JP5852334B2

JP5852334B2 - Automatic analysis method

Info

Publication number: JP5852334B2
Application number: JP2011127569A
Authority: JP
Inventors: 善寛山下; 卓坂詰
Original assignee: Hitachi High Technologies Corp
Current assignee: Hitachi High Tech Corp
Priority date: 2011-06-07
Filing date: 2011-06-07
Publication date: 2016-02-03
Anticipated expiration: 2031-06-07
Also published as: JP2012255664A

Description

本発明は、血清や尿等の検体を自動的に分析する自動分析方法に係り、特に、免疫分析ユニットと遺伝子分析ユニットとを備える自動分析システムを用いた自動分析方法に関する。 The present invention relates to an automatic analysis method for automatically analyzing a sample such as serum or urine, and more particularly to an automatic analysis method using an automatic analysis system including an immune analysis unit and a gene analysis unit.

検体中の極微量生体物質を測定する手法として、免疫学的な特異的結合に基づく免疫反応と、遺伝子増幅反応を利用するＩｍｍｕｎｏ−ＰＣＲ（Polymerase Chain Reaction）法（例えば、非特許文献１参照）やＦＡＣＴＴ（Fluorescent amplification catalyzed by T7 polymerase technique）法（例えば、非特許文献２参照）等の分析方法が知られている。 Immunological reaction based on immunological specific binding and Immuno-PCR (Polymerase Chain Reaction) method using gene amplification reaction as a method for measuring a trace amount of biological material in a specimen (for example, see Non-Patent Document 1) And analysis methods such as FACTT (Fluorescent amplification catalyzed by T7 polymerase technique) (for example, see Non-Patent Document 2) are known.

ここで、例えば、Ｉｍｍｕｎｏ−ＰＣＲ法は、検出対象に結合可能な一次抗体と、検出対象に結合可能で且つ核酸で標識化された二次抗体によって、検出対象物に一次抗体および二次抗体が結合した複合体を形成させ、未反応の二次抗体を除去した後に、二次抗体に標識した核酸をＰＣＲによって増幅させ、鋳型核酸量，即ち、検出対象物の濃度に依存する増幅産物を定量することにより、検出対象物を分析する方法である。このＩｍｍｕｎｏ−ＰＣＲ法では、例えば、二次抗体を酵素で標識するＥＬＩＳＡ（Enzyme-Linked ImmunoSorbent Assay）法（例えば、非特許文献３参照）に比較すると、検出感度が１０〜１００００倍に向上して、ｆｍｏｌ／Ｌオーダー以下の検出が可能であるとされている。 Here, for example, in the Immuno-PCR method, a primary antibody and a secondary antibody are bound to a detection target by a primary antibody that can bind to the detection target and a secondary antibody that can bind to the detection target and is labeled with a nucleic acid. After forming the bound complex and removing the unreacted secondary antibody, the nucleic acid labeled to the secondary antibody is amplified by PCR, and the amplification product depending on the amount of template nucleic acid, that is, the concentration of the detection target, is quantified This is a method for analyzing a detection object. In this Immuno-PCR method, for example, the detection sensitivity is improved 10 to 10,000 times compared to an ELISA (Enzyme-Linked ImmunoSorbent Assay) method (for example, see Non-Patent Document 3) in which a secondary antibody is labeled with an enzyme. , Fmol / L order or less can be detected.

臨床検査における体外診断分野では、自動分析装置としては、腫瘍マーカー，感染症，ホルモン等の生体物質を測定対象として、前述の免疫学的な特異的結合に基づくＥＩＡ（酵素免疫測定法），ＣＬＩＡ（化学発光免疫測定法），ＥＣＬＩＡ（電気化学発光免疫測定）等を測定原理とする免疫分析ユニットが用いられている。 In the field of in-vitro diagnosis in clinical examinations, automatic analyzers are used for measuring biological substances such as tumor markers, infections, hormones, etc. EIA (enzyme immunoassay) based on the above-mentioned immunological specific binding, CLIA Immunoassay units based on the measurement principle (chemiluminescence immunoassay), ECLIA (electrochemiluminescence immunoassay) and the like are used.

また、免疫分析法において検出感度が不足する感染症項目については、自動分析装置としては、病原体由来の遺伝子を測定対象として、ＰＣＲ（Polymerase Chain Reaction）による遺伝子増幅反応を測定原理とする遺伝子分析ユニットが用いられている。 In addition, for infectious disease items for which detection sensitivity is insufficient in immunoassay methods, the automatic analyzer is a gene analysis unit based on a gene amplification reaction by PCR (Polymerase Chain Reaction) with a pathogen-derived gene as a measurement target Is used.

Science 258, 120-122 (1992)Science 258, 120-122 (1992) Nature medicen 12, 473-475 (2006)Nature medicen 12, 473-475 (2006) Immunochemistry 8, 871-874 (1971)Immunochemistry 8, 871-874 (1971)

既存の免疫分析装置（免疫分析ユニットを備えた自動分析装置）は、ＥＩＡ（酵素免疫測定法），ＣＬＩＡ（化学発光免疫測定法），ＥＣＬＩＡ（電気化学発光免疫測定）等を測定原理として、測定対象物を含む検体、および検出対象に結合可能な一次抗体と、検出対象に結合可能且つ発光物質で標識化された二次抗体を含む試薬を、反応容器に分注し、検出対象物に一次抗体および二次抗体が結合した複合体を形成させ、一次抗体に結合した磁性体に対して磁気分離することで未反応の二次抗体を除去し、発光物質による発光を検出するものである。従って、二次抗体に標識した核酸をＰＣＲによって増幅させる工程を含むＩｍｍｕｎｏ−ＰＣＲ法を測定原理とする分析項目を適用することはできないものである。 Existing immunoanalyzers (automated analyzers equipped with immunoassay units) are measured using EIA (enzyme immunoassay), CLIA (chemiluminescence immunoassay), ECLIA (electrochemiluminescence immunoassay), etc. as measurement principles A reagent containing a specimen containing a target object, a primary antibody that can bind to the detection target, and a secondary antibody that can bind to the detection target and is labeled with a luminescent substance is dispensed into a reaction container, and the detection target is primary. A complex in which an antibody and a secondary antibody are bound to each other is formed, and a magnetic substance bound to the primary antibody is magnetically separated to remove unreacted secondary antibody and detect luminescence by the luminescent substance. Therefore, it is impossible to apply analysis items based on the immuno-PCR method, which includes a step of amplifying a nucleic acid labeled with a secondary antibody by PCR.

一方、遺伝子分析装置（遺伝子分析ユニットを備えた自動分析装置）は、蛍光色素と消光物質を利用して増幅遺伝子を定量する定量ＰＣＲを原理として、標的核酸を含む精製溶液、および核酸の増幅領域に相補的なプライマー核酸、核酸増幅に必要な核酸伸長酵素と基質を含む試薬を、反応容器に分注し、標的核酸の熱変性，標的核酸に対するプライマー核酸のアニール，プライマー核酸の伸長反応の為の温度条件を繰り返すことで標的核酸を増幅し、併せて増幅核酸量に依存する蛍光を検出するものである。従って、検出対象物に一次抗体および二次抗体が結合した複合体を形成させ、未反応の二次抗体を除去する工程を含むＩｍｍｕｎｏ−ＰＣＲ法を測定原理とする分析項目を適用することはできないものである。 On the other hand, gene analyzers (automated analyzers equipped with gene analysis units) are based on quantitative PCR that quantifies amplified genes using fluorescent dyes and quenching substances, and a purification solution containing a target nucleic acid and a nucleic acid amplification region A primer nucleic acid complementary to, and a reagent containing a nucleic acid extender and a substrate necessary for nucleic acid amplification are dispensed into a reaction container for thermal denaturation of the target nucleic acid, annealing of the primer nucleic acid to the target nucleic acid, and extension reaction of the primer nucleic acid. The target nucleic acid is amplified by repeating this temperature condition, and the fluorescence depending on the amount of the amplified nucleic acid is also detected. Therefore, it is not possible to apply an analysis item based on the immuno-PCR method, which includes a step of forming a complex in which a primary antibody and a secondary antibody are bound to a detection target and removing an unreacted secondary antibody. Is.

