JP4662580B2 - 自動化診断用分析器および方法 - Google Patents
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- JP4662580B2 JP4662580B2 JP2007151041A JP2007151041A JP4662580B2 JP 4662580 B2 JP4662580 B2 JP 4662580B2 JP 2007151041 A JP2007151041 A JP 2007151041A JP 2007151041 A JP2007151041 A JP 2007151041A JP 4662580 B2 JP4662580 B2 JP 4662580B2
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Description
本発明は、複数診断アッセイを同時に行うための自動化分析器に関する。
本明細書中に記載または参照される文献はいずれも本発明の特許請求の範囲の先行技術とはならないと認められる。
上記の必要性は、本発明の局面に従って構成されそして操作された自動臨床分析器により、表される。一般に自動化臨床分析器は、反応受容器に含まれる複数の反応混合物の1つ以上のアッセイを行う際に含まれる、多様な自動化されたステーションまたはモジュールの操作を統合または組み合わせる。この分析器は好ましくは、自給型の独立ユニットである。アッセイ標本材料および反応受容器、および種々の溶液、試薬、およびアッセイを行うのに使用される他の材料は、好ましくは分析器内に格納され、アッセイを行うときに生成される廃棄産物も同様である。
上記に加えて、本発明は、以下を提供する:
(項目1) 複数の反応受容器の各々に含有された流体試料中に存在し得る標的分析物を単離し増幅するための自動化プロセスであって、該プロセスは、複数のステーションで実行され、該ステーション間では、各反応受容器は、1個またはそれ以上の自動化受容器運搬機構を含む自動化受容器運搬システムにより、運搬され、各該自動化受容器運搬機構は、該反応受容器の少なくとも1個を該ステーションの1つから回収するように、そして該反応受容器を該ステーションの別のものへと運搬するように、構成され配置されており、該複数の反応受容器は、最初は、該プロセスの開始前に該複数の反応受容器を保持するための保持ステーションで保持されており、該プロセスは、該反応受容器の各々で実行される、以下:
該自動化受容器運搬システムを用いて、該反応受容器の1個を該保持ステーションから回収する工程であって、ここで、該保持ステーションから回収された各該反応受容器が、固体支持材料をさらに含有する、工程;
該自動化受容器運搬システムを用いて、該反応受容器を第一インキュベーションステーションへと運搬する工程であって、該第一インキュベーションステーションは、1個またはそれ以上のインキュベータを含み、各々は、密閉した温度制御インキュベーションチャンバを規定する、工程;
該標的分析物を該固体支持材料で固定化させるのに充分な条件下にて、一定時間にわたって、該第一インキュベーションステーションの該インキュベーションチャンバ内で、該反応受容器を滞留させる工程;
該自動化受容器運搬システムを用いて、該反応受容器を該第一インキュベーションステーションから回収する工程;
該自動化受容器運搬システムを用いて、該反応受容器を分離ステーションへと運搬する工程;
該分離ステーションにて、標的分析物分離手順を実行する工程であって、ここで、該標的分析物分離手順が、該反応受容器内にある該固体支持材料を該流体試料から単離すること、および該流体試料を該反応受容器から除去することを包含する、工程;
該自動化受容器運搬システムを用いて、該固体支持材料を含有する該反応受容器を該分離ステーションから回収する工程;
該自動化受容器運搬システムを用いて、該反応受容器を第二インキュベーションステーションへと運搬する工程であって、該第二インキュベーションステーションは、1個またはそれ以上のインキュベータを含み、各々は、密閉した温度制御インキュベーションチャンバを規定し、ここで、該第一および第二インキュベーションステーションは、互いに独立しているか、または少なくとも1個のインキュベータを共有している、工程;
該反応受容器を該第二インキュベーションステーションへと運搬する前または後にて、該反応受容器に増幅試薬を分配する工程;および
該標的分析物を増幅させるのに充分な条件下にて、一定時間にわたって、該第二インキュベーションステーションの該インキュベーションチャンバ内で、該反応受容器を滞留させる工程、
を包含する、プロセス。
(項目2) 前記標的分析物分離手順がさらに、以下:
前記流体試料を前記反応受容器から除去した後、該反応受容器に洗浄バッファを分配する工程;
