WO2019167539A1 - Procédé de confirmation d'état de dispositif de dosage immunologique, et dispositif de dosage immunologique - Google Patents

Procédé de confirmation d'état de dispositif de dosage immunologique, et dispositif de dosage immunologique Download PDF

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Publication number
WO2019167539A1
WO2019167539A1 PCT/JP2019/003455 JP2019003455W WO2019167539A1 WO 2019167539 A1 WO2019167539 A1 WO 2019167539A1 JP 2019003455 W JP2019003455 W JP 2019003455W WO 2019167539 A1 WO2019167539 A1 WO 2019167539A1
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Prior art keywords
container
labeling substance
liquid phase
solid phase
substance
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PCT/JP2019/003455
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English (en)
Japanese (ja)
Inventor
卓弥 能田
徹 植村
金子　周平
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シスメックス株式会社
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Publication of WO2019167539A1 publication Critical patent/WO2019167539A1/fr

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    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
    • G01N33/543—Immunoassay; Biospecific binding assay; Materials therefor with an insoluble carrier for immobilising immunochemicals
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
    • G01N33/543—Immunoassay; Biospecific binding assay; Materials therefor with an insoluble carrier for immobilising immunochemicals
    • G01N33/551—Immunoassay; Biospecific binding assay; Materials therefor with an insoluble carrier for immobilising immunochemicals the carrier being inorganic
    • G01N33/553—Metal or metal coated
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • G01N35/02—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor using a plurality of sample containers moved by a conveyor system past one or more treatment or analysis stations

Definitions

  • This invention relates to an immunoassay device for measuring a test substance in a specimen.
  • the immunoassay device disclosed in Patent Document 1 forms an immune complex 913 including a test substance 911 and a labeling substance 912 on a solid phase carrier 914 in a first container 901. Then, the immune complex 913 is released from the solid phase carrier 914 by the release reagent 915. Then, the immunoassay device performs the immune complex transfer method in which the liquid phase containing the released immune complex 913 is transferred to the second container 902 while leaving the solid phase carrier 914 in the first container 901, The signal based on the labeling substance 912 contained in the immune complex 913 in the two containers 902 is detected.
  • the measurement result obtained by the immunoassay device becomes a judgment material for diagnosing a disease or determining a treatment policy, the reliability of the measurement result is required.
  • a method for ensuring the reliability of measurement results there is a conventional method of measuring a quality control sample containing a known concentration of a test substance, which can be carried out easily. Used in measuring equipment.
  • the present invention is directed to making it possible to easily check the status of the function for executing the immune complex transfer method in the immunoassay device.
  • the method for confirming the state of an immunoassay device comprises an immune complex (84) comprising a test substance (81) and a labeling substance (21) in a specimen and supported on a solid phase carrier (22). ) Is released from the solid phase carrier (22) and the liquid phase in the first container (11) is transferred to the second container (12).
  • a complex is formed with respect to the first container (11) containing the control sample (20) containing the labeling substance (21) by being configured as described above.
  • the labeling substance (21) in the control sample (20) transferred to the second container (12) can be detected by performing a liquid phase transfer operation similar to the transfer process. If the complex transfer process is not performed normally, an abnormal detection result deviating from the expected detection result is acquired. Thereby, 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, such as whether or not the complex transfer process has been successfully performed. As a result, it is possible to easily check the status of the function for executing the immune complex transfer method in the immunoassay device.
  • the step of determining an abnormality in the complex transfer process based on the detection result of the labeling substance (21) in the second container (12). Prepare. With this configuration, for example, whether or not there is an abnormality in the complex transfer process by determining the detection result in the immunoassay device (100) that has detected the labeling substance (21) in the control sample (20). Can be determined.
  • the function of collecting the solid phase carrier (22) in the first container (11) and the liquid phase in the first container (11) are set to the second. Determining at least one abnormality of the function of transferring to the container (12).
  • the complex transfer treatment in order to move 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), Whether the function of collecting the solid phase carrier (22) in the first container (11) is normal is important.
  • the 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. Whether or not is normal is important. According to the above configuration, since it is possible to determine the presence / absence of at least one of these functions, it is particularly useful for ensuring the reliability of the measurement result.
  • the detected value of the labeling substance (21) in the second container (12) exceeds the reference value (V1), or the detected value is the reference value.
  • Abnormality is determined based on falling below (V2). If comprised in this way, based on the detection value obtained by the measurement in a normal state, the reference value (V1, V2) for distinguishing between normal and abnormality is preset, and a detection value and a reference
  • the method for confirming the state of the immunoassay device preferably, before the step of transferring the liquid phase in the first container (11) to the second container (12), by the immunoassay device (100), The method further includes the step of dispensing the control sample (20) into the first container (11). If comprised in this way, even if the user of the immunoassay apparatus (100) and the service staff who performs maintenance service of the apparatus do not prepare the management sample (20) in the first container (11) in advance, the immunoassay The management sample (20) can be easily accommodated in the first container (11) by the apparatus (100).
  • the management sample (20) includes a solid phase carrier (22) to which a labeling substance (21) is bound, and is contained in the first container (11).
  • the solid phase carrier (22) to which the labeling substance (21) is bound is collected in the first container (11).
  • the solid phase carrier (22) to which the labeling substance (21) is bound is collected in the first container (11).
  • the solid phase carrier (22) is a magnetic particle
  • the process of collecting the solid phase carrier (22) includes a process of collecting the magnetic particles by the magnetic force source (52) and includes the second container (12).
  • the process of collecting the solid phase carrier (22) includes a process of collecting the magnetic particles by the magnetic force source (52) and includes the second container (12).
  • the “magnetic collecting function” is a function of collecting magnetic particles
  • the normal magnetic collecting function means that the first container (11) to the second container (12 ) Indicates that the carry-over amount of the magnetic particles transferred together with the liquid phase is suppressed within an allowable range.
  • the magnetic particles to which the labeling substance (21) is bonded are collected, so that the magnetic source (52) collects the magnetic particles based on the detection value of the labeling substance (21) in the second container (12). It is possible to easily determine whether the magnetic function is normal or abnormal.
  • the abnormal magnetic flux collecting function by the magnetic source (52) is detected. Judge that there is. If comprised in this way, when the detection value of a labeled
  • 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 being collected. If comprised in this way, when the magnetic particle of the quantity exceeding an allowable upper limit amount is moved to the 2nd container (12), it can determine easily that the magnetism collection function by a magnetic source (52) is abnormal. . Therefore, the reliability of the measurement result can be ensured by confirming that the allowable upper limit amount is not exceeded.
  • the known concentration in the first container (11) is set before the step of transferring the liquid phase in the first container (11) to the second container (12).
  • a sample containing the test substance (81), a labeling substance (83) binding to the test substance (81), a capture substance (86) binding to the test substance (81), and binding to the capture substance (86) The method further includes a step of contacting the solid phase carrier (82). If comprised in this way, the solid-phase carrier (82) which the label
  • the control sample (20) includes the first solid phase carrier (82a) to be dispensed into the first container (11) before the complex transfer process when the specimen is measured. If comprised in this way, the solid-phase carrier which the label
  • the control sample (20) A second solid phase carrier (82b) to be dispensed into the second container (12) after the complex transfer treatment at the time of measurement is included. If comprised in this way, the solid-phase carrier which the label
  • the liquid in the first container (11) is preferably used.
  • a step of performing BF separation for separating the liquid phase If comprised in this way, the labeling substance (83) in the liquid phase which did not couple
  • the mixing of the labeling substance (83) in the liquid phase can be suppressed, so that the state of the immunoassay device (100) is confirmed.
  • the detection accuracy of the labeling substance (83) for the purpose can be improved.
  • the immune complex (84) is released from the solid phase carrier (82) by dispensing the free reagent (85) into the first container (11), and BF
  • the liquid phase not containing the free reagent (85) is separated into the first container (11).
  • the process of adding is further provided. If comprised in this way, it replaces with the free reagent (85) dispensed when actually measuring the test substance containing a test substance (81), and the liquid phase (25) which does not contain a free reagent (85) is used.
  • the state 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 function of collecting the solid phase carrier (82) can be appropriately confirmed.
  • control sample (20) includes the solid phase carrier (22) to which the labeling substance (21) is bound
  • the control sample (20) is not bound to the test substance (81) and the labeling substance ( 21) and a third solid phase carrier (23). If comprised in this way, using the 3rd solid-phase carrier (23) which does not contain the to-be-tested substance (81) as a reagent for exclusive use for the state confirmation of an immunoassay device (100), a solid-phase carrier (22 ) Can be confirmed.
  • the solid phase carrier (22) binds not only to the labeling substance (21) but also to the test substance (81), the solid phase carrier (22) and the labeling substance (which can be bound according to the type of the test substance (81)) 21), a plurality of types are prepared, whereas in the third solid phase carrier (23) that does not include the test substance (81), the immunoassay apparatus (100) is not dependent on the type of the test substance (81). The status can be checked. Therefore, it is possible to more easily check the state of the immunoassay device (100).
  • the control sample (20) includes a solution in which the labeling substance (21) is dissolved. If comprised in this way, since the labeling substance (21) exists as a liquid phase in the 1st container (11), for example, when the detection value of the labeling substance (21) does not rise, the liquid phase is set in the second container. When moving to (12), it can be determined that there is a high possibility that the liquid phase has not been properly transferred from the first container (11). 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.
  • the liquid phase in the first container (11) is sucked and the sucked liquid phase is sucked into the second container.
  • (12) includes a dispensing process to be discharged, and further 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).
  • the “dispensing function” includes a function of sucking the liquid phase in the first container (11) and a function of discharging the sucked liquid phase to the second container (12).
  • the 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). If comprised in this way, it can be easily determined whether the dispensing function which performs suction
  • the dispensing function When determining an abnormality in the dispensing function, preferably, 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).
  • the liquid containing the labeling substance (21) when the detected value of the labeling substance (21) is lower than the reference value (V2), the liquid containing the labeling substance (21) from the first container (11) to the second container (12). Since there is a high possibility that the phases have not been appropriately transferred, the dispensing function can be easily determined by comparing the detected value with the reference value (V2).
