (82) can be properly confirmed.

In the method for confirming the state of an immunoassay device according to the first aspect , preferably, the control sample (20) is a third solid-phase carrier ( 23). With this configuration, the solid phase carrier (22) is used as a dedicated reagent for confirming the state of the immunoassay device (100), using the third solid phase carrier (23) that does not contain the test substance (81). ) can be checked. When the solid phase carrier (22) binds not only the labeling substance (21) but also the test substance (81), the binding solid phase carrier (22) and the labeling substance ( 21) are prepared in a plurality of types, whereas the third solid-phase carrier (23) containing no test substance (81) is used for the immunoassay device (100) regardless of the type of the test substance (81). You can check the status. Therefore, the status of the immunoassay device (100) can be checked more easily.

In the method for confirming the state of an immunoassay device according to the second aspect , preferably, the step of transferring the liquid phase in the first container (11) to the second container (12) includes: and discharging the sucked liquid phase into the second container ( 12), and determine the state of the function of transferring the liquid phase in the first container (11) to the second container (12) The process includes a process of judging an abnormality in the pipetting function based on a comparison between the detected value of the labeling substance (21) in the second container (12) and the reference value . As used herein, the term "dispensing function" includes the function of aspirating the liquid phase in the first container (11) and the function of discharging the aspirated liquid phase into the second container (12). Normal function means that the liquid phase can be sucked from the first container (11) and the sucked liquid phase can be discharged to the second container (12). With this configuration, it is possible to easily determine whether the pipetting function of sucking the liquid phase and discharging the liquid phase is normal or abnormal based on the detected value of the labeling substance (21).

When judging an abnormality in the pipetting function, it is preferably judged that there is an abnormality in the pipetting function when the detected value of the labeling substance (21) is lower than the reference value (V2). With this configuration, when the detected value of the labeling substance (21) is below the reference value (V2), the liquid containing the labeling substance (21) is transferred from the first container (11) to the second container (12). Since there is a high possibility that the phase has not been properly transferred, the dispensing function can be easily determined by comparing the detected value with the reference value (V2).

In this case, preferably, the reference value (V2) is a value set as the allowable limit of the expected detection value of the labeling substance (21) contained in the controlled sample (20). With this configuration, if the detection value is below the reference value (V2) even after the step of transferring the liquid phase containing the labeling substance (21) to the second container (12) is performed, the dispensing function is abnormal. can be easily determined. Therefore, by confirming that the detected value exceeds the reference value (V2), the reliability of the measurement result can be ensured.

In the method for confirming the state of an immunoassay device according to the second aspect , the control sample (20) preferably contains a labeling substance (83) dispensed into the first container (11) during sample measurement. With this configuration, the liquid phase in the first container (11) is transferred to the second container using the labeling substance (83) dispensed when actually measuring the specimen containing the test substance (81). It can be confirmed whether the function transferred to (12) is normal. That is, since it is not necessary to separately prepare a dedicated labeling substance (21) for confirming the state of the immunoassay device (100), the convenience of the immunoassay device (100) can be improved.

In the immunoassay device state confirmation method according to the first or second aspect, the labeling substance (21) contained in the control sample (20) is an enzyme, and the labeling substance (21) in the second container (12) is The detecting step may be performed by adding a substrate for the enzyme to the second container (12) and measuring the signal generated from the reaction product produced by the enzymatic reaction.

An immunoassay device (100) according to the third aspect of the present invention is an immune complex (84) containing a test substance (81) in a sample and a labeling substance (83) and supported on a solid phase carrier (82). releasing the immunoconjugate (84) from the solid phase carrier (82) in the first container (11) containing the complex An immunoassay device (100) for performing transfer treatment, wherein a solid phase in a first container (11) containing a control sample (20) containing a solid phase carrier (82) to which at least a labeling substance (21) is bound a mechanism part (50) for collecting the carrier (82) in the first container (11) and transferring the liquid phase in the first container (11) to the second container (12); Based on the comparison between the detection unit (60) that detects the labeling substance (21) in the second container (12) to which the is transferred and the detection value of the detection unit (60) and the reference value, in the complex transfer treatment and a judgment unit (70) for judging abnormality of the function of collecting the solid phase carriers (82) in the first container (11) .
An immunoassay device (100) according to the fourth aspect of the present invention is an immune complex (84) containing a test substance (81) in a sample and a labeling substance (83) and supported on a solid phase carrier (82). releasing the immunoconjugate (84) from the solid phase carrier (82) in the first container (11) containing the complex An immunoassay device (100) for performing transfer treatment, wherein a liquid phase in a first container (11) containing a control sample (20) containing at least a labeling substance (21) as a liquid phase is transferred to a second container (12). ), a detection unit (60) for detecting the labeling substance (21) in the second container (12) to which the liquid phase has been transferred, and the detection value of the detection unit (60) and a determination unit (70) for determining an abnormality in the function of transferring the liquid phase in the first container (11) to the second container (12) in the complex transfer treatment based on the comparison between the .

In the immunoassay device (100) according to the third and fourth aspects, by being configured as described above, for the first container (11) containing the control sample (20) containing the labeling substance (21), A liquid phase transfer operation similar to the complex transfer treatment can be performed to detect the labeling substance (21) in the control sample (20) transferred to the second container (12). If the complex transfer process is not performed normally, an abnormal detection result deviating from the expected detection result will be obtained. As a result, the determination unit (70) can determine whether or not the complex transfer treatment was performed normally based on the detection result of the labeling substance (21) in the second container (12). It is possible to easily check the state of the function for executing the immune complex transfer method in In addition, in the immunoassay device (100) according to the third and fourth aspects, the determination unit (70) has a function of collecting the solid phase carrier (22) in the complex transfer treatment and transferring the liquid phase to the second container (12). It is particularly useful for ensuring the reliability of measurement results because it is possible to determine whether or not there is an abnormality in the function to be transferred to.

In the immunoassay device (100) according to the third aspect , the control sample (20) preferably contains magnetic particles bound with a labeling substance (21), and the mechanism section (50) comprises the first container (11) It includes a magnetic force source (52) that collects the magnetic particles to which the labeling substance (21) is bound, and a judging section (70) judges whether the magnetic force source (52) has an abnormality in the magnetic force collecting function. With this configuration, the solid phase carrier (22) to which the labeling substance (21) is bound is collected in the first container (11). , when the liquid phase is transferred to the second container (12), there is a possibility that the solid phase carrier (22) is not sufficiently collected and the solid phase carrier (22) is also transferred to the second container (12). can be determined to be high. Therefore, it can be easily determined whether the magnetic collecting function of the magnetic force source (52) in the complex transition process is normal or abnormal.

In the immunoassay device (100) according to the fourth aspect , the control sample (20) preferably contains a solution in which the labeling substance (21) is dissolved, and the mechanism section (50) is placed in the first container (11). aspiration tube (51) for aspirating the liquid phase and discharging the aspirated liquid phase into the second container (12); . With this configuration, the labeling substance (21) exists as a liquid phase in the first container (11). When dispensing to (12), it can be determined that there is a high possibility that the dispenser using the suction tube (51) for sucking and discharging the liquid phase is not normal. Therefore, it is possible to easily confirm whether or not there is an abnormality in the pipetting function of the suction tube (51) in the complex transfer process.

In the immunoassay device (100) according to the third aspect, the mechanism section (50) preferably includes a sample dispensing section (120) for dispensing a sample containing a test substance (81); a reagent dispensing unit (130) for dispensing a labeling reagent containing (21, 83) and a solid phase reagent containing a solid phase carrier (22, 82), in the first container (11) is configured to prepare a control sample (20) at With such a configuration, the immunoassay device (100) can be easily used without the user or service staff of the immunoassay device (100) having to prepare the control sample (20) in the first container (11) in advance. In addition, the control sample (20) can be accommodated in the first container (11).

In this case, preferably, the reagent dispensing section (130), when measuring the sample, supplies the release reagent (85) that releases the immune complex (84) from the solid phase carrier (82) to the first container ( 11), and when judging the abnormality of the function of collecting the solid phase carrier (82) in the first container (11), a liquid not containing the free reagent (85) is used instead of the free reagent (85). Dispense phase (25). With this configuration, the liquid phase (25) not containing the free reagent (85) is used instead of the free reagent (85) dispensed when actually measuring the specimen containing the test substance (81). Since the sample is dispensed, the status of the immunoassay device (100) can be confirmed by the same operation as dispensing the free reagent (85) during actual sample measurement. Even in this case, since the binding between the labeling substance (83) and the solid phase carrier (82) is not eliminated, the magnetic flux collection function of the solid phase carrier (82) can be properly confirmed.

In the configuration in which the mechanism part (50) prepares the control sample (20) in the first container (11), the mechanism part (50) preferably contains a test substance (81) and a labeling substance (83). A BF separation section (170) for separating a solid phase carrier (82) bound to an immune complex (84) and a liquid phase is included, and the BF separation section (170) is a control sample in the first container (11). BF separation for (20) is performed. With this configuration, the labeling substance (83) in the liquid phase that has not bound to the solid phase carrier (82) can be removed from the first container (11) by BF separation. Therefore, in the step of transferring the liquid phase in the first container (11) to the second container (12), it is possible to suppress the labeling substance (83) from being mixed in the liquid phase. The detection accuracy of the labeling substance (83) for the can be improved.

ADVANTAGE OF THE INVENTION According to this invention, the state confirmation of the function for performing the immune complex transfer method in an immunoassay apparatus can be performed simply.

FIG. 2 is a schematic diagram showing a first example of a method for confirming the state of an immunoassay device; FIG. 5 is a schematic diagram showing a second example of a method for checking the state of an immunoassay device; 1 is a schematic diagram showing an outline of an immunoassay device; FIG. FIG. 2 is a diagram for explaining an outline of sample measurement by an immunoassay device; FIG. FIG. 2 is a schematic plan view showing a specific configuration example of an immunoassay device; FIG. 4 is a schematic diagram for explaining a specimen pipetting unit; FIG. 4 is a schematic diagram for explaining a reagent dispensing section; It is a schematic diagram for demonstrating a BF separation part. FIG. 4 is a schematic diagram showing configuration examples (A) to (C) of a mechanism for transferring a liquid phase from a first container to a second container. It is a schematic diagram for demonstrating a detection part. FIG. 4 is a diagram for explaining a method of determining a magnetic collecting function; FIG. 3 is a diagram for explaining Embodiment 1 for confirming the magnetic collecting function of an immunoassay device. FIG. 10 is a diagram for explaining Embodiment 2 for confirming the magnetism collecting function of the immunoassay device. FIG. 10 is a diagram for explaining Embodiment 3 for confirming the magnetic collecting function of the immunoassay device. FIG. 10 is a diagram for explaining Example 1 performed to confirm the effect of Embodiment 3; 4 is a diagram showing measurement results of Example 1. FIG. FIG. 10 is a diagram for explaining a method of judging a dispensing function; FIG. 10 is a diagram for explaining Embodiment 4 for confirming the dispensing function of the immunoassay device. FIG. 10 is a diagram for explaining Embodiment 5 for confirming the dispensing function of the immunoassay device. FIG. 11 is a diagram for explaining Example 2 performed to confirm the effect of Embodiment 5; FIG. 10 is a diagram showing measurement results of Example 2; 4 is a flow chart for explaining the operation of the immunoassay device; It is a figure for demonstrating a prior art.

Hereinafter, embodiments will be described based on the drawings.

[Overview of method for confirming status of immunoassay device]
First, with reference to FIGS. 1 and 2, an outline of a method for confirming the state of an immunoassay device according to one embodiment will be described.

The method for confirming the state of the immunoassay device 100 is a method for confirming the state of the immunoassay device 100 that performs the complex transfer process of transferring the liquid phase in the first container 11 to the second container 12 .

Immunoassay apparatus 100 measures a test substance in a specimen using antigen-antibody reaction. A specimen is, for example, a biological sample such as blood collected from a living body. Blood may be whole blood, serum or plasma. The test substances are, for example, antigens or antibodies, proteins, peptides, etc. contained in blood.

The first container 11 and the second container 12 are, for example, cylindrical containers that are open on the upper end side and closed on the bottom on the lower end side, and are reaction containers (cuvettes) that can contain liquids such as specimens and reagents. These containers are, for example, disposable resin containers. In this case, the used container can be discarded as it is. The first container 11 and the second container 12 may have the same shape or may have different shapes.

