JP3991495B2 - Analysis equipment - Google Patents

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JP3991495B2
JP3991495B2 JP08122499A JP8122499A JP3991495B2 JP 3991495 B2 JP3991495 B2 JP 3991495B2 JP 08122499 A JP08122499 A JP 08122499A JP 8122499 A JP8122499 A JP 8122499A JP 3991495 B2 JP3991495 B2 JP 3991495B2
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JP2000275258A (en
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成仁 石原
哲史 松本
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Tosoh Corp
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Tosoh Corp
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Priority to JP08122499A priority Critical patent/JP3991495B2/en
Priority to EP00106420A priority patent/EP1041386B1/en
Priority to EP07006849.9A priority patent/EP1826572B1/en
Priority to DE60036746T priority patent/DE60036746T2/en
Priority to US09/534,627 priority patent/US6461570B2/en
Publication of JP2000275258A publication Critical patent/JP2000275258A/en
Priority to US10/199,126 priority patent/US6592818B2/en
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Description

【0001】
【発明の属する技術分野】
本発明は、例えば血液、血清、血漿、尿等の検体中に含まれる微量成分を自動的に分析する装置に関するものであり、特に、かかる検体中の微量成分を生化学的又は免疫学的に分析するための自動分析装置に関するものである。
【0002】
【従来の技術】
臨床診断の分野においては、被検者から採取した血液、血清、血漿、尿等の検体中に含まれる特定成分の存在や濃度を分析し、その結果から病気等の診断を行うために分析装置が広く用いられている。分析装置には、酵素反応や化学反応を利用して糖、脂質、蛋白質等を分析する多項目生化学分析装置や、抗原と抗体間の特異的な相互作用を利用してホルモンや腫瘍マーカ等を分析する多項目免疫化学分析装置等がある。これら分析装置では、検体又は反応液間の汚染を回避するために、生化学反応や免疫反応を使い捨ての反応容器中で個別に行うのが普通である。また反応容器に予め分析されるべき検体中の特定成分に対応した試薬が収容されている場合にも、使い捨ての反応容器を用いるのが普通である。
【0003】
従来の分析装置では、検体容器と反応容器を異なる2個の搬送手段で搬送しつつ、検体容器から一定量の検体を吸引して反応容器に吐出して反応を行い、検体中の特定物質を分析するのが一般的である。しかし、搬送手段は必然的に稼働部品を含むため、2個の搬送手段を具備した分析装置では構成が複雑化してメンテナンスが煩雑となり、装置の製造コストも高く、更に装置が大型化するため、検体容器と反応容器の搬送を単一の搬送手段により行うことが提案されている。
【0004】
【発明が解決しようとする課題】
生化学的又は免疫学的な分析では、被検者から採取した検体を有効に活用したり、複数種類の特定成分の存在等に基づいてより確実な診断を行う目的から、一検体当たり複数種類の特定成分を測定するのが一般的である。検体容器と反応容器の搬送を単一の搬送手段で行う分析装置では、この場合、搬送手段上の任意の位置に検体容器を載置し、該検体容器の下流側に当該検体容器中に収容された検体について行う分析の回数、即ち当該検体について分析しようとする特定成分の数、と同数の反応容器を載置し、検体と当該検体の分析に使用する反応容器が順次搬送されるようにすることとなる。また検体の希釈や前処理が必要な場合には、検体容器の下流側に希釈容器等を挟んで反応容器を載置することになる。
【0005】
分析装置は、搬送手段により検体容器と反応容器を搬送しつつ、検体容器から一定量の検体を吸引して反応容器に吐出し、必要により更に試薬を加える等して分析を開始し、検体を希釈又は前処理試薬と前反応させた後に前記のように分析を開始するが、単一の搬送手段では各容器の軌道も1本であることから、検体容器から吸引した検体を後続の反応容器に吐出するためには、移送路を移動させてノズル手段の直下に所定の検体容器を搬送して検体を吸引後、搬送手段を素早く駆動して同位置に所定の反応容器を搬送する必要がある。このため、処理速度を向上しようとすると搬送手段の駆動速度を速くし、しかも頻繁に駆動しなければならない。
【0006】
搬送手段の駆動が速く頻繁になると、実質的に分析装置を駆動している間は搬送手段上に新たな検体容器や反応容器を追加して載置できないことになり、搬送手段に多数の容器が載置し得るよう、当該手段を大型化しなければならない。これは装置の小型化できる、簡略化できるという利点を害することになる。しかも、緊急の分析が必要な検体について、いわゆる「割り込み」分析を行うことも非常に困難である。
【0007】
そこで本願発明の目的は、単一の搬送手段により検体容器と反応容器を混在した状態で搬送する構成により装置の簡略化、小型化を図るとともに、これら容器の搬送速度を緩慢にして搬送手段が駆動している間にも検体容器や反応容器を追加して載置し得る分析装置を提供することにある。
【0008】
【課題を解決するための手段】
前記目的を達成する本願発明の装置は、検体を収容する検体容器及び検体と試薬を反応させるための反応容器を搬送しつつ検体中の特定成分を分析するための分析装置であり、(1)検体容器と反応容器を両者が混在した状態で環状軌道上で搬送するための搬送手段を具備し、(2)反応容器を所定の温度に維持する温度調整機能を有する反応器、使用済反応容器を収容するための廃棄箱、一定量の液体を吸引吐出するための昇降可能なノズル手段及び反応容器を前記搬送手段、反応器及び廃棄箱の間で搬送するための昇降可能な反応容器担持手段を具備し、(3)前記ノズル手段及び/又は反応容器担持手段を直線軌道上で往復動させる別個又は単一の駆動手段を具備し、(4)前記反応器及び廃棄箱が反応容器担持手段の直線軌道上に配置され、(5)前記搬送手段の環状軌道の少なくとも一部が直線状であり、該移送路の直線状部分が前記ノズル手段及び反応容器担持手段の直線軌道の一部分と一致しており、及び、(6)前記搬送手段がその軌道の前記直線状部分に2個以上の容器を位置させ得るものであること、との各特徴を有する装置である。
【0009】
本願発明は、例えば多項目生化学分析装置や多項目免疫化学分析装置等に適用できるが、以下、多項目免疫化学測定装置として構成した場合について、図面に基づき詳細に説明する。
【0010】
【発明の実施の形態】
図1は本願発明の分析装置を上面から観察した図、図2は同装置を側面から観察した図である。
【0011】
検体容器10は検体を収容する反応容器である。免疫分析装置や生化学分析装置においては検体として血液、血清、血漿、尿等を用いるが、環境成分等を分析するための化学分析装置では、例えば河川の液体試料や土壌から抽出した成分を含む液体試料であっても良い。反応容器は検体を分析する際に、検体と反応に必要な試薬を反応させるために用いる容器であり、分析の様式によっては空の容器を使用したり、分析しようとする成分(以下「特定成分」という)に対応した試薬が予め収容された容器を用いる。生化学分析装置では反応容器中で検体を特定成分と生化学反応を生じて発色する化学試薬等を混合することが例示でき、免疫分析装置においては反応容器中で検体を特定成分と免疫反応を生じる抗原や抗体と混合することが例示できる。また、検体によっては特定成分の濃度が異常に高いために分析範囲を超えてしまうような場合や、所定の前処理を行う場合がある。そのような検体を分析する場合は検体を希釈したり、前処理試薬と混合するために希釈容器や前処理容器を用いることもできる。
【0012】
反応容器に予め試薬を収容しておく場合、当該試薬は液体状態であっても、凍結乾燥状態であっても良い。反応容器に分析に必要な全ての試薬を予め収容しておかない場合や空の反応容器を使用する場合には、搬送手段による反応容器搬送中に別途添加したり、後述する反応器上で添加されるように構成することもできる。特に免疫分析装置では、予め反応容器に前記試薬を収容しておくことも可能である。例えばヘテロジニアス1ステップサンドイッチEIAで特定物質を分析する場合には、特定物質と特異的に結合する抗体が固定化された水不溶性の磁性ビーズ及び特定物質と特異的に結合する酵素標識された抗体を凍結乾燥状態で収容しておくことが例示できる。なお、このような反応容器の構成はサンドイッチEIA以外にも、競合測定法によるEIAや、標識物質として酵素に代えて蛍光物質や化学発光物質等を採用する分析にも適用可能である。