  • the reference value (V2) is a value set as an allowable limit of an expected detection value of the labeling substance (21) contained in the control sample (20). If comprised in this way, even if the process which moves the liquid phase containing a labeling substance (21) to a 2nd container (12) is performed, when a detected value is less than a reference value (V2), a dispensing function is abnormal. It can be easily determined. Therefore, the reliability of the measurement result can be ensured by confirming that the detected value exceeds the reference value (V2).
  • the management sample (20) When the management sample includes a solution in which the labeling substance (21) is dissolved, the management sample (20) preferably includes the labeling substance (21) to be dispensed into the first container (11) at the time of measurement of the specimen. . If comprised in this way, the liquid phase in a 1st container (11) will be made into a 2nd container using the label
  • the labeling substance (21) contained in the control sample (20) is an enzyme
  • the labeling substance (21) in the second container (12) is detected. May be performed by adding a substrate of the enzyme to the second container (12) and measuring a signal generated from a reaction product generated by the enzyme reaction.
  • the first container (11) a sample containing a test substance (81) having a known concentration or a sample not containing the test substance (81), a test Contacting a labeling substance (83) that binds to the 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);
  • the first You may further provide the process of moving the liquid phase in a container (11) to a 2nd container (12), and the process of detecting the labeling substance (83) which exists in a 2nd container (12). That is, an accuracy control method for measuring a control sample in the second container (12) by performing an operation similar to that for measuring a specimen using a control sample having a known concentration or
  • the immunoassay device (100) comprises an immune complex (84) comprising a test substance (81) and a labeling substance (21) in a specimen and carried on a solid phase carrier (22).
  • the immune complex (84) is released from the solid phase carrier (22), and the liquid phase in the first container (11) is transferred to the second container (12).
  • An immunoassay device (100) for performing a transfer process wherein a liquid phase in a first container (11) containing a control sample (20) containing at least a labeling substance (21) is transferred to a second container (12).
  • the detection part (60) which detects the labeling substance (21) in the second container (12) to which the liquid phase has been transferred, and the detection part (60) And a determination unit (70) for determining an abnormality in the complex transfer process.
  • the immunoassay device (100) is configured as described above, whereby complex transfer is performed with respect to the first container (11) containing the control sample (20) containing the labeling substance (21).
  • the labeling substance (21) in the control sample (20) transferred to the second container (12) can be detected by performing a liquid phase transfer operation similar to the processing. If the complex transfer process is not performed normally, an abnormal detection result deviating from the expected detection result is acquired. Thus, the determination unit (70) can determine whether or not the complex transfer process has been successfully performed from the detection result of the labeling substance (21) in the second container (12). The status of the function for carrying out the immune complex transfer method in can be easily confirmed.
  • the determination unit (70) preferably has a function and a mechanism for collecting the solid phase carrier (22) in the first container (11) by the mechanism unit (50). An abnormality of at least one of the function of transferring the liquid phase in the first container (11) to the second container (12) by the unit (50) is determined.
  • the determination unit (70) causes at least one of the abnormality of the function of collecting the solid phase carrier (22) in the complex transfer process and the function of transferring the liquid phase to the second container (12). Since the presence or absence can be determined, it is particularly useful for ensuring the reliability of the measurement result.
  • the control sample (20) includes magnetic particles to which the labeling substance (21) is bound, and the mechanism part (50) is a magnetic material to which the labeling substance (21) is bound in the first container (11).
  • a magnetic source (52) for collecting particles is included, and the determination unit (70) determines abnormality of the magnetic collection function by the magnetic source (52).
  • the solid phase carrier (22) to which the labeling substance (21) is bound is collected in the first container (11). For example, when the detection value of the labeling substance (21) increases. There is a possibility that when the liquid phase is transferred to the second container (12), the solid phase carrier (22) is not sufficiently magnetized 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 flux collecting function by the magnetic force source (52) in the complex transition process is normal or abnormal.
  • the control sample ( 20) includes a solution in which the labeling substance (21) is dissolved.
  • the mechanism (50) sucks the liquid phase in the first container (11) and discharges the sucked liquid phase to the second container (12).
  • the determination unit (70) includes a suction pipe (51) that performs the determination, and determines an abnormality in the dispensing function of the suction pipe (51).
  • the labeling substance (21) exists as a liquid phase in the 1st container (11), for example, when the detection value of the labeling substance (21) does not rise, the liquid phase is set in the second container.
  • the dispenser by the suction pipe (51) that performs the suction of the liquid phase and the discharge of the liquid phase is not normal. Therefore, the presence or absence of abnormality in the dispensing function by the suction tube (51) in the complex transfer process can be easily confirmed.
  • the mechanism unit (50) includes a sample dispensing unit (120) for dispensing a sample containing the test substance (81), and a labeling substance.
  • the control sample (20) is prepared. If comprised in this way, even if the user and service staff of an immunoassay device (100) do not prepare the management sample (20) in the 1st container (11) in advance, it is easy by the immunoassay device (100).
  • the management sample (20) can be accommodated in the first container (11).
  • the reagent dispensing unit (130) removes the free reagent (85) that liberates the immune complex (84) from the solid phase carrier (82) when the sample is measured. 11), when determining an abnormality in the process of transferring the liquid phase in the first container (11) to the second container (12), the free reagent (85) is replaced with the free reagent (85). Dispense the free liquid phase (25). If comprised in this way, it replaces with the free reagent (85) dispensed when actually measuring the test substance containing a test substance (81), and the liquid phase (25) which does not contain a free reagent (85) is used.
  • the state 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 collecting function of the solid phase carrier (82) can be appropriately confirmed.
  • the mechanism part (50) preferably includes a test substance (81) and a labeling substance (83). It includes a solid phase carrier (82) bound to the immune complex (84) and a BF separation unit (170) for separating the liquid phase, and the BF separation unit (170) is a control sample in the first container (11). BF separation for (20) is performed. If comprised in this way, the labeling substance (83) in the liquid phase which was not couple
  • the mixing of the labeling substance (83) in the liquid phase can be suppressed, so that the state of the immunoassay device (100) is confirmed.
  • the detection accuracy of the labeling substance (83) for the purpose can be improved.
  • the present invention it is possible to easily confirm the state of the function for executing the immune complex transfer method in the immunoassay device.
  • FIG. 1 is a schematic diagram showing a first example of a state confirmation method for an immunoassay device.
  • FIG. 2 is a schematic diagram showing a second example of the state confirmation method of the immunoassay device.
  • FIG. 3 is a schematic diagram showing an outline of the immunoassay device.
  • FIG. 4 is a diagram for explaining an outline of measurement of a sample by the immunoassay device.
  • FIG. 5 is a schematic plan view showing a specific configuration example of the immunoassay device.
  • FIG. 6 is a schematic diagram for explaining the sample dispensing unit.
  • FIG. 7 is a schematic diagram for explaining the reagent dispensing unit.
  • FIG. 8 is a schematic diagram for explaining the BF separation unit.
  • FIG. 1 is a schematic diagram showing a first example of a state confirmation method for an immunoassay device.
  • FIG. 2 is a schematic diagram showing a second example of the state confirmation method of the immunoassay device.
  • FIG. 3 is a schematic diagram showing
  • FIG. 9A is a schematic diagram illustrating a configuration example of a mechanism unit for transferring the liquid phase from the first container to the second container.
  • FIG. 9B is a schematic diagram illustrating a configuration example of a mechanism unit for transferring the liquid phase from the first container to the second container.
  • FIG. 9C is a schematic diagram illustrating a configuration example of a mechanism unit for transferring the liquid phase from the first container to the second container.
  • FIG. 10 is a schematic diagram for explaining the detection unit.
  • FIG. 11 is a diagram for explaining a method of determining a magnetic flux collecting function.
  • FIG. 12 is a diagram for explaining the first embodiment for confirming the magnetism collecting function of the immunoassay device.
  • FIG. 13 is a diagram for explaining the second embodiment for confirming the magnetism collecting function of the immunoassay device.
  • FIG. 14 is a diagram for explaining the third embodiment for confirming the magnetism collecting function of the immunoassay device.
  • FIG. 15 is a diagram for explaining Example 1 performed to confirm the effect of the third embodiment.
  • FIG. 16 shows the measurement results of Example 1.
  • FIG. 17 is a diagram for explaining a method for determining the dispensing function.
  • FIG. 18 is a diagram for explaining the fourth embodiment for confirming the dispensing function of the immunoassay device.
  • FIG. 19 is a diagram for explaining the fifth embodiment for confirming the dispensing function of the immunoassay device.
  • FIG. 20 is a diagram for explaining Example 2 performed to confirm the effect of the fifth embodiment.
  • FIG. 21 is a diagram showing the measurement results of Example 2.
  • FIG. 22 is a flowchart for explaining the operation of the immunoassay device.
  • FIG. 23 is a diagram for explaining the prior art
  • the state confirmation method of the immunoassay apparatus 100 is a state confirmation method of the immunoassay apparatus 100 that performs a complex transfer process in which the liquid phase in the first container 11 is transferred to the second container 12.
  • the immunoassay apparatus 100 measures a test substance in a specimen using an antigen-antibody reaction.
  • the specimen is a biological sample such as blood collected from a living body, for example.
  • the blood may be whole blood, serum, or plasma.
  • the test substance is, for example, an antigen or antibody contained in blood, a protein, a peptide, or the like.
  • the first container 11 and the second container 12 are, for example, cylindrical containers that are open at the upper end and closed at the bottom at the lower end, 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 be containers having the same shape or different shapes.
  • the immunoassay apparatus 100 performs a complex transfer process by an immune complex transfer method.
  • a test substance 81 and a labeling substance 83 in a specimen are contained in an immunocomplex (conjugate by antigen-antibody reaction) 84 that is carried on a solid phase carrier 82.
  • the immune complex 84 is released from the solid phase carrier 82 in one container 11 and the released immune complex 84 is separated from the solid phase carrier 82.
  • the immunoassay apparatus 100 performs the complex transfer process 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 apparatus 100 prevents the solid phase carrier 82 from being carried over to the second container 12 together with the liquid phase. Collect the solid support 82.