In this embodiment, the immunoassay device 100 performs complex transfer processing by an immune complex transfer method. In the immune complex transfer method (see FIG. 4), an immune complex (combined by antigen-antibody reaction) 84 containing a test substance 81 and a labeling substance 83 in a sample and supported on a solid-phase carrier 82 is stored. This is a method of releasing the immune complex 84 from the solid phase carrier 82 and separating the released immune complex 84 from the solid phase carrier 82 in one container 11 . The immunoassay device 100 performs complex transfer processing by leaving the solid phase carrier 82 in the first container 11 and transferring the liquid phase in the first container 11 to the second container 12 . The immunoassay device 100 has a of solid support 82 are collected.

As a result, the unnecessary labeled substance 83 non-specifically bound to the solid phase carrier 82 during the process of forming the immune complex 84 on the solid phase carrier 82 is separated from the immune complex 84 together with the solid phase carrier 82. . As a result, the noise level can be lowered compared to the case where the measurement is performed without the immunocomplex transfer method, so the baseline of the measurement data can be lowered and the sensitivity of the immunoassay can be increased.

In this specification, the immune complex can be a labeling substance (an antibody that binds to the test substance or a labeling substance bound to a light source). An immunoconjugate can be a conjugate of a labeling substance and an antibody. An immunoconjugate can be a conjugate of a labeling substance, an antibody, and a test substance.

<Method for checking the status of the immunoassay device>
The method for confirming the state of the immunoassay device 100 of the present embodiment is to confirm whether or not the function for performing the complex transfer processing by the immunoassay device 100 is normal.

As shown in FIGS. 1 and 2, the method for confirming the state of the immunoassay device 100 includes a step of transferring the liquid phase in the first container 11 containing the control sample 20 containing at least the labeled substance 21 to the second container 12 ( a), step (b) of detecting the labeling substance 21 in the second container 12 to which the liquid phase has been transferred, and performing the complex transfer treatment based on the detection result of the labeling substance 21 in the second container 12. and a step (c) of determining the state of the immunoassay device 100 . That is, in the state confirmation method, as step (a), the same liquid phase transfer operation as in the complex transfer process at the time of sample measurement by the immunoassay device 100 is performed. Then, as step (b), the control sample 20 in the transferred second container 12 is measured. In step (c), state determination is performed based on the detection result obtained in step (b).

Step (a) is performed, for example, by a dispensing process in which the liquid phase in the first container 11 is sucked by the suction tube 51 provided in the immunoassay device 100 and the sucked liquid phase is discharged into the second container 12 .

In step (b), the labeling substance 21 in the second container 12 is detected, for example, by the detection unit provided in the immunoassay device 100 .

In step (c), for example, the determination unit provided in the immunoassay device 100 performs state determination based on the detection results. Step (c) can also be performed by, for example, a computer connected to the immunoassay device 100, a server device capable of communicating with the immunoassay device 100 via a network, or the like.

<Labeling substance>
The labeling substance is not particularly limited as long as it can emit a detectable or measurable signal. Examples include enzymes, fluorescent substances, and radioactive isotopes. Enzymes include, but are not limited to, alkaline phosphatase, β-galactosidase, peroxidase, glucose oxidase, tyrosinase, acid phosphatase, luciferase, and the like. Fluorescent substances include fluorescein isothiocyanate (FITC), coumarin, rhodamine, fluorescein, Cy3, Cy5, Hoechst 33342, 4′,6-diamidino-2-phenylindole (DAPI), propidium iodide (PI), Alexa Fluor ( Examples include, but are not limited to, fluorescent dyes such as the Molecular Probes (registered trademark) series, and fluorescent proteins such as green fluorescent protein (GFP). Radioisotopes include, but are not limited to, 125I, 14C, 32P, and the like.

In the present specification, the labeling substance 21 is a concept including a labeling antibody (an antibody that binds to a test substance and a labeling substance bound thereto) used as a measurement reagent.

Further, in the present specification, the labeling substance 21 contained in the control sample 20 may be the same labeling substance as the labeling substance 83 (see FIG. 4) contained in the immune complex 84 during measurement of the sample, or may be different. It may be a labeling substance.

Detection of the labeling substance may be performed by an appropriate method according to the type of label used for the labeling substance, and the detection method is not particularly limited. The abundance of the labeling substance may be detected using detection means compatible with the labeling substance. For example, when the label used for the labeling substance is an enzyme, the measurement can be performed by measuring the light, color, etc. generated by reacting the substrate with the enzyme. A photomultiplier tube, a spectrophotometer, a luminometer, or the like can be used as the detector in this case. Moreover, when the labeling substance is a radioactive isotope, a scintillation counter or the like can be used as the detection unit. When the labeling substance is a fluorescent substance, the labeling substance can be detected using a fluorescence detector capable of detecting emitted fluorescence.

When the labeling substance is an enzyme, a known substrate may be appropriately selected according to the enzyme used. For example, CDP-Star (registered trademark), (4-chloro-3-(methoxyspiro[1,2-dioxetane-3,2′-(5′-chloro)trixyl) as a substrate when alkaline phosphatase is used as an enzyme [3.3.1.13,7]Decan]-4-yl)phenyl phosphate disodium), CSPD® (3-(4-methoxyspiro[1,2-dioxetane-3,2-( chemiluminescent substrates such as 5′-chloro)tricyclo[3.3.1.13,7]decane]-4-yl)phenylphosphate); p-nitrophenyl phosphate, 5-bromo-4-chloro- Luminescent substrates such as 3-indolyl phosphate (BCIP), 4-nitrobluetetrazolium chloride (NBT), iodonitrotetrazolium (INT); fluorescent substrates such as 4-methylumberiphenyl phosphate (4MUP); 5-bromo Chromogenic substrates such as 4-chloro-3-indolyl phosphate (BCIP), disodium 5-bromo-6-chloro-indolyl phosphate, p-nitrophenyl phosphate, and the like can be used.

A detection result reflecting the abundance of the labeling substance 21 is obtained by the detection. The detection result can be acquired in the form of numerical information as a detection value corresponding to the abundance of the labeling substance 21 .

(Control Sample Containing Solid-Phase Carrier Bound with Labeling Substance)
As shown in FIG. 1, when the control sample 20 contains a solid phase carrier 22 bound with a labeling substance 21, a process of collecting the solid phase carrier 22 is performed when performing step (a). According to step (a), the liquid phase is transferred from the first container 11 to the second container 12 leaving the solid phase carrier 22 behind. Therefore, the second container 12 contains a liquid phase that does not contain the solid phase carrier 22 to which the labeling substance 21 is bound.

<Solid phase carrier>
Solid phase carriers are known particles used in immunoassays, for example. Particles include, for example, magnetic particles, latex particles, red blood cells, gelatin particles, and the like. Magnetic particles are preferably used as the solid phase carrier 22 in order to separate the liquid phase from the first container 11 . The magnetic particles may be particles that contain a material having magnetism as a base material and that are used for normal immunoassays. For example, magnetic particles using Fe ₂ O ₃ and/or Fe ₃ O ₄ , cobalt, nickel, phyllite, magnetite, etc. as the substrate can be used.

In the present specification, the solid-phase carrier 22 contained in the control sample 20 may be the same solid-phase carrier as the solid-phase carrier 82 that binds to the immune complex 84 during sample measurement, or may be a different solid-phase carrier. may be

The binding between the labeling substance and the solid phase carrier may be carried out by direct binding of the two by chemical bonding or the like, or by indirect binding via a capture substance. For indirect binding, combinations such as biotin and avidins, hapten and anti-hapten antibody, nickel and histidine tag, glutathione and glutathione-S-transferase can be used. In addition, "avidins" means including avidin and streptavidin.

As an example, a biotin-conjugated fluorescent dye can be bound to a streptavidin-coated solid support. As such a solid phase carrier 22 to which a labeling substance 21 is bound, a commercially available product can be preferably used.

In addition, instead of the sample, a test substance of known concentration is used as a quality control sample (calibrator), and measurement processing is performed using a measurement reagent for each measurement item, so that the solid phase to which the labeling substance 21 is bound A carrier 22 may be formed. That is, the solid phase carrier 22 bound with the labeling substance 21 is produced by forming an immune complex 84 consisting of the labeling substance 83, the test substance 81 and the capture substance 86 on the solid phase carrier 82 shown in FIG. may be In this case, such a substance can be produced by causing the immunoassay device 100 to perform part or all of the immunoassay operation, as will be described later.

In FIG. 1, when step (b) is performed, the labeling substance 21 in the second container 12 is detected. When the complex transfer processing of the immunoassay device 100 functions normally, the solid phase carrier 22 is not carried over to the second container 12 in excess of the allowable upper limit for use. Therefore, when the immunoassay device 100 has a normal function of collecting the solid-phase carrier 22, the detection value of the labeling substance 21 in step (b) is as low as when a blank sample containing no labeling substance 21 is measured. becomes. Here, the blank sample is a sample that does not contain the labeling substance 21 . On the other hand, when the function of collecting the solid-phase carriers 22 of the immunoassay device 100 is abnormal, for example, when the solid-phase carriers 22 are in a dispersed state without being collected in the first container 11, in step (a), The solid phase carrier 22 bound with the labeling substance 21 is transferred to the second container 12 together with the liquid phase. Therefore, when the function of the immunoassay device 100 to collect the solid-phase carrier 22 is abnormal, the detected value of the labeling substance 21 in step (b) becomes an abnormally high value outside the allowable range of the detected value in the normal state.

Therefore, in step (c), the detection result obtained in step (b) is obtained. Based on the detection result, the state of the immunoassay device 100 in the complex transfer processing is determined. That is, it is determined from the detection result whether or not the complex transfer processing has been performed normally. The status to be determined can be a binary classification of "normal" or "abnormal" or "0 (no abnormality)" or "1 (abnormal)". As for the state to be determined, the degree of normality or abnormality may be determined according to the detected value. For example, within the normal state, set the judgment range such as completely within the normal range, outside the normal range but within the allowable range, within the allowable range but within the boundary range close to the abnormal value (outside the allowable range). to determine which range it belongs to. In this case, the user can obtain information for determining the necessity of maintenance of the immunoassay device 100, for example, based on the determination result.

(Control Sample Containing Liquid with Labeled Substance Dissolved)
As shown in FIG. 2, when the controlled sample 20 contains a liquid in which the labeling substance 21 is dissolved, the liquid phase containing the labeling substance 21 is transferred from the first container 11 to the second container 12 in step (a). . Therefore, the liquid phase containing the labeling substance 21 is accommodated in the second container 12 .

In FIG. 2, when step (b) is performed, the labeling substance 21 in the second container 12 is detected. When the function of transferring the liquid phase in the first container 11 of the immunoassay device 100 to the second container 12 is normal, the labeled substance 21 in the liquid phase is sufficiently transferred into the second container 12 . Therefore, when the function of transferring the liquid phase in the first container 11 of the immunoassay device 100 to the second container 12 is normal, the detected value of the labeling substance 21 in step (b) is the labeling substance contained in the controlled sample 20. It falls within the tolerance expected from the 21 known concentrations. On the other hand, when the function of transferring the liquid phase in the first container 11 of the immunoassay device 100 to the second container 12 is abnormal, for example, the liquid phase cannot be transferred from the first container 11 to the second container 12. In this case, the liquid phase containing the labeling substance 21 is not transferred to the second container 12 even in step (a). Therefore, when the function of transferring the liquid phase in the first container 11 of the immunoassay device 100 to the second container 12 is abnormal, the detection value of the labeling substance 21 in step (b) is different from the known concentration of the labeling substance 21. A value outside the expected acceptable range.

Therefore, in step (c), from the detection results obtained by performing steps (a) and (b) on the control sample 20 containing the liquid in which the labeling substance 21 is dissolved, immunoassay in the complex transfer treatment The state of device 100 is determined. That is, it is determined whether or not the complex transfer processing was performed normally.

As described above, in the method for confirming the state of an immunoassay device according to the present embodiment, the same operation as the complex transfer processing is performed on the first container 11 containing the controlled sample 20 containing the labeling substance 21, and the second The labeled substance 21 in the control sample 20 transferred to the container 12 can be detected. If the complex transfer process is not performed normally, an abnormal detection result deviating from the expected detection result will be obtained. Thus, based on the detection result of the labeling substance 21 in the second container 12, it is possible to determine the state of the immunoassay device 100, such as whether or not the complex transfer processing was normally performed. As a result, it is possible to easily check the state of the function for executing the immune complex transfer method in the immunoassay device 100 .

<Treatment for collecting the solid-phase carrier>
As shown in FIG. 1, when the control sample 20 contains the solid-phase carrier 22 to which the labeling substance 21 is bound, in the step (a) of transferring the liquid phase in the first container 11 to the second container 12, the first container 11 A process of collecting the solid-phase carrier 22 bound with the labeling substance 21 is performed inside.