【0013】
上記した検体容器と反応容器は、単一の搬送手段1に載置され、環状軌道上で搬送される。搬送手段は、例えば図1に示したようにベルトコンベアやスネークチェイン等の無限軌道とスプロケット18等の駆動装置、そして無限軌道を支持する支持体により構成することができる。なお図1の例では、スプロケット18が支持体の役割を兼ねている。なお検体容器と反応容器、更には希釈容器や前処理容器は、それぞれ異なった形状・寸法でも良いし、同様の形状・寸法であっても良い。異なる寸法・形状の容器を使用する場合には、例えばアダプターを用いる等して搬送手段に載置可能とすることもできる。
【0014】
搬送手段1は、検体容器と反応容器を混在した状態で環状軌道上で搬送するものである。搬送手段は、後述する理由により、載置された各容器の中心間の距離が均一となるように構成されていることが好ましい。このため本願発明の自動測定装置は、容器の種類毎に異なる搬送手段を配置する装置と比較した場合、装置の小型化が可能である。また搬送手段の駆動は、各容器の中心間の距離と等しい距離ごとに間欠的になされることが好ましい。図1に例示したように、検体容器10の下流(又は上流)には検体容器10に収容された検体について測定されるべき特定成分に対応した試薬を収容した反応容器12が、必要に応じて載置される希釈容器11を挟んで続く。このように、本願発明の分析装置では、検体容器は2個連続して搬送手段上に載置されず、少なくとも1個の反応容器を挟んで載置される。なお希釈容器は1検体の分析に際して必ず1個使用される訳ではなく、希釈が不必要な検体では使用されないし、2段階以上の希釈が必要な場合には1検体であっても2個以上の希釈容器が使用される場合もある。前処理容器についても同様である。
【0015】
搬送手段1による搬送中に、反応容器に対し、検体容器から吸引された検体と反応容器に予め試薬が収容されていない場合には試薬が吐出され、また必要に応じて溶解液又は別の試薬が加えられることにより所定の反応が開始される。その後、適宜洗浄手段を用いて洗浄操作(B/F分離操作)を行ったり追加の試薬を分注する等の操作を行い、所定の時間経過後に発色、発蛍光、発光等等の特定物質の存在又は濃度に関連する信号を検出し、検出した信号強度等に基づいて特定物質の存在や濃度を定量することになる。
【0016】
本願発明の分析装置では、分析を行う過程で反応容器を搬送手段1から反応器6に搬送し、ここで反応を進行させ、前記信号の検出を行う。このため、後述する反応容器担持手段を具備するほか、反応器6には種々の装置が配置される。反応器6は少なくとも反応容器を所定の温度に維持する温度調整機能を備えており、搬送された反応容器中で所定の反応が効率よく生じるようにその温度を維持するものである。温度調整機能は、例えば温度センサーと熱源の組み合わせにより構成することができる。また反応器6は、検出手段8における高感度の検出を妨げる要因を排除し得るような構成を採用することが好ましい。例えば検出手段が蛍光や発光等の光学的な検出手段である場合には、検出手段の外部から外乱光が入射すると検出感度に悪影響を与えることがあるため、反応器全体を開口部16を残して遮光板14で覆うことが特に好ましい。このように遮光板で反応器6を覆うと、遮光効果以外に反応器の温度が外気温の影響を受けにくくなるという効果もある。
【0017】
反応器6自体は図1に示したように回転動可能な円盤であっても良いし、搬送手段1と同様の無限軌道であっても良い。装置を簡略化しかつ小型化するという観点からは円盤とすることが特に好ましい。また円盤であれば、その正逆回転により任意の反応容器を開口部16直下の反応容器を載置したり取り出したりする場所に位置付けることが容易だからである。図1の円盤状の反応器6では、同心円状に3重の容器保持穴を配置することにより、検体及び所定の試薬を吐出した反応容器を最内周あるいは中間周の保持穴に搬送し、所定の時間が経過した時に反応容器担持手段26で最外周に搬送し、最外周において洗浄手段7での洗浄操作、検出手段8での検出を行うように構成されている。
【0018】
反応器6には、本願発明を適用する分析装置により、種々の手段が付加される。例えば先に説明した酵素を標識として使用するヘテロジニアスな免疫分析を行うための分析装置では、反応器6に対し、反応容器内に予め収容された水不溶性の磁性ビーズを運動させて反応容器内部を撹拌するための磁石振動装置(不図示)、免疫反応の後に磁性ビーズに結合しなかった標識抗体等を分離するための洗浄装置7(いわゆるB/F分離装置)、標識酵素の基質を反応容器に添加するための分注装置9、標識酵素の活性を測定するための蛍光、吸光、発光等の検出手段8等が作用可能なように配置することが例示できる。
【0019】
特に前記洗浄装置7は、水不溶性の磁性ビーズに結合した成分と未反応の液体成分を分離するために使われる装置であり、反応容器の中に洗浄液を吐出するとともに、固相を排出せずに液体だけを排出することができるように、洗浄液吐出管と液体排出管の二重管等構造を有し、前者を洗浄液吐出ポンプ、後者を液体トラップを介して真空ポンプ等に接続する構成を例示できる。なお水不溶性担体としては直径が1から10mm程度のビーズを使用することもあれば、直径がサブミクロンから数ミクロンの微小粒子を使うこともあるため、その形状や大きさに応じて適宜洗浄装置の構成は選択することが好ましい。なお、水不溶性担体として磁性ビーズを用いる場合には、磁石で磁性ビーズを反応容器の隅に寄せ、洗浄液の吸引、排出を行うことも可能である。
【0020】
また特に検出手段8は、最終的に当該手段で検出しようとする信号に応じて適宜選択される。より具体的には、例えば発色、発蛍光、発光等を検出する場合にはそれぞれ吸光モニタ、蛍光検出器、発光検出器等を選択すれば良い。反応液は、反応容器から出すことなしに又は検出セル等に吸引して検出すれば良いが、装置を簡略化しかつ小型化するという観点からは前者が特に好ましい。このような検出を行うためには、上方から反応液に向かって励起光を放射し、反応液が発した信号を上方で検出するように検出器を構成することが例示できる(この場合、遮蔽板には開口を設けておく)。また検出の仕方は、検出回数に着眼して分類した場合、1回だけ検出を行う方法、一定時間の前後で2回の検出を行い、その差を用いる方法、そして経時的に3回以上の検出を行い、検出結果の変化率を用いる方法があるが、検出しようとする信号の発生メカニズム等を検討して適宜決定すれば良い。例えば標識としてアルカリ性フォスファターゼを用いた場合には、酵素基質として4メチルウンベリフェリルリン酸を基質として用いることが例示できる。4メチルウンベリフェリルリン酸はアルカリ性フォスファターゼにより脱リン酸化されると蛍光を発するようになるから、蛍光検出手段を設け、基質溶液を添加してから一定時間経過後の蛍光強度等を測定すれば良い。
【0021】
なお図1の例において、酵素基質はノズル手段で各反応容器に吐出するように構成することも可能であるが、専用の分注装置9を設けたのは、酵素基質の添加が免疫反応の終了後に行われ、免疫反応自体には不要であること、更には全ての反応容器に対して最終的に酵素基質を添加するため専用装置を設けた方が所要時間の短縮等の面から効果的であるという理由による。
【0022】
通常の分析では、前述したような理由から使い捨ての反応容器を使用するのが一般的である。本願発明の分析装置では、反応器6上で検出を終え、分析を終了した反応容器は反応容器担持手段により搬送され、廃棄箱17に廃棄、収容される。このため反応容器担持手段は昇降可能に構成される。反応容器担持手段は、反応容器の廃棄時以外に、検体と試薬を吐出した後に反応容器を搬送手段1から反応器6上に搬送する際にも使用する。反応容器を担持するには、例えば反応容器担持手段に3本の爪からなる吊持部等を具備する一方で、反応容器開口部近傍に該爪を掛けるための凹部やフランジ等を設けることが例示できる。
【0023】
反応容器担持手段は、上記のために駆動手段により搬送手段1、反応器6及び廃棄箱17を結ぶ直線軌道上で往復動可能に構成する。ここで、搬送手段1の環状軌道は少なくともその一部が直線状に構成され、反応容器担持手段は少なくとも該直線状の軌道と重複する軌道上を往復動可能に構成される。なお反応容器担持手段を昇降するにはノズルを適当な架台に取り付け、該架台をモーターとタンジェントスクリュー機構を利用して昇降する構成を採用することが例示できる。また反応容器担持手段を直線軌道上で往復動するにも、モーターとタンジェントスクリュー機構を利用することが例示できる。なお反応容器担持手段26を用いた反応器6への反応容器の搬送又は反応器6からの反応容器の搬送は、反応器6において反応容器担持手段の直線軌道上で行われることになるため、前記したように反応器6を遮光板14で覆う場合、その開口部16及び該直線軌道を一致させることが重要である。特に好ましい例として、反応器6を円盤とし、その直径の一部又は全部と前記直線軌道及び開口部16を一致させることを例示できる。
【0024】
検体容器中の検体を吸引して反応容器に吐出したり、試薬容器から試薬を吸引して反応容器に吐出するため、本願発明の分析装置は、一定量の液体を吸引吐出するための昇降可能なノズル手段を具備する。ノズル手段はノズルとシリンジポンプ等の吸引装置から構成すれば良いが、ノズル手段を昇降するにはノズルを適当な架台に取り付け、該架台をモーターとタンジェントスクリュー機構を利用して昇降する構成を採用することが例示できる。