即ち、従来の免疫分析装置または遺伝子分析装置の各々単体では、Ｉｍｍｕｎｏ−ＰＣＲ法を測定原理とする分析項目を実施することはできないものである。従って、臨床検査室の運営においては、Ｉｍｍｕｎｏ−ＰＣＲ法の工程を実施する為の機構を備える専用の分析装置が必要となり、経済的負担を伴うものである。 That is, each of the conventional immune analyzers or gene analyzers alone cannot carry out analysis items based on the immuno-PCR method as a measurement principle. Therefore, in the operation of a clinical laboratory, a dedicated analyzer equipped with a mechanism for carrying out the steps of the Immuno-PCR method is required, which involves an economic burden.

本発明の目的は、専用の分析装置を備えることなく、Ｉｍｍｕｎｏ−ＰＣＲ法を測定原理とする分析が可能な自動分析方法を提供することにある。 An object of the present invention is to provide an automatic analysis method capable of performing analysis based on the immuno-PCR method without providing a dedicated analyzer.

（１）上記目的を達成するために、本発明は、免疫分析ユニットと、遺伝子分析ユニットと、検体投入部から前記免疫分析ユニットや遺伝子分析ユニットに検体容器を保持した検体ラックを搬送する検体搬送部とを有し、前記免疫分析ユニットは、恒温機構に設置された反応容器に、前記検体ラックにより搬送された検体容器中の検体を分注する検体分注機構と、前記恒温機構に設置された反応容器に、免疫試薬保管部に保持された試薬ボトルから所定の試薬を分注する試薬分注機構と、前記恒温機構において所定温度で所定時間の反応が経過した反応溶液から、磁性体を磁気的に分離して溶液置換する洗浄機構と、該洗浄機構による洗浄工程を終えた反応溶液に含まれる発光標識の発光を検出する発光検出機構と、前記洗浄機構による洗浄工程を終えた反応容器を前記検体搬送部まで移送する反応容器移送機構とを有し、前記遺伝子分析ユニットは、反応容器収納部に保持された反応容器を、反応容器設置部に設置する反応容器設置機構と、前記反応容器設置部に設置された反応容器に、前記検体ラックにより搬送された検体容器中の検体を分注する検体分注機構と、前記反応容器設置部に設置された反応容器に、遺伝子試薬保管部に保持された試薬ボトルから所定の試薬を分注する試薬分注機構と、検体と試薬が分注された反応容器を所定温度で所定時間保持するサイクルを繰り返す温度サイクル機構と、該温度サイクル機構により所定の温度サイクルが繰り返された反応溶液に含まれる蛍光標識の蛍光を検出する蛍光検出機構とを有する自動分析システムを用い、前記検体を自動的に分析する自動分析方法であって、前記免疫分析ユニットの前記免疫試薬保管部に保持された、測定対象物を含む検体、および検出対象に結合可能な一次抗体と、検出対象に結合可能且つ発光物質で標識化された二次抗体を含む第1の試薬と、前記遺伝子分析ユニットの前記遺伝子試薬保管部に保持された、二次抗体の標的核酸の増幅領域に相補的なプライマー核酸、核酸増幅に必要な核酸伸長酵素と基質を含む第２の試薬とを用い、前記免疫分析ユニットにおいて、前記恒温機構に設置された反応容器に、前記検体分注機構により検体を分注し、前記試薬分注機構により前記第1の試薬を分注し、前記恒温槽で反応させることにより、前記検出対象物に前記一次抗体および前記二次抗体が結合した複合体を形成させ、前記洗浄機構により、前記一次抗体に結合した磁性体に対して磁気分離することで未反応の二次抗体を除去し、洗浄工程の終了した溶液を、前記反応容器移送機構により、前記検体搬送部まで移送するとを有し、前記検体搬送部により、前記洗浄工程の終了した溶液を、前記遺伝子分析ユニットに搬送し、前記遺伝子分析ユニットにおいて、前記検体分注機構により、前記反応容器設置部に設置された反応容器に、前記洗浄工程の終了した溶液を分注し、前記試薬分注機構により、前記反応容器設置部に設置された反応容器に、前記遺伝子試薬保管部に保持された前記第２の試薬を分注し、前記温度サイクル機構により、標的核酸の熱変性，標的核酸に対するプライマー核酸のアニール，プライマー核酸の伸長反応の為の温度条件を繰り返すことで標的核酸を増幅し、前記蛍光検出機構により、増幅核酸量に依存する蛍光を検出することにより、Ｉｍｍｕｎｏ−ＰＣＲ法を測定原理とする分析項目を分析するようにしたものである。
かかる方法により、専用の分析装置を備えることなく、Ｉｍｍｕｎｏ−ＰＣＲ法を測定原理とする分析が可能となる。 (1) In order to achieve the above object, the present invention provides an immunoassay unit, a gene analysis unit, and a sample transport for transporting a sample rack holding a sample container from the sample input unit to the immune analysis unit or the gene analysis unit. The immunoassay unit is installed in a reaction container installed in the constant temperature mechanism, a sample dispensing mechanism that dispenses the sample in the sample container conveyed by the sample rack, and the constant temperature mechanism. A magnetic substance from a reagent dispensing mechanism that dispenses a predetermined reagent from a reagent bottle held in an immunoreagent storage unit into the reaction container, and a reaction solution that has undergone a predetermined time reaction at a predetermined temperature in the constant temperature mechanism. A cleaning mechanism that magnetically separates and replaces the solution, a luminescence detection mechanism that detects luminescence of the luminescent label contained in the reaction solution after the cleaning process by the cleaning mechanism, and a cleaning mechanism that uses the cleaning mechanism A reaction container transfer mechanism for transferring the reaction container after completion of the process to the sample transport unit, wherein the gene analysis unit installs the reaction container held in the reaction container storage unit in the reaction container installation unit An installation mechanism, a sample dispensing mechanism for dispensing a sample in the sample container transported by the sample rack into a reaction container installed in the reaction container installation unit, and a reaction container installed in the reaction container installation unit In addition, a reagent dispensing mechanism that dispenses a predetermined reagent from a reagent bottle held in a genetic reagent storage unit, and a temperature cycle mechanism that repeats a cycle that holds a reaction container in which a specimen and a reagent are dispensed at a predetermined temperature for a predetermined time And an automatic analysis system having a fluorescence detection mechanism for detecting fluorescence of a fluorescent label contained in a reaction solution in which a predetermined temperature cycle is repeated by the temperature cycle mechanism, An automatic analysis method for dynamic analysis, in which a specimen including a measurement target and a primary antibody that can be bound to a detection target held in the immunoreagent storage unit of the immunological analysis unit can be bound to the detection target. A first nucleic acid containing a secondary antibody labeled with a luminescent substance, and a primer nucleic acid complementary to the target antibody amplification region of the secondary antibody held in the genetic reagent storage unit of the genetic analysis unit, Using a nucleic acid elongation enzyme necessary for nucleic acid amplification and a second reagent containing a substrate, in the immunoassay unit, the sample is dispensed by the sample dispensing mechanism into a reaction vessel installed in the constant temperature mechanism, The first reagent is dispensed by a reagent dispensing mechanism and reacted in the constant temperature bath to form a complex in which the primary antibody and the secondary antibody are bound to the detection target, and by the washing mechanism The magnetic substance bound to the primary antibody is magnetically separated to remove the unreacted secondary antibody, and the solution after the washing process is transferred to the specimen transport section by the reaction container transfer mechanism. Then, the sample transport unit transports the solution after the washing step to the gene analysis unit, and in the gene analysis unit, the sample dispensing mechanism moves the solution to the reaction container installed in the reaction container installation unit. The solution after the washing step is dispensed, and the second reagent held in the genetic reagent storage unit is dispensed into the reaction vessel installed in the reaction vessel installation unit by the reagent dispensing mechanism. The temperature cycle mechanism increases the target nucleic acid by repeating the temperature conditions for thermal denaturation of the target nucleic acid, annealing of the primer nucleic acid to the target nucleic acid, and extension reaction of the primer nucleic acid. And, by the fluorescence detection mechanism, by detecting the fluorescence depends on the amplified nucleic acid amount is obtained so as to analyze the analysis item as measurement principle the Immuno-PCR method.
By this method, an analysis based on the immuno-PCR method can be performed without providing a dedicated analyzer.