  • the immune complex may be a labeling substance (an antibody that binds to the test substance or a labeling substance bound to a light source).
  • the immune complex can be a conjugate of a labeling substance and an antibody.
  • the immune complex can be a conjugate of a labeling substance, an antibody, and a test substance.
  • the method for confirming the state of the immunoassay apparatus 100 according to the present embodiment confirms whether or not the function for performing the complex transfer process by the immunoassay apparatus 100 is normal.
  • the method for confirming the state of the immunoassay device 100 is a step 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), a step (b) of detecting the labeling substance 21 in the second container 12 to which the liquid phase has been transferred, and a detection result of the labeling substance 21 in the second container 12, and a complex transfer process is performed. And (c) determining the state of the immunoassay device 100. That is, in the state confirmation method, as the step (a), the liquid phase transfer operation similar to the complex transfer process at the time of sample measurement by the immunoassay apparatus 100 is performed. In step (b), the control sample 20 in the transferred second container 12 is measured. In step (c), the state is determined based on the detection result obtained in step (b).
  • Step (a) is performed by, for example, a dispensing process in which the liquid phase in the first container 11 is sucked by the suction tube 51 provided in the immunoassay apparatus 100 and the sucked liquid phase is discharged into the second container 12.
  • step (b) for example, the labeling substance 21 in the second container 12 is detected by a detection unit provided in the immunoassay apparatus 100.
  • step (c) for example, the determination unit provided in the immunoassay apparatus 100 performs state determination based on the detection result.
  • Step (c) can also be performed by, for example, a computer connected to the immunoassay device 100, a server device that can communicate with the immunoassay device 100 via a network, and the like.
  • the labeling substance is not particularly limited as long as it can emit a detectable or measurable signal.
  • an enzyme, a fluorescent substance, a radioisotope, etc. are mentioned.
  • the enzyme include alkaline phosphatase, ⁇ -galactosidase, peroxidase, glucose oxidase, tyrosinase, acid phosphatase, and luciferase, but are not particularly limited.
  • Fluorescent substances include fluorescein isothiocyanate (FITC), coumarin, rhodamine, fluorescein, Cy3, Cy5, Hoechst 33342, 4 ′, 6-diamidino-2-phenylindole (DAPI), propidium iodide (PI), Alexa Fluor ( Fluorescent dyes such as Molecular Probes (registered trademark) series, fluorescent proteins such as green fluorescent protein (GFP), and the like are exemplified, but not limited thereto. Examples of the radioisotope include 125I, 14C, and 32P, but are not particularly limited.
  • the labeling substance 21 is a concept including a labeling antibody (an antibody that binds to a test substance and a labeling substance bound) used as a measurement reagent.
  • the labeling substance 21 included in the management sample 20 may be the same labeling substance as the labeling substance 83 (see FIG. 4) included in the immune complex 84 at the time of measurement of the specimen, or different. It may be a labeling substance.
  • the detection of the labeling substance is not particularly limited as long as it is performed by an appropriate method according to the type of label used for the labeling substance. What is necessary is just to detect the abundance of a labeling substance using the detection means corresponding to the labeling substance.
  • the label used for the labeling substance is an enzyme
  • the measurement can be performed by measuring light, color, etc. generated by reacting a substrate with the enzyme.
  • a detection unit in this case, a photomultiplier tube, a spectrophotometer, a luminometer, or the like can be used.
  • the labeling substance is a radioisotope, a scintillation counter or the like can be used as the detection unit.
  • the labeling substance is a fluorescent substance
  • the labeling substance can be detected using a fluorescence detector capable of detecting the emitted fluorescence.
  • a known substrate may be appropriately selected according to the enzyme used.
  • the substrate is CDP-Star®, (4-chloro-3- (methoxyspiro ⁇ 1,2-dioxetane-3,2 ′-(5′-chloro) trixiro [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] decan ⁇ -4-yl) phenyl phosphate disodium); p-nitrophenyl phosphate, 5-bromo-4-chloro- Luminescent substrates such as 3-indolyl phosphate (BCIP), 4-nitroblue tetrazolium chloride (NBT).
  • the detection result reflecting the abundance of the labeling substance 21 is acquired by the detection.
  • the detection result can be acquired in the form of numerical information as a detection value corresponding to the amount of the labeling substance 21 present.
  • Management sample including solid phase carrier bound with labeling substance As shown in FIG. 1, when the management sample 20 includes a solid phase carrier 22 to which a labeling substance 21 is bound, a process of collecting the solid phase carrier 22 is performed when performing the step (a). By the step (a), the liquid phase is moved from the first container 11 to the second container 12 while leaving the solid phase carrier 22. For this reason, the second container 12 contains a liquid phase that does not include the solid phase carrier 22 to which the labeling substance 21 is bound.
  • the solid phase carrier is, for example, a known particle used in immunoassay.
  • the particles include magnetic particles, latex particles, erythrocytes, and gelatin particles.
  • the magnetic particle may be any particle that contains a magnetic material as a base material and is used for normal immunoassay. 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.
  • the solid phase carrier 22 included in the management sample 20 may be the same solid phase carrier 82 as the solid phase carrier 82 that binds to the immune complex 84 when the specimen is measured, or a different solid phase carrier. It may be.
  • the binding between the labeling substance and the solid phase carrier may be performed directly by chemical bonding or indirectly through a capturing substance.
  • a combination of biotin and avidin, hapten and anti-hapten antibody, nickel and histatidine tag, glutathione and glutathione-S-transferase, etc. can be used.
  • “Avidins” means containing avidin and streptavidin.
  • a fluorescent dye conjugated with biotin can be bound to a solid phase carrier coated with streptavidin.
  • a solid phase carrier 22 to which the labeling substance 21 is bound a commercially available one can be suitably used.
  • a solid phase to which the labeling substance 21 is bound is bound.
  • the carrier 22 may be formed. That is, the solid phase carrier 22 to which the labeling substance 21 is bound is prepared by forming an immune complex 84 composed 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, as described later, such a substance can be produced by causing the immunoassay apparatus 100 to execute part or all of the immunoassay operation.
  • the labeling substance 21 in the second container 12 is detected.
  • the solid phase carrier 22 is not carried over to the second container 12 beyond the allowable upper limit for use. Therefore, when the function of collecting the solid phase carrier 22 of the immunoassay apparatus 100 is normal, the detection value of the labeling substance 21 in step (b) is as low as that obtained when a blank sample not containing the labeling substance 21 is measured. It becomes.
  • the blank sample is a sample that does not contain the labeling substance 21.
  • step (a) the step (a) The solid phase carrier 22 to which the labeling substance 21 is bound is transferred to the second container 12 together with the liquid phase. Therefore, when the function of collecting the solid phase carrier 22 of the immunoassay apparatus 100 is abnormal, the detected value of the labeling substance 21 in step (b) becomes an abnormally high value that is outside the allowable range of the detected value in the normal state.
  • the detection result by the step (b) is acquired in the step (c).
  • the state of the immunoassay apparatus 100 in the complex transfer process is determined. That is, it is determined from the detection result whether the complex transfer process has been successfully performed.
  • the state of determination may be a binary classification of “normal” or “abnormal”, “0 (no abnormality)” or “1 (abnormal)”.
  • the degree of normality or abnormality may be determined according to the detection value.
  • the judgment range such as within the complete 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), and depending on the detection value It may be determined which range belongs.
  • 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 in which labeling substance is dissolved As shown in FIG. 2, when the control 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). . For this reason, the liquid phase containing the labeling substance 21 is accommodated in the second container 12.
  • the labeling substance 21 in the second container 12 is detected.
  • the function of transferring the liquid phase in the first container 11 of the immunoassay apparatus 100 to the second container 12 is normal, the labeling 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 apparatus 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 management sample 20. Within the tolerances expected from 21 known concentrations.
  • the function of transferring the liquid phase in the first container 11 of the immunoassay apparatus 100 to the second container 12 is abnormal, for example, the liquid phase could not 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 by the step (a). Therefore, when the function of transferring the liquid phase in the first container 11 of the immunoassay apparatus 100 to the second container 12 is abnormal, the detection value of the labeling substance 21 in step (b) is determined from the known concentration of the labeling substance 21. The value deviates from the expected allowable range.
  • 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 complex transfer treatment is performed.
  • the state of the device 100 is determined. That is, it is determined whether the complex transfer process has been successfully performed.
  • the same operation as the complex transfer process is performed on the first container 11 containing the management sample 20 including the labeling substance 21, and the second The labeling 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 is acquired. Thereby, 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 the complex transfer process has been successfully performed. As a result, it is possible to easily check the status of the function for executing the immune complex transfer method in the immunoassay apparatus 100.
  • ⁇ Treatment of collecting the solid support> As shown in FIG. 1, when the management sample 20 includes a solid phase carrier 22 to which a 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. The solid phase carrier 22 to which the labeling substance 21 is bound is collected.
  • the process of collecting the solid phase carrier 22 is performed, for example, by centrifuging the first container 11 with the immunoassay apparatus 100 and allowing the solid phase carrier 22 to settle at the bottom of the container.
  • the process of collecting the solid support 22 includes a process of collecting the magnetic particles by the magnetic force source 52.
  • magnetic particles are collected by a magnetic source 52 provided in the immunoassay apparatus 100.
  • the solid phase carrier 22 to which the labeling substance 21 is bound is collected in the first container 11, for example, when the detection value of the labeling substance 21 increases, the solid phase is transferred when the liquid phase is transferred to the second container 12.
  • the carrier 22 is not sufficiently collected and the solid phase carrier 22 is also transferred. Therefore, it can be easily confirmed whether or not the function of collecting the solid phase carrier 22 in the first container 11 in the complex transfer process is normal.
  • steps (a) and (b) there may be the following steps.
  • the method for confirming the state of the immunoassay apparatus further includes a step of determining an abnormality in the complex transfer process based on the detection result of the labeling substance 21 in the second container 12.
  • the presence or absence of abnormality in the complex transfer process can be determined by determining the magnitude of the detection value acquired in step (b).
  • the determination can be performed by, for example, a determination unit 70 (see FIG. 3) included in the immunoassay apparatus 100 or an external apparatus such as a host computer connected to the immunoassay apparatus 100 so as to be communicable.