The process of collecting the solid phase carriers 22 is performed, for example, by centrifuging the first container 11 using the immunoassay device 100 to sediment the solid phase carriers 22 to the bottom of the container. When the solid phase carriers 22 are magnetic particles, the process of collecting the solid phase carriers 22 includes the process of collecting the magnetic particles by the magnetic force source 52 . For example, the magnetic particles are collected by the magnetic force source 52 provided in the immunoassay device 100 .

As a result, the solid-phase carrier 22 to which the labeling substance 21 is bound is collected in the first container 11. Therefore, when the detection value of the labeling substance 21 increases, for example, when the liquid phase is transferred to the second container 12, the solid-phase carrier 22 is It is highly probable that the solid phase carrier 22 was also transferred because the carrier 22 was not sufficiently collected. Therefore, it can be easily confirmed whether or not the function of collecting the solid phase carriers 22 in the first container 11 in the complex transfer treatment is normal.

In addition to steps (a) and (b), the following steps may be included.

(Step of judging abnormality in complex transfer treatment)
For example, in FIGS. 1 and 2, the immunoassay device state confirmation method further includes a step of determining abnormality in the complex transfer process based on the detection result of the labeling substance 21 in the second container 12 . As described above, the presence or absence of an abnormality in the complex transfer process can be determined by determining the magnitude of the detection value obtained in step (b). Thus, for example, by judging the detection result in the immunoassay device 100 that has detected the labeling substance 21 in the controlled sample 20, it is possible to judge whether or not there is an abnormality in the complex transfer process. Determination can be performed by, for example, the determining unit 70 (see FIG. 3) provided in the immunoassay device 100, or an external device such as a host computer communicably connected to the immunoassay device 100, or the like.

Specifically, the function for performing the complex transfer treatment includes the function of collecting the solid phase carrier 22 in the first container 11 and the function of transferring the liquid phase in the first container 11 to the second container 12. include. Therefore, the step of determining abnormality in the complex transfer treatment includes at least one of the function of collecting the solid phase carriers 22 in the first container 11 and the function of transferring the liquid phase in the first container 11 to the second container 12. including determining any anomalies.

In the complex transfer treatment, in order to transfer the liquid phase containing the immune complex 84 to the second container 12 and leave the solid phase carrier 22 in the first container 11, the solid phase carrier 22 in the first container 11 is removed. It is important whether the collection function is normal or not. As shown in FIG. 1, when the control sample 20 contains the solid phase carrier 22 bound with the labeling substance 21, the solid phase carrier 22 in the first container 11 is removed based on the detection result of step (b). It can be determined whether the collection function is normal.

In addition, in the complex transfer treatment, whether or not the function of transferring the liquid phase in the first container 11 to the second container 12 to detect the immune complex 84 transferred to the second container 12 is normal. important. As shown in FIG. 2, when the control sample 20 contains a liquid in which the labeling substance 21 is dissolved, the liquid phase in the first container 11 is transferred to the second container 12 based on the detection result of step (b). It can be determined whether or not the transfer function is normal. According to the above configuration, it is possible to determine whether or not there is an abnormality in at least one of these functions, which is particularly useful for ensuring the reliability of measurement results. In order to ensure high reliability, both the determination of the function of collecting the solid phase carriers 22 in the first container 11 and the determination of the function of transferring the liquid phase in the first container 11 to the second container 12 should be performed. are preferably performed respectively.

When performing the step of determining abnormality in the complex transfer treatment, abnormality is detected based on whether the detected value of the labeling substance 21 in the second container 12 exceeds the reference value V1 or the detected value is lower than the reference value V1. judge. As a result, by setting a reference value V1 for distinguishing between normality and abnormality from the detection value obtained by measuring the control sample 20 in advance, the complex can be detected simply by comparing the detection value with the reference value V1. It is possible to easily determine whether the transition process is abnormal.

<Step of dispensing the control sample into the first container>
In FIGS. 1 and 2, before the step of transferring the liquid phase in the first container 11 to the second container 12, the step of dispensing the control sample 20 into the first container 11 by the immunoassay device 100 may be further provided. . For example, the immunoassay device 100 aspirates the control sample 20 from a container (not shown) containing the control sample 20 in advance using the suction tube 51 and discharges it into the first container 11 . As a result, even if the user or service staff of the immunoassay device 100 does not prepare the control sample 20 in the first container 11 in advance, the immunoassay device 100 can easily store the control sample 20 in the first container 11. can be made

[Outline of immunoassay device]
Next, an overview of the immunoassay device 100 according to one embodiment will be described with reference to FIG.

The immunoassay device 100 is a device that measures a test substance in a specimen using an antigen-antibody reaction. The immunoassay device 100 performs complex transfer processing by an immune complex transfer method. That is, as shown in FIG. 4, the immunoassay apparatus 100 has a first container 11 containing an immune complex 84 containing a test substance 81 in a sample and a labeling substance 83 and supported on a solid-phase carrier 82. , the immune complex 84 is released from the solid phase carrier 82 and the liquid phase in the first container 11 is transferred to the second container 12 to perform a complex transfer process.

As shown in FIG. 3, the immunoassay device 100 includes a mechanism section 50 that performs a process of transferring the liquid phase in the first container 11 containing the control sample 20 containing at least the labeling substance 21 to the second container 12; A detection unit 60 that detects the labeling substance 21 in the second container 12 to which the phase has been shifted, and a determination unit 70 that determines abnormality in the complex transition process based on the detection result of the detection unit 60 are provided.

The mechanism unit 50 has at least a function of executing complex transfer processing. That is, the mechanism section 50 is configured to perform a process of transferring the liquid phase in the first container 11 to the second container 12 . The mechanism unit 50 can have a function of performing not only complex transfer processing but also processing necessary for immunoassay on the reaction container. For example, the mechanism section 50 can perform a process of forming an immune complex containing the test substance 81 in the specimen and the labeling substance 21 on the solid phase carrier 22 in the first container 11 .

The mechanism section 50 can include one or more processing units according to the type and number of processing steps performed by the immunoassay device 100 . One processing unit may perform one type of processing step, or may be a processing unit capable of performing a plurality of types of processing steps.

The mechanism section 50 includes, for example, a suction tube 51 that sucks the liquid phase in the first container 11 and discharges the sucked liquid phase to the second container 12 . The suction tube 51 is connected to a pressure source (not shown) such as a metering pump, for example, and can suction a predetermined amount of liquid from the tip and dispense a fixed amount.

When the controlled sample 20 contains the solid-phase carrier 22 bound with the labeling substance 21 , the mechanism section 50 includes a magnetic force source 52 that collects the magnetic particles bound with the labeling substance 21 in the first container 11 . The magnetic force source 52 is positioned near the first container 11 . Magnetic particles can be magnetically collected by the magnetic force of the magnetic force source 52 . Magnetic collection is to collect magnetic bodies by applying a magnetic force. The magnetic force source 52 applies a magnetic force to the magnetic particles in the first container 11 , for example, and concentrates the magnetic particles at a predetermined position such as the inner surface or the bottom of the first container 11 . A permanent magnet or an electromagnet, for example, can be used as the magnetic force source 52 .

For example, the mechanism section 50 may include a sample dispensing section for dispensing the sample into the first container 11 . In this case, the mechanism section 50 can perform the step of dispensing the specimen containing the test substance 81 . When the mechanism unit 50 processes the first container 11 into which the sample has been dispensed in advance, the mechanism unit 50 does not need to be provided with a sample dispensing unit.

Further, the mechanism section 50 may include a reagent dispensing section for dispensing the reagent into the first container 11 . In this case, the mechanism unit 50 performs a step of dispensing a solid phase reagent containing solid phase carriers 22 and 82 such as magnetic particles, a step of dispensing a labeling reagent containing labeling substances 21 and 83, and a free reagent 85. A step of dispensing can be performed. When the mechanism section 50 processes the first container 11 into which these reagents have been dispensed in advance, the mechanism section 50 need not be provided with a reagent dispensing section.

Various reagents to be dispensed into the first container 11 are liquid reagents, and are stored in separate reagent containers for each type. The solid phase reagent is a liquid reagent containing solid phase carriers 22 and 82 such as magnetic particles in a liquid, and the labeling reagent is a liquid reagent containing labeling substances 21 and 83 in a liquid. The free reagent 85 is a liquid reagent containing components for breaking the bond between the immune complex 84 and the solid phase carrier 82 .

The release reagent 85 dissolves the bond between the immune complex 84 containing the test substance 81 and the labeling substance 83 and the solid phase carrier 82 and releases the immune complex 84 from the solid phase carrier 82 . When the solid phase carrier 82 and the test substance 81 bind, the free reagent 85 dissolves the binding between the solid phase carrier 82 and the test substance 81 . When the solid phase carrier 82 binds to the test substance 81 via the capture substance 86, the free reagent 85 is formed by the binding between the solid phase carrier 82 and the capture substance 86 or the binding between the test substance 81 and the capture substance 86. should be resolved. The free reagent 85 is selected according to the type of binding between the immune complex 84 and the solid phase carrier 82 .

For example, if the binding between immune complex 84 and solid phase carrier 82 is hapten-anti-hapten antibody binding, a hapten or hapten derivative can be used as free reagent 85 . In addition, when the binding between the immune complex 84 and the solid phase carrier 82 is by ionic bonding, a solution containing ions can be used as the free reagent 85 . Also, when the binding between the immune complex 84 and the solid phase carrier 82 is a ligand-receptor binding as a separable bond, a ligand or ligand analogue can be used as the free reagent 85 . When the bond between the immune complex 84 and the solid phase carrier 82 is a lectin-sugar chain bond as a separable bond, sugar can be used as the free reagent 85 . Biotin can be used as the free reagent 85 when the immune complex 84 and the solid phase carrier 82 are bound by biotin-avidin.

In addition, the mechanical section 50 may include a reaction section for heating and reacting the sample in the first container 11 . In this case, the mechanism unit 50 can promote the reaction of the sample in a temperature environment suitable for the reaction during the process of forming the immune complex 84 and the process of releasing the immune complex 84, so that efficient processing can be achieved. can be done. If the reaction proceeds sufficiently without heating the sample in the first container 11, or if the entire mechanical section 50 is configured as a constant temperature bath at a predetermined temperature, a reaction section is provided in the mechanical section 50. No need.

The detection unit 60 has a function of detecting the labeling substances 21 and 83 in the liquid phase dispensed into the second container 12 . As described above, detection may be performed by an appropriate method depending on the types of labeling substances 21 and 83, and the detection method is not particularly limited. A photomultiplier tube, a spectrophotometer, a luminometer, or the like can be used as the detection unit 60 . When detecting fluorescence, the detection unit 60 can include a light source for irradiating excitation light. Moreover, when the labeling substance is a radioactive isotope, a scintillation counter or the like can be used as the detection unit 60 .

The determination unit 70 acquires the detection result of the detection unit 60 . The determination unit 70 is configured by, for example, a computer including a processor such as a CPU and a storage unit such as a hard disk drive or flash memory. The processor functions as the determination section 70 of the immunoassay device 100 by executing the control program stored in the storage section. The determination unit 70 determines abnormality in the complex transfer process based on the detection result of the detection unit 60 .

The immunoassay device 100 according to the present embodiment implements the state confirmation method of the immunoassay device 100 shown in at least one of FIGS. 1 and 2 with the above configuration. As a result, the same liquid phase transfer operation as in the complex transfer treatment is performed on the first container 11 containing the control sample 20 containing the labeling substance 21, and the control sample 20 transferred to the second container 12. The labeling substance 21 inside can be detected. If the complex transfer process is not performed normally, an abnormal detection result deviating from the expected detection result will be obtained. As a result, it is possible to confirm whether or not the complex transfer process was performed normally from the detection result of the labeling substance 21 in the second container 12. It is possible to easily check the state of the function.

[Specific Configuration Example of Immunoassay Device]
Next, a specific configuration example of the immunoassay device 100 will be described in detail with reference to FIG.

Immunoassay apparatus 100 includes mechanism section 50 , detection section 60 , and determination section 70 . In the configuration example of FIG. 5, the immunoassay device 100 includes an analysis unit 110 for analyzing the immunoassay results. The determination unit 70 is implemented as part of the functions executed by the analysis unit 110 .

The mechanism section 50 includes a specimen dispensing section 120 , a reagent dispensing section 130 , a container supply section 140 , a reagent storage section 150 , a reaction section 160 and a BF separating section 170 . The mechanism section 50 also includes a container transfer section 180 that transfers containers to these sections. The immunoassay apparatus 100 also includes a sample transport section 190 and a housing 105 that accommodates the mechanism section 50 and the detection section 60 .

The housing 105 has a box-like shape that accommodates each part of the immunoassay device 100 inside. Note that the housing 105 may be configured in one or more layers.