（２）上記（１）において、好ましくは、前記免疫分析ユニットにおいて、第１及び第２の反応容器にそれぞれ同じ検体を分注し、前記第1の反応容器に、免疫分析項目の試薬を分注し、前記第２の反応容器に、前記第1の試薬を分注し、前記第1及び第２の反応容器を、前記恒温機構にて洗浄した後、前記第1の反応容器を、前記発光検出機構において分析し、分析結果が、前記免疫分析項目の測定範囲よりも低値であった場合は、前記第２の反応容器は、前記検体搬送機構により、前記遺伝子分析ユニットに搬送され、前記遺伝子分析ユニットにおいて、前記第２の試薬を用いて、Ｉｍｍｕｎｏ−ＰＣＲ法を測定原理とする分析項目を分析するようにしたものである。 (2) In the above (1), preferably, in the immunoassay unit, the same specimen is dispensed into the first and second reaction containers, respectively, and the reagent of the immunological analysis item is dispensed into the first reaction container. And after dispensing the first reagent into the second reaction vessel and washing the first and second reaction vessels with the thermostatic mechanism, the first reaction vessel When the analysis result is analyzed by a luminescence detection mechanism and the analysis result is lower than the measurement range of the immunological analysis item, the second reaction container is transported to the gene analysis unit by the sample transport mechanism, In the gene analysis unit, the second reagent is used to analyze analysis items based on the immuno-PCR method as a measurement principle.

（３）上記（１）において、好ましくは、前記免疫分析ユットにおいて、第1の反応容器に、検体を分注し、検体分注を終えた検体容器に収納された検体が架設された検体ラックを、バッファ部に移送し、前記第1の反応容器に、免疫分析項目の試薬を分注し、前記第1の反応容器を、前記恒温機構にて洗浄した後、前記第1の反応容器を、前記発光検出機構において分析し、分析結果が、前記免疫分析項目の測定範囲よりも低値であった場合は、前記バッファ部に待機した検体ラックが、再検搬送部により検体搬送部のスタート位置に搬送され、前記免疫分析ユニットにおいて、第２の反応容器に、検体を分注し、前記第２の反応容器に、前記第1の試薬を分注し、前記第２の反応容器を、前記恒温機構にて洗浄した後、前記検体搬送機構により、前記遺伝子分析ユニットに搬送され、前記遺伝子分析ユニットにおいて、前記第２の試薬を用いて、Ｉｍｍｕｎｏ−ＰＣＲ法を測定原理とする分析項目を分析するようにしたものである。 (3) In the above (1), preferably, in the immunoassay unit, a sample rack in which a sample is dispensed in the first reaction container and the sample stored in the sample container after the sample dispensing is installed Is transferred to the buffer unit, and the reagent of the immunological analysis item is dispensed into the first reaction container, and the first reaction container is washed with the thermostatic mechanism, and then the first reaction container is removed. When the analysis result is analyzed by the luminescence detection mechanism and the analysis result is lower than the measurement range of the immunological analysis item, the sample rack waiting in the buffer unit is moved to the start position of the sample transport unit by the retest transport unit. In the immunoassay unit, the specimen is dispensed into a second reaction container, the first reagent is dispensed into the second reaction container, and the second reaction container is filled with the second reaction container. After washing with a constant temperature mechanism, the specimen transport mechanism The conveyed to genetic analysis unit, in the genetic analysis unit, by using the second reagent, it is obtained so as to analyze the analysis item as measurement principle the Immuno-PCR method.

本発明によれば、専用の分析装置を備えることなく、Ｉｍｍｕｎｏ−ＰＣＲ法を測定原理とする分析が可能となる。 According to the present invention, an analysis based on the immuno-PCR method can be performed without providing a dedicated analyzer.

本発明の一実施形態による自動分析方法を用いる自動分析システムの構成を示すブロック図である。It is a block diagram which shows the structure of the automatic analysis system using the automatic analysis method by one Embodiment of this invention.

以下、図１を用いて、本発明の一実施形態による自動分析方法を用いる自動分析システムの構成について説明する。
図１は、本発明の一実施形態による自動分析方法を用いる自動分析システムの構成を示すブロック図である。 Hereinafter, the configuration of an automatic analysis system using an automatic analysis method according to an embodiment of the present invention will be described with reference to FIG.
FIG. 1 is a block diagram showing a configuration of an automatic analysis system using an automatic analysis method according to an embodiment of the present invention.

本分析システムは、免疫分析ユニットＡＵ１と、遺伝子分析ユニットＡＵ２と、検体投入部４と、検体搬送部５と、再検搬送部８と、待機バッファ６と、検体回収部７と、制御部１とから構成される。 This analysis system includes an immune analysis unit AU1, a gene analysis unit AU2, a sample input unit 4, a sample transport unit 5, a retest transport unit 8, a standby buffer 6, a sample recovery unit 7, a control unit 1, Consists of

検体投入部４には、検体ラック２が投入される。検体ラック２には、複数の検体容器３が保持されている。検体容器３には、それぞれ分析対象の検体が収納されている。 The sample rack 2 is loaded into the sample loading unit 4. The sample rack 2 holds a plurality of sample containers 3. Each sample container 3 stores a sample to be analyzed.

検体投入部４に投入された検体ラック２は、検体搬送部５によって、免疫分析ユニットＡＵ１や遺伝子分析ユニットＡＵ２に搬送される。検体ラック２に保持された検体容器３に収納された検体は、免疫分析ユニットＡＵ１や遺伝子分析ユニットＡＵ２によって分析される。検体ラック２は、検体搬送部５によって、待機バッファ６や検体回収部７に搬送される。待機バッファ６には、再検査の要否等が判定されるまで待機される。再検査が必要と判定されると、検体ラック２は、再検搬送部８によって、検体搬送部５のスタート位置（図示の左側の位置）まで戻され、再び、検体搬送部５によって、疫分析ユニットＡＵ１や遺伝子分析ユニットＡＵ２に搬送される。一方、疫分析ユニットＡＵ１や遺伝子分析ユニットＡＵ２によって分析の終了した検体は、検体回収部７で回収される。 The sample rack 2 loaded into the sample loading unit 4 is transported by the sample transport unit 5 to the immune analysis unit AU1 and the gene analysis unit AU2. The sample stored in the sample container 3 held in the sample rack 2 is analyzed by the immune analysis unit AU1 and the gene analysis unit AU2. The sample rack 2 is transported to the standby buffer 6 and the sample recovery unit 7 by the sample transport unit 5. The standby buffer 6 waits until it is determined whether reexamination is necessary. If it is determined that reexamination is necessary, the sample rack 2 is returned to the start position (the left position in the figure) of the sample transport unit 5 by the retest transport unit 8, and again by the sample transport unit 5, the epidemiological analysis unit. It is transported to AU1 and gene analysis unit AU2. On the other hand, the sample that has been analyzed by the epidemiological analysis unit AU1 and the gene analysis unit AU2 is collected by the sample collection unit 7.