  • the function for performing the complex transfer process includes a function of collecting the solid phase carrier 22 in the first container 11 and a function of transferring the liquid phase in the first container 11 to the second container 12. Including. Therefore, the step of determining abnormality in the complex transfer process includes at least one of a function of collecting the solid phase carrier 22 in the first container 11 and a function of transferring the liquid phase in the first container 11 to the second container 12. Including determining any abnormality.
  • the liquid phase containing the immune complex 84 is transferred to the second container 12, and the solid phase carrier 22 in the first container 11 is left in the first container 11 to leave the solid phase carrier 22.
  • the collecting function is normal or not is important.
  • the management sample 20 includes the solid phase carrier 22 to which the labeling substance 21 is bound
  • the solid phase carrier 22 in the first container 11 is changed based on the detection result of the step (b). It is possible to determine whether or not the function to be collected is normal.
  • the 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.
  • the composite value can be obtained simply by comparing the detection value with the reference value V1. Abnormality determination of the transfer process can be easily performed.
  • a step of dispensing the management sample 20 into the first container 11 by the immunoassay device 100 may be further provided.
  • the immunoassay apparatus 100 sucks the management sample 20 from a container (not shown) that stores the management sample 20 in advance by the suction tube 51 and discharges the management sample 20 into the first container 11. Thereby, even if the user or service staff of the immunoassay apparatus 100 does not prepare the management sample 20 in the first container 11 in advance, the management sample 20 is easily accommodated in the first container 11 by the immunoassay apparatus 100. Can be made.
  • the immunoassay device 100 is a device that measures a test substance in a specimen using an antigen-antibody reaction.
  • the immunoassay apparatus 100 performs a complex transfer process by an immune complex transfer method. That is, as shown in FIG. 4, the immunoassay device 100 includes an inside of the first container 11 that contains an immune complex 84 that includes a test substance 81 and a labeling substance 83 in a sample and is carried on a solid phase carrier 82.
  • the immunoassay apparatus 100 performs the complex transfer process in which 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.
  • the immunoassay apparatus 100 includes a mechanism unit 50 that performs a process of transferring the liquid phase in the first container 11 in which the management sample 20 containing at least the labeling substance 21 is stored to the second container 12, and the liquid
  • the detection part 60 which detects the labeled
  • the mechanism unit 50 has at least a function of executing a complex transfer process. That is, the mechanism unit 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 may have a function of performing not only the complex transfer process but also a process necessary for the immunoassay on the reaction container.
  • the mechanism unit 50 can perform a process of forming an immune complex including the test substance 81 and the labeling substance 21 in the sample on the solid phase carrier 22 in the first container 11.
  • the mechanism unit 50 can include one or a plurality of processing units depending on the type and number of processing steps performed by the immunoassay apparatus 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 unit 50 includes, for example, a suction pipe 51 that sucks the liquid phase in the first container 11 and discharges the sucked liquid phase to the second container 12.
  • the suction pipe 51 is connected to a pressure source (not shown) such as a metering pump, for example, and sucks a predetermined amount of liquid from the tip and can dispense a fixed amount.
  • the mechanism unit 50 includes a magnetic force source 52 that collects magnetic particles bound to the labeling substance 21 in the first container 11.
  • the magnetic source 52 is positioned in the vicinity of the first container 11. Magnetic particles can be collected by the magnetic force of the magnetic source 52.
  • the magnetic collection is to collect magnetic materials by applying a magnetic force.
  • the magnetic force source 52 applies a magnetic force to the magnetic particles in the first container 11 to collect 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 can be employed.
  • the mechanism unit 50 may include a sample dispensing unit for dispensing the sample into the first container 11.
  • the mechanism unit 50 can perform a step of dispensing a specimen containing the test substance 81.
  • the mechanism unit 50 processes the first container 11 in which the sample has been dispensed in advance, it is not necessary to provide the sample dispensing unit in the mechanism unit 50.
  • the mechanism unit 50 may include a reagent dispensing unit for dispensing the reagent to the first container 11.
  • the mechanism unit 50 includes a step of dispensing a solid phase reagent including solid phase carriers 22 and 82 such as magnetic particles, a step of dispensing a labeling reagent including labeling substances 21 and 83, and a free reagent 85. A dispensing process can be performed.
  • the mechanism unit 50 processes the first container 11 in which these reagents are dispensed in advance, it is not necessary to provide the reagent dispensing unit in the mechanism unit 50.
  • the various reagents 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
  • the labeling reagent is a liquid reagent containing labeling substances 21 and 83 in the liquid.
  • the free reagent 85 is a liquid reagent containing a component for eliminating the binding between the immune complex 84 and the solid phase carrier 82.
  • the release reagent 85 eliminates the binding between the immune complex 84 including 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.
  • the free reagent 85 cancels the binding between the solid phase carrier 82 and the test substance 81.
  • the free reagent 85 binds to the solid phase carrier 82 and the capture substance 86, or the test substance 81 and the capture substance 86 bind to each other. Can be eliminated.
  • the free reagent 85 is selected according to the type of binding between the immune complex 84 and the solid phase carrier 82.
  • a hapten or a hapten derivative can be used as the free reagent 85.
  • a solution containing ions can be used as the free reagent 85.
  • a ligand or a ligand analog can be used as the free reagent 85.
  • the bond between the immune complex 84 and the solid phase carrier 82 is a lectin-sugar chain bond as a separable bond
  • a carbohydrate can be used as the free reagent 85.
  • biotin can be used as the free reagent 85.
  • the mechanism unit 50 may include a reaction unit for heating and reacting the sample in the first container 11.
  • 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 or the process of releasing the immune complex 84, so that the process is efficiently performed. Can do.
  • the reaction unit is provided in the mechanism unit 50. There is 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, the detection may be performed by an appropriate method according to the types of the labeling substances 21 and 83, and the detection method is not particularly limited. As the detection unit 60, a photomultiplier tube, a spectrophotometer, a luminometer, or the like can be used. When detecting fluorescence, the detection unit 60 may include a light source for irradiating excitation light. Further, when the labeling substance is a radioisotope, 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 a computer including a processor such as a CPU and a storage unit such as a hard disk drive and a flash memory, for example.
  • the processor functions as the determination unit 70 of the immunoassay device 100 by executing the control program stored in the storage unit.
  • the determination unit 70 determines an abnormality in the complex transfer process based on the detection result of the detection unit 60.
  • the immunoassay device 100 performs the state confirmation method of the immunoassay device 100 shown in at least one of FIGS. 1 and 2 with the above-described configuration. Thereby, the liquid phase transfer operation similar to the complex transfer process is performed on the first container 11 containing the management sample 20 including the labeling substance 21, and the management 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 is acquired. Thereby, it can be confirmed from the detection result of the labeling substance 21 in the second container 12 whether or not the complex transfer process has been normally performed, so that the immune complex transfer method in the immunoassay device is executed. The function status can be easily checked.
  • the immunoassay apparatus 100 includes a mechanism unit 50, a detection unit 60, and a determination unit 70.
  • the immunoassay device 100 includes an analysis unit 110 for analyzing an immunoassay result.
  • the determination unit 70 is realized as part of the function executed by the analysis unit 110.
  • the mechanism unit 50 includes a sample dispensing unit 120, a reagent dispensing unit 130, a container supply unit 140, a reagent storage 150, a reaction unit 160, and a BF separation unit 170. Moreover, the mechanism part 50 contains the container transfer part 180 which conveys a container to each of these parts.
  • the immunoassay apparatus 100 includes a sample transport unit 190 and a housing 105 that houses the mechanism unit 50 and the detection unit 60.
  • the housing 105 has a box shape that houses each part of the immunoassay device 100 therein.
  • the housing 105 can be configured with one or a plurality of layers.
  • the sample transport unit 190 is configured to transport a sample collected from the subject to a suction position by the sample dispensing unit 120.
  • the sample transport unit 190 can transport a rack in which a plurality of sample containers 191 (see FIG. 6) containing a sample are installed to a predetermined sample suction position.
  • the sample dispensing unit 120 can aspirate the sample conveyed by the sample conveyance unit 190 and dispense the aspirated sample into the first container 11.
  • the sample dispensing unit 120 includes a suction tube 121 connected to a fluid circuit for performing suction and discharge, and a moving mechanism (not shown) that moves the suction tube 121.
  • the sample dispensing unit 120 attaches a dispensing tip 122 to the tip of the suction tube 121 from a tip supply unit (not shown), for example, and sucks a predetermined amount of the sample in the transported sample container 191 into the dispensing tip 122.
  • the sample dispensing unit 120 dispenses the aspirated sample into the first container 11 disposed at a predetermined sample dispensing position. After dispensing, the sample dispensing unit 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 containers having the same shape and the same material are used as the first container 11 and the second container 12. That is, the unused reaction container supplied from the container supply unit 140 can be used as both the first container 11 and the second container 12. In addition, when the 1st container 11 and the 2nd container 12 correspond in common, and it is not necessary to distinguish, it is only called "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 puts the container at each processing position such as the sample dispensing unit 120, the reagent dispensing unit 130, the reaction unit 160, the BF separation unit 170, the detection unit 60, and the like.
  • Transport The container transfer unit 180 includes, for example, a catcher that holds the container or a holding unit having a container installation hole, and a moving mechanism that moves the catcher or the holding unit.
  • the moving mechanism moves in the direction of one axis or a plurality of axes by, for example, one or more linear motion mechanisms capable of linear movement.
  • the moving mechanism can move, for example, in three orthogonal directions in the vertical direction and two horizontal directions.
  • the moving mechanism may include an arm mechanism that rotates horizontally around the rotation axis and 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 unit 160 includes a heater and a temperature sensor, holds the reaction vessel 10, and heats and reacts the sample stored in the vessel. By heating, the specimen and reagent contained in the container 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 movably provided in the housing 105. When the reaction unit 160 is configured to be movable, the reaction unit 160 can also function as a part of the container transfer unit 180.
  • the reagent storage 150 has a box shape and includes a container holding portion 151 and a cooling mechanism inside.
  • the container holding unit 151 holds the reagent container 155.