【0025】
本願発明の分析装置では、搬送手段の環状軌道の少なくとも一部が直線状であるが、ノズル手段は、少なくとも該直線状の軌道と重複する軌道上を往復動可能に構成される。もっとも、検体や試薬の汚染を回避する目的で先端に使い捨てのチップを装着して検体等の吸引を行うノズル手段を本願発明の分析装置で採用する場合は、ノズル手段の直線軌道をこの廃棄箱まで延長することにより、使用済のチップを収容するように構成することが好ましい。また試薬を反応器6上の反応容器に吐出するような反応を行う場合は、ノズル手段の直線軌道は反応器6まで延長することが必要である。このようにノズル手段の直線軌道は、好ましい実施形態では反応容器担持手段の直線軌道と同一になる。
【0026】
ノズル手段の駆動手段と反応容器担持手段の駆動手段は別個のものであっても良いが、両者が往復動する直線軌道は同一又は重複したものとなるため、図2に示したように単一の駆動手段を用いることもできる。
【0027】
本願発明の分析装置では、搬送手段1の環状軌道の少なくとも一部が直線状となるように構成する。例えば図1に示したように、軌道を概ね長方形状とし、そのいずれかの辺を該直線状部分とすることが例示できる。これ以外にも、軌道を概ね楕円形状又は円形状としておき、その一部分のみを直線状とすることもできる。搬送手段の環状軌道の直線状部分には、2個以上の容器が位置し得るように該直線状部分の長さは調整される。図1の例では、合計6個の容器が該直線状部分に位置する例である。
【0028】
2個以上の容器を前記直線状部分に位置させ得るように搬送手段を構成するのは、分析の際に1の検体について少なくも1種類の特定物質を分析するため、1個の検体容器と少なくとも1個の反応容器が要求されるからである。1の検体について複数種類の特定物質を分析することが見込まれる場合には、見込まれる数と同数程度の容器が当該部分に位置し得るように搬送手段を構成することが好ましいが、その数が大きい場合には、上限を10個程度に抑える一方で搬送手段を駆動制御し、装置が大型化することを防止することが好ましい。本願発明では、希釈や前処理等の付加的な操作を勘案して3個以上の容器が該直線状部分に位置し得るように搬送手段を構成することが好ましい。
【0029】
搬送手段の環状軌道の前記直線状部分に検体容器と当該検体容器に関する分析に要求される全て容器を位置するようにできる場合は、これら容器の全てを該直線状部分に搬送後搬送手段の駆動を停止し、ノズル手段を検体容器上で昇降させて検体を吸引し、ノズル手段駆動手段によりノズルを反応容器の上部に搬送し、その位置で昇降させて検体を反応容器に吐出することが例示できる。一方で前記直線状部分に全容器を位置するようにできない場合には、検体容器から検体を吸引後、ノズル手段を駆動せずに搬送手段を駆動して反応容器をノズルの直下に搬送するという操作を必要回数繰り返したり、一定回数繰り返した後に搬送手段の駆動を停止しノズル手段を搬送して残りの吐出を行うことが例示できる。後者のように搬送手段を制御して検体を反応容器に吐出しようとする場合には、搬送手段の駆動を搬送手段に載置された各容器の中心間の距離ごとの間欠的なものとしておくことが好ましい。
【0030】
これまで説明してきたように、予め反応容器に反応に要する全試薬が収容されていない場合には、別途反応容器に当該不足の試薬を吐出する操作が必要になる。本願発明の装置においてこのような操作を行う場合には、ノズル手段の直線状の往復動軌道上に試薬を収容した試薬容器13を配置すれば良い。反応容器に吐出すべき試薬が多数種類以上ある場合等には、これら試薬容器を直線状の軌道19上で搬送するための試薬搬送手段を具備するとともに、該軌道をノズル手段の直線状往復動軌道と交差、より好ましくは直交するように構成することが例示できる。また前記したように使い捨てチップをノズルに装着して検体等の吸引、吐出を行う場合には、ノズル手段の直線状の往復動軌道上にチップ4を載置するチップラック5を配置すれば良い。大量のチップを使用する場合には、これらチップを直線状の軌道19上で搬送するためのチップ搬送手段を具備するとともに、該軌道をノズル手段の直線状往復動軌道と交差、より好ましくは直交するように構成することが例示できる。なお図1では、試薬容器13とチップラック5を一体に構成し、単一の搬送手段を用いて直線状の軌道19上で搬送する例を示している。チップラックとしては、市販の、最大96本のチップを格子状に並べた状態で収容できるチップラック等を使用することができる。
【0031】
以下に、本願発明を免疫分析装置に適用した場合の各部の機能について説明する。なおこの装置では、前述したように特定物質との免疫反応に必要な試薬の全てが予め反応容器の中に収容されている。
【0032】
検体10’を希釈する場合は、ノズル手段を駆動してまず希釈倍率から算出された比率で検体と試薬として提供される希釈液13を検体容器の下流側に載置された希釈容器11’に吐出し、攪拌する。なお攪拌は、搬送手段の直下に搬送手段に載置された容器に対して機械的な振動を与えるような振動発生装置を配置しても良いが、ノズル手段を用いて希釈容器内の混合液の吸引と吐出を繰り返すことが、装置構成を簡略化するという点で好ましい。攪拌後、ノズル手段で希釈済みの検体を一定量吸引し、反応容器12−1’及び12−2’に吐出する。
【0033】
必要に応じて希釈された検体が吐出された反応容器は、反応容器担持機構26で搬送手段1から所定温度の反応器6に搬送される。一定時間の反応後、固相に結合しなかった未反応成分を除去するため、反応器6が回転して反応容器を洗浄手段7に搬送する。洗浄終了後、反応器6の回転により反応容器は基質分注装置に搬送され、そこで標識として使用した酵素の作用を受けて検出手段8で検出可能な信号を発生する基質を添加し、更に反応器6の回転により検出手段8に搬送され、検出が行われる。検出が終了した反応容器は、反応容器担持手段により廃棄箱17に廃棄、収容される。なお、検出手段8により検出結果は不図示の計算手段に出力される。
【0034】
ところで、例えば検体をいったん前処理した後に所定の反応に供する必要が生じる場合があるが、このような場合であっても、検体と前処理用の試薬を混合しておく時間が短いのであれば、上記の希釈を行う場合と同様に分析装置を制御すれば良いが、長時間混合しておくことが必要な場合では搬送手段を停止しておく時間等が長くなり、処理時間の短縮をはかれない。そこで本願発明の分析装置では、ノズル手段を駆動して検体10と試薬として提供される前処理液13を検体容器の下流側に載置された前処理容器11’に吐出した後、前処理容器とともに反応容器を反応容器担持手段26を駆動して反応器6に搬送し、反応器26上で前処理反応させる。前処理反応終了後、反応容器担持手段26を用いてその直線状往復動の軌道上に配置された仮置き場15に前処理容器と反応容器を置き、ここでノズル手段を用いて前処理容器から前処理済み検体を吸引し、反応容器に吐出するのである。前処理済検体を吐出した反応容器は、その後、再度反応容器担持手段26を用いて反応器6に搬送し、ここで前記同様に処理される。なお仮置き場は、前処理容器とともに反応容器を仮に置いておくために2個以上の容器を収容可能に構成する。仮置き場の場所は反応容器担持手段3の軌道上にあれば良く、例えば反応器6の中に設けることも可能である。また、仮置き場を設けることなく反応器中で前処理反応が終了した時点で目的の容器をノズルの下に移動し、前処理容器から反応容器への分注を行うことも可能である。
【0035】
【発明の効果】
本願発明の分析装置は、検体容器と反応容器を、両者が混在した状態で単一の搬送手段を用いて搬送することにより、従来の2個の搬送手段で検体容器と反応容器を別個に搬送するタイプの分析装置より構成を簡略化することができる。この結果、装置を小型化することが容易で、しかも搬送手段という稼働部分を省略できるためにメンテナンスの頻度等を減らしたり、装置の製造コストを低減可能である。また搬送手段は環状軌道で反応容器を搬送するものであるから、分析を終えた検体を取り出した後、新たに分析しようとする検体と該分析に対応する反応容器等を装置を停止することなく搬送手段に載置することができ、分析操作を効率的に行い得るという効果もある。
【0036】
また本願発明の分析装置では、反応のため反応容器を所定温度に調整し、検出等を行う反応器を搬送手段とは別に設け、搬送手段と反応器の間での反応容器の搬送を直線往復動する反応容器担持手段で行うように構成したことで、搬送手段と反応器の構成を簡略化できるという効果もある。分析を終えた反応容器を廃棄、収容するための廃棄箱をも反応容器担持手段の前記直線軌道上に配置することにより、反応容器担持手段の駆動は直線軌道上の往復動と該直線軌道上での昇降のみとなり、簡便な駆動手段を具備するのみである。
【0037】
検体容器からの検体の吸引、吐出等はノズル手段により行うが、ノズル手段も反応容器担持手段と同様に直線軌道上を往復動し任意地点で昇降するのみであるから、その簡便な駆動手段を具備するのみである。しかもノズル手段の直線軌道は前記反応容器担持手段の直線軌道に含まれる(同一又は反応容器担持手段の直線軌道の一部となる)から、これらを該直線軌道上で往復動させるための駆動手段を兼用とすることで更に装置を簡略化することも可能である。
【0038】