該反応受容器を攪拌して、該洗浄バッファおよび前記固体支持材料を混合する工程;
該反応受容器内の該固体支持材料を、該洗浄バッファから単離する工程;および
該洗浄バッファを該反応受容器から除去する工程、
を包含する、項目1に記載の方法。
(項目3) 自動化分析器のステーション間で反応受容器を運搬するための運搬機構であって、該反応受容器は、操作構造体を含み、該運搬機構は、以下:
受容器キャリアアセンブリであって、回転軸の周りで回転可能であるように、そして該受容器キャリアアセンブリが該回転軸の周りで回転している間、反応受容器を受容して該反応受容器を運ぶように、構成され配置されている、受容器キャリアアセンブリ;
操作フック部材であって、該操作フック部材は、該受容器キャリアアセンブリと相互関係に置かれて、それに対して移動可能であるようにされており、該反応受容器の該操作構造体と噛み合い可能であるように、構成され配置されている、操作フック部材;および
フック部材駆動アセンブリであって、該フック部材駆動アセンブリは、フックモーターおよび親ネジ機構を含み、該フックモーターは、それに対して定位置で該受容器キャリアアセンブリに備えられた固定構造体を有し、そして該親ネジ機構は、該回転軸に対して略半径方向で配向されたネジ付きシャフトを含み、そして該操作フック部材に連結された末端を有し、ここで、該親ネジ機構は、該フックモーターに操作可能に連結されており、そして該フックモーターの動力運動を、該ネジ付きシャフトのいずれかの軸方向で、該フックモーターの該固定構造体に対して、該ネジ付きシャフトの運動へと変換するように、構成され配置されて、それにより、該操作フック部材により噛み合わされた反応受容器が該受容器キャリアアセンブリに対して移動できるように、該受容器キャリアアセンブリに対して、該操作フック部材の対応する運動を引き起こす、フック部材駆動アセンブリ、
を含む、機構。
(項目4) 反応流体を含有する複数の反応受容器を受容し、該反応流体を温度制御環境で維持するためのインキュベータであって、該インキュベータは、以下:
ハウジングであって、該ハウジングは、その中に形成された受容器アクセス開口部を含み、該受容器アクセス開口部は、該受容器アクセス開口部を通って、該ハウジングの中または外へ該反応受容器を移動させるためにある、ハウジング;
コマンド応答性閉鎖機構であって、該コマンド応答性閉鎖機構は、該受容器アクセス開口部に近接した関係で、該ハウジングに接続されており、ここで、該コマンド応答性閉鎖機構は、該アクセス開口部を通しての該ハウジングへのアクセスを防止または許容するために、対応する閉鎖運動コマンドに応答して、該受容器アクセス開口部に対して、閉鎖位置と開放位置との間で移動可能であるように、構成され配置されており、
該ハウジングおよび該コマンド応答性閉鎖機構は、その中でインキュベーションチャンバを規定する囲壁を構成する、コマンド応答性閉鎖機構;
該インキュベーションチャンバと熱連絡している、熱源;
動力ファン機構であって、該動力ファン機構は、該インキュベーションチャンバ内に配置されており、そして該インキュベーションチャンバ内で空気運動を発生させて該インキュベーションチャンバの内部でのほぼ均一な温度分布を促進するように、構成され配置されている、動力ファン機構;
受容器キャリアであって、該受容器キャリアは、該インキュベーションチャンバ内に配置されており、そして複数の受容器ステーションを含み、該受容器ステーションの各々は、単一の反応受容器を運ぶように、構成され配置されており、該受容器キャリアは、該アクセス開口部に対して受容器運搬位置で、該複数の受容器ステーションのいずれかを提供するように、構成され配置されている、受容器キャリア、
を含む、インキュベータ。
(項目5) 反応流体を含有する複数の反応受容器を受容し、該反応流体を温度制御環境で維持するためのインキュベータであって、該インキュベータは、以下:
ハウジングであって、該ハウジングは、その中に形成された受容器アクセス開口部を含み、該受容器アクセス開口部は、該受容器アクセス開口部を通って、該ハウジングの中または外へ該反応受容器を移動させるためにある、ハウジング;
コマンド応答性閉鎖機構であって、該コマンド応答性閉鎖機構は、該受容器アクセス開口部に近接した関係で、該ハウジングに接続されており、ここで、該コマンド応答性閉鎖機構は、該アクセス開口部を通しての該ハウジングへのアクセスを防止または許容するために、対応する閉鎖運動コマンドに応答して、該受容器アクセス開口部に対して、閉鎖位置と開放位置との間で移動可能であるように、構成され配置されており、
該ハウジングおよび該コマンド応答性閉鎖機構は、その中でインキュベーションチャンバを規定する囲壁を構成する、コマンド応答性閉鎖機構;