  • the cooling mechanism keeps the reagent in the reagent container 155 at a constant temperature suitable for storage.
  • the reagent storage 150 has a plurality of holes 152 on the upper surface for allowing the reagent dispensing unit 130 to enter the inside of the reagent storage 150.
  • the container holding part 151 is formed 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 the row
  • the container holding part 151 can independently rotate the row of a plurality of concentric reagent containers 155 in the circumferential direction.
  • the container holding unit 151 has a desired reagent container selected from the row of the corresponding reagent containers 155 at a position immediately below each of the plurality of holes 152 provided in accordance with the reagent dispensing unit 130. 155 can be arranged. As a result, the reagent in the reagent container 155 arranged at a position immediately below the hole 152 is aspirated by the reagent dispensing unit 130.
  • a reagent container 155 that stores r1 reagent, r4 reagent, r5 reagent, r6 reagent, and r7 reagent, which will be described later, is set.
  • 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 sucks the reagent in the reagent container 155 and dispenses the sucked reagent into the reaction container 10.
  • the reagent dispensing unit 130 can move a suction tube 131 for performing aspiration and discharge of the reagent in the horizontal direction between the hole 152 and a predetermined reagent dispensing position.
  • the reagent dispensing unit 130 can move the suction tube 131 in the vertical direction and pass through the hole 152 from above the hole 152 to 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 holding unit 151, and dispenses the reagent into the reaction container 10 transferred to the reagent dispensing position.
  • reagent dispensing units 130 are provided.
  • three reagent dispensing units 130 are provided on the reagent storage 150.
  • Each of the three reagent dispensing units 130 is set in advance as to which of the r1 reagent, r4 reagent, r5 reagent, r6 reagent, and r7 reagent is to be dispensed.
  • the mechanism unit 50 includes an R4 reagent dispensing unit 134 for dispensing the R4 reagent and an R5 reagent dispensing unit 135 for dispensing the 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 dispensing unit 134 and the R5 reagent dispensing unit 135 are connected to a reagent container (not shown) containing the R4 reagent and the R5 reagent via a liquid feeding tube, respectively, and are transferred by the container transfer unit 180.
  • the reagent can be discharged into the reaction container 10.
  • the BF separation unit 170 has a function of executing BF separation for separating the liquid phase and the solid phase from the reaction vessel 10.
  • one or a plurality of BF separation units 170 are provided in the immunoassay apparatus 100.
  • the BF separation unit 170 sucks the liquid component in the reaction vessel 10 with the suction tube 171 while collecting the magnetic particles with the magnetic collection unit 173, and supplies the cleaning liquid with the discharge tube 172 To do.
  • the suction pipe 171 and the discharge pipe 172 are each connected to a fluid circuit (not shown). Thereby, the unnecessary substance contained in the liquid component can be separated and removed from the magnetic particles.
  • the mechanism unit 50 has a function of performing a complex transfer process.
  • the mechanism unit 50 includes a magnetic source 52 that collects magnetic particles to which the labeling substance 21 is bound in the first container 11.
  • the magnetic force source 52 is provided in the holding member 210 in which a holding hole 211 for holding the first container 11 is formed, for example.
  • the magnetic source 52 is constituted by a permanent magnet, for example.
  • the holding member 210 may be fixedly installed in the housing 105, may be configured to be movable, and may function as a part of the container transfer unit 180.
  • the mechanism unit 50 includes a suction pipe 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 and puts it into the second container 12 held by the container transfer part 180 or another container holding part (not shown). Dispense the sucked liquid phase.
  • the liquid phase transfer in the complex transfer process is performed by a configuration including a suction tube.
  • the complex transfer process can be executed by the suction tube 121 of the sample dispensing unit 120.
  • the suction tube 121 also functions as the suction tube 51 that performs the complex transfer process.
  • the complex transfer process can be executed by the suction tube 131 of the reagent dispensing unit 130.
  • the suction tube 131 also functions as the suction tube 51 that performs the complex transfer process.
  • the mechanism unit 50 may include a dedicated immune complex dispensing unit 220 for performing the complex transfer process. In that case, the liquid phase in the first container 11 is sucked by the suction tube 51 provided in the immune complex dispensing unit 220, and the sucked liquid phase is discharged to the second container 12.
  • the detection unit 60 includes a photodetector 61 such as a photomultiplier tube.
  • the detection unit 60 receives the second container 12 inside, and detects light generated in the reaction process of the labeling substance 83 (see FIG. 4) that binds to the analyte 81 of the specimen and the luminescent substrate by the photodetector 61. .
  • the detection unit 60 counts the number of photons detected by the photodetector 61 and outputs it as a detection value.
  • the analysis unit 110 is configured by a personal computer, for example.
  • the analysis unit 110 includes, for example, a processor 111 such as a CPU and a storage unit 112 such as a ROM, a RAM, and a hard disk.
  • the processor 111 functions as the analysis unit 110 of the immunoassay device 100 by executing the control program stored in the storage unit 112.
  • the analysis unit 110 is electrically connected to the mechanism unit 50, and controls the mechanism unit 50 so as to execute measurement of a sample 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 the measurement order acquired from a host computer (not shown), and analyzes the detection result by the detection unit 60. That is, the analysis unit 110 compares the detection value obtained by the detection unit 60 with a calibration curve prepared in advance, so that the abundance of the test substance 81 in the sample (that is, the labeling substance bound to the test substance 81). 83 abundance).
  • the analysis unit 110 includes a determination unit 70. That is, 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 is at least one of the function of collecting the solid phase carrier 22 in the first container 11 by the mechanism unit 50 and the function of transferring the liquid phase in the first container 11 by the mechanism unit 50 to the second container 12.
  • Judge abnormalities Accordingly, since it is possible to determine whether or not there is an abnormality in at least one of the function of collecting the solid phase carrier 22 in the complex transfer process and the function of transferring the liquid phase to the second container 12, the reliability of the measurement result is ensured. Is particularly useful.
  • the determination unit 70 determines an abnormality in the magnetic collection function by the magnetic force source 52 (see FIGS. 9A to 9C) based on the detection result for the management sample including the magnetic particles to which the labeling substance 21 is bound.
  • the solid phase carrier 22 to which the labeling substance 21 is bound is collected in the first container 11.
  • the detection value of the labeling substance 21 increases, the liquid phase is transferred to the second container 12.
  • the solid phase carrier 22 is not sufficiently magnetized and the solid phase carrier 22 is also transferred. Therefore, it can be easily determined whether the magnetic flux collecting function by the magnetic source 52 in the composite transition process is normal or abnormal.
  • the determination unit 70 determines abnormality of the dispensing function by the suction tube 51 (see FIGS. 9A to 9C) based on the detection result for the management sample including the solution in which the labeling substance 21 is dissolved.
  • the labeling substance 21 exists in the first container 11 as the liquid phase, for example, when the detection value of the labeling substance 21 does not increase, the liquid phase is dispensed into the second container 12.
  • the dispenser by the suction pipe 51 that performs the suction and the liquid phase discharge is not normal. Therefore, the presence or absence of abnormality in the dispensing function by the suction tube 51 in the complex transfer process can be easily confirmed.
  • immunoassay is performed using the r1 reagent to r7 reagent, the R4 reagent, and the R5 reagent.
  • test substance 81 is hepatitis B surface antigen (HBsAg)
  • HBsAg hepatitis B surface antigen
  • the reagent dispensing unit 130 dispenses the r1 reagent into the first container 11.
  • the r1 reagent is a labeling reagent containing the labeling substance 83.
  • the labeling substance 83 reacts with and binds to the test substance 81.
  • the labeling substance is an ALP (alkaline phosphatase) labeled antibody.
  • the specimen dispensing unit 120 dispenses a specimen containing the test substance 81 in the first container 11.
  • the test substance 81 binds to the labeling substance 83.
  • a reagent (r2 reagent) for alkali denaturation of the specimen as a pretreatment for releasing the antigen present in the specimen in a state in which the antibody is bound in advance from the antibody, or the alkali of the specimen is neutralized.
  • a reagent (r3 reagent) or the like may be further dispensed.
  • the reagent dispensing unit 130 dispenses the r4 reagent into the first container 11.
  • the r4 reagent is a capture reagent containing a capture substance 86 that reacts with and binds to the test substance 81.
  • the capture substance 86 includes a first binding substance 86a for binding the capture substance 86 to a first solid phase carrier 82a described later, and a second binding substance for binding the capture substance 86 to a 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 abilities.
  • the capture substance 86 is an antibody (DNP / biotin antibody) modified with DNP (dinitrophenyl group) and biotin. That is, the capture substance 86 is modified with DNP (dinitrophenyl group) as the first binding substance 86a and biotin as the second binding substance 86b.
  • the reagent dispensing unit 130 dispenses the r5 reagent into the first container 11.
  • the r5 reagent is a solid phase reagent containing a solid phase carrier 82.
  • the r5 reagent contains the first solid phase carrier 82a as the solid phase carrier 82.
  • 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-modified magnetic particle).
  • the anti-DNP antibody-antimagnetic DNP antibody which is an anti-hapten, reacts with and binds to the DNP of the capture substance 86, which is a hapten.
  • an immune complex 84 including the test substance 81, the labeling substance 83, and the capture 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 the primary BF separation process. Unnecessary components such as the unreacted labeling substance 83 are removed from the first container 11 by the primary BF separation process.
  • the primary BF separation process is performed by the BF separation unit 170 (see FIG. 8).
  • the reagent dispensing unit 130 dispenses the r6 reagent into the first container 11.
  • the r6 reagent is the free reagent 85.
  • DNP-Lys (DNP-Lysine) is used as the free reagent 85.
  • DNP-Lys reacts and binds to the anti-DNP-antibody magnetic particles that are the first solid phase carrier 82a. Therefore, when the r6 reagent is dispensed into the first container 11, the binding between the DNP of the capture substance 86 and the first solid phase carrier 82a, the free reagent 85 (DNP-Lys), and the first solid phase carrier 82a. The binding competes 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.
  • a complex transfer process is performed. That is, the liquid phase containing the immune complex 84 released by the r6 reagent is sucked from the first container 11 by the suction tube 51 and dispensed into the second container 12.