The specimen transporting section 190 is configured to transport a specimen collected from a subject to an aspiration position by the specimen dispensing section 120 . The sample transport unit 190 can transport a rack in which a plurality of sample containers 191 (see FIG. 6) containing samples are installed to a predetermined sample aspiration position.

The specimen dispensing section 120 can aspirate the specimen transported by the specimen transporting section 190 and dispense the aspirated specimen into the first container 11 . As shown in FIG. 6, the specimen dispensing section 120 includes an aspiration tube 121 connected to a fluid circuit for aspiration and ejection, and a moving mechanism (not shown) for moving the aspiration tube 121 . The sample dispensing unit 120 attaches a dispensing tip 122 from a tip supplying unit (not shown) to the tip of the suction tube 121 , and aspirates a predetermined amount of the sample in the transported sample container 191 into the dispensing tip 122 . The specimen dispensing unit 120 dispenses the aspirated specimen into the first container 11 arranged at a predetermined specimen dispensing position. After dispensing, the sample dispensing section 120 removes the dispensing tip 122 from the tip of the suction tube 121 and discards it.

The container supply unit 140 can store a plurality of unused reaction containers. That is, the container supply unit 140 can store a plurality of unused first containers 11 and second containers 12 and supply them to predetermined container supply positions. In this configuration example, reaction vessels having the same shape and the same material are used as the first vessel 11 and the second vessel 12 . In other words, the unused reaction container supplied from the container supply section 140 can be used as both the first container 11 and the second container 12 . In addition, when the first container 11 and the second container 12 are commonly applicable and need not be distinguished, they are simply referred to as the "reaction container 10".

The container transfer unit 180 can transfer the reaction container 10 . The container transfer unit 180 acquires an empty container from the container supply position, and transports the container to each processing position such as the specimen pipetting unit 120, the reagent pipetting unit 130, the reaction unit 160, the BF separation unit 170, the detection unit 60, and the like. transfer. The container transfer section 180 is composed of, for example, a catcher for gripping a container or a holding section having an installation hole for the container, and a moving mechanism for moving the catcher or holding section. The moving mechanism moves in one or more axial directions, for example, by one or more linear motion mechanisms capable of linear movement. The moving mechanism can move, for example, in two orthogonal three-axis directions, i.e., vertical and horizontal directions. The movement mechanism may include an arm mechanism that horizontally rotates around a rotation axis, or an articulated robot mechanism. One or a plurality of container transfer units 180 are provided according to the arrangement of the processing positions of the units in the housing 105 .

The reaction section 160 includes a heater and a temperature sensor, holds the reaction vessel 10, and heats and reacts the sample contained in the vessel. The heating causes the specimen and reagent contained in the container to react. One or more reaction units 160 are provided in the housing 105 . The reaction unit 160 may be fixedly installed in the housing 105 or may be provided movably within the housing 105 . If the reaction section 160 is configured to be movable, the reaction section 160 can also function as part of the container transfer section 180 .

The reagent storage 150 has a box-like shape and has a container holder 151 and a cooling mechanism inside. The container holding part 151 holds a reagent container 155 . The cooling mechanism keeps the reagent in the reagent container 155 at a constant temperature suitable for storage. Reagent storage 150 has a plurality of holes 152 on its top surface for allowing reagent dispensing section 130 to enter inside reagent storage 150 .

The container holding part 151 is formed so as to hold a plurality of reagent containers 155 side by side in the circumferential direction. The container holding part 151 can hold a plurality of reagent containers 155 side by side in the radial direction. That is, the container holding part 151 can arrange a plurality of rows of the reagent containers 155 arranged in a circular shape concentrically in the radial direction. The container holder 151 can independently rotate a row of a plurality of concentric reagent containers 155 in the circumferential direction. As a result, the container holding unit 151 places the desired reagent container selected from the row of the corresponding reagent containers 155 directly below each of the plurality of holes 152 provided corresponding to the reagent dispensing unit 130 . 155 can be placed. As a result, the reagent in the reagent container 155 positioned directly below the hole 152 is sucked by the reagent dispensing section 130 . Reagent containers 155 each containing an r1 reagent, an r4 reagent, an r5 reagent, an r6 reagent, and an r7 reagent, which will be described later, are set in the container holding portion 151 . The reagent container 155 may have a structure that has a plurality of storage chambers and can store a plurality of types of reagents.

The reagent dispensing unit 130 aspirates the reagent in the reagent container 155 and dispenses the aspirated reagent into the reaction container 10 . The reagent pipetting unit 130 can horizontally move the suction tube 131 for sucking and discharging the reagent between the hole 152 and a predetermined reagent pipetting position. In addition, as shown in FIG. 7, the reagent dispensing unit 130 can move the aspirating tube 131 in the vertical direction to pass through the hole 152 from above and enter the reagent container 155 . , the suction tube 131 can be retracted to a position above the hole 152 . The suction tube 131 is connected to a fluid circuit (not shown), sucks a predetermined amount of reagent from the reagent container 155 of the container holder 151, and dispenses the reagent into the reaction container 10 transferred to the reagent dispensing position.

One or a plurality of reagent dispensing units 130 are provided, for example. In the example of FIG. 5, three reagent dispensing units 130 are provided above the reagent storage 150 . Which of the r1 reagent, r4 reagent, r5 reagent, r6 reagent, and r7 reagent is to be dispensed by each of the three reagent dispensing units 130 is set in advance. There is no particular limitation as to whether to inject. Mechanism unit 50 also includes an R4 reagent dispensing unit 134 for dispensing R4 reagent and an R5 reagent dispensing unit 135 for dispensing R5 reagent.

The R4 reagent dispensing unit 134 and the R5 reagent dispensing unit 135 are provided at positions separated from the reagent storage 150 . The R4 reagent pipetting unit 134 and the R5 reagent pipetting unit 135 are connected to reagent containers (not shown) containing the R4 reagent and the R5 reagent, respectively, via liquid transfer tubes, and are transferred by the container transfer unit 180. A reagent can be discharged into the reaction container 10 which has been opened.

The BF separation section 170 has a function of performing BF separation to separate the liquid phase and the solid phase from the reaction vessel 10 . In the immunoassay device 100, one or more BF separators 170 are provided. As shown in FIG. 8, the BF separating unit 170 sucks the liquid component in the reaction vessel 10 through the suction tube 171 while the magnetic particles are collected by the magnetic flux collecting unit 173, and supplies the cleaning liquid through the discharge tube 172. do. The suction tube 171 and the discharge tube 172 are each connected to a fluid circuit (not shown). Thereby, unnecessary substances contained in the liquid component can be separated and removed from the magnetic particles.

The mechanism unit 50 has a function of performing complex transfer processing.

As shown in FIG. 9 , the mechanism section 50 includes a magnetic force source 52 that collects the magnetic particles bound with the labeling substance 21 in the first container 11 . The magnetic force source 52 is provided in a holding member 210 formed with a holding hole 211 for holding the first container 11, for example. The magnetic force source 52 is composed of, for example, a permanent magnet. The holding member 210 may be fixedly installed within the housing 105 , or may be configured to be movable and function as part of the container transfer section 180 .

The mechanical section 50 includes a suction tube 51 that sucks the liquid phase in the first container 11 and discharges the sucked liquid phase to the second container 12 . The suction tube 51 sucks the liquid phase from the first container 11 held by the holding member 210 into the second container 12 held by the container transfer section 180 or another container holding section (not shown). , dispense the aspirated liquid phase.

Transfer of the liquid phase in the complex transfer treatment is carried out by a structure provided with a suction tube. For example, as shown in FIG. 9A, complex transfer processing can be performed by aspiration tube 121 of specimen dispensing section 120 . The suction tube 121 also functions as a suction tube 51 for performing complex transfer processing. As shown in FIG. 9(B), the complex transfer process can be performed using the suction tube 131 of the reagent dispensing section 130 . The suction tube 131 also functions as the suction tube 51 for performing complex transfer processing. As shown in FIG. 9(C), the mechanism section 50 may include a dedicated immune complex dispensing section 220 for performing complex transfer processing. In this case, the liquid phase in the first container 11 is sucked by the suction tube 51 provided in the immune complex dispensing section 220 and the sucked liquid phase is discharged into the second container 12 .

As shown in FIG. 10, the detector 60 includes a photodetector 61 such as a photomultiplier tube. The detection unit 60 receives the second container 12 inside, and the photodetector 61 detects light generated in the reaction process between the labeling substance 83 (see FIG. 4) that binds to the test substance 81 of the specimen and the luminescent substrate. . The detector 60 counts the number of photons detected by the photodetector 61 and outputs it as a detection value.

Returning to FIG. 4, the analysis unit 110 is configured by, for example, a personal computer. The analysis unit 110 includes, for example, a processor 111 such as a CPU, and a storage unit 112 such as ROM, RAM and hard disk. The processor 111 functions as the analysis section 110 of the immunoassay device 100 by executing the control program stored in the storage section 112 .

The analysis unit 110 is electrically connected to the mechanism unit 50 and controls the mechanism unit 50 so as to perform sample measurement and confirmation of the state of the immunoassay device 100 . The analysis unit 110 causes the mechanism unit 50 to perform sample measurement according to a measurement order obtained from a host computer (not shown), and analyzes the detection result by the detection unit 60 . That is, the analysis unit 110 compares the values detected by the detection unit 60 with a calibration curve prepared in advance to determine the abundance of the test substance 81 in the sample (i.e., the labeled substance bound to the test substance 81). 83 abundance). Analysis unit 110 includes determination unit 70 . In other words, the analysis unit 110 also functions as the determination unit 70 when the processor 111 executes the control program. A dedicated processor that functions as the determination unit 70 may be provided.

The determination unit 70 has at least one of a function of collecting the solid phase carriers 22 in the first container 11 by the mechanism unit 50 and a function of transferring the liquid phase in the first container 11 to the second container 12 by the mechanism unit 50. determine the abnormality. As a result, it is possible to determine whether or not there is an abnormality in at least one of the function of collecting the solid phase carriers 22 and the function of transferring the liquid phase to the second container 12 in the complex transfer treatment, so that the reliability of the measurement results can be ensured. is particularly useful for

Specifically, the determining unit 70 determines whether the magnetic force collection function of the magnetic force source 52 (see FIG. 9) is abnormal based on the detection result for the control sample containing the magnetic particles to which the labeling substance 21 is bound. As a result, the solid-phase carrier 22 to which the labeling substance 21 is bound in the first container 11 is magnetically collected. There is a high possibility that the solid phase carrier 22 is not sufficiently collected and the solid phase carrier 22 is also moved. Therefore, it can be easily determined whether the magnetic collecting function of the magnetic force source 52 in the complex transition process is normal or abnormal.

Further, the determination unit 70 determines abnormality of the pipetting function by the suction tube 51 (see FIG. 9) based on the detection result for the controlled sample containing the solution in which the labeling substance 21 is dissolved. As a result, since the labeling substance 21 exists as a liquid phase in the first container 11, for example, if the detection value of the labeling substance 21 does not increase, when the liquid phase is dispensed into the second container 12, the liquid phase There is a high possibility that the dispensing machine using the suction tube 51 for suctioning and discharging the liquid phase is not normal. Therefore, it is possible to easily confirm whether or not there is an abnormality in the pipetting function of the suction tube 51 in the complex transfer process.

(Overview of immunoassay)
In the configuration example shown in FIG. 5, as shown in FIG. 4, immunoassays are performed using the r1 to r7 reagents and the R4 and R5 reagents. Here, as an example of immunoassay, an example in which the test substance 81 is hepatitis B surface antigen (HBsAg) will be described.

First, the reagent dispensing unit 130 dispenses the r1 reagent into the first container 11 . The r1 reagent is a labeling reagent containing labeling substance 83 . The labeling substance 83 reacts with and binds to the test substance 81 . In the example of FIG. 4, the labeling substance is an ALP (alkaline phosphatase)-labeled antibody. After each reagent is dispensed, the reaction unit 160 heats the sample in the reaction container 10 to a predetermined temperature for a predetermined time. In the following description, description of the reaction section 160 is omitted.

Next, the sample dispensing unit 120 dispenses the sample containing the test substance 81 into the first container 11 . The test substance 81 binds to the labeling substance 83 . Depending on the test substance 81, a reagent (r2 reagent) that alkali-denatures the sample as a pretreatment for releasing the antigen present in the sample in a state in which the antibody is bound in advance from the antibody (r2 reagent), or a reagent that neutralizes the alkali of the sample. A reagent (r3 reagent) and the like may also be dispensed.