該インキュベーションチャンバと熱連絡している、熱源;
受容器キャリアであって、該受容器キャリアは、該インキュベーションチャンバ内で配置されており、そして複数の受容器ステーションを含み、該受容器ステーションの各々は、単一の反応受容器を運ぶように、構成され配置されており、該受容器キャリアは、該アクセス開口部に対して受容器運搬位置で、該複数の受容器ステーションのいずれかを提供するように、構成され配置されている、受容器キャリア;ならびに
受容器混合機構であって、該受容器混合機構は、該ハウジングに取り付けられており、そして該混合機構に対して操作可能な位置に配置された受容器ステーションで運ばれる反応受容器を攪拌して、それにより、該反応受容器に含有された該反応流体を混合するように、構成され配置されている、受容器混合機構、
を含む、インキュベータ。
(項目6) 自動化分析器のためのモジュールであって、該モジュールは、以下:
(A)該モジュールの1つから該モジュールの別のものへと反応受容器を運搬するための運搬機構であって、該反応受容器は、操作構造体を含み、該運搬機構が、以下:
(1)受容器キャリアアセンブリであって、該受容器キャリアアセンブリは、回転軸の周りで回転可能であるように、そして該受容器キャリアアセンブリが該回転軸の周りで回転している間、反応受容器を受容して該反応受容器を運ぶように、構成され配置されている、受容器キャリアアセンブリ;
(2)操作フック部材であって、該操作フック部材は、該受容器キャリアアセンブリと相互関係に置かれて、それに対して移動可能であるようにされており、該操作フック部材は、該反応受容器の該操作構造体と噛み合い可能であるように、構成され配置されている、操作フック部材;および
(3)フック部材駆動アセンブリであって、該フック部材駆動アセンブリは、フックモーターおよび親ネジ機構を含み、該フックモーターは、それに対して定位置で該受容器キャリアアセンブリに備えられた固定構造体を有し、そして該親ネジ機構は、該回転軸に対して略半径方向で配向されたネジ付きシャフトを含み、そして該操作フック部材に連結された末端を有し、ここで、該親ネジ機構は、該フックモーターに操作可能に連結されており、そして該フックモーターの動力運動を、該ネジ付きシャフトのいずれかの軸方向で、該フックモーターの該固定構造体に対して、該ネジ付きシャフトの運動へと変換するように、構成され配置されて、それにより、該操作フック部材により噛み合わされた反応受容器が該受容器キャリアアセンブリに対して移動できるように、該受容器キャリアアセンブリに対して、該操作フック部材の対応する運動を引き起こす、フック部材駆動アセンブリ、
を含む、運搬機構;ならびに
(B)反応流体を含有する複数の該反応受容器を受容し、該反応流体を温度制御環境で維持するためのインキュベータであって、該インキュベータは、以下:
(1)ハウジングであって、該ハウジングは、その中に形成された受容器アクセス開口部を含み、該受容器アクセス開口部は、該受容器アクセス開口部を通って、該ハウジングの中または外へ該反応受容器を移動させるためにある、ハウジング;
(2)コマンド応答性閉鎖機構であって、該コマンド応答性閉鎖機構は、該受容器アクセス開口部に近接した関係で、該ハウジングに接続されており、ここで、該コマンド応答性閉鎖機構は、該アクセス開口部を通しての該ハウジングへのアクセスを防止または許容するために、対応する閉鎖運動コマンドに応答して、該受容器アクセス開口部に対して、閉鎖位置と開放位置との間で移動可能であるように、構成され配置されている、コマンド応答性閉鎖機構、
ここで、該ハウジングおよび該コマンド応答性閉鎖機構は、その中でインキュベーションチャンバを規定する囲壁を構成する;
(3)該インキュベーションチャンバと熱連絡している、熱源;
(4)受容器キャリアであって、該受容器キャリアは、該インキュベーションチャンバ内に配置されており、そして複数の受容器ステーションを含み、該受容器ステーションの各々は、単一の反応受容器を運ぶように、構成され配置されており、該受容器キャリアは、該アクセス開口部に対して受容器運搬位置で、該複数の受容器ステーションのいずれかを提供するように、構成され配置されている、受容器キャリア、
を含む、インキュベータ、
を含み、
該インキュベータは、該インキュベータからの妨害なしで、該受容器キャリアアセンブリを回転させるように、該運搬機構の該受容器キャリアアセンブリにより揺り動かされる円弧の半径方向外側に配置され、そして該インキュベータは、該運搬機構の該受容器キャリアアセンブリにより揺り動かされる円弧に隣接して該アクセス開口部が配置されるよう配向され、それによって、該運搬機構が、以下:
(a)該コマンド応答性閉鎖機構が該開放位置にあるとき、該受容器キャリアアセンブリを該受容器アクセス開口部と協同して整列するように回転することにより、そして該操作フック部材を、該受容器キャリアアセンブリに対して第一方向で移動して、該反応受容器を、該受容器キャリアアセンブリから、該受容器アクセス開口部を通って、該複数の受容器ステーションの空の1個内で支持されて噛み合うように移動することにより、該運搬機構により運ばれる該反応受容器を、該アクセス開口部を通って、該空の受容器ステーションへと挿入すること、および
(b)該コマンド応答性閉鎖機構が該開放位置にあるとき、該受容器キャリアアセンブリを該受容器アクセス開口部と協同して整列するように回転することにより、そして該操作フック部材を、該第一方向で移動して、該操作フック部材の少なくとも一部を、該受容器アクセス開口部を通って挿入し、該受容器ステーションで運ばれる反応受容器の該操作構造体を噛み合わせることにより、引き続いて、該操作フック部材を、該反応受容器キャリアアセンブリに対して第二方向で移動して、該反応受容器を、該受容器ステーションから、該受容器アクセス開口部を通って、該受容器キャリアアセンブリ内で支持されて噛み合うように引き出すことにより、該受容器キャリアの該受容器ステーションから該反応受容器を取り除くこと、
を可能とする、モジュール。
(項目7) 磁気応答性粒子を含みかつ反応受容器に含有される溶液に対して磁気分離精製操作を実行するための装置であって、該装置は、以下:
受容器キャリアユニットであって、磁気応答性粒子を含む溶液を含有する反応受容器を受容するように、そして該磁気分離精製操作を通じて該反応受容器を運ぶように、構成され配置されている、受容器キャリアユニット;
磁石移動構造体であって、磁場を発生させる少なくとも1個の磁石を含み、ここで、該磁石移動構造体は、該受容器キャリアユニットで運ばれる該反応受容器に対して、第一位置と第二位置との間で、該少なくとも1個の磁石を移動するように、構成され配置されている、磁石移動構造体、
ここで、該少なくとも1個の磁石が該第一位置にあるとき、該少なくとも1個の磁石の該磁場は、該磁気応答性粒子を、該少なくとも1個の磁石に隣接した該反応受容器の内面へと引き出し、そしてここで、該磁気応答性粒子に対する該磁場の効果は、該少なくとも1個の磁石が該第一位置にあるときよりも、該少なくとも1個の磁石が該第二位置にあるときの方が少ない;
流体運搬機構であって、該受容器キャリアユニットで運ばれる該反応受容器へと流体を選択的に分配するように、そして該反応受容器から流体を引き出すように、構成され配置されている、流体運搬機構;および
キャリア攪拌機構であって、該キャリア攪拌機構は、該受容器キャリアユニットに操作可能に連結されており、そして該受容器キャリアユニットに周期運動を与えて該受容器キャリアユニットで運ばれる該反応受容器に含有される該溶液を攪拌し混合するように、構成され配置されている、キャリア攪拌機構、
を含む、装置。
(項目8) アセンブリであって、以下:
第一リングアセンブリであって、該第一リングアセンブリは、第一回転軸の周りで回転可能であるように、構成され配置されており、該第一リングアセンブリは、内周および外周を有する環状流体コンテナキャリア部分を含み、該内周と該外周との間で、該流体コンテナキャリア部分が規定されており、該流体コンテナキャリア部分は、複数の流体コンテナを運ぶように、構成され配置されている、第一リングアセンブリ;および
第二リングアセンブリであって、該第二リングアセンブリは、該第一回転軸とほぼ平行な第二回転軸の周りで、該第一リングアセンブリとは無関係に回転可能であるように、構成され配置されており、該第二リングアセンブリは、該第二リングアセンブリの外周の少なくとも一部が該第一リングアセンブリの該流体コンテナキャリア部分の該内周に半径方向内側に配置されるように、該第一リングアセンブリに対して、位置づけられており、該第二リングアセンブリは、その上に複数のピペットチップを備えるように、構成され配置されている、第二リングアセンブリ;
を含む、アセンブリ。
(項目9) 前記第二リングアセンブリが、内周および外周を有するピペットチップキャリア部分を含み、該内周と該外周との間で、該ピペットチップキャリア部分が規定されており、ここで該アセンブリは、内部回転アセンブリをさらに含み、該内部回転アセンブリは、第一回転軸および第二回転軸に対して概して平行である第三回転軸の周りに第一リングアセンブリおよび第二リングアセンブリとは独立して回転可能であるように構成され配置されており、該内部回転アセンブリは、該第二リングアセンブリに対して配置されており、その結果、該内部回転アセンブリの外周の少なくとも一部が、該第二リングアセンブリの該ピペットチップキャリア部分の該内周に半径方向内向きに配置されており、該内部回転アセンブリがその上の複数の流体容器を運搬するために構成され配置されている、項目8に記載のアセンブリ。