  • the liquid phase containing the immune complex 84 released from the first solid phase carrier 82a is transferred 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 is aspirated.
  • the labeling substance 83 nonspecifically bound to the first solid phase carrier 82a is separated from the immune complex 84.
  • the reagent 7 is then dispensed with the r7 reagent into the second container 12 into which the immune complex 84 has been dispensed.
  • the r7 reagent contains the second solid phase carrier 82b.
  • the second solid phase carrier 82b binds to the second binding substance 86b of the capture substance 86.
  • the second solid phase carrier 82b is a magnetic particle, specifically, a magnetic particle (StAvi-binding magnetic particle) to which streptavidin that binds to biotin is immobilized. StAvi-bound magnetic particles streptavidin reacts with and binds to biotin as the second binding substance 86b.
  • the immune complex 84 including the test substance 81, the labeling substance 83, and the capture substance 86 is bound 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 the secondary BF separation process, and the unnecessary components are secondly separated.
  • the container 12 is removed.
  • the unnecessary component is, for example, a free reagent 85 contained in the liquid phase, a labeling substance 83 contained in the liquid phase together with the immune complex 84 without being bound to the test substance 81, and the like.
  • the secondary BF separation process is performed by the BF separation unit 170 (see FIG. 8).
  • the R4 reagent dispensing unit 134 and the R5 reagent dispensing unit 135 respectively dispense the R4 reagent and the R5 reagent into the second container 12.
  • 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 solution 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 detection unit 60 (see FIG. 10).
  • the labeling substance 21 contained in the control sample 20 is an enzyme.
  • the step (b) of detecting the labeling substance 21 in the second container 12 is performed by adding an enzyme substrate to the second container 12 and measuring a signal generated from a reaction product generated by the enzyme reaction.
  • the management sample 20 includes a solid phase carrier 22 to which a labeling substance 21 is bound, and the solid phase carrier 22 is a magnetic particle.
  • the process of collecting the solid phase carrier 22 includes a process of collecting magnetic particles by the magnetic force source 52.
  • the state confirmation method includes a step of determining abnormality of the magnetic flux collecting function by the magnetic source 52 based on the detection result of the labeling substance 21 in the second container 12. Thereby, in order to collect the magnetic particles to which the labeling substance 21 is bound, whether the magnetism collection function by the magnetic source 52 is normal or abnormal is determined based on the detection value of the labeling substance 21 in the second container 12. Easy to judge.
  • the determination unit 70 determines that there is an abnormality in the magnetic collection function by the magnetic source 52. That is, when the detection value of the labeling substance 21 exceeds the reference value V1, there is a high possibility that the magnetic particles cannot be sufficiently collected when the liquid phase is transferred to the second container 12. Thereby, the magnetism collecting function by the magnetic source 52 can be easily determined by comparing the detected value with the reference value V1.
  • the reference value V1 when 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 that are transferred to the second container 12 without being magnetized.
  • the management sample 20 includes a third solid phase carrier 23 that does not bind to the test substance 81 but binds to the labeling substance 21.
  • the third solid phase carrier 23 is, for example, a magnetic particle to which the labeling substance 21 is fixed in advance.
  • the third solid phase carrier 23 does not have a binding ability to the test substance 81. That is, the third solid phase carrier 23 when confirming the magnetism collecting function is the first solid phase carrier 82a included in the r5 reagent when the sample is measured, and the second solid phase carrier included in the r7 reagent. It is included in the quality control reagent prepared separately from 82b.
  • the function of collecting the solid phase carrier 22 can be confirmed using the third solid phase carrier 23 not containing the test substance 81 as a dedicated reagent for checking the state of the immunoassay apparatus 100.
  • the solid phase carrier 22 is bound not only to the labeling substance 21 but also to the test substance 81, a plurality of types of solid phase carriers 22 and labeling substances 21 that can be bound according to the type of the test substance 81 are prepared.
  • the third solid phase carrier 23 not including the test substance 81 the state of the immunoassay apparatus 100 can be confirmed regardless of the type of the test substance 81. Therefore, the state of the immunoassay device 100 can be confirmed more easily.
  • the management sample 20 including the third solid phase carrier 23 bound to the labeling substance 21 is accommodated in the first container 11.
  • the management sample 20 is dispensed into the first container 11 by the mechanism unit 50.
  • the control sample 20 is set in the sample transport unit 190 while being stored in a predetermined control sample container in the same manner as the sample container 191, and is dispensed into the first container 11 by the sample dispensing unit 120.
  • the management sample 20 is set in the reagent storage 150 while being accommodated in a predetermined management sample container in the same manner as the reagent container 155, and is dispensed into the first container 11 by the reagent dispensing unit 130.
  • the third solid phase carrier 23 in the first container 11 is Magnetized in the container 11.
  • the liquid phase in the first container 11 is sucked and dispensed into the second container 12 by the suction pipe 51 in the state of being magnetized.
  • the third solid phase carrier 23 remains collected in the first container 11.
  • 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.
  • a detection value indicating the abundance of the labeling substance 21 is acquired.
  • the dispensing operation of the r1 reagent, the specimen, the r4 reagent, the r5 reagent, the r6 reagent, and the r7 reagent shown in FIG. 4 can be skipped.
  • an alternative liquid that does not cause an antigen-antibody reaction such as a buffer solution, may be dispensed instead of each reagent and sample.
  • the primary BF separation process and the secondary BF separation process shown in FIG. 4 are skipped.
  • BF separation may also be performed.
  • FIG. 12 shows an example in which the management sample 20 is dispensed at the dispensing timing of the r6 reagent shown in FIG. 4, but the management sample 20 is dispensed at any timing before the complex transfer process. May be.
  • the state confirmation method includes a sample containing a test substance 81 having a known concentration in the first container 11, a sample containing the test substance 81 before the step of transferring the liquid phase in the first container 11 to the second container 12.
  • the management sample 20 includes the solid phase carrier 82 bound to the immune complex 84 including the test substance 81, the labeling substance 83, and the capture substance 86. That is, FIG. 13 shows an example in which the labeling substance 83 and the solid phase carrier 82 used in actual sample measurement are used as the labeling substance 21 and the solid phase carrier 22 used in the state confirmation method of the immunoassay apparatus 100.
  • 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 in the case of actually measuring the specimen including the test substance 81.
  • the labeling substance 83 is substantially not contained.
  • the r1 reagent containing the labeling substance 83 is dispensed into the first container 11.
  • a quality control sample containing a test substance 81 having a known concentration is dispensed.
  • the r4 reagent containing the capture substance 86 is dispensed.
  • the r5 reagent containing the first solid phase carrier 82a is dispensed.
  • the immune complex 84 including the test substance 81, the labeling substance 83, and the capture substance 86 is bound to the first solid phase carrier 82a.
  • Reagent dispensing is performed by the reagent dispensing unit 130, and dispensing of the quality control sample is performed by the sample dispensing unit 120.
  • the management sample 20 includes the first solid phase carrier 82a dispensed into the first container 11 before the complex transfer process at the time of measurement of the specimen. That is, the control sample 20 includes the first solid phase carrier 82a that is a magnetic particle contained in the r5 reagent.
  • the solid phase carrier 82 to which the labeling substance 83 is bound is formed in the first container 11 by using the first solid phase carrier 82a dispensed when the specimen including 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.
  • the state confirmation method includes an immune complex including the test substance 81, the labeling substance 83, and the capture substance 86 before the step of transferring the liquid phase in the first container 11 to the second container 12. And a step of performing BF separation for separating the solid phase carrier 82 bonded to 84 and the liquid phase.
  • the labeling substance 83 in the liquid phase that has not been bonded to the solid phase carrier 82 can be separated and removed from the solid phase carrier by BF separation.
  • the reagent phase dispensing unit 130 dispenses the liquid phase 25 that does not contain the free reagent 85 into the first container 11. That is, when the sample is measured, 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.
  • the state confirmation method does not include the free reagent 85 after the step of performing BF separation and before the step of transferring the liquid phase in the first container 11 to the second container 12. The liquid phase is dispensed into the first container 11.
  • the liquid phase 25 that does not contain the 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 by the same operation 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 bonded.
  • a complex transfer process is performed.
  • the first solid phase carrier 82 a in the first container 11 is Magnetized in the container 11.
  • the liquid phase in the first container 11 is sucked and dispensed into the second container 12 by the suction pipe 51 in the state of being magnetized.
  • the first solid phase carrier 82a is left magnetized in the first container 11. Since the immune complex 84 remains bound to the first solid phase carrier 82a, the liquid phase not containing the labeling substance 83 is transferred to the second container 12.
  • the reagent dispensing unit 130 dispenses the r7 reagent including the second solid phase carrier 82b into the second container 12 to which the liquid phase has been transferred. Then, the BF separation unit 170 performs a secondary BF separation process on the control sample in the second container 12. Next, the R4 reagent dispensing unit 134 and the R5 reagent dispensing unit 135 dispense the R4 reagent containing the buffer solution and the R5 reagent containing the substrate into 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 is performed by the detection unit 60.
  • a detection value indicating the abundance of the labeling substance 21 is acquired.
  • FIG. 14 is basically the same as the example shown in FIG. 13, but the solid phase carrier 82 to be bound to the labeling substance 83 is different.
  • the reagent dispensing order is different from the example of FIG.
  • the state confirmation method includes a sample containing a test substance 81 having a known concentration in the first container 11 before the step of transferring the liquid phase in the first container 11 to the second container 12.
  • the r4 reagent containing the capture substance 86 is dispensed into the first container 11.
  • a quality control sample containing a test substance 81 having a known concentration is dispensed.
  • the r1 reagent containing the labeling substance 83 is dispensed into the first container 11.
  • the r7 reagent containing the second solid phase carrier 82b is dispensed.
  • the immune complex 84 including the test substance 81, the labeling substance 83, and the capture substance 86 is bound to the second solid phase carrier 82b.
  • Reagent dispensing is performed by the reagent dispensing unit 130, and dispensing of the quality control sample is performed by the sample dispensing unit 120.