制御部１は、免疫分析ユニットＡＵ１，遺伝子分析ユニットＡＵ２，検体投入部４，検体搬送部５，再検搬送部８などの各部の動作を制御する。 The control unit 1 controls the operation of each unit such as the immune analysis unit AU1, the gene analysis unit AU2, the sample input unit 4, the sample transport unit 5, and the retest transport unit 8.

免疫分析ユニットＡＵ１は、検体分注機構１０と、反応容器設置機構１２と、試薬分注機構１３と、免疫試薬保管部１４と、洗浄機構１６と、反応容器移送機構１７と、恒温機構１８と、発光検出機構１９とから、主として構成される。 The immunological analysis unit AU1 includes a specimen dispensing mechanism 10, a reaction container installation mechanism 12, a reagent dispensing mechanism 13, an immune reagent storage unit 14, a cleaning mechanism 16, a reaction container transfer mechanism 17, and a constant temperature mechanism 18. The light emission detection mechanism 19 is mainly configured.

反応容器設置機構１２は、反応容器収納部に保持された複数の反応容器１１の中から任意の反応容器１１を把持して、恒温機構１８の所定位置に移動し、設置する。 The reaction vessel installation mechanism 12 holds an arbitrary reaction vessel 11 from among the plurality of reaction vessels 11 held in the reaction vessel storage unit, moves to a predetermined position of the constant temperature mechanism 18 and installs it.

検体分注機構１０は、検体投入部４から検体搬送部５を経由して供給される検体ラック２に保持された検体容器３から、所定量の検体を吸引する。そして、検体分注機構１０は、恒温機構１８に設置された反応容器１１に、吸引した検体を吐出して、分注する。 The sample dispensing mechanism 10 aspirates a predetermined amount of sample from the sample container 3 held in the sample rack 2 supplied from the sample input unit 4 via the sample transport unit 5. Then, the sample dispensing mechanism 10 discharges and dispenses the aspirated sample into the reaction container 11 installed in the constant temperature mechanism 18.

免疫試薬保管部１４には、複数の試薬ボトル１５が保持されている。複数の試薬ボトル１５には、それぞれ免疫分析ユニットＡＵ１で使用される試薬が収納されている。試薬分注機構１３は、所定の試薬ボトル１５から所定の試薬を吸引して、さきほど検体が分注された反応容器１１に吐出する。 The immunoreagent storage unit 14 holds a plurality of reagent bottles 15. Each of the plurality of reagent bottles 15 stores a reagent used in the immunological analysis unit AU1. The reagent dispensing mechanism 13 sucks a predetermined reagent from the predetermined reagent bottle 15 and discharges it to the reaction container 11 into which the sample has been dispensed.

恒温機構１８は、検体および試薬が分注された反応容器１１を、所定温度で所定時間保持する。洗浄機構１６は、恒温機構１８において所定温度で所定時間の反応が経過した反応溶液から、磁性体を磁気的に分離して溶液置換する。発光検出機構１９は、洗浄機構１６による洗浄工程を終えた反応溶液に含まれる発光標識の発光を検出する。 The constant temperature mechanism 18 holds the reaction container 11 into which the specimen and the reagent are dispensed at a predetermined temperature for a predetermined time. The cleaning mechanism 16 magnetically separates the magnetic material from the reaction solution that has undergone the reaction for a predetermined time at the predetermined temperature in the thermostatic mechanism 18 and replaces the solution. The luminescence detection mechanism 19 detects the luminescence of the luminescent label contained in the reaction solution after the washing process by the washing mechanism 16 is completed.

反応容器移送機構１７は、洗浄機構１６による洗浄工程を終えた反応容器を検体搬送部５まで移送する。 The reaction container transfer mechanism 17 transfers the reaction container that has completed the cleaning process by the cleaning mechanism 16 to the sample transport unit 5.

遺伝子分析ユニットＡＵ２は、検体分注機構２０と、反応容器設置機構２２と、試薬分注機構２３と、遺伝子試薬保管部２４と、反応容器搬送機構２７と、反応容器設置部２８と、蛍光検出機構２９と、温度サイクル機構３０とから、主として構成される。 The gene analysis unit AU2 includes a sample dispensing mechanism 20, a reaction container installation mechanism 22, a reagent dispensing mechanism 23, a gene reagent storage unit 24, a reaction container transport mechanism 27, a reaction container installation unit 28, and fluorescence detection. The mechanism 29 and the temperature cycle mechanism 30 are mainly configured.

反応容器設置機構２７は、反応容器収納部に保持された複数の反応容器２１の中から任意の反応容器２１を把持して、反応容器設置部２８の所定位置に移動し、設置する。 The reaction vessel installation mechanism 27 holds an arbitrary reaction vessel 21 from among the plurality of reaction vessels 21 held in the reaction vessel storage unit, moves to a predetermined position of the reaction vessel installation unit 28, and installs it.

検体分注機構２０は、検体投入部４から検体搬送部５を経由して供給される検体ラック２に保持された検体容器３から、所定量の検体を吸引する。そして、検体分注機構２０は、反応容器設置部２８に設置された反応容器２１に、吸引した検体を吐出して、分注する。 The sample dispensing mechanism 20 aspirates a predetermined amount of sample from the sample container 3 held in the sample rack 2 supplied from the sample input unit 4 via the sample transport unit 5. Then, the specimen dispensing mechanism 20 discharges and dispenses the sucked specimen into the reaction container 21 installed in the reaction container installation section 28.

遺伝子試薬保管部２４には、複数の試薬ボトル２５が保持されている。複数の試薬ボトル２５には、それぞれ遺伝子分析ユニットＡＵ２で使用される試薬が収納されている。試薬分注機構２３は、所定の試薬ボトル２５から所定の試薬を吸引して、さきほど検体が分注された反応容器２１に吐出する。 The gene reagent storage unit 24 holds a plurality of reagent bottles 25. Each of the reagent bottles 25 stores a reagent used in the gene analysis unit AU2. The reagent dispensing mechanism 23 sucks a predetermined reagent from a predetermined reagent bottle 25 and discharges it to the reaction container 21 into which the sample has been dispensed.

温度サイクル機構３０は、検体と試薬または試薬が分注された反応容器２１を所定温度で所定時間保持するサイクルを繰り返す。蛍光検出機構２９は、温度サイクル機構３０により所定の温度サイクルが繰り返された反応溶液に含まれる蛍光標識の蛍光を検出する。 The temperature cycle mechanism 30 repeats a cycle in which the reaction container 21 into which the specimen and the reagent or the reagent are dispensed is held at a predetermined temperature for a predetermined time. The fluorescence detection mechanism 29 detects the fluorescence of the fluorescent label contained in the reaction solution in which a predetermined temperature cycle is repeated by the temperature cycle mechanism 30.