(項目10) 少なくとも1個のコンテナの流体内容物を攪拌するための装置であって、以下:
第一回転軸の周りで回転可能であるように構成され配置されている、ターンテーブル構造体;
1個またはそれ以上のコンテナホルダーであって、各々は、回転軸を有し、その中でコンテナを保持するように、構成され配置されており、該ターンテーブル構造体と共に回転可能であるように、また、各コンテナホルダーの該回転軸が該第一回転軸とほぼ平行になるように、該ターンテーブル構造体に取り付けられている、コンテナホルダー;
コンテナホルダー取付アセンブリであって、該コンテナホルダー取付アセンブリは、各1個のコンテナホルダーに付随しており、ここで、該コンテナホルダー取付アセンブリは、該付随コンテナホルダーを該ターンテーブル構造体に取り付けるように、そして該付随コンテナホルダーを、該第一回転軸および該コンテナホルダーの該回転軸の両方とほぼ平行であってそれらから間隔を置いて配置された第二回転軸の周りで、回転させるように、構成され配置されている、コンテナホルダー取付アセンブリ;および
回転運動連結要素であって、該回転運動連結要素は、該回転構造体および該コンテナホルダー取付構造体に操作可能に付随しており、そして該ターンテーブル構造体が該第一回転軸の周りで回転するにつれて、各コンテナホルダーを該第二回転軸の周りで回転させるように、構成され配置されている、回転運動連結要素、
を含む、装置。
(分析器概要)
本発明に従った自動化診断分析器は、図1および2において一般に参照番号50により示される。分析器50は、好適には鋼で作製された内部フレーム構造62上に構築されたハウジング60を含む。分析器50は、好ましくは分析器を可動にさせるようにフレーム構造62に構造的に取りつけられたキャスタホイール64により支持される。
上記に記載の、分析器50の操作、ならびにステーション、構成要素、およびモジュールの構成、協同作用、および相互作用は、分析器50を用いて実施され得る1つのタイプのアッセイの実施における単一の試験標本について、分析器50の操作を記載することにより、説明される。本明細書中に記載される1つ以上のステーション、構成要素、およびモジュールの使用を要求する他の診断アッセイもまた、分析器50を用いて実施され得る。本明細書中の特定のアッセイ手順の記載は、単に、分析器50の多様なステーション、構成要素、およびモジュールの、操作および相互作用を例示する目的のためであり、限定の意図はない。診断試験の当業者は、多様な化学的および生物的アッセイが、本発明の分析器50を使用して自動化された様式で、実施され得ることを理解する。
図58に示されるように、MTU160は、複数の、好ましくは5個の個別の容器162を備える。容器162は、好ましくは開放頂部端と閉鎖底部端を備える円筒形管の形態であり、互いに接続リブ構造164により接続される。この接続リブ構造164は、MTU160のいずれかの側に沿った長手に延びる下向きに面するショルダを規定する。
本発明の低部シャーシの実施形態は、図52から54に示される。低部シャーシ1110はブラックポリウレタンパウダーコートを有する鋼フレーム1101、シャーシの下方に配置された引き出しドリップトレイ1102、右側引出し1104、および左側引出し1106を含む。左側引出し1106は実際には低部シャーシ1100内の中央に配置される。低部シャーシ1100のさらに左側には多様な電力供給システム構成装置および他の分析器装置(例えば取りつけプラットフォーム1154に装着された7つのシリンジポンプ1152、振動分離器(示されず)上の低部シャーシ1100のフロアに好ましくは装着された真空ポンプ1162、電力供給ユニット1156、電源フィルタ1158およびファン1160など)を収容する。
標本は標本管320に含まれ、そして管320は分析器50の外側の管トレイ300に充填される。標本管320を有するトレイ300は、はじき上げカルーセルドア80を開くことにより提供されるアクセス開口を通じて、標本リング250上に配置される。
図5および6で主に示すように、好ましい実施形態の第二リングアセンブリは、ピペットチップホイール350であり、これは、その下部にある円形リング352、上部パネル374(これは、円形内周および5個の円周に沿って間隔を置いて配置された放射状に突出している部分370を規定している)、および複数のほぼ長方形のライザ354(これは、上部パネル374をリング352から分離しており、好ましくは、上部パネル374およびリング352を通ってライザ354へと延びている機械的ファスナー356により、適切な位置で保持されている)を含む。上部パネル374には、部分370の各々に近接して、5個の長方形開口部358が形成されており、パネル374の下には、各開口部358で1個ずつ、長方形ボックス376が配置されている。上部パネル374、リング352およびライザ354は、好ましくは機械加工されたアルミニウムから形成され、そしてボックス376は好ましくは、ステンレス鋼シートストックから形成されている。