本願発明の装置では、前記した搬送手段の環状軌道の少なくとも一部を直線状とし、該部分に少なくとも2個以上の容器を位置させ得るようにしたうえで、ノズル手段及び反応容器担持手段がこれら上部を往復動するように両手段の直線軌道と搬送手段の直線状部分を一致させるという構成により、この直線状部分に位置させることのできる容器数によっては、分析に必要な容器群を直線状部分に搬送した後はノズル手段及び反応容器担持手段の往復及び昇降動により、搬送手段を駆動すること無しに、所定の操作を行うことが可能である。
【0039】
このように本願発明の分析装置では、分析に要する時間を短縮して分析効率の向上を図るに際して搬送手段の駆動速度を速くし頻繁に駆動する必要がないから、分析装置を駆動している間に搬送手段上に新たな検体容器や反応容器を追加載置することも容易となる。この結果、搬送手段を大型化しなくとも、大量の検体を分析する場合は次々と検体容器及び反応容器を追加載置して対処できるという効果もある。また、一刻も早い分析が要求される臨床診断の分野等に本願発明の分析装置を適用すれば、検体容器や反応容器の入れ替え等が容易になり、緊急の分析が必要な検体について割り込み分析を行うことができる。
【図面の簡単な説明】
【図1】図1は、本願発明の分析装置について、発明の一実施形態を示す図である。
【図2】図2は、図1に示した分析装置の側面図(ノズル手段2及び反応容器担持手段3の往復動の軌道に沿った側面図)である。
【符号の説明】
1 搬送手段、2 ノズル手段、3 反応容器担持手段、4 使い捨てチップ、5 チップラック、6 反応器、7 洗浄手段、8 検手段、9 基質分注装置、10 検体容器、11希釈容器(前処理容器)、12 反応容器、13試薬容器、14 遮蔽板、 15 仮置き場、 16 開口部、17 廃棄箱 、18 ノズル手段及び反応容器担持手段の往復動の軌道、 19 試薬搬送手段及びチップ搬送手段の往復動の軌道、20 駆動手段(モータ)、21 駆動手段、22ノズル手段昇降用モータ、23反応容器担持手段昇降用モータ、24 昇降用送りネジ、25 昇降用ガイドシャフト、26 ソレノイド 、27 ラックアンドピニオン 、28 試薬搬送手段及びチップ搬送手段の往復動用駆動モータ、29試薬搬送手段及びチップ搬送手段の指示手段、30 反応器駆動用モータ、31 減速歯車、32 軸受け
[0001]
BACKGROUND OF THE INVENTION
The present invention relates to an apparatus for automatically analyzing a trace component contained in a specimen such as blood, serum, plasma, urine, etc., and in particular, the trace component in such a specimen is biochemically or immunologically analyzed. The present invention relates to an automatic analyzer for analysis.
[0002]
[Prior art]
In the field of clinical diagnosis, an analyzer is used to analyze the presence and concentration of specific components contained in specimens such as blood, serum, plasma, and urine collected from a subject, and to diagnose diseases from the results. Is widely used. Analytical instruments include multi-item biochemical analyzers that analyze sugars, lipids, proteins, etc. using enzymatic and chemical reactions, and hormones, tumor markers, etc., using specific interactions between antigens and antibodies. There are multi-item immunochemical analyzers that analyze In these analyzers, in order to avoid contamination between specimens or reaction solutions, biochemical reactions and immune reactions are usually performed individually in disposable reaction containers. In addition, when a reagent corresponding to a specific component in a specimen to be analyzed in advance is stored in the reaction container, it is common to use a disposable reaction container.
[0003]
In a conventional analyzer, while a sample container and a reaction container are transported by two different transport means, a certain amount of sample is sucked from the sample container and discharged into the reaction container to perform a reaction, and a specific substance in the sample is collected. It is common to analyze. However, since the transport means inevitably include operating parts, the analysis apparatus having two transport means has a complicated configuration and complicated maintenance, and the manufacturing cost of the apparatus is high, and the apparatus is further enlarged. It has been proposed that the sample container and the reaction container be transported by a single transport means.
[0004]
[Problems to be solved by the invention]
In biochemical or immunological analysis, multiple types of specimens are used for each specimen in order to effectively use specimens collected from subjects or to make more reliable diagnoses based on the presence of multiple types of specific components. It is common to measure specific components. In an analyzer in which the sample container and the reaction container are transported by a single transport means, in this case, the sample container is placed at an arbitrary position on the transport means and accommodated in the sample container on the downstream side of the sample container. Place the same number of reaction containers as the number of analyzes performed on the sample, that is, the number of specific components to be analyzed for the sample, so that the sample and the reaction container used for the analysis of the sample are sequentially transported. Will be. When sample dilution or pretreatment is required, the reaction container is placed on the downstream side of the sample container with a dilution container or the like sandwiched therebetween.