次に、上記の分析システムを用いて、Ｉｍｍｕｎｏ−ＰＣＲ法を測定原理とする分析項目の第1の分析方法について説明する。 Next, a first analysis method for analysis items based on the immuno-PCR method as a measurement principle using the above analysis system will be described.

Ｉｍｍｕｎｏ−ＰＣＲ法により分析を行うために、２種類の試薬を用いる。第1の試薬は、検出対象に結合可能且つ磁性粒子と結合した一次抗体と、検出対象に結合可能且つ核酸標識化された二次抗体を含む試薬である。第1の試薬を収納した試薬ボトル１５は、免疫分析ユニットＡＵ１の免疫試薬保管部１４に設置される。 Two types of reagents are used for analysis by the Immuno-PCR method. The first reagent is a reagent that includes a primary antibody that can be bound to a detection target and bound to a magnetic particle, and a secondary antibody that can bind to the detection target and is labeled with a nucleic acid. The reagent bottle 15 containing the first reagent is installed in the immune reagent storage unit 14 of the immune analysis unit AU1.

第２の試薬は、二次抗体の標的核酸の増幅領域に相補的なプライマー核酸、核酸増幅に必要な核酸伸長酵素と基質を含む試薬である。第２の試薬を収納した試薬ボトル２５は、遺伝子分析ユニットＡＵ２の遺伝子試薬保管部２４に設置される。 The second reagent is a reagent containing a primer nucleic acid complementary to the target nucleic acid amplification region of the secondary antibody, a nucleic acid elongation enzyme necessary for nucleic acid amplification, and a substrate. The reagent bottle 25 containing the second reagent is installed in the gene reagent storage unit 24 of the gene analysis unit AU2.

本実施形態の分析方法では、先ず、測定対象物を含む検体、および検出対象に結合可能な一次抗体と、検出対象に結合可能且つ発光物質で標識化された二次抗体を含む第1の試薬を、反応容器に分注し、検出対象物に一次抗体および二次抗体が結合した複合体を形成させ、一次抗体に結合した磁性体に対して磁気分離することで未反応の二次抗体を除去する工程を免疫分析用ユニットで実施する。次いで、この工程を終了した溶液を試料搬送機構によって遺伝子分析ユニットへと移送し、二次抗体の標的核酸の増幅領域に相補的なプライマー核酸、核酸増幅に必要な核酸伸長酵素と基質を含む第２の試薬を、反応容器に分注し、標的核酸の熱変性、標的核酸に対するプライマー核酸のアニール、プライマー核酸の伸長反応、の為の温度条件を繰り返すことで標的核酸を増幅し、増幅核酸量に依存する蛍光を検出する工程を遺伝子分析ユニットで実施するものである。 In the analysis method of the present embodiment, first, a first reagent including a specimen containing a measurement target, a primary antibody that can bind to the detection target, and a secondary antibody that can bind to the detection target and is labeled with a luminescent substance. The reaction product is dispensed into a reaction container to form a complex in which the primary antibody and the secondary antibody are bound to the detection target, and the unreacted secondary antibody is separated by magnetic separation of the magnetic material bound to the primary antibody. The removing step is performed in the immunoassay unit. Next, the solution after completion of this step is transferred to the gene analysis unit by the sample transport mechanism, and a primer nucleic acid complementary to the target nucleic acid amplification region of the secondary antibody, a nucleic acid extending enzyme necessary for nucleic acid amplification, and a substrate containing the substrate. 2 reagents are dispensed into a reaction vessel, and the target nucleic acid is amplified by repeating the temperature conditions for thermal denaturation of the target nucleic acid, annealing of the primer nucleic acid to the target nucleic acid, and extension reaction of the primer nucleic acid. The step of detecting the fluorescence depending on is performed in the gene analysis unit.

以下、自動分析システムの各部の構成を用いて、上記方法を実施するための具体的な自動分析の第1の方法について、以下説明する。 Hereinafter, a specific first method of automatic analysis for implementing the above method using the configuration of each part of the automatic analysis system will be described.

オペレーターは、制御部１から分析項目の依頼を実施し、測定対象とする血清あるいは尿等の検体を収納した検体容器３を架設した検体ラック２を、検体投入部４に投入し、分析を開始する。 The operator requests an analysis item from the control unit 1, puts the sample rack 2 in which the sample container 3 containing the sample such as serum or urine to be measured is loaded into the sample loading unit 4 and starts the analysis To do.

検体容器３に収納された検体は、検体搬送部５により、検体投入部４から免疫分析ユニットＡＵ１の検体分注機構１０の近傍位置まで搬送される。検体分注機構１０は、検体容器３に収納された検体から所定量の検体を吸引し、反応容器設置機構１２によって恒温機構１８の所定位置に設置された反応容器１１に吐出する。次いで、試薬分注機構１３によって免疫試薬保管部１４に架設された試薬の内、前述の第1の試薬が所定量吸引され、反応容器１１に吐出される。この反応容器１１を恒温機構１８において所定時間保持することにより、免疫反応が進行し、検出対象物に一次抗体および二次抗体が結合した複合体が形成される。なお、一次抗体には磁性粒子が結合しており、二次抗体には標識核酸が結合している。 The sample stored in the sample container 3 is transported by the sample transport unit 5 from the sample input unit 4 to a position in the vicinity of the sample dispensing mechanism 10 of the immune analysis unit AU1. The sample dispensing mechanism 10 sucks a predetermined amount of sample from the sample stored in the sample container 3 and discharges it to the reaction container 11 installed at a predetermined position of the constant temperature mechanism 18 by the reaction container installation mechanism 12. Next, a predetermined amount of the first reagent out of the reagents installed in the immune reagent storage unit 14 by the reagent dispensing mechanism 13 is sucked and discharged into the reaction container 11. By holding the reaction vessel 11 in the thermostatic mechanism 18 for a predetermined time, an immune reaction proceeds, and a complex in which the primary antibody and the secondary antibody are bound to the detection target is formed. Note that magnetic particles are bound to the primary antibody, and labeled nucleic acid is bound to the secondary antibody.

反応容器移送機構１７は、免疫反応を完了した反応容器１１を、洗浄機構１６に移設する。洗浄機構１６では、反応液中の磁性粒子と液相を磁気的に分離し、溶液置換することにより、測定対象物を介して磁性粒子を含む一次抗体と結合し得なかった二次抗体を液相から除去する。洗浄機構１６による洗浄工程を終えた反応容器１１は、反応容器搬送機構１７によって免疫分析ユニットＡＵ１から検体搬送部５まで搬送され、検体ラック２の空ポジションに設置される。 The reaction container transfer mechanism 17 moves the reaction container 11 that has completed the immune reaction to the cleaning mechanism 16. The cleaning mechanism 16 magnetically separates the magnetic particles and the liquid phase in the reaction solution and replaces the solution, thereby removing the secondary antibody that could not bind to the primary antibody containing the magnetic particles via the measurement object. Remove from phase. The reaction container 11 that has finished the cleaning process by the cleaning mechanism 16 is transported from the immunoassay unit AU1 to the sample transport unit 5 by the reaction container transport mechanism 17, and is set in an empty position of the sample rack 2.

なお、従来の免疫分析項目では、洗浄機構１６による洗浄工程を終えた反応容器１１は、発光検出機構１９において二次抗体に標識された発光標識の発光が検出される。 In the conventional immunological analysis item, the luminescence detection mechanism 19 detects the luminescence of the luminescent label labeled on the secondary antibody in the reaction vessel 11 that has completed the cleaning process by the cleaning mechanism 16.