図7〜12を参照すると、多軸ミキサ400は、回転しているターンテーブル414(図10を参照)を含み、これは、中心ベアリング430で支持された中心シャフト428で、固定ベース402(これは、固定ベース402の外周の周りで形成された開口部419を通って延びている機械的ファスナー(図示せず)によって、ジグプレート130に取り付けられている)に回転可能に取り付けられている。カバー部材404がターンテーブル414に取り付けられ、共に回転する。
標本調製を開始するために、ピペットユニット456は、多軸ミキサ400に備えられたコンテナ440から、MTU160の容器(receptacle vessel)162の各々へと、標的捕捉試薬(好ましくは、マグ−オリゴ(mag−oligo)試薬)を運搬するように、移動する。この標的捕捉試薬は、標的分析物に結合して固定化できる支持材料を含有する。この支持材料は、好ましくは、磁気応答性粒子を含む。この標本調製手順の開始時にて、右側ピペットアセンブリ450のピペットユニット456は、プローブ457がトレイ372の1個でピペットチップ上に操作可能に配置された位置へと、側方および長手軸方向に移動する。
右側および左側運搬機構500、502を、今ここで、詳細に記述する。図13〜16を参照すると、右側運搬機構500は、(左側運搬機構502と同様に)、操作フック部材を有し、これは、図示した実施形態では、プレート512上のスロット510に放射状にスライドして移動可能なフック取付構造体508から延びている伸長可能分配器フック506を含む。プレート512の上部にあるハウジング504は、開口部505を有し、これは、MTU160の上部を受容するように、構成されている。プレート512に取り付けられたステッパーモーター514は、ネジ付きシャフト516を回転させ、これは、リードネジ機構と共に、図13および15で示した伸長位置から、図14で示した後退位置まで、分配器フック506を移動し、モーター514およびネジ付きシャフト516は、好ましいフック部材駆動アセンブリの要素を構成する。ステッパーモーター514は、好ましくは、改良型HSIシリーズ46000である。HSIステッパーモーターは、Waterbury,ConnecticutのHaydon Switch and Instrument,Inc.から入手できる。このHISモーターは、ネジ付きシャフト516の一端からネジを機械切削することにより、改良されており、その結果、シャフト516は、フック取付構造体508を受容できる。
1個またはそれ以上の温度ランピングステーション700は、好ましくは、ジグプレート130および標本リング250の下に配置される(標本リング250の下に位置している温度ランピングステーションは、図面では、示されていない)。MTU160の内容物を軌道ミキサ550内で混合した後、右側運搬機構500は、そのアッセイプロトコルに依存して、右軌道ミキサー550から、温度ランピングステーション700へと、MTU160を移動し得る。
このアッセイ手順の一般的な記述と連続して、ランピングステーション700での充分な温度ランプアップに続いて、右側運搬機構500は、ランプステーション700から、MTUを回収し、そしてMTU160を標的捕捉およびアニーリングインキュベータ600に置く。分析器50の好ましい操作モードでは、標的捕捉およびアニーリングインキュベータ600は、約60℃で、MTU160の内容物をインキュベートする。ある種の試験のためには、このアニーリングインキュベーション温度は±0.5℃よりも大きく変わらないこと、および増幅インキュベーション(以下で記述する)温度は±0.1℃よりも大きく変わらないことが重要である。結果的に、これらのインキュベータは、一貫した均一な温度を与えるように、設計されている。
図24〜25に目を向けると、各磁気分離洗浄ステーション800は、上部801および下部803を有するモジュールハウジング802を含む。適当な機械的ファスナーによって磁気分離洗浄ステーション800をデータプレート82に取り付けるために、下部803から、取付フランジ805、806が延びている。ロケータピン807および811は、ハウジング802の下部803の底部から延びている。ハウジング802をファスナーで確保する前に、磁気分離洗浄ステーション800をデータプレート82に位置づけるのを助けるために、データプレート82に形成された開口部(図示せず)と、ピン807および811とが正しく合わせられている。