[0005]
The analyzer starts the analysis by transporting the sample container and the reaction container by the transport means, sucking a predetermined amount of the sample from the sample container and discharging it to the reaction container, and adding more reagents as necessary. The analysis is started as described above after pre-reaction with the diluted or pretreated reagent. However, since there is only one trajectory for each container in a single transport means, the sample aspirated from the sample container is used as the subsequent reaction container. In order to discharge the liquid, it is necessary to move the transfer path and transport the predetermined sample container directly below the nozzle means to suck the sample, and then quickly drive the transport means to transport the predetermined reaction container to the same position. is there. For this reason, in order to improve the processing speed, the driving speed of the conveying means must be increased and frequently driven.
[0006]
If the transport means is driven quickly and frequently, a new sample container or reaction container cannot be added and placed on the transport means while the analyzer is substantially driven. The means must be enlarged so that can be placed. This detracts from the advantage that the apparatus can be miniaturized and simplified. In addition, it is very difficult to perform a so-called “interrupt” analysis for a sample that requires urgent analysis.
[0007]
Accordingly, an object of the present invention is to simplify and reduce the size of the apparatus by a configuration in which the sample container and the reaction container are mixed in a single transfer means, and to reduce the transfer speed of these containers to reduce the transfer means. An object of the present invention is to provide an analyzer that can be additionally mounted with a sample container and a reaction container even during driving.
[0008]
[Means for Solving the Problems]
The apparatus of the present invention that achieves the above object is an analyzer for analyzing a specific component in a specimen while transporting a specimen container for containing the specimen and a reaction container for reacting the specimen and the reagent, (1) (2) A reactor having a temperature adjusting function for maintaining the reaction container at a predetermined temperature, a used reaction container, having a transport means for transporting the sample container and the reaction container on an annular track in a mixed state A waste container for storing a container, a vertically movable nozzle means for sucking and discharging a certain amount of liquid, and a reaction container supporting means for transporting a reaction container between the transport means, the reactor and the waste box (3) a separate or single drive means for reciprocating the nozzle means and / or the reaction vessel carrying means on a linear track, and (4) the reactor and the waste box being a reaction vessel carrying means. On a straight orbit (5) at least a part of the annular track of the transfer means is linear, and the linear part of the transfer path coincides with a part of the linear track of the nozzle means and the reaction vessel support means; and (6) The apparatus having the characteristics that the conveying means can position two or more containers in the linear portion of the track.
[0009]
The present invention can be applied to, for example, a multi-item biochemical analyzer, a multi-item immunochemical analyzer, and the like. Hereinafter, a case where it is configured as a multi-item immunochemical analyzer will be described in detail with reference to the drawings.
[0010]
DETAILED DESCRIPTION OF THE INVENTION
FIG. 1 is a view of the analyzer of the present invention observed from the top surface, and FIG. 2 is a view of the same device observed from the side.
[0011]
The sample container 10 is a reaction container that contains a sample. In immunological analyzers and biochemical analyzers, blood, serum, plasma, urine, etc. are used as specimens, but chemical analyzers for analyzing environmental components and the like include, for example, river liquid samples and components extracted from soil. It may be a liquid sample. A reaction container is a container used to react a specimen with reagents necessary for the reaction when analyzing the specimen. Depending on the type of analysis, an empty container may be used, or the component to be analyzed (hereinafter referred to as “specific component”). And a container in which a reagent corresponding to the above is previously stored. In the biochemical analyzer, the sample can be mixed with a specific component in the reaction container and a chemical reagent that produces a color by generating a biochemical reaction. In the immunoanalyzer, the specimen is immunoreacted with the specific component in the reaction container. Mixing with the resulting antigen or antibody can be exemplified. In addition, depending on the specimen, the concentration of the specific component is abnormally high, so that the analysis range may be exceeded, or predetermined preprocessing may be performed. When analyzing such a specimen, a dilution container or a pretreatment container can be used for diluting the specimen or mixing with a pretreatment reagent.
[0012]
When the reagent is previously stored in the reaction container, the reagent may be in a liquid state or in a lyophilized state. If the reaction vessel does not contain all the reagents necessary for the analysis in advance or if an empty reaction vessel is used, add it separately during transfer of the reaction vessel by the transfer means, or add it on the reactor described later It can also be configured. In particular, in an immunoanalyzer, it is possible to store the reagent in a reaction container in advance. For example, when analyzing a specific substance by heterogeneous one-step sandwich EIA, water-insoluble magnetic beads to which an antibody that specifically binds to the specific substance is immobilized and an enzyme-labeled antibody that specifically binds to the specific substance Can be illustrated as being stored in a lyophilized state. In addition to the sandwich EIA, such a configuration of the reaction container can be applied to EIA based on a competitive measurement method, and analysis employing a fluorescent substance or a chemiluminescent substance instead of an enzyme as a labeling substance.
[0013]
The sample container and the reaction container described above are placed on a single transport means 1 and transported on an annular track. For example, as shown in FIG. 1, the conveying means can be constituted by an endless track such as a belt conveyor or a snake chain, a driving device such as a sprocket 18, and a support that supports the endless track. In the example of FIG. 1, the sprocket 18 also serves as a support. Note that the specimen container and the reaction container, as well as the dilution container and the pretreatment container, may have different shapes and dimensions, or may have the same shape and dimensions. In the case of using containers of different sizes and shapes, for example, an adapter may be used so that the container can be placed on the conveying means.
[0014]
The transport means 1 transports a sample container and a reaction container on an annular track in a mixed state. The transport means is preferably configured so that the distance between the centers of the placed containers is uniform for reasons that will be described later. For this reason, the automatic measuring device of the present invention can be downsized when compared with a device in which different conveying means are arranged for each type of container. Moreover, it is preferable that the drive of the conveying means is intermittently performed every distance equal to the distance between the centers of the containers. As illustrated in FIG. 1, a reaction container 12 containing a reagent corresponding to a specific component to be measured for a specimen contained in the specimen container 10 is provided downstream (or upstream) of the specimen container 10 as necessary. It continues across the dilution container 11 to be placed. As described above, in the analyzer of the present invention, two specimen containers are not placed on the conveying means in succession, but are placed with at least one reaction container interposed therebetween. In addition, one dilution container is not necessarily used for the analysis of one sample, but it is not used for a sample that does not require dilution, and two or more even if one sample is required when two or more stages of dilution are required. In some cases, a dilution container is used. The same applies to the pretreatment container.
[0015]
When the reagent is not previously stored in the reaction container and the sample aspirated from the sample container during the transport by the transport means 1, the reagent is discharged, and if necessary, a solution or another reagent Is added to initiate a predetermined reaction. After that, perform a washing operation (B / F separation operation) using appropriate washing means or dispense additional reagents, etc. After a predetermined time has passed, the specific substances such as coloring, fluorescence, luminescence, etc. A signal related to the presence or concentration is detected, and the presence or concentration of the specific substance is quantified based on the detected signal intensity or the like.
[0016]
In the analyzer of the present invention, the reaction vessel is transported from the transport means 1 to the reactor 6 in the course of the analysis, where the reaction proceeds to detect the signal. For this reason, in addition to the reaction vessel support means described later, various devices are arranged in the reactor 6. The reactor 6 has at least a temperature adjustment function for maintaining the reaction vessel at a predetermined temperature, and maintains the temperature so that a predetermined reaction occurs efficiently in the transported reaction vessel. The temperature adjustment function can be configured by a combination of a temperature sensor and a heat source, for example. Moreover, it is preferable that the reactor 6 adopts a configuration that can eliminate a factor that hinders high-sensitivity detection in the detection means 8. For example, when the detection means is an optical detection means such as fluorescence or luminescence, if disturbance light enters from the outside of the detection means, the detection sensitivity may be adversely affected, so the entire reactor is left with the opening 16 left. It is particularly preferable to cover with the light shielding plate 14. When the reactor 6 is covered with the light shielding plate in this way, there is an effect that the temperature of the reactor is not easily influenced by the outside air temperature in addition to the light shielding effect.
