JP4806410B2 - 流体を生物学的試料に適用するための方法および装置 - Google Patents
流体を生物学的試料に適用するための方法および装置 Download PDFInfo
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Description
本発明は一般的には生物学的試料処理の自動化に関し、そして具体的には低−容量接線流体方式(tangential fluid approach)を用いる生物学的試料の自動化された染色のための方法および装置に関する。
形態学的な可視化用の生検組織または細胞標本物(preparations)の染色は100年以上もさかのぼる近代的標準による昔ながらの技術である。最近では、異なるタイプの化学的染色剤および生物学的複合体分子を組織切片に適用する工程を自動化する試みがなされてきた。この目的のために設計された器具は二重カロウセルをベースとしたベンタナ・メディカル・システムの系統、例えば320/ES(R)、NexES(R)、BENCHMARK(R)、およびBENCHMARK(R)XT、を包含する。これらのシステムを記載している特許は、全てが引用することにより本発明の内容となる特許文献1、特許文献2、特許文献3、および特許文献4を包含する。別のタイプの自動化されたステイナー(stainer)は、両者とも引用することにより本発明の内容となる特許文献5および6に記載されているTechMate(R)系統のステイナーである。
本発明の態様は、生物学的試料を溶液と接触させる方法であって、溶液で湿らせた曲面を生物学的試料近くに移動させ、それにより該湿らせた曲面および該生物学的試料を分離する距離を、移動する液体メニスカス層を両者の間に形成するのに充分にする段階を含んでなる方法に関する。
図1は右側からの立面図である。
図2は、キャップの中央を通して部分的に切断された、左側からの別の立面図である。
図3は、これもキャップを通して部分的に切断された、左側からの断面図である。
図4は並進キャップ、保持された試薬およびそのメニスカスの断面図の詳細である。
図5はスライド上の揺動キャップを示す別の態様の立面図である。
図6は貯蔵ドラム、引っぱりドラムおよび回転キャップを包含する膜をベースにした接触機構を示す別の態様の立面図である。
本発明は、複合体生物分子を含有する溶液で湿らせた曲面を生物学的試料近くに移動させる段階を含んでなる、生物標識を含有する疑いのある生物学的試料を溶液と接触させる方法であって、ここで、湿らせた曲面および生物学的試料を分離する距離を、移動する液体メニスカス層を両者の間に形成するのに充分にする方法に関する。
ことができる。電気伝導性の利点は、電気泳動効果が与えられて荷電された分子が電気泳動により組織中に推進されうることである。
に沿って伸びていることができるため、ロッドにより生物学的試料上で前後に推進される必要はない。その代わり、それは揺動するため、メニスカス層が図5に示された揺動する曲面下で前後に動き、ここで201は揺動キャップでありそして202は約50ミクロンの高さの外側レールでありそして図1、2および4の滑動ガイド21および22に対する機能と同等である。
Claims (29)
- 生物学的試料を溶液と接触させる方法であって、
生物学的試料を溶液と接触させるにあたり、生物学的試料が顕微鏡スライドの表面に載置させられ、溶液が生物学的試料の少なくとも一部分を覆う溶液層を形成し、
上記溶液で湿らせた曲面が生物学的試料近くに移動させられ、溶液で湿らせた曲面と上記溶液層が接触させられて曲面上の溶液と溶液層が混合させられ、
該湿らせた曲面が顕微鏡スライドの表面から距離を置いて分離させられることより、湿らせた曲面と顕微鏡スライド表面の間の溶液層中に液体メニスカス層が形成される
方法。 - 該溶液が、抗体、RNA/DNAプローブ、または検出において使用される化学的染色剤もしくは化学物質よりなる群から選択される複合生物分子を含有する請求項1の方法。
- 該生物学的試料が、組織切片、細胞標本、またはRNA/DNA、組織、蛋白質もしくはペプチドのアレイである請求項1の方法。
- 該組織が、抗原、エピトープ、細胞蛋白質、またはDNA/RNA配列よりなる群から選択される生物標識を含有する請求項1の方法。
- 該曲面が、金属、プラスチックまたはセラミックから製造される請求項1の方法。