Next, the r4 reagent is dispensed into the first container 11 by the reagent dispensing unit 130 . The r4 reagent is a capture reagent containing a capture substance 86 that reacts with and binds to the analyte 81 . The capture substance 86 consists of a first binding substance 86a for binding the capture substance 86 to the first solid phase carrier 82a described later, and a second binding substance for the capture substance 86 to bind to the second solid phase carrier 82b described later. 86b. The first binding substance 86a and the second binding substance 86b are substances that bind to the solid phase carrier with different binding capacities.

In the example of FIG. 4, the capture substance 86 is an antibody modified with DNP (dinitrophenyl group) and biotin (DNP/biotin antibody). That is, the capturing substance 86 is modified with DNP (dinitrophenyl group) as the first binding substance 86a and biotin as the second binding substance 86b.

Next, the reagent dispensing unit 130 dispenses the r5 reagent into the first container 11 . The r5 reagent is a solid phase reagent containing solid phase carrier 82 . Specifically, the r5 reagent contains, as the solid phase carrier 82, a first solid phase carrier 82a. The first solid-phase carrier 82a is a magnetic particle, specifically, a magnetic particle to which an anti-DNP antibody is immobilized (anti-DNP antibody-coated magnetic particle). The anti-DNP antibody of the anti-DNP antibody-coated magnetic particles, which is an anti-hapten, reacts with and binds to the DNP of the capture substance 86, which is a hapten. As a result, an immune complex 84 containing the test substance 81, the labeling substance 83, and the capturing substance 86 is formed on the first solid phase carrier 82a.

The immune complex 84 formed on the first solid phase carrier 82a and the unreacted labeling substance 83 are separated by primary BF separation treatment. Unreacted labeling substances 83 and other unnecessary components are removed from the first container 11 by the primary BF separation process. The primary BF separation processing is performed by the BF separation section 170 (see FIG. 8).

After the primary BF separation process, the reagent dispensing unit 130 dispenses the r6 reagent into the first container 11 . The r6 reagent is the free reagent 85. In the example of FIG. 4, DNP-Lys (DNP-Lysine) is used as the release reagent 85 . DNP-Lys reacts and binds to the anti-DNP antibody magnetic particles, which are the first solid phase carrier 82a. Therefore, when the r6 reagent is dispensed into the first container 11, the binding of DNP of the capture substance 86 to the first solid phase carrier 82a and the binding of the free reagent 85 (DNP-Lys) to the first solid phase carrier 82a binding, and the binding between the capture substance 86 and the first solid phase carrier 82a is eliminated. As a result, the immune complex 84 is released from the first solid phase carrier 82a.

Next, complex transfer processing is performed. That is, the liquid phase containing the immune complex 84 liberated by the r6 reagent is sucked from the first container 11 by the suction tube 51 and dispensed into the second container 12 .

The complex transfer treatment transfers the liquid phase containing the immune complex 84 released from the first solid phase carrier 82 a from the first container 11 to the second container 12 . The first solid phase carrier 82a remains in the first container 11 after the liquid phase containing the immune complex 84 has been aspirated. As a result, the labeled substance 83 non-specifically bound to the first solid phase carrier 82 a is separated from the immune complex 84 .

Next, the r7 reagent is dispensed by the reagent dispensing unit 130 into the second container 12 to which the immune complex 84 has been dispensed. The r7 reagent contains a second solid support 82b. Second solid phase carrier 82 b binds to second binding substance 86 b of capture substance 86 . The second solid-phase carrier 82b is a magnetic particle, specifically, a magnetic particle (StAvi-bound magnetic particle) to which streptavidin that binds to biotin is immobilized. The streptavidin of the StAvi-bound magnetic particles reacts with and binds to biotin, which is the second binding substance 86b. As a result, an immune complex 84 containing the test substance 81, the labeling substance 83, and the capture substance 86 binds to the second solid phase carrier 82b.

The immune complex 84 bound to the second solid-phase carrier 82b and unnecessary components other than the second solid-phase carrier 82b on which the immune complex 84 is formed are separated by secondary BF separation treatment, and the unnecessary components are separated from the second It is removed from inside the container 12 . The unnecessary components include, for example, the free reagent 85 contained in the liquid phase and the labeling substance 83 that did not bind to the test substance 81 and was contained in the liquid phase together with the immune complex 84 . The secondary BF separation processing is performed by the BF separation section 170 (see FIG. 8).

Thereafter, the R4 reagent dispensing section 134 and the R5 reagent dispensing section 135 dispense the R4 reagent and the R5 reagent into the second container 12, respectively. The R4 reagent contains a buffer. The immune complex 84 bound to the second solid phase carrier 82b is dispersed in the buffer. The R5 reagent contains a chemiluminescent substrate. The buffer contained in the R4 reagent has a composition that promotes the reaction between the label (enzyme) of the labeling substance 83 contained in the immune complex 84 and the substrate. Light is generated by reacting the substrate with the label, and the intensity of the generated light is measured by the detector 60 (see FIG. 10).

(Method for confirming the state of the immunoassay device)
Next, a state confirmation method in the specific configuration example of the immunoassay device 100 shown in FIG. 5 will be described.

In the following example, the labeling substance 21 contained in the controlled sample 20 is an enzyme. The step (b) of detecting the labeling substance 21 in the second container 12 is performed by adding the substrate of the enzyme to the second container 12 and measuring the signal generated from the reaction product produced by the enzymatic reaction.

<Confirmation of magnet collection function>
12 to 14, an example of confirming the magnet collecting function of the immunoassay device 100 is shown. In the examples of FIGS. 12 to 14, the controlled sample 20 includes a solid phase carrier 22 bound with a labeling substance 21, and the solid phase carrier 22 is magnetic particles. The process of collecting the solid-phase carrier 22 includes the process of magnetizing the magnetic particles with the magnetic force source 52 . The state confirmation method includes a step of determining abnormality in the magnetic collecting function of the magnetic force source 52 based on the detection result of the labeling substance 21 in the second container 12 . As a result, since the magnetic particles to which the labeling substance 21 is bound are collected, based on the detection value of the labeling substance 21 in the second container 12, it is determined whether the magnetic collection function of the magnetic force source 52 is normal or abnormal. easily determined.

Specifically, as shown in FIG. 11, the determination unit 70 determines that there is an abnormality in the magnetic collecting function of the magnetic force source 52 when the detected value of the labeling substance 21 exceeds the reference value V1. That is, when the detected value of the labeling substance 21 exceeds the reference value V1, there is a high possibility that the magnetic particles are not sufficiently magnetized when the liquid phase is transferred to the second container 12 . Accordingly, the magnetic collecting function of the magnetic force source 52 can be easily determined by comparing the detected value with the reference value V1.

The reference value V1 for confirming the magnetism collecting function is an expected detection value of the labeling substance 21 corresponding to the allowable upper limit amount of the magnetic particles transferred to the second container 12 without being magnetized. Accordingly, when the amount of magnetic particles exceeding the allowable upper limit amount is transferred to the second container 12, it can be easily determined that the magnetic force collection function of the magnetic force source 52 is abnormal. Therefore, by confirming that the allowable upper limit amount is not exceeded, the reliability of the measurement result can be ensured.

(Embodiment 1)
In the example of FIG. 12, the control sample 20 contains the third solid-phase carrier 23 bound to the labeling substance 21 without binding to the test substance 81 . The liquid phase does not substantially contain the labeling substance 21 . The third solid-phase carrier 23 is, for example, magnetic particles to which the labeling substance 21 is fixed in advance. The third solid-phase carrier 23 does not have binding ability to the test substance 81 . That is, the third solid-phase carrier 23 for confirming the magnetic collecting function is the first solid-phase carrier 82a contained in the r5 reagent for the measurement of the specimen, and the second solid-phase carrier 82a for the r7 reagent. 82b is included in the quality control reagent prepared separately.

As a result, the third solid-phase carrier 23 that does not contain the test substance 81 can be used as a dedicated reagent for confirming the state of the immunoassay device 100, and the function of collecting the solid-phase carriers 22 can be confirmed. When the solid-phase carrier 22 binds not only the labeling substance 21 but also the test substance 81, a plurality of types of solid-phase carriers 22 and labeling substances 21 that can bind according to the type of the test substance 81 are prepared. With the third solid-phase carrier 23 that does not contain the test substance 81 , the state of the immunoassay device 100 can be confirmed regardless of the type of the test substance 81 . Therefore, it is possible to check the state of the immunoassay device 100 more easily.

In the example of FIG. 12, the controlled sample 20 containing the third solid-phase carrier 23 bound to the labeling substance 21 is accommodated in the first container 11 . The controlled sample 20 is dispensed into the first container 11 by the mechanism section 50 . For example, the controlled sample 20 is set in the sample transport section 190 while being accommodated in a predetermined controlled sample container like the sample container 191 , and dispensed into the first container 11 by the sample dispensing section 120 . Also, for example, the control sample 20 is set in the reagent storage 150 while being accommodated in a predetermined control sample container like the reagent container 155 , and dispensed into the first container 11 by the reagent dispensing section 130 .

During the step (a) of transferring the liquid phase in the first container 11 containing the control sample 20 to the second container 12, the third solid-phase carrier 23 in the first container 11 is moved to the first position by the magnetic force source 52. Magnetism is collected in the container 11 . The liquid phase in the first container 11 is sucked by the suction tube 51 and dispensed into the second container 12 while the magnetic flux is collected. The third solid-phase carrier 23 is left in the first container 11 while magnetism is collected.

Next, a step (b) of detecting the labeling substance 21 in the second container 12 to which the liquid phase has been transferred is performed by the detection unit 60 . Through step (b), a detection value indicating the abundance of the labeling substance 21 is obtained.

In the example of FIG. 12, the pipetting operations of the r1 reagent, the sample, the r4 reagent, the r5 reagent, the r6 reagent, and the r7 reagent shown in FIG. 4 can be skipped. If the dispensing operation of the immunoassay device 100 is not skipped, an alternative liquid such as a buffer solution that does not cause an antigen-antibody reaction may be dispensed instead of the respective reagents and specimens. Also, in the example of FIG. 12, the primary BF separation process and the secondary BF separation process shown in FIG. 4 are skipped. BF separation may also be performed when alternate liquid dispensing is performed. FIG. 12 shows an example in which the control sample 20 is dispensed at the dispensing timing of the r6 reagent shown in FIG. You may

(Embodiment 2)
In the example of FIG. 13 , the state confirmation method includes, before the step of transferring the liquid phase in the first container 11 to the second container 12, in the first container 11, a sample containing a test substance 81 with a known concentration, a A step of contacting the labeling substance 83 that binds to the test substance 81, the capture substance 86 that binds to the test substance 81, and the solid phase carrier 82 that binds to the capture substance 86 is provided. That is, in the state confirmation method, the quality control sample containing the test substance 81 and various reagents are dispensed into the first container 11 to prepare the control sample 20, as in the case of measuring the sample. As a result, controlled sample 20 contains solid phase carrier 82 bound to immune complex 84 containing test substance 81 , labeling substance 83 and capture substance 86 . In other words, FIG. 13 shows an example of using the labeling substance 83 and the solid phase carrier 82 used in the actual sample measurement as the labeling substance 21 and the solid phase carrier 22 used in the state confirmation method of the immunoassay device 100 .

As a result, the solid-phase carrier 82 to which the labeling substance 83 is bound can be formed in the first container 11 by the same processing steps as when actually measuring the sample containing the test substance 81 . The liquid phase does not substantially contain the labeling substance 83 .

In the example of FIG. 13, first, the r1 reagent containing the labeling substance 83 is dispensed into the first container 11 . Next, a quality control sample containing the test substance 81 of known concentration is dispensed. The r4 reagent containing capture material 86 is then dispensed. Then, the r5 reagent containing the first solid phase carrier 82a is dispensed. As a result, immune complex 84 containing test substance 81, labeling substance 83 and capturing substance 86 binds to first solid phase carrier 82a. The reagent dispensing section 130 dispenses the reagent, and the sample dispensing section 120 dispenses the quality control sample.

Thus, in the example of FIG. 13, the control sample 20 includes the first solid phase carrier 82a dispensed into the first container 11 prior to the complex transfer treatment during sample measurement. In other words, the controlled sample 20 contains the first solid-phase carrier 82a, which is the magnetic particle contained in the r5 reagent. As a result, the solid phase carrier 82 to which the labeling substance 83 is bound is formed in the first container 11 using the first solid phase carrier 82a that is dispensed when the sample containing the test substance 81 is actually measured. be able to. That is, since it is not necessary to separately prepare a dedicated solid phase carrier 22 for confirming the state of the immunoassay device 100, the convenience of the immunoassay device 100 can be improved.