[0017]
The reactor 6 itself may be a rotatable disk as shown in FIG. 1, or may be an endless track similar to the transport means 1. A disk is particularly preferable from the viewpoint of simplifying and downsizing the apparatus. Moreover, if it is a disk, it is because it is easy to position arbitrary reaction containers in the place where the reaction container directly under the opening part 16 is mounted or taken out by the forward / reverse rotation. In the disc-shaped reactor 6 of FIG. 1, by disposing the three container holding holes concentrically, the reaction container in which the specimen and the predetermined reagent are discharged is transferred to the innermost or intermediate holding hole, When a predetermined time has elapsed, the reaction container support means 26 transports it to the outermost periphery, and the cleaning operation by the cleaning means 7 and the detection by the detection means 8 are performed on the outermost periphery.
[0018]
Various means are added to the reactor 6 by an analyzer to which the present invention is applied. For example, in the analysis apparatus for performing heterogeneous immunoassay using the enzyme described above as a label, the water-insoluble magnetic beads previously accommodated in the reaction vessel are moved with respect to the reactor 6 to move the inside of the reaction vessel. A magnetic vibration device (not shown) for stirring the liquid, a cleaning device 7 (so-called B / F separation device) for separating labeled antibodies that did not bind to the magnetic beads after the immune reaction, and a substrate of the labeled enzyme are reacted. It can be exemplified that the dispensing device 9 for adding to the container and the detecting means 8 for detecting the activity of the labeling enzyme, such as fluorescence, light absorption, and luminescence, can be used.
[0019]
In particular, the cleaning device 7 is a device used to separate a component bound to a water-insoluble magnetic bead from an unreacted liquid component. The cleaning device 7 discharges a cleaning liquid into a reaction vessel and does not discharge a solid phase. So that only the liquid can be discharged, the cleaning liquid discharge pipe and the liquid discharge pipe have a double tube structure, etc., and the former is connected to the cleaning liquid discharge pump and the latter is connected to the vacuum pump etc. via the liquid trap. It can be illustrated. The water-insoluble carrier may be a bead with a diameter of about 1 to 10 mm or a microparticle with a diameter of submicron to several microns. The configuration is preferably selected. When magnetic beads are used as the water-insoluble carrier, the magnetic beads can be brought to the corner of the reaction vessel with a magnet, and the cleaning liquid can be sucked and discharged.
[0020]
In particular, the detection means 8 is appropriately selected according to the signal to be finally detected by the means. More specifically, for example, when detecting color development, fluorescence, luminescence, etc., an absorption monitor, a fluorescence detector, a luminescence detector, etc. may be selected. The reaction solution may be detected without being taken out of the reaction vessel or sucked into a detection cell or the like, but the former is particularly preferable from the viewpoint of simplifying and downsizing the apparatus. In order to perform such detection, it is possible to exemplify that the detector is configured to emit excitation light from above to the reaction solution and detect the signal emitted from the reaction solution upward (in this case, shielding). An opening is provided in the plate). The method of detection is classified by focusing on the number of times of detection, a method of performing detection only once, a method of performing detection twice before and after a certain time, and using the difference between them, and more than 3 times over time. There is a method of performing detection and using the rate of change of the detection result, but it may be determined as appropriate by examining the generation mechanism of the signal to be detected. For example, when alkaline phosphatase is used as a label, 4-methylumbelliferyl phosphate can be used as a substrate as an enzyme substrate. Since 4-methylumbelliferyl phosphate emits fluorescence when it is dephosphorylated by alkaline phosphatase, if fluorescence detection means is provided and the fluorescence intensity after a certain time has elapsed after adding the substrate solution, etc. good.
[0021]
In the example of FIG. 1, the enzyme substrate can be configured to be discharged into each reaction container by a nozzle means, but the dedicated dispensing device 9 is provided because the addition of the enzyme substrate is an immune reaction. It is performed after completion and is unnecessary for the immune reaction itself, and it is more effective to shorten the required time by providing a dedicated device to add the enzyme substrate to all reaction vessels. Because it is.
[0022]
In normal analysis, a disposable reaction vessel is generally used for the reasons described above. In the analysis apparatus of the present invention, the reaction container that has finished detection on the reactor 6 and has been analyzed is transported by the reaction container carrying means and discarded and accommodated in the disposal box 17. For this reason, the reaction vessel support means is configured to be movable up and down. The reaction container holding means is used not only when the reaction container is discarded, but also when the reaction container is transported from the transport means 1 onto the reactor 6 after the specimen and the reagent are discharged. In order to carry the reaction vessel, for example, the reaction vessel carrying means is provided with a suspension portion composed of three claws and the like, and a recess or a flange for hanging the claws is provided near the reaction vessel opening. It can be illustrated.
[0023]
For this reason, the reaction vessel support means is configured to be reciprocable on a straight track connecting the transport means 1, the reactor 6 and the waste box 17 by the drive means. Here, at least a part of the annular track of the transport unit 1 is configured in a straight line, and the reaction vessel support unit is configured to be able to reciprocate on a track that overlaps at least the linear track. In order to raise and lower the reaction vessel support means, it is possible to exemplify a configuration in which a nozzle is attached to a suitable base and the base is lifted and lowered using a motor and a tangent screw mechanism. Further, it is possible to exemplify the use of a motor and a tangent screw mechanism for reciprocating the reaction vessel support means on a linear track. In addition, since the transfer of the reaction container to the reactor 6 using the reaction container support means 26 or the transfer of the reaction container from the reactor 6 is performed on the linear orbit of the reaction container support means in the reactor 6, When the reactor 6 is covered with the light shielding plate 14 as described above, it is important to match the opening 16 and the linear trajectory. As a particularly preferred example, the reactor 6 can be a disk, and a part or all of its diameter can be matched with the linear track and the opening 16.
[0024]
Since the sample in the sample container is aspirated and discharged into the reaction container, or the reagent is aspirated from the reagent container and discharged into the reaction container, the analyzer of the present invention can be moved up and down to aspirate and discharge a certain amount of liquid Nozzle means. The nozzle means may be composed of a nozzle and a suction device such as a syringe pump. To raise and lower the nozzle means, the nozzle is attached to a suitable base, and the base is lifted and lowered using a motor and a tangent screw mechanism. Can be exemplified.
[0025]
In the analyzer of the present invention, at least a part of the annular track of the conveying means is linear, but the nozzle means is configured to be able to reciprocate on a track overlapping at least the linear track. However, when a nozzle means for aspirating a specimen or the like by attaching a disposable tip at the tip for the purpose of avoiding contamination of the specimen or reagent is employed in the analyzer of the present invention, the linear trajectory of the nozzle means is used as the disposal box. It is preferable that the used chip is accommodated by extending to the end. Further, when performing a reaction in which the reagent is discharged into the reaction vessel on the reactor 6, it is necessary to extend the linear trajectory of the nozzle means to the reactor 6. Thus, in a preferred embodiment, the linear trajectory of the nozzle means is the same as the linear trajectory of the reaction vessel support means.
[0026]
The drive means of the nozzle means and the drive means of the reaction vessel support means may be separate, but the linear orbits in which they reciprocate are the same or overlap, so a single as shown in FIG. The driving means can also be used.
[0027]
The analyzer according to the present invention is configured such that at least a part of the annular track of the transport means 1 is linear. For example, as shown in FIG. 1, it is possible to exemplify that the trajectory has a substantially rectangular shape and any one of the sides is the linear portion. In addition to this, the trajectory may be approximately elliptical or circular, and only a part of the trajectory may be linear. The length of the linear portion is adjusted so that two or more containers can be positioned on the linear portion of the annular track of the conveying means. The example of FIG. 1 is an example in which a total of six containers are located in the linear portion.
[0028]
The conveying means is configured so that two or more containers can be positioned in the linear portion, because at least one kind of specific substance is analyzed for one sample at the time of analysis. This is because at least one reaction vessel is required. When it is expected to analyze a plurality of types of specific substances for one specimen, it is preferable to configure the transport means so that as many containers as the expected number can be located in the part. In the case of a large size, it is preferable to suppress the upper limit to about 10 while controlling the driving of the conveying means to prevent the apparatus from becoming large. In the present invention, it is preferable to configure the conveying means so that three or more containers can be positioned in the linear portion in consideration of additional operations such as dilution and pretreatment.