次に、検体搬送部５は、検体ラック２の空ポジションに反応容器１１が設置された検体ラック2を、遺伝子分析ユニットＡＵ２の検体分注機構２０の近傍に搬送する。検体分注機構２０は、反応容器１１から所定量の反応液を吸引し、反応容器設置機構２２によって反応容器設置部２８に設置された反応容器２１に吐出する。 Next, the sample transport unit 5 transports the sample rack 2 in which the reaction container 11 is installed at the empty position of the sample rack 2 to the vicinity of the sample dispensing mechanism 20 of the gene analysis unit AU2. The sample dispensing mechanism 20 sucks a predetermined amount of the reaction solution from the reaction container 11 and discharges it to the reaction container 21 installed in the reaction container installation unit 28 by the reaction container installation mechanism 22.

次いで、試薬分注機構２３は、遺伝子試薬保管部２４に架設された試薬ボトル２５から、前述の第２の試薬を所定量吸引し、反応容器２１に吐出する。次いで、反応容器２１は、反応容器搬送機構２７によって、温度サイクル機構３０に設置され所定の温度サイクルが実施される。併せて、蛍光検出機構２９は、増幅核酸量に依存する蛍光量を検出する。そして、温度サイクル数と蛍光測定値の結果は、制御部１に送られ、検体に含まれる測定対象物を定量または定性分析する。 Next, the reagent dispensing mechanism 23 sucks a predetermined amount of the second reagent from the reagent bottle 25 installed in the gene reagent storage unit 24 and discharges the second reagent to the reaction container 21. Next, the reaction vessel 21 is installed in the temperature cycle mechanism 30 by the reaction vessel transport mechanism 27 and a predetermined temperature cycle is performed. In addition, the fluorescence detection mechanism 29 detects the amount of fluorescence that depends on the amount of amplified nucleic acid. Then, the number of temperature cycles and the result of the fluorescence measurement value are sent to the control unit 1, and the measurement object contained in the specimen is quantitatively or qualitatively analyzed.

次に、上記の分析システムを用いて、Ｉｍｍｕｎｏ−ＰＣＲ法を測定原理とする分析項目の他の分析方法について説明する。この第２の分析方法においては、従来の免疫分析項目の分析結果に基づいて、Ｉｍｍｕｎｏ−ＰＣＲ法を測定原理とする分析項目の分析を実施する。 Next, another analysis method for analysis items based on the immuno-PCR method as a measurement principle will be described using the above analysis system. In the second analysis method, analysis items are analyzed based on the immuno-PCR method as a measurement principle based on the analysis results of conventional immune analysis items.

上述のように、免疫分析項目とＩｍｍｕｎｏ−ＰＣＲ法に基づく分析項目では、測定対象物と一次抗体および二次抗体の複合体を生成する工程は共通であり、二次抗体の標識物質と検出方法が異なる分析方法である。従って、二次抗体の標識を発光物質にした場合は通常の免疫分析感度において、一方、二次抗体の標識を核酸にした場合はＩｍｍｕｎｏ−ＰＣＲ法による高感度において、同一物質を検出対象として分析することが可能である。 As described above, in the immunological analysis item and the analysis item based on the Immuno-PCR method, the process of generating the complex of the measurement target, the primary antibody and the secondary antibody is common, and the labeling substance of the secondary antibody and the detection method Is a different analysis method. Therefore, when the label of the secondary antibody is a luminescent substance, it is analyzed with the same substance as the detection target in the normal immunoassay sensitivity, while when the label of the secondary antibody is a nucleic acid, it is highly sensitive by the Immuno-PCR method. Is possible.

分析システムの制御部１は、同一の測定対象物に対する免疫分析項目およびＩｍｍｕｎｏ−ＰＣＲ法を測定原理とする分析項目の分析を実施する分析が依頼された場合は、先ず、免疫分析項目の分析を実行し、この分析結果に基づいて、より高感度な分析が必要であると判断した場合に、Ｉｍｍｕｎｏ−ＰＣＲ法を測定原理とする分析項目の分析を実行する。 The control unit 1 of the analysis system first analyzes an immune analysis item when an analysis is performed to analyze an analysis item based on the immunological analysis item and the immuno-PCR method as the measurement principle for the same measurement object. When it is determined that more sensitive analysis is necessary based on the analysis result, analysis of an analysis item based on the immuno-PCR method is performed.

この免疫分析項目とＩｍｍｕｎｏ−ＰＣＲ法を測定原理とする分析項目を実施する分析においては、分析結果出力の「迅速性」の観点による第２の分析方法、或いは、試薬消費量抑制による「経済性」の観点による第３の分析方法を選択可能である。 In the analysis for carrying out the analysis item based on the immunological analysis item and the immuno-PCR method as a measurement principle, the second analysis method from the viewpoint of “rapidity” of the analysis result output, or “economic efficiency by reducing reagent consumption” It is possible to select the third analysis method from the viewpoint of "."

最初に、分析結果出力の迅速性を優先する場合の第２の分析方法について以下説明する。 First, the second analysis method when priority is given to the quickness of the analysis result output will be described below.

オペレーターは、免疫分析項目の試薬、およびＩｍｍｕｎｏ−ＰＣＲ法を測定原理とする分析項目に必要な前述の第1の試薬を含む試薬ボトル１５を免疫試薬保管部１４に設置する。また、Ｉｍｍｕｎｏ−ＰＣＲ法を測定原理とする分析項目に必要な試薬のうち、前述の第２の試薬を含む試薬ボトル２５を遺伝子試薬保管部２４に架設する。 The operator installs in the immune reagent storage unit 14 the reagent bottle 15 containing the reagent for the immunological analysis item and the first reagent necessary for the analysis item based on the immuno-PCR method. In addition, among the reagents necessary for the analysis item based on the immuno-PCR method, the reagent bottle 25 containing the above-mentioned second reagent is installed in the genetic reagent storage unit 24.

分析が開始されると、免疫分析ユニットＡＵ１において、反応容器移送機構１７によって、二つの反応容器１１が恒温機構１８の所定位置に設置され、検体分注機構１０によって各々の反応容器に検体容器３に収納された同一の検体が分注される。次いで、第1の反応容器１１には免疫分析項目の試薬が分注され、第２の反応容器にはＩｍｍｕｎｏ−ＰＣＲ法を測定原理とする分析項目の試薬（前述の第1の試薬）が分注される。各々の反応容器１１は、恒温機構１８において所定時間保持された後に、洗浄機構１６において洗浄工程が実施される。 When the analysis is started, in the immunological analysis unit AU1, the two reaction containers 11 are installed at predetermined positions of the constant temperature mechanism 18 by the reaction container transfer mechanism 17, and the sample container 3 is placed in each reaction container by the sample dispensing mechanism 10. The same specimen stored in the is dispensed. Next, the reagent for the immunological analysis item is dispensed into the first reaction container 11, and the reagent for the analysis item based on the immuno-PCR method (the above-mentioned first reagent) is dispensed into the second reaction container. Noted. Each reaction vessel 11 is held in the constant temperature mechanism 18 for a predetermined time, and then a cleaning process is performed in the cleaning mechanism 16.

その後、免疫分析項目の試薬が分注された反応容器１１は、発光検出機構１９において分析され、免疫分析項目の分析結果が制御部１に出力される。 Thereafter, the reaction container 11 into which the reagent of the immunological analysis item has been dispensed is analyzed by the luminescence detection mechanism 19, and the analysis result of the immunological analysis item is output to the control unit 1.