Next, the BF separation unit 170 performs primary BF separation processing. In other words, in the example of FIG. 13, the state confirmation method is such that before the step of transferring the liquid phase in the first container 11 to the second container 12, an immune complex containing the test substance 81, the labeling substance 83, and the capturing substance 86 A step of performing BF separation for separating the solid phase carrier 82 bound to 84 from the liquid phase is provided. Thereby, by BF separation, the labeling substance 83 in the liquid phase that has not bound to the solid phase carrier 82 can be separated from the solid phase carrier and eliminated. Therefore, in the step of transferring the liquid phase in the first container 11 to the second container 12, it is possible to suppress the labeling substance 83 from being mixed in the liquid phase. Accuracy can be improved.

After the primary BF separation process, the reagent dispensing unit 130 dispenses the liquid phase 25 that does not contain the free reagent 85 into the first container 11 . That is, during the measurement of the specimen, the immune complex 84 is released from the solid phase carrier 22 by dispensing the free reagent 85 into the first container 11 in the complex transfer process. On the other hand, in the example of FIG. 13, the method for confirming the state does not contain the free reagent 85 before the step of transferring the liquid phase in the first container 11 to the second container 12 after the step of performing BF separation. A step of dispensing the liquid phase into the first container 11 is provided.

Liquid phase 25 that does not contain free reagent 85 is not particularly limited, but is, for example, a buffer solution. As a result, the state of the immunoassay device 100 is confirmed in the same manner as dispensing the free reagent 85 during actual sample measurement. In this case, since the liquid phase 25 does not contain the free reagent 85, the labeling substance 83 and the solid phase carrier 82 remain bound.

Next, complex transfer processing is performed. During the step (a) of transferring the liquid phase in the first container 11 containing the control sample 20 to the second container 12, the first solid phase carrier 82a in the first container 11 is moved to the first position by the magnetic force source 52. Magnetism is collected in the container 11 . The liquid phase in the first container 11 is sucked by the suction tube 51 and dispensed into the second container 12 while the magnetic flux is collected. The first solid-phase carrier 82a is left in the first container 11 while the magnetism is collected. Since the immune complex 84 remains bound to the first solid-phase carrier 82 a , the liquid phase without the labeling substance 83 is transferred to the second container 12 .

Next, the reagent dispensing unit 130 dispenses the r7 reagent containing the second solid phase carrier 82b into the second container 12 to which the liquid phase has been transferred. Then, the controlled sample in the second container 12 is subjected to secondary BF separation processing by the BF separation unit 170 . Next, the R4 reagent dispensing section 134 and the R5 reagent dispensing section 135 dispense the R4 reagent containing the buffer solution and the R5 reagent containing the substrate into the second container 12 .

Next, a step (b) of detecting the labeling substance 21 in the second container 12 to which the liquid phase has been transferred is performed by the detection unit 60 . Through step (b), a detection value indicating the abundance of the labeling substance 21 is obtained.

(Embodiment 3)
The example of FIG. 14 is basically the same as the example shown in FIG. 13, but the solid phase carrier 82 to which the labeling substance 83 is bound is different. Also, in the example of FIG. 14, the dispensing order of reagents is different from the example of FIG.

In the example of FIG. 14 as well, the state confirmation method includes, before the step of transferring the liquid phase in the first container 11 to the second container 12, a sample containing a known concentration of the test substance 81 in the first container 11, A step of contacting a labeling substance 83 that binds to the test substance 81, a capture substance 86 that binds to the test substance 81, and a solid phase carrier 82 that binds to the capture substance 86 is provided.

In the example of FIG. 14, the r4 reagent containing the capture substance 86 is first dispensed into the first container 11 . Next, a quality control sample containing the test substance 81 of known concentration is dispensed. Next, the r1 reagent containing the labeling substance 83 is dispensed into the first container 11 . Then, the r7 reagent containing the second solid phase carrier 82b is dispensed. As a result, immune complex 84 containing test substance 81, labeling substance 83 and capturing substance 86 binds to second solid phase carrier 82b. The reagent dispensing section 130 dispenses the reagent, and the sample dispensing section 120 dispenses the quality control sample.

Thus, in the example of FIG. 14, the control sample 20 includes the second solid-phase carrier 82b dispensed into the second container 12 after the complex transfer treatment at the time of sample measurement. In other words, the control sample 20 contains the second solid-phase carrier 82b, which is the magnetic particle contained in the r7 reagent. As a result, the solid phase carrier 82 to which the labeling substance 21 is bound is formed in the first container 11 using the second solid phase carrier 82b that is dispensed when the sample containing the test substance 81 is actually measured. be able to. That is, since it is not necessary to separately prepare a dedicated solid phase carrier 22 for confirming the state of the immunoassay device 100, the convenience of the immunoassay device 100 can be improved.

Next, the BF separation unit 170 performs primary BF separation processing. In the state confirmation method, before the step of transferring the liquid phase in the first container 11 to the second container 12, the solid phase carrier 82 bound with the immune complex 84 containing the test substance 81, the labeling substance 83, and the capture substance 86 and a step of performing BF separation for separating the liquid phase.

After the primary BF separation process, liquid phase 25 free of free reagent 85 is dispensed into first container 11 . In the state confirmation method, after the step of performing BF separation, before the step of transferring the liquid phase in the first container 11 to the second container 12, the liquid phase 25 not containing the free reagent 85 is dispensed into the first container 11. It has a process to do. Liquid phase 25 that does not contain free reagent 85 is, for example, a buffer solution. Since liquid phase 25 does not contain free reagent 85, labeling substance 83 and solid phase carrier 82 remain bound.

Next, complex transfer processing is performed. During the step (a) of transferring the liquid phase in the first container 11 containing the control sample 20 to the second container 12, the second solid phase carrier 82b in the first container 11 is moved to the first position by the magnetic force source 52. Magnetism is collected in the container 11 . The liquid phase in the first container 11 is sucked by the suction tube 51 and dispensed into the second container 12 while the magnetic flux is collected. The second solid-phase carrier 82b is left in the first container 11 while the magnetism is collected. Since the immune complex 84 remains bound to the second solid-phase carrier 82b, the liquid phase that does not contain the labeling substance 83 is transferred to the second container 12. FIG.

Next, the reagent dispensing unit 130 dispenses the r7 reagent containing the second solid phase carrier 82b into the second container 12 to which the liquid phase has been transferred. Thus, in the example of FIG. 14, the r7 reagent containing the second solid phase carrier 82b is dispensed before and after the complex transfer treatment. Then, the controlled sample in the second container 12 is subjected to secondary BF separation processing by the BF separation section 170 . Next, the R4 reagent dispensing section 134 and the R5 reagent dispensing section 135 dispense the R4 reagent containing the buffer solution and the R5 reagent containing the substrate into the second container 12 .

Next, a step (b) of detecting the labeling substance 83 in the second container 12 to which the liquid phase has been transferred is performed by the detection unit 60 . Through step (b), a detection value indicating the abundance of the labeling substance 83 is obtained.

Thus, in the example shown in FIGS. 13 and 14, the mechanism section 50 includes the sample dispensing section 120 for dispensing the sample containing the test substance 81 and the labeling reagent (r1 reagent) containing the labeling substance 83. ), and a solid phase reagent (r5 reagent or r7 reagent) containing the solid phase carrier 82, and a reagent dispensing unit 130 for dispensing a solid phase reagent (r5 reagent or r7 reagent), and a control sample 20 is prepared in the first container 11 It is configured. As a result, even if the user or service staff of the immunoassay device 100 does not prepare the control sample 20 in the first container 11 in advance, the immunoassay device 100 can easily store the control sample 20 in the first container 11. can be made

In the example shown in FIGS. 13 and 14, the reagent dispensing unit 130 supplies the first container 11 with a free reagent 85 that separates the immune complex 84 from the solid-phase carrier 82 when measuring a specimen. When judging an abnormality in the process of dispensing and transferring the liquid phase in the first container 11 to the second container 12 , instead of the free reagent 85 , the liquid phase 25 that does not contain the free reagent 85 is dispensed. As a result, instead of the free reagent 85 that is dispensed when the specimen containing the test substance 81 is actually measured, the liquid phase that does not contain the free reagent 85 is dispensed. The state of the immunoassay device 100 can be confirmed by the same operation as dispensing the . Even in this case, since the binding of the labeling substance 21 to the solid phase carrier 22 is not eliminated, the magnetic flux collecting function of the solid phase carrier 22 can be properly confirmed.

In the examples shown in FIGS. 13 and 14, the mechanism unit 50 includes a solid-phase carrier 82 bound to an immune complex 84 containing a test substance 81 and a labeling substance 83, and a BF separation unit that separates the liquid phase. 170 , the BF separation unit 170 performs BF separation on the control sample 20 in the first container 11 . That is, the BF separation unit 170 performs primary BF separation processing. Thereby, by BF separation, the labeling substance 83 in the liquid phase that has not bound to the solid phase carrier 82 can be separated from the solid phase carrier 82 and eliminated. Therefore, in the step of transferring the liquid phase in the first container 11 to the second container 12, it is possible to suppress the labeling substance 83 from being mixed in the liquid phase. Accuracy can be improved.

<Process for judging the magnetic collecting function>
As described above, in the examples of Embodiments 1 to 3 shown in FIGS. 12 to 14, the labeling substance 21 is bound to the solid phase carrier 22 in the controlled sample 20, and the magnetic field is collected in the first container 11. , the labeling substance 21 remains in the first container 11 together with the solid phase carrier 22 after the step (a) of transferring the liquid phase to the second container 12 . Therefore, in the examples of Embodiments 1 to 3, when the magnetic flux collection function is normal, the detection result in step (b) is when a blank sample that does not substantially contain the labeling substance 21 is measured. A detection value similar to that of is obtained. More precisely, even if the magnetic collecting function is normal, not all the solid phase carriers 22 in the first container 11 can be magnetically collected. A part is carried over to the second container 12 together with the liquid phase. Therefore, the permissible carryover amount of the solid phase carrier 22 in terms of specifications is set for the magnetism collecting function. The allowable carryover amount is set as a variation within a range that does not affect the detection result. As the reference value V1 (see 17) for judging whether or not the magnetic collecting function is normal, a value obtained by adding the upper limit range of the allowable carryover amount to the expected detection value when measuring a blank sample is set. be done. If the acquired detection value is less than the reference value V1, it is determined that the magnetic collecting function is normal.

On the other hand, when the magnetism collection function is abnormal, for example, when the solid phase carrier 22 cannot collect magnetism and becomes dispersed in the liquid phase of the first container 11, the solid phase carrier 22 bound to the labeling substance 21 is Phase carrier 22 will be transferred to second vessel 12 along with the liquid phase. As a result, in the examples of Embodiments 1 to 3, when the magnetic collecting function is abnormal, the detected value significantly increases beyond the upper limit of the allowable carryover amount as the detection result in step (b). Therefore, when the acquired detection value is greater than or equal to the reference value V1, it is determined that the magnetic collecting function is abnormal.

(Example 1)
FIG. 15 shows the experimental conditions of Example 1 performed to confirm the effect of the determination processing of the magnetic collecting function, and FIG. 16 shows the experimental results of Example 1. In Example 1, the procedure of Embodiment 3 shown in FIG. 14 was performed using an immunoassay device 100.

In the comparative example of FIG. 15, in order to compare with the first example, each processing step during the measurement shown in FIG. 4 is listed. As shown in FIG. 15, in Example 1, HISCL HBsAg R1 reagent (manufactured by Sysmex Corporation) was used as the r4 reagent, HISCL HBsAg Calibrator C4 (manufactured by Sysmex Corporation) was used as the quality control sample, and HISCL HBsAg R3 reagent was used as the r1 reagent. (manufactured by Sysmex Corporation), HISCL HBsAg R2 reagent (manufactured by Sysmex Corporation) as the r7 reagent, HISCL washing solution (manufactured by Sysmex Corporation) as the liquid phase 25 that does not contain the free reagent 85, and HISCL R4 reagent (manufactured by Sysmex Corporation) as the R4 reagent. Sysmex Corporation) was used, and HISCL R5 reagent (manufactured by Sysmex Corporation) was used as the R5 reagent. The dispensed amount is as shown in FIG.

As shown in FIG. 16, in Example 1, in order to compare the normal state and the abnormal state of the magnetism collecting function, the magnetism collection by the magnetic force source 52 (with magnet) and the magnetism collection by the magnetic force source 52 are performed. Experiments were conducted according to the procedure shown in FIG. Each experiment was performed 20 times, and the average value, standard deviation (SD), coefficient of variation (CV), maximum value, minimum value, and range (difference between maximum and minimum values) of detected values were obtained. . The detection value is the count number of photons obtained by the photodetector 61 of the detection unit 60 .