[0029]
If the sample container and all the containers required for the analysis related to the sample container can be positioned in the linear portion of the annular track of the transport means, the transport means is driven after transporting all of these containers to the linear portion. The nozzle means is moved up and down on the sample container to suck the sample, the nozzle is driven to the upper part of the reaction container by the nozzle means driving means, and the sample is moved up and down at that position to discharge the sample to the reaction container. it can. On the other hand, if the entire container cannot be positioned in the linear portion, after the sample is aspirated from the sample container, the transport means is driven without driving the nozzle means to transport the reaction container directly below the nozzle. It can be exemplified that the operation is repeated the required number of times, or the driving of the conveying unit is stopped after the predetermined number of times is repeated and the nozzle unit is conveyed to perform the remaining discharge. In the latter case, when the sample is to be discharged into the reaction container by controlling the transfer means, the drive of the transfer means is intermittent for each distance between the centers of the containers placed on the transfer means. It is preferable.
[0030]
As described above, when all the reagents required for the reaction are not stored in the reaction container in advance, an operation for discharging the insufficient reagent into the reaction container is required. When such an operation is performed in the apparatus of the present invention, the reagent container 13 containing the reagent may be disposed on the linear reciprocating orbit of the nozzle means. When there are a large number of types of reagents to be discharged into the reaction container, etc., the apparatus is provided with reagent transport means for transporting these reagent containers on the linear track 19 and linear reciprocation of the nozzle means along the track. For example, it may be configured to intersect with the trajectory, more preferably orthogonal. Further, as described above, when a disposable chip is attached to a nozzle to suck and discharge a sample or the like, a chip rack 5 for mounting the chip 4 may be disposed on a linear reciprocating track of the nozzle means. . When a large number of chips are used, chip conveying means for conveying these chips on the linear track 19 is provided, and the track intersects the linear reciprocating track of the nozzle means, more preferably orthogonal. It can be illustrated that it is configured to. FIG. 1 shows an example in which the reagent container 13 and the chip rack 5 are integrally formed and transported on a linear track 19 using a single transport means. As the chip rack, a commercially available chip rack or the like that can accommodate up to 96 chips arranged in a grid pattern can be used.
[0031]
The function of each part when the present invention is applied to an immune analyzer will be described below. In this apparatus, as described above, all the reagents necessary for an immune reaction with a specific substance are stored in advance in a reaction container.
[0032]
In the case of diluting the specimen 10 ′, the nozzle means is driven to first dilute the liquid 13 provided as the specimen and the reagent at a ratio calculated from the dilution rate into the dilution container 11 ′ placed on the downstream side of the specimen container. Dispense and stir. For stirring, a vibration generating device that gives mechanical vibration to the container placed on the conveying means immediately below the conveying means may be arranged. It is preferable to repeat the suction and discharge in terms of simplifying the apparatus configuration. After stirring, a certain amount of diluted specimen is sucked by the nozzle means and discharged to the reaction containers 12-1 ′ and 12-2 ′.
[0033]
The reaction container in which the specimen diluted as necessary is discharged is transported from the transport means 1 to the reactor 6 at a predetermined temperature by the reaction container support mechanism 26. After the reaction for a certain time, in order to remove unreacted components not bonded to the solid phase, the reactor 6 rotates and conveys the reaction vessel to the cleaning means 7. After completion of the washing, the reaction vessel is transported to the substrate dispensing device by the rotation of the reactor 6, where a substrate that generates a signal that can be detected by the detection means 8 under the action of the enzyme used as a label is added, and the reaction is further performed. It is conveyed to the detection means 8 by the rotation of the device 6 and detection is performed. The reaction container for which detection has been completed is discarded and accommodated in the disposal box 17 by the reaction container supporting means. The detection result is output to the calculation means (not shown) by the detection means 8.
[0034]
By the way, for example, it may be necessary to pre-process the sample once and then subject to a predetermined reaction. Even in such a case, if the time for mixing the sample and the pre-processing reagent is short The analyzer may be controlled in the same manner as in the case of performing the above dilution, but when mixing for a long time is required, the time for stopping the conveying means is lengthened and the processing time is shortened. I can't take it. Therefore, in the analyzer of the present invention, after the nozzle means is driven and the pretreatment liquid 13 provided as the specimen 10 and the reagent is discharged to the pretreatment container 11 ′ placed on the downstream side of the specimen container, the pretreatment container At the same time, the reaction vessel is transported to the reactor 6 by driving the reaction vessel supporting means 26, and a pretreatment reaction is performed on the reactor 26. After completion of the pretreatment reaction, the pretreatment vessel and the reaction vessel are placed on the temporary storage place 15 arranged on the linear reciprocating motion using the reaction vessel holding means 26, and the nozzle means is used here to remove the pretreatment vessel from the pretreatment vessel. The pretreated specimen is aspirated and discharged into the reaction container. The reaction container from which the pretreated specimen has been discharged is then transported again to the reactor 6 using the reaction container holding means 26, where it is processed in the same manner as described above. The temporary storage place is configured to accommodate two or more containers in order to temporarily place the reaction container together with the pretreatment container. The temporary storage place may be located on the orbit of the reaction vessel holding means 3, and may be provided in the reactor 6, for example. In addition, when the pretreatment reaction is completed in the reactor without providing a temporary storage place, it is possible to move the target container under the nozzle and perform dispensing from the pretreatment container to the reaction container.
[0035]
【The invention's effect】
The analyzer of the present invention transports the sample container and the reaction container separately by using the two conventional transport means by transporting the sample container and the reaction container using a single transport means. It is possible to simplify the configuration from the type of analyzer. As a result, it is easy to reduce the size of the apparatus, and the operating part of the conveying means can be omitted, so that the frequency of maintenance and the like can be reduced, and the manufacturing cost of the apparatus can be reduced. In addition, since the transport means transports the reaction container in an annular track, after the sample that has been analyzed is taken out, the sample to be newly analyzed and the reaction container corresponding to the analysis are not stopped. It can be placed on the conveying means, and there is an effect that the analysis operation can be performed efficiently.
[0036]
In the analyzer of the present invention, the reaction vessel is adjusted to a predetermined temperature for the reaction, and a reactor for performing detection or the like is provided separately from the conveyance means, and the conveyance of the reaction container between the conveyance means and the reactor is linearly reciprocated. Since it is configured to be performed by the moving reaction vessel support means, there is an effect that the structure of the transport means and the reactor can be simplified. By disposing a disposal box for discarding and storing the reaction container after the analysis on the linear track of the reaction container support means, the reaction container support means is driven on the straight track and on the linear track. Only the raising and lowering is performed, and simple driving means is provided.
[0037]
The sample is aspirated and discharged from the sample container by the nozzle means, but the nozzle means also reciprocates on a straight track and moves up and down at an arbitrary point in the same manner as the reaction container support means. It only has. Moreover, since the linear track of the nozzle means is included in the linear track of the reaction vessel carrying means (is the same or a part of the linear track of the reaction vessel carrying means), the drive means for reciprocating these on the linear track. It is also possible to further simplify the apparatus by using both.
[0038]
In the apparatus of the present invention, at least a part of the annular orbit of the conveying means described above is linear, and at least two or more containers can be positioned in the part, and the nozzle means and the reaction container holding means are provided with these parts. Depending on the number of containers that can be positioned on this linear part, the group of containers required for the analysis is linear. After being conveyed to the part, it is possible to perform a predetermined operation without driving the conveying means by reciprocating and raising / lowering the nozzle means and the reaction container supporting means.
[0039]
Thus, in the analyzer of the present invention, it is not necessary to increase the driving speed of the conveying means and drive it frequently in order to shorten the time required for analysis and improve the analysis efficiency. It is also easy to additionally place a new sample container or reaction container on the transport means. As a result, there is an effect that even when a large amount of samples are analyzed, it is possible to deal with additional sample containers and reaction containers one after another without increasing the size of the transport means. In addition, if the analyzer of the present invention is applied to the field of clinical diagnosis that requires analysis as soon as possible, it becomes easy to replace sample containers and reaction containers, and interrupt analysis is performed for samples that require urgent analysis. It can be carried out.