そして、免疫分析項目の分析結果が、免疫分析項目の測定範囲内であれば、Ｉｍｍｕｎｏ−ＰＣＲ法を測定原理とする分析項目の分析をキャンセルされる。すなわち、既に、Ｉｍｍｕｎｏ−ＰＣＲ法を測定原理とする分析項目の試薬（前述の第１の試薬）が分注され、また、洗浄機構１６における洗浄工程が行われた反応容器１１は廃棄される。 If the analysis result of the immunological analysis item is within the measurement range of the immunological analysis item, the analysis of the analysis item based on the immuno-PCR method is canceled. That is, the reagent of the analysis item (the first reagent described above) based on the immuno-PCR method is already dispensed, and the reaction vessel 11 in which the cleaning process in the cleaning mechanism 16 has been performed is discarded.

一方、免疫分析項目の分析結果が、免疫分析項目の測定範囲よりも低値であった場合は、Ｉｍｍｕｎｏ−ＰＣＲ法を測定原理とする分析項目の分析を再開される。すなわち、既に、Ｉｍｍｕｎｏ−ＰＣＲ法を測定原理とする分析項目の試薬（前述の第1の試薬）が分注され、洗浄機構１６における洗浄工程が行われた反応容器１１は、反応容器搬送機構１７によって免疫分析ユニットＡＵ１から検体搬送部５まで搬送され、検体ラック２の空ポジションに設置される。反応容器１１は、検体搬送機構４により、遺伝子分析ユニットＡＵ２へと搬送される。 On the other hand, when the analysis result of the immunological analysis item is lower than the measurement range of the immunological analysis item, the analysis of the analysis item based on the immuno-PCR method is resumed. That is, the reaction vessel 11 that has already been dispensed with the analysis item reagent (the above-mentioned first reagent) based on the immuno-PCR method as the measurement principle and the washing step in the washing mechanism 16 is performed is the reaction vessel transport mechanism 17. Thus, the sample is transported from the immunological analysis unit AU1 to the sample transport unit 5 and installed in the empty position of the sample rack 2. The reaction container 11 is transported to the gene analysis unit AU2 by the sample transport mechanism 4.

そして、遺伝子分析ユニットＡＵ２において、検体分注機構２０は、反応容器１１から所定量の反応液を吸引し、反応容器設置機構２２によって反応容器設置部２８に設置された反応容器２１に吐出する。次に、試薬分注機構２３は、遺伝子試薬保管部２４に架設された試薬ボトル２５から、前述の第２の試薬を所定量吸引し、反応容器２１に吐出する。次いで、反応容器２１は、反応容器搬送機構２７によって、温度サイクル機構３０に設置され所定の温度サイクルが実施される。併せて、蛍光検出機構２９は、増幅核酸量に依存する蛍光量を検出する。そして、温度サイクル数と蛍光測定値の結果は、制御部１に送られ、検体に含まれる測定対象物を定量または定性分析する。 In the gene analysis unit AU2, the sample dispensing mechanism 20 sucks a predetermined amount of the reaction solution from the reaction container 11 and discharges it to the reaction container 21 installed in the reaction container installation unit 28 by the reaction container installation mechanism 22. Next, the reagent dispensing mechanism 23 sucks a predetermined amount of the above-mentioned second reagent from the reagent bottle 25 installed in the genetic reagent storage unit 24 and discharges it to the reaction container 21. Next, the reaction vessel 21 is installed in the temperature cycle mechanism 30 by the reaction vessel transport mechanism 27 and a predetermined temperature cycle is performed. In addition, the fluorescence detection mechanism 29 detects the amount of fluorescence that depends on the amount of amplified nucleic acid. Then, the number of temperature cycles and the result of the fluorescence measurement value are sent to the control unit 1, and the measurement object contained in the specimen is quantitatively or qualitatively analyzed.

従って、この第２の分析方法においては、免疫分析項目の分析結果判断によってＩｍｍｕｎｏ−ＰＣＲ法を測定原理とする分析項目が必要となった場合は、Ｉｍｍｕｎｏ−ＰＣＲ法を測定原理とする分析項目の分析結果を迅速に報告することが可能である。 Therefore, in this second analysis method, when an analysis item based on the immuno-PCR method is required by judging the analysis result of the immunological analysis item, the analysis item based on the immuno-PCR method is determined. It is possible to report the analysis result quickly.

次に、試薬消費量抑制による経済性を考慮する場合の第３の分析方法について以下説明する。 Next, a third analysis method in the case where economics due to reagent consumption suppression is considered will be described below.

分析が開始されると、先ず、免疫分析ユニットＡＵ１において、免疫分析項目のみが分析される。反応容器移送機構１７によって、反応容器１１が恒温機構１８の所定位置に設置され、検体分注機構１０によって反応容器に検体容器３に収納された検体が分注される。ここで、検体分注を終えた検体容器３に収納された検体が架設された検体ラック２は、バッファ部６に移送され、免疫分析項目の分析結果に基づく判断が提示されるまで待機させる。 When the analysis is started, first, only the immunological analysis items are analyzed in the immunological analysis unit AU1. The reaction container 11 is installed at a predetermined position of the constant temperature mechanism 18 by the reaction container transfer mechanism 17, and the sample stored in the sample container 3 is dispensed into the reaction container by the sample dispensing mechanism 10. Here, the sample rack 2 on which the sample housed in the sample container 3 that has been subjected to the sample dispensing is erected is transferred to the buffer unit 6 and waits until a judgment based on the analysis result of the immunological analysis item is presented.

次に、反応容器１１には免疫分析項目の試薬が分注される。反応容器１１は、恒温機構１８において所定時間保持された後に、洗浄機構１６において洗浄工程が実施される。その後、免疫分析項目の試薬が分注された反応容器１１は、発光検出機構１９において分析され、免疫分析項目の分析結果が制御部１に出力される。 Next, the reagent of the immunological analysis item is dispensed into the reaction container 11. After the reaction container 11 is held in the constant temperature mechanism 18 for a predetermined time, a cleaning process is performed in the cleaning mechanism 16. Thereafter, the reaction container 11 into which the reagent for the immunological analysis item is dispensed is analyzed by the luminescence detection mechanism 19, and the analysis result of the immunological analysis item is output to the control unit 1.

そして、免疫分析項目の分析結果が制御部１に出力され、この分析結果が免疫分析項目の測定範囲内であれば、Ｉｍｍｕｎｏ−ＰＣＲ法を測定原理とする分析項目の分析依頼はキャンセルされる。 Then, the analysis result of the immunological analysis item is output to the control unit 1, and if this analysis result is within the measurement range of the immunological analysis item, the analysis item analysis request based on the immuno-PCR method is canceled.

一方、免疫分析項目の分析結果が、免疫分析項目の測定範囲よりも低値であった場合は、Ｉｍｍｕｎｏ−ＰＣＲ法を測定原理とする分析項目の分析が開始される。すなわち、バッファ部６に待機した検体ラック２は、再検搬送部８により検体搬送部４のスタート位置に搬送される。そして、免疫分析ユニットＡＵ１において、反応容器移送機構１７によって、反応容器１１が恒温機構１８の所定位置に設置され、検体分注機構１０によって反応容器に検体容器３に収納された検体が分注される。次いで、反応容器１１にはＩｍｍｕｎｏ−ＰＣＲ法を測定原理とする分析項目の試薬（前述の第1の試薬）が分注される。反応容器１１は、恒温機構１８において所定時間保持された後に、洗浄機構１６において洗浄工程が実施される。 On the other hand, when the analysis result of the immunological analysis item is lower than the measurement range of the immunological analysis item, the analysis of the analysis item based on the immuno-PCR method is started. That is, the sample rack 2 waiting in the buffer unit 6 is transported to the start position of the sample transport unit 4 by the retest transport unit 8. In the immunological analysis unit AU1, the reaction container 11 is placed at a predetermined position of the constant temperature mechanism 18 by the reaction container transfer mechanism 17, and the sample stored in the sample container 3 is dispensed into the reaction container by the sample dispensing mechanism 10. The Next, a reagent for analysis items (the above-mentioned first reagent) based on the immuno-PCR method is dispensed into the reaction vessel 11. After the reaction container 11 is held in the constant temperature mechanism 18 for a predetermined time, a cleaning process is performed in the cleaning mechanism 16.