From FIG. 16, the detection value is acquired in the range of about 1000 to 2000 counts in normal (with magnet), and in the range of about 16 to 19 million counts in abnormal (without magnet). was done. The normal (with magnet) detected value generally agrees with the measured value when measuring the blank sample. The detected value of abnormality (no magnet) generally agrees with the detected value when the quality control sample is measured in the processing steps shown in FIG. There is a difference of about 10,000 times in the detected value between normal (with magnet) and abnormal (without magnet). From Example 1, it can be seen that the normal range and the abnormal range of the detected values can be clearly distinguished even in consideration of the carryover amount of the magnetic particles in the normal state and fluctuations in the detected values due to aging of the immunoassay device. It was confirmed that it is possible to determine whether the magnetic flux collecting function is normal or abnormal in the complex transition process by appropriately setting the reference value V1 for determination.

<Checking the dispensing function>
18 and 19 show an example of confirming the dispensing function of the immunoassay device 100. FIG. In the examples of FIGS. 18 and 19, the controlled sample 20 contains a solution in which the labeled substance 21 is dissolved. That is, in the control sample 20, the labeling substance 21 exists as a liquid phase rather than being bound to a solid phase. In this case, since the labeling substance 21 exists as a liquid phase in the first container 11, for example, when the detection value of the labeling substance 21 does not increase, when the liquid phase is transferred to the second container 12, the first container 11 There is a high possibility that the liquid phase has not been properly transferred from the Therefore, it can be easily confirmed whether or not the function of transferring the liquid phase in the first container 11 to the second container 12 in the complex transfer treatment is normal.

Specifically, in the examples of FIGS. 18 and 19, the step (a) of transferring the liquid phase in the first container 11 to the second container 12 involves sucking the liquid phase in the first container 11, It includes a dispensing process that dispenses the phase into the second container 12 . Then, the state confirmation method includes a step of determining abnormality of the dispensing function based on the detection result of the labeling substance 21 in the second container 12 . As a result, based on the detected value of the labeling substance 21, it can be easily determined whether the pipetting function of sucking the liquid phase and discharging the liquid phase is normal or abnormal.

As for the determination of the dispensing function, as shown in FIG. 17, it is determined that there is an abnormality in the dispensing function when the detected value of the labeling substance 21 is lower than the reference value V2. As a result, when the detected value of the labeling substance 21 is lower than the reference value V2, it is highly likely that the liquid phase containing the labeling substance 21 is not properly transferred from the first container 11 to the second container 12. The dispensing function can be easily determined by comparing the value with the reference value V2.

The reference value V2 for judging the dispensing function is a value set as the allowable limit of the expected detection value of the labeling substance 21 contained in the controlled sample 20. FIG. This makes it easy to determine that the dispensing function is abnormal when the detected value is below the reference value V2 even after the step of transferring the liquid phase containing the labeling substance 21 to the second container 12 is executed. Therefore, by confirming that the detected value exceeds the reference value V2, the reliability of the measurement result can be ensured.

(Embodiment 4)
The example of FIG. 18 is an example in which a labeling substance different from the labeling substance 83 used during sample measurement is used as the labeling substance 21 for confirming the dispensing function. That is, in the example of FIG. 18, the labeling substance 21 for confirming the pipetting function is a quality control reagent prepared separately from the labeling substance 83 contained in the r1 reagent for measuring the sample. It is included.

In the example of FIG. 18, the first container 11 accommodates the controlled sample 20 in which the labeling substance 21 is dissolved in the liquid phase. The labeling substance 21 is contained in the first container 11 as a liquid phase without being bound to the solid phase. The controlled sample 20 is dispensed into the first container 11 by the mechanism section 50 . For example, the controlled sample 20 is set in the sample transport section 190 while being accommodated in a predetermined controlled sample container like the sample container 191 , and dispensed into the first container 11 by the sample dispensing section 120 . Also, for example, the control sample 20 is set in the reagent storage 150 while being accommodated in a predetermined control sample container like the reagent container 155 , and dispensed into the first container 11 by the reagent dispensing section 130 .

In the example of FIG. 18, the dispensing of the r1 reagent, r4 reagent, r5 reagent, and r6 reagent is skipped or replaced with a buffer or the like. In the example of FIG. 18, the primary BF separation process is skipped. If alternate liquid dispensing is performed, a primary BF separation process may be performed.

Next, in the step (a) of transferring the liquid phase in the first container 11 containing the control sample 20 to the second container 12, the liquid phase in the first container 11 is sucked by the suction tube 51 to form the second container. Dispensed into container 12 .

In the example of FIG. 18, the dispensing of the r7 reagent after the complex transfer treatment is skipped or replaced with a buffer solution, washing solution, or the like. In the example of FIG. 18, the secondary BF separation process is skipped. When the labeling substance 21 is an enzyme label, a substrate corresponding to the enzyme is dispensed as the R5 reagent.

Next, a step (b) of detecting the labeling substance 21 in the second container 12 to which the liquid phase has been transferred is performed by the detection unit 60 . Through step (b), a detection value indicating the abundance of the labeling substance 21 is obtained.

The example of FIG. 18 shows an example in which the control sample 20 is dispensed at the timing of dispensing the r6 reagent shown in FIG. You can dispense.

(Embodiment 5)
The example of FIG. 19 is an example in which the same labeling substance as the labeling substance 83 used during sample measurement is used as the labeling substance 21 for confirming the dispensing function. That is, in the example of FIG. 19, the controlled sample 20 contains the labeled substance 83 of the r1 reagent dispensed into the first container 11 at the time of sample measurement. As a result, whether or not the function of transferring the liquid phase in the first container 11 to the second container 12 is normal using the labeling substance 83 that is dispensed when the sample containing the test substance 81 is actually measured. I can confirm. That is, since it is not necessary to separately prepare the dedicated labeling substance 83 for confirming the state of the immunoassay device 100, the convenience of the immunoassay device 100 can be improved.

In the example of FIG. 19, the first container 11 contains a control sample in which the labeling substance 83 is dissolved in the liquid phase. The labeling substance 83 is contained in the first container 11 as a liquid phase without being bound to the solid phase. The r1 reagent containing the labeling substance 83 is aspirated by the reagent dispensing section 130 from the reagent container 155 set in the reagent storage 150 and dispensed into the first container 11 .

The example of FIG. 19 shows an example in which a buffer solution is dispensed as an alternative liquid at the dispensing timings of the r1 reagent and specimen shown in FIG. Dispensing of r4, r5 and r6 reagents is skipped. The dispensing of the buffer solution may also be skipped, in which case the control sample 20 may be the r1 reagent itself. The example of FIG. 19 shows an example in which the r1 reagent is dispensed at the timing of dispensing the r6 reagent shown in FIG. You may After dispensing the r1 reagent, the primary BF separation process is skipped.

Next, in the step (a) of transferring the liquid phase in the first container 11 containing the control sample 20 to the second container 12, the liquid phase in the first container 11 is sucked by the suction tube 51 to form the second container. Dispensed into container 12 .

In the example of FIG. 19, the dispensing of the r7 reagent after the complex transfer treatment is skipped or replaced with a buffer or the like. In the example of FIG. 19, the secondary BF separation process is skipped. In the example of FIG. 19, R4 reagent and R5 reagent are dispensed into the second container 12 .

Next, a step (b) of detecting the labeling substance 83 in the second container 12 to which the liquid phase has been transferred is performed by the detection unit 60 . Through step (b), a detection value indicating the abundance of the labeling substance 83 is obtained.

(Example 2)
FIG. 20 shows the experimental conditions of Example 2 conducted to confirm whether the dispensing function can be determined, and FIG. 21 shows the experimental results of Example 2. In FIG. In Example 2, the procedure of Embodiment 5 shown in FIG. 19 was performed using the immunoassay device 100. In order to compare with Example 2, the comparative example in FIG. 20 lists the processing steps during the measurement shown in FIG.

As shown in FIG. 20, in Example 2, the HISCL HBsAg R3 reagent (manufactured by Sysmex Corporation) was dispensed as the r1 reagent containing the labeling substance 83 at the timing of dispensing the r6 reagent during measurement. The secondary BF separation treatment after the complex transfer treatment was skipped. HISCL R4 reagent (manufactured by Sysmex Corporation) was used as the R4 reagent, and HISCL R5 reagent (manufactured by Sysmex Corporation) was used as the R5 reagent.

As shown in FIG. 21, in Example 2, the dispensing amount in the step (a) of transferring the liquid phase in the first container 11 to the second container 12 is varied in order to compare the normal state and the abnormal state of the dispensing function. The experiment was conducted under the conditions of In Example 2, the dispensing volume in the normal state was set to 20 [μL] and the dispensing volume in the abnormal state was set to 10 [μL], and the experiment was performed according to the procedure shown in FIG. 20 . Each experiment was performed 20 times, and the average value, standard deviation (SD), coefficient of variation (CV), maximum value, minimum value, and range (difference between maximum and minimum values) of detected values were obtained. . The detection value is the count number of photons obtained by the photodetector 61 of the detection unit 60 .

From FIG. 21, in normal (20 μL), the detected value is obtained in the range of about 130 million counts to about 150 million counts, and in abnormal (10 μL), the detected value is obtained in the range of about 80 million counts to about 90 million counts. was done. There is a difference of 1.5 times or more in the detected value between normal (20 μL) and abnormal (10 μL). From Example 2, it can be seen that when the amount of the liquid phase dispensed into the second container 12 fluctuates due to an abnormality, the detected value fluctuates according to the dispensed amount. Therefore, by setting in advance the reference value V2 that defines the allowable range of the expected detection value of the labeling substance 83 contained in the control sample 20 from the set value of the liquid phase dispensed amount, the separation in the complex transfer treatment can be performed. It was confirmed that it is possible to determine whether the note function is normal or abnormal. For example, even if a range of (average ±2SD) is set as the allowable range, it is possible to sufficiently determine the normal state and the abnormal state.

Note that the immunoassay device 100 may be able to arbitrarily set the dispensing amount of the liquid phase in the complex transfer treatment within a variable range. For example, the immunoassay device 100 allows the user to arbitrarily set the dispensing volume of the liquid phase within the range of 10 μL to 80 μL. In this case as well, it can be seen from Example 2 that the detected value fluctuates according to the dispensed amount. should be obtained in advance. The judging unit 70 acquires the set value of the dispensing amount of the liquid phase, selects the reference value V2 according to the set value, and compares it with the detected value to determine whether the dispensing function in the complex transfer process is normal. Abnormality can be determined.

(Modified example of state confirmation method)
The state confirmation method may perform another state confirmation step in addition to the steps for confirming the magnetic collecting function and confirming the dispensing function.

Specifically, the state confirmation method includes, in the first container 11, a sample containing a known concentration of the test substance 81 or a sample not containing the test substance 81, a labeling substance 21 that binds to the test substance 81, a sample The step of contacting the capture substance 86 that binds to the substance 81 and the solid phase carrier 22 that binds to the capture substance 86, the state confirmation method, is performed by placing an immune complex containing the labeling substance 21 and the capture substance 86 in the first container 11. A step of transferring the liquid phase in the first container 11 to the second container 12 after dispensing the release reagent 85 that releases 84 from the solid phase carrier 22, and detecting the labeling substance 21 present in the second container 12. You may further comprise a step.

That is, instead of the sample shown in FIG. 4, a quality control sample containing a known concentration of the test substance 81 or a sample not containing the test substance 81 is used, and the same operation as a normal sample measurement operation is performed. , you may check the status. Measurement of a control sample containing a known concentration of test substance 81 confirms that the detected value obtained in step (b) falls within the range of reference values expected from a control sample of known concentration. In addition, by measuring the control sample that does not contain the test substance 81, the detection value obtained in step (b) is within the range of the reference value expected from the control sample (blank sample) that does not contain the test substance 81. Confirmed to fit. This confirms that the measurement accuracy of the immunoassay using the complex transfer treatment is normal.

(Explanation of the operation of the immunoassay device)
Next, the operation of the immunoassay device 100 shown in FIG. 5 will be described using FIG. 22 for each step of the operation of the immunoassay device 100, and FIG. 5 to FIG. 10 for each part of the immunoassay device 100 in the following description. 11 to 14 and FIGS. 17 to 19 are referred to for the state confirmation processing. Operation control of each step below is performed by the analysis unit 110 of the immunoassay device 100 .

In step S<b>1 , the analysis unit 110 determines whether or not to check the state of the immunoassay device 100 . The state confirmation is performed, for example, when the user inputs a state confirmation execution command via an input device (not shown) such as a touch panel or a mouse. The state confirmation is executed, for example, when a preset state confirmation execution timing comes. The execution timing of the status check is at least before the start of the first measurement of the day, or at the time of the first startup of the device of the day. The execution timing of status confirmation can be arbitrarily set by the user in advance.