[Brief description of the drawings]
FIG. 1 is a diagram showing an embodiment of an analysis apparatus according to the present invention.
FIG. 2 is a side view of the analyzer shown in FIG. 1 (a side view along a reciprocating orbit of the nozzle means 2 and the reaction vessel support means 3).
[Explanation of symbols]
DESCRIPTION OF SYMBOLS 1 Conveyance means, 2 Nozzle means, 3 Reaction container support means, 4 Disposable tip, 5 Chip rack, 6 Reactor, 7 Cleaning means, 8 Inspection means, 9 Substrate dispensing device, 10 Sample container, 11 Dilution container (Pretreatment Container), 12 reaction container, 13 reagent container, 14 shielding plate, 15 temporary storage place, 16 opening, 17 waste box, 18 orbit of reciprocating movement of nozzle means and reaction container support means, 19 reagent transport means and chip transport means Reciprocating orbit, 20 driving means (motor), 21 driving means, 22 nozzle means raising / lowering motor, 23 reaction vessel supporting means raising / lowering motor, 24 raising / lowering feed screw, 25 raising / lowering guide shaft, 26 solenoid, 27 rack and Pinion, 28 Reciprocating drive motor for reagent conveying means and chip conveying means, 29 Reagent conveying means and indicating means for chip conveying means, 30 reaction Motor, 31 reduction gear, 32 bearing

Claims (7)

検体を収容する検体容器及び検体と試薬を反応させるための反応容器を搬送しつつ検体中の特定成分を分析するための分析装置であり、以下の特徴を有する装置;
(1)検体容器と反応容器を両者が混在した状態で環状軌道上で搬送するための搬送手段を具備し、
(2)反応容器を所定の温度に維持する温度調整機能を有する反応器、使用済反応容器を収容するための廃棄箱、一定量の液体を吸引吐出するための昇降可能なノズル手段、及び、反応容器を前記搬送手段、反応器及び廃棄箱の間で搬送するための昇降可能な反応容器担持手段を具備し、
(3)前記ノズル手段及び反応容器担持手段を直線軌道上で往復動させる別個又は単一の駆動手段を具備し、
(4)前記反応器及び廃棄箱が反応容器担持手段の直線軌道上に配置され、
(5)前記搬送手段の環状軌道の少なくとも一部が直線状であり、該移送路の直線状部分が前記ノズル手段及び反応容器担持手段の直線軌道の一部分と一致しており、そして、
(6)前記搬送手段がその軌道の前記直線状部分に2個以上の容器を位置させ得るものである。
An analyzer for analyzing a specific component in a sample while transporting a sample container for storing the sample and a reaction container for reacting the sample and the reagent, and having the following characteristics:
(1) comprising a transport means for transporting the sample container and the reaction container on an annular track in a mixed state;
(2) a reactor having a temperature adjusting function for maintaining the reaction vessel at a predetermined temperature, a waste box for containing the used reaction vessel, a nozzle means capable of moving up and down for sucking and discharging a certain amount of liquid, and Comprising a reaction container supporting means capable of moving up and down for transporting the reaction container between the transport means, the reactor and the waste box,
(3) Provided with separate or single drive means for reciprocating the nozzle means and the reaction vessel support means on a linear track,
(4) The reactor and the disposal box are arranged on a linear track of the reaction vessel support means,
(5) At least a part of the annular track of the transfer means is linear, the linear part of the transfer path coincides with a part of the linear track of the nozzle means and the reaction vessel support means, and
(6) The conveying means can position two or more containers on the linear portion of the track.
前記ノズルと前記反応容器担持手段が、前記直線軌道上での往復動に関して同架され、単一の駆動手段により搬送されるものであることを特徴とする請求項1の分析装置。The analyzer according to claim 1, wherein the nozzle and the reaction container supporting unit are installed in a concentric manner with respect to the reciprocating motion on the linear track and are conveyed by a single driving unit. 前記装置は、反応用試薬を収容した試薬容器を搬送するための試薬搬送手段を具備するとともに、該軌道が前記ノズル手段の直線軌道と交差することを特徴とする請求項1の分析装置。2. The analyzer according to claim 1, wherein the apparatus includes a reagent conveying means for conveying a reagent container containing a reagent for reaction, and the trajectory intersects with a linear trajectory of the nozzle means. 前記装置は、前記ノズル手段に装着されるチップを搬送するためのチップ搬送手段を具備するとともに、該軌道が前記ノズル手段の直線軌道と交差することを特徴とする請求項1の分析装置。2. The analyzer according to claim 1, wherein the apparatus includes a chip transport unit for transporting a chip mounted on the nozzle unit, and the track intersects a straight track of the nozzle unit. 前記装置は、前記反応器上の反応容器中の成分を検出するための検出手段を具備することを特徴とする請求項1の分析装置。2. The analysis apparatus according to claim 1, wherein the apparatus includes a detection unit for detecting a component in a reaction vessel on the reactor. 前記装置は、前記反応器上の反応容器中の、水不溶性の磁性ビーズに結合した成分と未反応の液体成分を分離するための洗浄手段を具備することを特徴とする請求項1の分析装置。2. The analyzer according to claim 1, further comprising a cleaning means for separating a component bound to water-insoluble magnetic beads and an unreacted liquid component in a reaction vessel on the reactor. . 分析されるべき検体中の特定成分に対応した試薬が予め収容された反応容器を用いて分析を行うことを特徴とする請求項1の分析装置。The analysis apparatus according to claim 1, wherein the analysis is performed using a reaction container in which a reagent corresponding to a specific component in a specimen to be analyzed is stored in advance.
JP08122499A 1999-03-25 1999-03-25 Analysis equipment Expired - Fee Related JP3991495B2 (en)

Priority Applications (6)

Application Number Priority Date Filing Date Title
JP08122499A JP3991495B2 (en) 1999-03-25 1999-03-25 Analysis equipment
EP00106420A EP1041386B1 (en) 1999-03-25 2000-03-24 Analyzer
EP07006849.9A EP1826572B1 (en) 1999-03-25 2000-03-24 Analyzer with scheduling verification
DE60036746T DE60036746T2 (en) 1999-03-25 2000-03-24 analyzer
US09/534,627 US6461570B2 (en) 1999-03-25 2000-03-27 Analyzer
US10/199,126 US6592818B2 (en) 1999-03-25 2002-07-22 Automatic analyzer

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JP2000275258A JP2000275258A (en) 2000-10-06
JP3991495B2 true JP3991495B2 (en) 2007-10-17

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JP2010151670A (en) * 2008-12-25 2010-07-08 Tosoh Corp Automatic analysis apparatus

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EP2340301A4 (en) 2008-09-24 2012-05-09 Straus Holdings Inc Imaging analyzer for testing analytes
EP2192411B1 (en) * 2008-11-28 2017-08-09 F. Hoffmann-La Roche AG System and method for the processing of liquid samples
JP5321324B2 (en) * 2009-07-30 2013-10-23 東ソー株式会社 Automatic analyzer capable of switching reaction vessel supply means
JP6031229B2 (en) * 2011-12-28 2016-11-24 シスメックス株式会社 Sample measuring apparatus and sample measuring method
CN106324265A (en) * 2015-06-22 2017-01-11 深圳迈瑞生物医疗电子股份有限公司 Bench-type immunoassay analyzer
US11280741B2 (en) * 2017-07-14 2022-03-22 Horiba Advanced Techno, Co., Ltd. Biological sample analysis device
CN112005116A (en) * 2018-02-02 2020-11-27 日本化学药品株式会社 Substrate for biochemical reaction and analyzer
JP7347849B2 (en) 2018-04-19 2023-09-20 ファースト ライト ダイアグノスティクス, インコーポレイテッド Target detection
CN109444444A (en) * 2018-10-10 2019-03-08 深圳市国赛生物技术有限公司 A kind of detection analysis instrument and its application method

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Publication number Priority date Publication date Assignee Title
JP2010151670A (en) * 2008-12-25 2010-07-08 Tosoh Corp Automatic analysis apparatus

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