  • the management sample 20 includes the second solid phase carrier 82b to be dispensed into the second container 12 after the complex transfer process at the time of measurement of the specimen. That is, the management sample 20 includes the second solid phase carrier 82b that is a magnetic particle included in the r7 reagent.
  • the solid phase carrier 82 to which the labeling substance 21 is bound is formed in the first container 11 by using the second solid phase carrier 82b dispensed when the specimen including 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.
  • the BF separation unit 170 Next, primary BF separation processing is performed by the BF separation unit 170.
  • a step of performing BF separation for separating the liquid phase is performed by the BF separation unit 170.
  • the liquid phase 25 not containing the free reagent 85 is dispensed into the first container 11.
  • the liquid phase 25 that does not contain the free reagent 85 is dispensed into the first container 11.
  • the process of carrying out is provided.
  • the liquid phase 25 not containing the free reagent 85 is, for example, a buffer solution. Since the liquid phase 25 does not contain the free reagent 85, the labeling substance 83 and the solid phase carrier 82 remain bonded.
  • a complex transfer process is performed.
  • the second solid phase carrier 82 b in the first container 11 is Magnetized in the container 11.
  • the liquid phase in the first container 11 is sucked and dispensed into the second container 12 by the suction pipe 51 in the state of being magnetized.
  • the second solid phase carrier 82b is left magnetized in the first container 11. Since the immune complex 84 remains bound to the second solid phase carrier 82b, the liquid phase not containing the labeling substance 83 is transferred to the second container 12.
  • the reagent dispensing unit 130 dispenses the r7 reagent including the second solid phase carrier 82b into the second container 12 to which the liquid phase has been transferred.
  • the r7 reagent including the second solid phase carrier 82b is dispensed before and after the complex transfer treatment.
  • the BF separation unit 170 performs a secondary BF separation process on the control sample in the second container 12.
  • the R4 reagent dispensing unit 134 and the R5 reagent dispensing unit 135 dispense the R4 reagent containing the buffer solution and the R5 reagent containing the substrate into the second container 12.
  • 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.
  • a detection value indicating the abundance of the labeling substance 83 is acquired.
  • the mechanism unit 50 includes the sample dispensing unit 120 for dispensing the sample including the test substance 81 and the labeling reagent (r1 reagent including the labeling substance 83). And a reagent dispensing unit 130 for dispensing a solid phase reagent (r5 reagent or r7 reagent) including the solid phase carrier 82, and the management sample 20 is prepared in the first container 11. It is configured. Thereby, even if the user or service staff of the immunoassay apparatus 100 does not prepare the management sample 20 in the first container 11 in advance, the management sample 20 is easily accommodated in the first container 11 by the immunoassay apparatus 100. Can be made.
  • the reagent dispensing unit 130 provides the first container 11 with a free reagent 85 that releases the immune complex 84 from the solid phase carrier 82 when measuring the sample.
  • the liquid phase 25 not containing the free reagent 85 is dispensed instead of the free reagent 85.
  • the liquid phase that does not contain the free reagent 85 is dispensed, so that the free reagent 85 is measured during the actual specimen measurement.
  • the state of the immunoassay device 100 can be confirmed by the same operation as that of dispensing. 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 appropriately confirmed.
  • the mechanism unit 50 includes a BF separation unit that separates the solid phase carrier 82 bound to the immune complex 84 including the test substance 81 and the labeling substance 83 from 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 the primary BF separation process. Thereby, the labeling substance 83 in the liquid phase that has not been bonded to the solid phase carrier 82 can be separated from the solid phase carrier 82 and eliminated by BF separation.
  • the allowable carryover amount of the solid phase carrier 22 in the specification is set for the magnetism collecting function.
  • the allowable carryover amount is set as a variation in a range that does not affect the detection result.
  • a reference value V1 (see FIG. 11) for determining whether or not the magnetic flux collecting function is normal, a value obtained by adding an upper limit range of the allowable carryover amount to an expected detection value when a blank sample is measured. Is set. When the acquired detection value is lower than the reference value V1, it is determined that the magnetism collecting function is normal.
  • the magnetism collecting function when the magnetism collecting function is abnormal, for example, when the solid phase carrier 22 cannot be magnetized and is dispersed in the liquid phase of the first container 11, the solid substance bonded to the labeling substance 21 in step (a) The phase carrier 22 is transferred to the second container 12 together with the liquid phase.
  • the detection value when the magnetic flux collecting function is abnormal, the detection value significantly increases as the detection result in the step (b) exceeds the upper limit of the allowable carryover amount. Therefore, when the acquired detection value becomes the reference value V1 or more, it is determined that the magnetism collecting function is abnormal.
  • FIG. 15 shows experimental conditions of Example 1 performed for confirming the effect of the magnetic flux collecting function determination process
  • FIG. 16 shows experimental results of Example 1.
  • Example 1 In the comparative example of FIG. 15, in order to contrast with Example 1, each processing step at the time of measurement shown in FIG. 4 is listed.
  • the HISCL HBsAg R1 reagent manufactured by Sysmex
  • the HISCL HBsAg calibrator C4 manufactured by Sysmex
  • the HISCL HBsAg R3 reagent was used as the r1 reagent.
  • HICL CLB4 reagent Manufactured by Sysmex Corporation
  • HISCL HBsAg R2 reagent Manufactured by Sysmex Corporation
  • HICL CL wash solution manufactured by Sysmex Corporation
  • the amount dispensed is as shown in FIG.
  • Example 1 in order to compare the normal state and the abnormal state of the magnetic flux collection function, when magnetic flux collection is performed (with magnets), magnetic flux collection is performed using the magnetic force source 52.
  • the experiment was performed in the case of no (no magnet) and the procedure of FIG. Each experiment was performed 20 times, and the average value, standard deviation (SD), coefficient of variation (C.V.), maximum value, minimum value, and range (difference between the maximum value and the minimum value) of the detected values were obtained.
  • the detection value is a count number of photons acquired by the photodetector 61 of the detection unit 60.
  • the detection value is acquired in the range of about 1000 counts to about 2000 counts in normal (with magnets), and the detection value is acquired in the range of about 16 million counts to about 19 million counts in the abnormal (without magnets). It was done.
  • the detection value of normal (with a magnet) is approximately the same as the measurement value when a blank sample is measured.
  • the detected value of the abnormality (no magnet) substantially matches the detected value when the quality control sample is measured in the processing step shown in FIG. There is a difference of about 10,000 times in the detected value between normal (with magnet) and abnormal (without magnet).
  • Example 1 From Example 1, it is possible to clearly distinguish the normal range and the abnormal range of the detected value even in consideration of the carry-over amount of the magnetic particles in the normal state and the fluctuation of the detected value due to the secular change of the immunoassay device. It was confirmed that it was possible to determine normality and abnormality of the magnetic flux collecting function in the complex transition process by appropriately setting the reference value V1 for determination.
  • the management sample 20 includes a solution in which the labeling substance 21 is dissolved. That is, in the control sample 20, the labeling substance 21 does not bind to the solid phase but exists as a liquid phase. In this case, since the labeling substance 21 exists in the first container 11 as the liquid phase, for example, when the detection value of the labeling substance 21 does not increase, the first container 11 is transferred when the liquid phase is transferred to the second container 12. The liquid phase may not be transferred properly. 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 process is normal.
  • the state confirmation method includes a step of determining an abnormality in the dispensing function based on the detection result of the labeling substance 21 in the second container 12. Thereby, based on the detected value of the labeling substance 21, it can be easily determined whether the dispensing function for sucking the liquid phase and discharging the liquid phase is normal or abnormal.
  • the determination of the dispensing function determines that there is an abnormality in the dispensing function when the detected value of the labeling substance 21 is below the reference value V2, as shown in FIG. Thereby, when the detection 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 determining the dispensing function is a value set as an allowable limit of the expected detection value of the labeling substance 21 included in the control sample 20.
  • a labeling substance different from the labeling substance 83 used at the time of measuring the sample 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 dispensing function is a quality control reagent prepared separately from the labeling substance 83 included in the r1 reagent when measuring the sample. It is included.
  • the management sample 20 in which the labeling substance 21 is dissolved in the liquid phase is accommodated in the first container 11.
  • the labeling substance 21 is accommodated in the first container 11 as a liquid phase without being bound to the solid phase.
  • the management sample 20 is dispensed into the first container 11 by the mechanism unit 50.
  • the control sample 20 is set in the sample transport unit 190 while being stored in a predetermined control sample container in the same manner as the sample container 191, and is dispensed into the first container 11 by the sample dispensing unit 120.
  • the management sample 20 is set in the reagent storage 150 while being accommodated in a predetermined management sample container in the same manner as the reagent container 155, and is dispensed into the first container 11 by the reagent dispensing unit 130.
  • the dispensing of the r1 reagent, the r4 reagent, the r5 reagent, and the r6 reagent is skipped or dispensed with a buffer solution or the like.
  • the primary BF separation process is skipped.
  • a primary BF separation process may be performed.
  • the liquid phase in the first container 11 is sucked by the suction tube 51 and the second phase is moved. It is dispensed into the container 12.
  • the dispensing of the r7 reagent after the complex transfer treatment is skipped or dispensed with a buffer solution or a washing solution.
  • the secondary BF separation process is skipped.
  • the labeling substance 21 is an enzyme label
  • a substrate corresponding to the enzyme is dispensed as the R5 reagent.
  • 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.
  • a detection value indicating the abundance of the labeling substance 21 is acquired.
  • FIG. 18 an example in which the management sample 20 is dispensed at the r6 reagent dispensing timing shown in FIG. 4 is shown, but at any timing the management sample 20 is before the complex transfer process. You may dispense.
  • the example of FIG. 19 is an example in which the same labeling substance as the labeling substance 83 used when measuring the specimen is used as the labeling substance 21 for confirming the dispensing function. That is, in the example of FIG. 19, the management sample 20 includes the labeling substance 83 of the r1 reagent dispensed into the first container 11 when the specimen is measured. Accordingly, 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 dispensed when the specimen including the test substance 81 is actually measured. I can confirm. That is, it is not necessary to separately prepare a dedicated labeling substance 83 for confirming the state of the immunoassay device 100, so that the convenience of the immunoassay device 100 can be improved.