If the state of the immunoassay device 100 is not to be confirmed, the analysis unit 110 determines whether or not to perform immunoassay on the specimen in step S2. The analysis unit 110 determines whether or not to perform an immunoassay based on whether or not a measurement order is registered in the host computer. When the measurement order is registered, the analysis unit 110 causes the mechanism unit 50 to start the measurement process in step S3. Immunoassay is performed according to the procedure shown in FIG. When the detection result of the detection unit 60 is obtained, the analysis unit 110 compares the detection value with the calibration curve to obtain the abundance of the test substance 81 . If the measurement order is not registered in step S2, the process returns to step S1 and waits until the start timing of status confirmation or immunoassay.

If the status of the immunoassay device 100 is to be checked in step S1, the process proceeds to step S4. In steps S4 to S7, the analysis unit 110 causes the mechanism unit 50 to perform the state confirmation operation shown in FIGS. 12 to 19. FIG. Here, for the sake of convenience, the dispensing and primary BF separation processing performed before the complex transfer processing are described as the control sample preparation processing in step S4. In addition, for the sake of convenience, the dispensing and the secondary BF separation process performed after the complex transfer process are described as the post-process of step S6.

Here, an example is shown in which both the confirmation of the magnet collection function and the confirmation of the dispensing function of the immunoassay device 100 are performed. In this case, the analysis unit 110 includes the first container 11 containing the controlled sample 20 containing the solid-phase carrier 22 or 82 to which the labeling substance 21 or 83 is bound as shown in FIGS. As shown in FIG. 19, the first container 11 containing the control sample 20 containing the solution in which the labeling substance 21 or 83 is dissolved is prepared. Then, the first container 11 containing the control sample containing the solid phase carrier 22 or 82 bound with the labeling substance 21 or 83 is used to confirm the magnetic collecting function, and the solution in which the labeling substance 21 or 83 is dissolved is prepared. Confirmation of the dispensing function is performed using the first container 11 containing the controlled sample 20 containing the liquid.

In step S5, the analysis unit 110 causes the mechanism unit 50 to perform complex transfer processing. That is, the analysis unit 110 causes the mechanism unit 50 to perform the step (a) of transferring the liquid phase in the first container 11 containing the controlled sample 20 containing the labeling substance 21 to the second container 12 .

In step S7, the analysis unit 110 causes the detection unit 60 to perform the step (b) of detecting the labeling substance 21 in the second container 12 to which the liquid phase has been transferred. As a result of step S5, the measurement result of the control sample is obtained.

In step S8, the determination unit 70 determines the function for executing the complex transition process. The determination unit 70 determines whether the magnetic collection function is normal or abnormal based on whether the detection value of the detection unit 60 is lower than the reference value V1 (see FIG. 11). . Regarding the dispensing function, the determination unit 70 determines whether the dispensing function is normal or abnormal based on whether the detection value of the detection unit 60 exceeds the reference value V2 (see FIG. 17). .

If it is determined that the magnetic flux collection function and the dispensing function are normal, the analysis unit 110 stands by to perform the immunoassay of the sample. When it is determined that the magnetic flux collection function or the dispensing function is abnormal, the analysis unit 110 displays a message on a display device (not shown), for example, and the complex transfer processing function of the immunoassay device 100 is abnormal. Notify the user that At this time, the analysis unit 110 may suspend the function of immunoassaying the specimen until the state is confirmed again and the magnetic flux collection function and the dispensing function are determined to be normal.

It should be noted that the embodiments disclosed this time should be considered as examples and not restrictive in all respects. The scope of the present invention is indicated by the scope of the claims rather than the description of the above-described embodiments, and includes all modifications within the meaning and scope equivalent to the scope of the claims.

11: First container, 12: Second container, 20: Control sample, 21: Labeling substance, 22: Solid phase carrier, 23: Third solid phase carrier, 50: Mechanism unit, 51: Suction tube, 52: Magnetic force source , 60: detection unit, 70: determination unit, 81: test substance, 82: magnetic particles, 82a: first solid phase carrier, 82b: second solid phase carrier, 83: labeling substance, 84: immune complex, 85 : free reagent, 86: capture substance, 100: immunoassay device, 110: analysis unit, 120: specimen dispensing unit, 121: aspiration tube, 130: reagent dispensing unit, 131: aspiration tube, 170: BF separation unit, V1: reference value, V2: reference value

Claims (26)

In a first container containing a test substance in a specimen and a labeling substance and supported on a solid-phase carrier, the immune complex is released from the solid-phase carrier, and A method for checking the state of an immunoassay device that performs complex transfer processing for transferring a liquid phase to a second container, comprising:
a step of collecting in the first container the solid phase carriers in the first container containing a control sample containing at least the solid phase carrier to which the labeling substance is bound;
transferring the liquid phase in the first vessel to the second vessel;
detecting the labeled substance in the second container to which the liquid phase has been transferred;
Based on the comparison between the detected value of the labeling substance in the second container and a reference value, an abnormality in the function of collecting the solid phase carrier in the first container in the immunoassay device that performs the complex transfer treatment is determined. and determining the presence or absence or the degree of abnormality . In a first container containing a test substance in a specimen and a labeling substance and supported on a solid-phase carrier, the immune complex is released from the solid-phase carrier, and A method for checking the state of an immunoassay device that performs complex transfer processing for transferring a liquid phase to a second container, comprising:
a step of transferring the liquid phase in the first container containing the control sample containing at least the labeling substance as a liquid phase to the second container;
detecting the labeled substance in the second container to which the liquid phase has been transferred;
Transferring the liquid phase in the first container to the second container in the immunoassay device that performs the complex transfer treatment based on the comparison between the detected value of the labeling substance in the second container and the reference value A method for checking the state of an immunoassay device, comprising the step of determining the presence or absence of abnormality in function or the degree of abnormality. A function of collecting the solid phase carriers in the first container based on, in the step of determining the state of the function of collecting the solid phase carriers, the detection value of the labeled substance in the second container exceeding a reference value. 2. The method for confirming the state of an immunoassay device according to claim 1, wherein the abnormality is determined. In the step of determining the state of the function to transfer the liquid phase in the first container to the second container, the first 3. The method for confirming the state of an immunoassay device according to claim 2, wherein abnormality in the function of transferring the liquid phase in the container to the second container is determined. Any one of claims 1 to 4, further comprising the step of dispensing the control sample into the first container by the immunoassay device before the step of transferring the liquid phase in the first container to the second container. 2. The method for checking the state of the immunoassay device according to 1 or 2 above. the solid phase carrier is a magnetic particle,
The process of collecting the solid-phase carrier includes a process of collecting the magnetic particles with a magnetic force source,
The step of judging the state of the function of collecting the solid phase carrier is the step of judging abnormality of the magnetic force collection function by the magnetic force source based on a comparison between the detected value of the labeling substance in the second container and a reference value. The method for checking the state of an immunoassay device according to claim 1, comprising: 7. The method of confirming the state of an immunoassay device according to claim 6, wherein it is determined that there is an abnormality in the magnetic collecting function of the magnetic force source when the detected value of the labeling substance exceeds a reference value. 8. The immunoassay apparatus state confirmation method according to claim 7, wherein said reference value is an expected detected value of said labeling substance corresponding to an allowable upper limit amount of said magnetic particles transferred to said second container without magnetization. . Before the step of transferring the liquid phase in the first container to the second container, in the first container, a sample containing the test substance at a known concentration, the labeling substance that binds to the test substance, the 2. The method according to claim 1, further comprising the step of preparing the control sample in the first container by contacting a capture substance that binds to the test substance and the solid phase carrier that binds to the capture substance. A method for checking the state of an immunoassay device. 10. The method for confirming the state of an immunoassay device according to claim 9, wherein said control sample includes a first solid-phase carrier dispensed into said first container prior to complex transfer treatment at the time of specimen measurement. 10. The method for confirming the state of an immunoassay device according to claim 9, wherein said control sample includes a second solid-phase carrier dispensed into said second container after complex transfer treatment at the time of specimen measurement. Before the step of transferring the liquid phase in the first container to the second container, the solid phase carrier bound to the immune complex containing the test substance, the labeling substance, and the capture substance, and the liquid phase The immunoassay device state confirmation method according to any one of claims 9 to 11, further comprising a step of performing BF separation. In the complex transfer treatment, the immune complex is released from the solid phase carrier by dispensing a free reagent into the first container,
After the step of performing BF separation, and before the step of transferring the liquid phase in the first container to the second container, the step of dispensing the liquid phase free of the free reagent into the first container. The method for checking the state of an immunoassay device according to claim 12. 2. The method for confirming the state of an immunoassay device according to claim 1, wherein said control sample contains a third solid-phase carrier that is bound to said labeling substance without being bound to a test substance. The step of transferring the liquid phase in the first container to the second container includes a dispensing process of aspirating the liquid phase in the first container and discharging the aspirated liquid phase into the second container;
The step of determining the state of the function of transferring the liquid phase in the first container to the second container includes the dispensing function based on a comparison between the detected value of the labeled substance in the second container and a reference value. 3. The method for confirming the state of an immunoassay device according to claim 2, comprising a step of judging the abnormality of the immunoassay device. 16. The method for confirming the state of an immunoassay device according to claim 15, wherein it is determined that there is an abnormality in the dispensing function when the detected value of the labeling substance is below a reference value. 17. The method for confirming the state of an immunoassay device according to claim 16, wherein said reference value is a value set as an allowable limit of an expected detected value of said labeling substance contained in said control sample. 3. The method for confirming the state of an immunoassay device according to claim 2, wherein the control sample contains the labeling substance dispensed into the first container during measurement of the specimen. the labeling substance contained in the control sample is an enzyme,
The step of detecting the labeling substance in the second container is performed by adding the substrate of the enzyme to the second container and measuring a signal generated from a reaction product produced by the enzymatic reaction. 19. The method for checking the state of an immunoassay device according to any one of 18. In a first container containing a test substance in a specimen and a labeling substance and supported on a solid-phase carrier, the immune complex is released from the solid-phase carrier, and An immunoassay device that performs a complex transfer process for transferring a liquid phase to a second container,
performing a process of collecting the solid-phase carrier in the first container containing the control sample containing the solid-phase carrier to which at least the labeling substance is bound, and collecting the solid-phase carrier in the first container; to the second container; and
a detection unit that detects the labeled substance in the second container to which the liquid phase has been transferred;
an immunoassay device, comprising: a judgment unit that judges abnormality in the function of collecting the solid-phase carriers in the first container in the complex transfer treatment, based on a comparison between the detection value of the detection unit and a reference value. . In a first container containing a test substance in a specimen and a labeling substance and supported on a solid-phase carrier, the immune complex is released from the solid-phase carrier, and An immunoassay device that performs a complex transfer process for transferring a liquid phase to a second container,
a mechanical unit that performs a process of transferring the liquid phase in the first container containing the control sample containing at least the labeling substance as a liquid phase to the second container;
a detection unit that detects the labeled substance in the second container to which the liquid phase has been transferred;
a determination unit that determines an abnormality in the function of transferring the liquid phase in the first container to the second container in the complex transfer treatment, based on a comparison between the detection value of the detection unit and a reference value. , an immunoassay device. The control sample contains magnetic particles to which the labeling substance is bound,
The mechanism unit includes a magnetic force source that attracts the magnetic particles bound with the labeling substance in the first container,
21. The immunoassay device according to claim 20, wherein said determination unit determines an abnormality in the magnetic collecting function of said magnetic force source. The control sample contains a solution in which the labeling substance is dissolved,
The mechanism unit includes a suction tube that sucks the liquid phase in the first container and discharges the sucked liquid phase into the second container,
22. The immunoassay device according to claim 21, wherein said determination unit determines an abnormality in the pipetting function of said suction tube. The mechanism section includes a specimen dispensing section for dispensing a specimen containing the test substance, a reagent for dispensing a labeling reagent containing the labeling substance, and a solid-phase reagent containing the solid-phase carrier. 21. The immunoassay device of claim 20, comprising a pipetting unit and configured to prepare the control sample in the first container. The reagent dispensing unit
When measuring the specimen, dispensing a release reagent that releases the immune complex from the solid phase carrier into the first container,
25. The immunoassay device according to claim 24, wherein a liquid phase containing no free reagent is dispensed instead of the free reagent when determining an abnormality in the function of collecting the solid phase carriers in the first container. . The mechanism unit includes a BF separation unit that separates the solid phase carrier bound to the immune complex containing the test substance and the labeling substance from a liquid phase,
The immunoassay device according to claim 24 or 25, wherein said BF separation section performs BF separation on said control sample in said first container.

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