図32〜34で示すような左軌道ミキサ552(および右軌道ミキサ550)は、上記磁気分離洗浄ステーション800の下部ハウジング部分803および軌道ミキサアセンブリ828と同じ様式で、構成され操作される。具体的には、軌道ミキサ550(552)は、ハウジング554を含み、これは、前部プレート551、後部プレート、および軌道ミキサ550(552)をデータプレート82に取り付けるための取付フランジ555、556を含む。ハウジング554の前端では、挿入開口部557が形成されている。MTUキャリア558は、フォークプレート560(これは、その下部に装着されている)およびMTU保持クリップ562(これは、このMTUを収容するキャリア558の内部空洞へと延びているクリップ562の対向プロングを備えたキャリア558の後部に装着されている)を有する。軌道ミキサアセンブリ564は、駆動モーター566(これは、モーター取付板567に取り付けられている)、駆動ホイール568(これは、偏心ピン570を有する)、遊びホイール572(これは、偏心ピン573を有する)、およびベルト574を含む。駆動モーター566は、好ましくは、ステッパーモーターであり、最も好ましくは、VEXTAのモデル番号PK245−02A(これは、Tokyo,JapanのOriental Motors Ltd.から入手できる)である。ベルト574は、好ましくは、タイミングベルト、モデル番号A 6G16−170012(これは、New Hyde Park,New YorkのSDP/SIから入手できる)である。軌道ミキサアセンブリ564は、偏心ピン570、573を通って、MTUキャリア558に連結されて、MTUキャリア558をその軌道経路で移動し、このMTUの内容物をかき混ぜる。駆動ホイール568は、ロケータプレート576を含み、これは、センサ取付ブラケット579に取り付けられたセンサ578と共に、MTU160を軌道ミキサ552(550)に挿入してMTU160をこの軌道ミキサから回収するためのMTUキャリア558の正しい位置決めを検証する。センサ578は、好ましくは、Optek Technology,Inc.のモデル番号OPB980T11センサであり、これは、Carrollton,TexasのOptek Technology,Inc.から入手できる。
今ここで、試薬冷却ベイ900を記述する。
図40〜42Cを参照すると、照度計950の第一実施形態は、ハウジング954内にて、電子機器ユニット952を含む。電子機器ユニット952に連結された光電子増倍管チューブ(PMT)956は、PMTプレート955を通って、ハウジング954内から延びているが、PMTプレート956の前端は、開口部953と整列している。好ましいPMTは、モデルHC135として、Bridgewater,New JerseyのHamamatsu Corp.から入手できる。好ましいPMTを用いた信号測定は、周知の光子計数システムに基づいている。
アンプリコン不活化ステーション750では、専用送達ライン(図示せず)は、不活化溶液(例えば、緩衝化漂白剤)をMTU160の容器162へと添加して、MTU160内に残留している流体を不活化する。これらの容器の流体内容物は、専用吸引ラインに接続された管状要素(図示せず)により吸引され、そして低部シャーシ1100にある専用液体廃棄物コンテナに集められる。これらの管状要素は、好ましくは、4.7インチの長さおよび0.041インチの内径を有する。
Claims (27)
- 核酸に基づく増幅反応を実施するためのプロセスであって、該プロセスは、以下の自動化工程:
a)処理デッキ上の第一位置に配置された分離ステーションにおいて、磁気応答性の固体支持体上に固定化された標的核酸を、流体試料中に存在する他の材料から分離する工程であって、該分離ステーションは、該処理デッキ上に配置された複数のステーションのうちの1つである、工程;
b)該処理デッキ上の第二位置に配置された増幅ステーションにおいて、前記分離された標的核酸を、反応受容器中で1つ以上の増幅試薬とともに、該標的核酸中に含まれる標的配列を増幅させるのに十分な時間および条件下でインキュベートする工程であって、該反応受容器は、開放頂部端と閉鎖底部端とを有するように形成されている、工程;
c)該分離された標的核酸を含む反応受容器を、工程b)の前に該増幅ステーションへと運搬する工程、
を包含し、
コンピュータコントローラが、異なるステーションに位置する異なる反応受容器において複数の異なるアッセイ手順を同時に実施するために、該複数のステーションを並行して操作する、プロセス。 - 前記反応受容器に、プローブを、該プローブを、前記標的配列または該標的配列もしくはその相補体を含むアンプリコンにハイブリダイズするのに十分な時間および条件下で、提供する自動化工程をさらに包含する、請求項1に記載のプロセス。