  • a management sample in which the labeling substance 83 is dissolved in the liquid phase is accommodated in the first container 11.
  • the labeling substance 83 is accommodated 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 from the reagent container 155 set in the reagent container 150 by the reagent dispensing unit 130 and dispensed into the first container 11.
  • FIG. 19 shows an example in which the buffer solution is dispensed as an alternative liquid at the dispensing timing of the r1 reagent and the specimen shown in FIG. Dispensing of the r4 reagent, r5 reagent, and r6 reagent is skipped. Dispensing of the buffer solution may be skipped, and in this 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 r6 reagent dispensing timing shown in FIG. 4, but at any timing the r1 reagent is dispensed before the complex transfer treatment. May be. After dispensing the r1 reagent, the primary BF separation process is skipped.
  • the liquid phase in the first container 11 is sucked by the suction tube 51 and the second phase is moved. It is dispensed into the container 12.
  • the dispensing of the r7 reagent after the complex transfer treatment is skipped or dispensed with a buffer solution or the like.
  • the secondary BF separation process is skipped.
  • the R4 reagent and the R5 reagent are dispensed into the second container 12.
  • 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.
  • a detection value indicating the abundance of the labeling substance 83 is acquired.
  • FIG. 20 shows the experimental conditions of Example 2 performed to confirm whether the dispensing function can be determined
  • FIG. 21 shows the experimental results of Example 2.
  • Example 2 the procedure of the fifth embodiment shown in FIG.
  • the comparative example of FIG. 20 lists each processing step at the time of measurement shown in FIG.
  • Example 2 the HISCL HBsAg R3 reagent (manufactured by Sysmex Corporation) was dispensed as the r1 reagent containing the labeling substance 83 at the dispensing timing of the r6 reagent at the time of measurement.
  • the secondary BF separation process after the complex transfer process was skipped.
  • HICL CL4 reagent manufactured by Sysmex
  • HISCL R5 reagent manufactured by Sysmex
  • Example 2 the dispensing amount in the step (a) of transferring the liquid phase of the first container 11 to the second container 12 is different in order to compare the normal state and the abnormal state of the dispensing function.
  • the experiment was conducted under the conditions described above.
  • the dispensing amount in the normal state was set to 20 [ ⁇ L]
  • the dispensing amount in the abnormal state was set to 10 [ ⁇ L]
  • the experiment was performed according to the procedure of FIG.
  • Each experiment was performed 20 times, and the average value, standard deviation (SD), coefficient of variation (C.V.), maximum value, minimum value, and range (difference between the maximum value and the minimum value) of the detected values were obtained.
  • the detection value is a count number of photons acquired by the photodetector 61 of the detection unit 60.
  • the immunoassay apparatus 100 may be capable of arbitrarily setting the amount of liquid phase dispensed in the complex transfer process within a variable range.
  • the user can arbitrarily set the dispensing amount of the liquid phase in the range of 10 ⁇ L to 80 ⁇ L.
  • the reference value V2 that defines the allowable range of the predicted detected value corresponding to the preset dispensed amount of the liquid phase. Can be obtained in advance.
  • the determination unit 70 acquires the set value of the liquid phase dispensing amount, selects the reference value V2 corresponding to the set value, and compares it with the detected value, so that the dispensing function in the complex transfer process is normal. Can determine if it is abnormal.
  • the state confirmation method includes a sample containing a test substance 81 having a known concentration or a sample not containing the test substance 81 in the first container 11, a labeling substance 21 that binds to the test substance 81, a test
  • 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 and the state confirmation method include an immune complex including the labeling substance 21 and the capture substance 86 in the first container 11.
  • the step of transferring the liquid phase in the first container 11 to the second container 12 and the labeling substance 21 present in the second container 12 are detected. You may further provide a process.
  • the same operation as the measurement operation for a normal specimen is performed.
  • the status may be checked.
  • the control sample containing the test substance 81 having a known concentration it is confirmed that the detection value obtained in the step (b) falls within the range of the reference value expected from the control sample having the known concentration.
  • the measurement value of the control sample that does not include the test substance 81 causes the detection value obtained in the step (b) to be within the range of reference values expected from the control sample that does not include the test substance 81 (blank sample). Confirmed to fit. Thereby, it is confirmed that the measurement accuracy of the immunoassay using the complex transfer treatment is normal.
  • each step of the operation of the immunoassay apparatus 100 is referred to FIG. 22, and each part of the immunoassay apparatus 100 is referred to FIGS.
  • For the status confirmation processing refer to FIG. 11 to FIG. 14 and FIG. 17 to FIG. Operation control of the following steps is performed by the analysis unit 110 of the immunoassay device 100.
  • step S1 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 a 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 predetermined state confirmation execution timing comes.
  • the execution timing of the status check is at least before the start of the first measurement on the first day, or at the first device startup on the first day.
  • the execution timing of the state confirmation can be arbitrarily set in advance by the user.
  • the analysis unit 110 determines whether or not to perform immunoassay of the sample in step S2.
  • the analysis unit 110 determines whether or not to perform immunoassay based on whether or not the measurement order is registered in the host computer.
  • the analysis unit 110 causes the mechanism unit 50 to start measurement processing.
  • the immunoassay is performed according to the procedure shown in FIG.
  • the analysis unit 110 compares the detection value with the calibration curve and obtains 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 for state confirmation or immunoassay.
  • step S1 when the state of the immunoassay apparatus 100 is confirmed, the process proceeds to step S4.
  • steps S4 to S7 the analysis unit 110 causes the mechanism unit 50 to perform the state confirmation operation shown in FIGS.
  • the dispensing and the primary BF separation process performed before the complex transfer process are described as the preparation process of the control sample in step S4 for convenience.
  • the dispensing and the secondary BF separation process performed after the complex transfer process are described as post-processing of step S6 for convenience.
  • the analysis unit 110 includes the first container 11 containing the management sample 20 including the solid phase carrier 22 or 82 to which the labeling substance 21 or 83 is bound, as shown in FIGS.
  • the first container 11 containing the control sample 20 containing the solution in which the labeling substance 21 or 83 is dissolved is prepared.
  • the magnetic flux collecting function is confirmed using the first container 11 containing the control sample containing the solid phase carrier 22 or 82 to which the labeling substance 21 or 83 is bound, and the solution in which the labeling substance 21 or 83 is dissolved is obtained.
  • the dispensing function is confirmed using the first container 11 containing the management sample 20 including the control sample 20.
  • step S5 the analysis unit 110 causes the mechanism unit 50 to perform a complex transfer process. 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 management sample 20 including the labeling substance 21 to the second container 12.
  • 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 S7, the measurement result of the control sample is acquired.
  • step S8 the determination unit 70 determines a function for performing the complex transfer 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).
  • 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). .
  • the analysis unit 110 waits for immunoassay of the specimen.
  • the analysis unit 110 has an abnormality in the function of performing the complex transfer process of the immunoassay device 100 by, for example, displaying a message on a display device (not shown). This is notified to the user.
  • the analysis unit 110 may stop the function of performing the immunoassay of the specimen until the state confirmation is performed again and it is determined that the magnetism collecting function and the dispensing function are normal.
  • the present invention can be suitably used for confirmation of the state of an immunoassay device using, for example, an immune complex transfer method.

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Abstract

L'objectif de la présente invention est de permettre à l'état d'une fonction pour réaliser un transfert d'immunoconjugué dans un dispositif de dosage immunologique d'être confirmé de manière simple . Ce procédé de confirmation de l'état d'un dispositif de dosage immunologique (100) est un procédé de confirmation de l'état du dispositif de dosage immunologique (100) qui réalise un processus de transfert d'immunoconjugué dans lequel un immunoconjugué (84), porté sur le support de phase solide (22) et comprenant une substance (81) testée pour un échantillon et une substance de marquage (21), est libéré du support de phase solide (22) dans un premier récipient (11) recevant l'immunoconjugué (84), et une phase liquide dans le premier récipient (11) est transférée vers un second récipient (12), le procédé comprenant : une étape consistant à transférer la phase liquide dans le premier récipient (11) recevant un échantillon témoin (20) contenant au moins la substance de marquage (21) vers le second récipient (12) ; une étape consistant à détecter la substance de marquage (21) dans le second récipient (12) dans lequel la phase liquide a été transférée ; et une étape consistant à évaluer l'état du dispositif de dosage immunologique (100) qui réalise le processus de transfert d'immunoconjugué, sur la base du résultat de détection de la substance de marquage (21) dans le second récipient (12).
PCT/JP2019/003455 2018-02-28 2019-01-31 Procédé de confirmation d'état de dispositif de dosage immunologique, et dispositif de dosage immunologique WO2019167539A1 (fr)

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JP2018034674A JP7161851B2 (ja) 2018-02-28 2018-02-28 免疫測定装置の状態確認方法および免疫測定装置
JP2018-034674 2018-02-28

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Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2008044311A1 (fr) * 2006-10-13 2008-04-17 Olympus Corporation Procédé d'identification d'état anormal, analyseur, et réactif
WO2008044313A1 (fr) * 2006-10-13 2008-04-17 Olympus Corporation Procédé de détermination d'anomalie et analyseur
WO2016159319A1 (fr) * 2015-03-31 2016-10-06 シスメックス株式会社 Dispositif de dosage immunologique

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Publication number Priority date Publication date Assignee Title
JP4043132B2 (ja) * 1998-03-19 2008-02-06 オリンパス株式会社 自動分析装置
KR20100009645A (ko) * 2007-06-19 2010-01-28 베크만 컬터, 인코포레이티드 이상 특정 방법 및 분석 장치
JP2010133870A (ja) * 2008-12-05 2010-06-17 Beckman Coulter Inc 自動分析装置及び自動分析装置の精度管理方法

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2008044311A1 (fr) * 2006-10-13 2008-04-17 Olympus Corporation Procédé d'identification d'état anormal, analyseur, et réactif
WO2008044313A1 (fr) * 2006-10-13 2008-04-17 Olympus Corporation Procédé de détermination d'anomalie et analyseur
WO2016159319A1 (fr) * 2015-03-31 2016-10-06 シスメックス株式会社 Dispositif de dosage immunologique

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