既に、Ｉｍｍｕｎｏ−ＰＣＲ法を測定原理とする分析項目の試薬（前述の第1の試薬）が分注され、洗浄機構１６における洗浄工程が行われた反応容器１１は、反応容器搬送機構１７によって免疫分析ユニットＡＵ１から検体搬送部５まで搬送され、検体ラック２の空ポジションに設置される。反応容器１１は、検体搬送機構４により、遺伝子分析ユニットＡＵ２へと搬送される。 The reaction container 11 that has already been dispensed with the analysis item reagent (the first reagent described above) based on the immuno-PCR method and subjected to the washing process in the washing mechanism 16 is immunized by the reaction container transport mechanism 17. The sample is transported from the analysis unit AU1 to the sample transport unit 5 and installed in the empty position of the sample rack 2. The reaction container 11 is transported to the gene analysis unit AU2 by the sample transport mechanism 4.

従って、この第３の分析方法においては、免疫分析項目の分析結果判断によってＩｍｍｕｎｏ−ＰＣＲ法を測定原理とする分析項目の依頼がキャンセルされた場合、Ｉｍｍｕｎｏ−ＰＣＲ法を測定原理とする分析項目の試薬消費を回避することが可能である。 Therefore, in the third analysis method, when the analysis item request based on the immuno-PCR method is canceled by the determination of the analysis result of the immunological analysis item, the analysis item based on the immuno-PCR method is determined. It is possible to avoid reagent consumption.

１…制御部
２…検体ラック
３…検体
４…検体投入部
５…検体搬送部
６…待機バッファ
７…検体回収部
８…再検搬送部
ＡＵ１…免疫分析ユニット
１０，２０…検体分注機構
１１，２１…反応容器
１２，２２…反応容器設置機構
１３，２３…試薬分注機構
１４…免疫試薬保管部
１５…免疫試薬ボトル
１６…洗浄機構
１７，２７…反応容器搬送機構
１８…恒温機構
１９…発光検出機構
ＡＵ２…遺伝子分析ユニット
２４…遺伝子試薬保管部
２５…遺伝子試薬ボトル
２８…反応容器設置部
２９…蛍光検出機構
３０…温度サイクル機構 DESCRIPTION OF SYMBOLS 1 ... Control part 2 ... Specimen rack 3 ... Specimen 4 ... Specimen input part 5 ... Specimen conveyance part 6 ... Standby buffer 7 ... Specimen collection part 8 ... Re-examination conveyance part AU1 ... Immune analysis unit 10,20 ... Specimen dispensing mechanism 11, 21 ... Reaction vessel
12, 22 ... Reaction container installation mechanism 13, 23 ... Reagent dispensing mechanism 14 ... Immune reagent storage unit 15 ... Immune reagent bottle 16 ... Washing mechanism 17, 27 ... Reaction container transport mechanism 18 ... Constant temperature mechanism 19 ... Luminescence detection mechanism AU2 ... Gene analysis unit 24 ... gene reagent storage unit 25 ... gene reagent bottle 28 ... reaction container installation unit 29 ... fluorescence detection mechanism 30 ... temperature cycle mechanism

Claims

In the immunological analysis unit and the first reaction step of creating a first reaction mixture with an immune reaction by mixing a first reagent comprising a test body and a magnetic body,
In the immunoassay unit, a washing step for performing solution replacement by magnetically separating the magnetic material from the first reaction solution;
A transporting step of automatically transporting the first reaction solution that has finished the first reaction step and the washing step from the immune analysis unit to the gene analysis unit;
In the gene analysis unit, a second reaction step of preparing a second reaction solution used for gene amplification by mixing the first reaction solution and a second reagent;
In the genetic analysis unit, a temperature cycle step of performing a temperature cycle on the second reaction solution;
In the genetic analysis unit, an automatic analysis method and having a measurement step of measuring the second reaction solution after the temperature cycle process.

The automatic analysis method according to claim 1,
And the immunological analysis step of measuring a third reaction liquid obtained by mixing the specimen and the reagent of the immunological analysis items in the immunological analysis unit for immune analysis item,
A determination step of determining whether or not to carry out the transport step, the second reaction step, and the measurement step based on a measurement result of the immunoassay step in the immune analysis unit. Automatic analysis method to do.

The automatic analysis method according to claim 1,
The first reaction step is a step of forming a complex from a measurement target component and an antibody holding a gene label by an immune reaction,
The second reaction step is a step of mixing a primer nucleic acid, a nucleic acid extender enzyme and a substrate in a reaction solution.

An immunoassay unit for performing an analysis utilizing an immune reaction;
A gene analysis unit for performing analysis using gene amplification;
A sample transport unit that connects the immune analysis unit and the gene analysis unit and transports a rack on which at least one sample is mounted, and
The immunoassay unit includes a first reagent dispensing mechanism that creates a first reaction liquid by mixing a specimen and a first reagent in a first reaction container ;
A cleaning mechanism for performing a cleaning step of removing unreacted reagent components from the first reaction solution in the first reaction vessel;
A reaction container transfer mechanism for transferring the first reaction container after the washing step to an empty position of a rack on the sample transport unit;
The gene analysis unit includes
Wherein is accommodated in the first reaction vessel is created in the immunological analysis unit, a second reaction solution and the second reagent to the first reaction liquid that is transported through the sample transport unit to dispense A second reagent dispensing mechanism to be created ;
A temperature cycle mechanism for performing a temperature cycle step on the second reaction liquid;
A gene measurement mechanism for measuring the second reaction solution after the temperature cycle step ,
Control unit for controlling the reaction container transfer mechanism and the sample transport unit to transport the first reaction vessel containing a first reaction solution created in the immunological analysis unit, automatically to the genetic analysis unit The automatic analysis system characterized by comprising.

The automatic analysis system according to claim 4 , wherein
The immunoassay unit has an immunoassay mechanism for measuring the immunological analysis item by mixing the reagent of the immunological analysis item and the sample in the second reaction container ,
When the measurement result of the immunoassay mechanism is outside a predetermined range, the control unit transfers the first reaction container to the rack on the sample transport unit by the transfer mechanism, and An automatic analysis system, wherein the system is controlled so as to be conveyed to the gene analysis unit.

The automatic analysis system according to claim 4, wherein
The immunological analysis unit, before the creation of the first reaction liquid, and the immunoassay mechanism for measuring the immune analysis item by mixing the reagent and the specimen of the immune analysis item in a second reaction vessel,
And a standby buffer to wait the sample until the measurement at the immunological analysis unit completion,
When the measurement result of the immunoassay mechanism is out of a predetermined range, the control unit transports the sample waiting in the standby buffer to the immune analysis unit, and stores the sample in the first reaction container. An automatic analysis system, wherein a first reaction solution is prepared by dispensing a first reagent, and thereafter, the first reaction solution is controlled to be conveyed to the gene analysis unit.