- 前記プローブが、検出可能な標識を含む、請求項2に記載のプロセス。
- 前記標識が、蛍光色素または化学発光化合物である、請求項3に記載のプロセス。
- 前記流体試料中の生物またはウイルスの標的群のメンバーの存在または不存在の指標として、前記標的配列または該標的配列もしくはその相補体を含むアンプリコンにハイブリダイズされた前記プローブの存在または不存在を検出する自動化工程をさらに包含し、該標的群は、少なくとも1つの生物またはウイルスからなる、請求項2〜4のいずれか一項に記載のプロセス。
- 前記検出する工程が、前記流体試料中の生物またはウイルスの標的群のメンバーの存在または不存在の指標として、前記反応受容器から発生した光の量を決定することを含む、請求項5に記載のプロセス。
- 前記流体試料中の生物またはウイルスの標的群のメンバーの量を決定する自動化工程をさらに包含する、請求項5または請求項6に記載のプロセス。
- 請求項2〜7のいずれか一項に記載のプロセスであって、該プロセスは、前記プローブを、前記反応受容器に提供する前に、該反応受容器を、前記増幅ステーションから、前記処理デッキ上の第三位置において配置された温度制御ハイブリダイゼーションステーションに運搬する自動化工程をさらに包含する、プロセス。
- 前記プローブが、前記反応受容器の前記増幅ステーションから前記ハイブリダイゼーションステーションへの運搬の後に、該反応受容器に提供される、請求項8に記載のプロセス。
- 請求項8または請求項9に記載のプロセスであって、該プロセスは、前記反応受容器を前記ハイブリダイゼーションステーションから前記処理デッキ上の第四位置に配置された検出ステーションに運搬する自動化工程をさらに包含し、ここで、ハイブリダイズされたプローブの存在または量が、該検出ステーションにおいて決定される、プロセス。
- 前記検出ステーションが、前記反応受容器の内容物により発生した光の量を決定するための照度計を備える、請求項10に記載のプロセス。
- 前記増幅ステーションへの前記反応受容器の運搬の前に、該反応受容器の内容物の温度を上昇または降下させる自動化工程をさらに包含する、請求項1〜11のいずれか一項に記載のプロセス。
- 前記増幅ステーションおよび前記ハイブリダイゼーションステーションのうち少なくとも1つへの前記反応受容器の運搬の前に、該反応受容器の内容物の温度を上昇または降下させる自動化工程をさらに包含する、請求項8〜11のいずれか一項に記載のプロセス。
- 前記反応受容器中に存在する核酸を破壊するための不活性化試薬を、該反応受容器に提供する自動化工程をさらに包含する、請求項1〜13のいずれか一項に記載のプロセス。
- 前記不活性化試薬が、過マンガン酸カリウムの溶液、ギ酸、次亜塩素酸ナトリウムの溶液、ヒドラジンおよび硫酸ジメチルからなる群より選択される化学薬品を含む、請求項14に記載のプロセス。
- 請求項14または請求項15に記載のプロセスであって、該プロセスは、前記不活性化試薬を前記反応受容器に提供する前に、該反応受容器を、前記検出ステーションから前記処理デッキ上の第五位置に配置された不活性化ステーションに運搬する自動化工程をさらに包含する、プロセス。
- 前記標的核酸が前記固体支持体上に固定化される前に、該標的核酸が、捕捉プローブにハイブリダイズされる、請求項1に記載のプロセス。
- 前記流体試料が、前記分離する工程の間に磁場に供される、請求項1〜17のいずれか1項に記載のプロセス。
- 前記運搬する工程の各々が、受容器運搬機構を用いて実施される、請求項1〜18のいずれか一項に記載のプロセス。
- 前記増幅ステーションにおいて前記反応容器の内容物をインキュベートする前に、該反応受容器に、油層が提供される、請求項1〜19のいずれか一項に記載のプロセス。
- 請求項1〜20のいずれか一項に記載のプロセスであって、前記反応受容器が、一体化されて形成された複数の受容器容器のうちの1つを含む、プロセス。
- 前記複数の受容器のうちの各受容器容器は、同じかまたは異なる標的核酸を同時に分離し、該受容器容器の流体サンプル中に存在し得る同じかまたは異なる標的配列を増幅するための同じかまたは異なる流体サンプルを含む、請求項21に記載のプロセス。
- 前記受容器の各々が円筒形管である、請求項21または22に記載のプロセス。
- 前記ステーションはハウジング内に含まれる、請求項1〜23のいずれか1項に記載のプロセス。
- 前記ハウジングが、自給型の分析器ユニットを規定する、請求項24に記載のプロセス。
- 前記分析器ユニットが可動式である、請求項25に記載のプロセス。
- 前記他の材料が非ハイブリダイズ核酸を含む、請求項1〜26のいずれか一項に記載のプロセス。
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