- 該曲面が、顕微鏡スライド表面に関して凸面である請求項1の方法。
- 該曲面を、顕微鏡スライドの上部表面と実質的に平行に且つ生物学的試料の表面上を直線方式で移動させる請求項1の方法。
- 溶液で湿らせた曲面の生物学的試料近くへの移動が、生物学的試料の表面上であって顕微鏡スライドの上部表面を横切る、曲面のその軸の周りの回転による前後の揺動を含む、請求項1の方法。
- 該湿らせた曲面および該生物学的試料を分離する距離が、10ミクロン〜100ミクロンである請求項1の方法。
- 生物標識を含有する疑いのある生物学的試料を溶液と接触させる自動化された方法であって、該溶液で湿らせた曲面をコンピューター調節下で該生物学的試料近くに移動させ、該溶液が複合生物分子を含有しており、それによって、該湿らせた曲面および該生物学的試料を分離する距離を、移動する液体メニスカス層を両者の間に形成するのに充分にする段階を含んでなる、方法。
- 該溶液が、抗体、RNA/DNAプローブ、または検出において使用される化学的染色剤もしくは化学物質よりなる群から選択される複合生物分子を含有する請求項10の方法。
- 該生物学的試料が、組織切片、細胞標本、またはRNA/DNA、組織、蛋白質もしくはペプチドのアレイである請求項10の方法。
- 該組織が、抗原、エピトープ、細胞蛋白質、またはDNA/RNA配列よりなる群から選択される生物標識を含有する請求項10の方法。
- 該曲面が、金属、プラスチックまたはセラミックから製造される請求項10の方法。
- 該曲面が、顕微鏡スライド表面に関して凸面である請求項10の方法。
- 該曲面が、顕微鏡スライドの上部表面と実質的に平行に且つ生物学的試料の表面上に直線方式で移動させられる請求項10の方法。
- 曲面が、生物学的試料の表面上で顕微鏡スライドの上部表面を横切って、その軸の周りで回転して揺動する請求項10の方法。
- 該湿らせた曲面および該生物学的試料を分離する距離が、10ミクロン〜100ミクロンである請求項10の方法。
- (a)生物学的試料を上部に有する顕微鏡スライドを支持するための台、
(b)下部曲面が、操作時に該生物学的試料の近くにあるように該台の上に置かれた、下部曲面を有するキャップ、
(c)該キャップを回転させて該生物学的試料上で前後に移動させるための手段、および
(d)液体を該キャップに適用し、かつそこから除去するための手段
を含んでなる、生物標識を含有する疑いのある生物学的試料を溶液と接触させるための装置。 - 該台が上部に置かれたスライドを加熱することができる請求項19の装置。
- 該キャップが該顕微鏡スライドの長さを実質的に覆う請求項19の装置。
- 該キャップがプラスチックまたはセラミックから製造される請求項19の装置。
- 該キャップが、下部曲面と上部スライド表面との間で形成される液体のメニスカスを支持することが可能な下部曲面を有する請求項19の装置。
- 該下部曲面が25mmの半径を有する請求項19の装置。
- 該キャップのメニスカス−形成部分の最下部が該スライドより0.01〜0.10mm上にある請求項19の装置。
- 該キャップを前後に移動させるための該手段が、キャップに揺動を与えるための機構を含んでなる請求項19の装置。
- 液体を該キャップに適用し、かつそこから除去するための該手段が、すすぎパッドを含み、該キャップが該すすぎパッド近くにもたらされた時に液体を該キャップに適用するように適合されている請求項19の装置。
- 液体を該キャップに適用するための該手段が、液体を顕微鏡スライド表面に適用するピペッター装置、ここで、その後液体がキャップに引き込まれる、を含んでなる請求項19の装置。
- (a)生物学的試料を上部に有する顕微鏡スライドを支持するための台、
(b)下部曲面が操作時に該生物学的試料の近くにあるように該台の上に置かれた、下部曲面を有する並進するキャップ、
(c)該並進するキャップを該生物学的試料上で前後に移動させるための手段、
(d)液体を該キャップに適用し、かつそこから除去するための手段、および
(e)該装置の動作の全てを電子的に調節するための手段
を含んでなる、複合生物分子を、生物標識を含有する疑いのある生物学的試料に加えるための自動装置。
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