JP4668334B2 - 微量分析方法及び装置 - Google Patents
微量分析方法及び装置 Download PDFInfo
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Description
本発明の望ましい実施形態により、化学的又は生化学的反応の分析に用いられる各空所(ウエル)の容量は、概して100ナノリットル(10−10m3)未満に低減される。空所の(配列)密度は、それによって先行技術に対して数桁増加され得る。図1を参照すると、本明細書ではさもなければ「下層」又は「サンプルウエーファ」と呼ばれる、定盤、即ち、プラテン10の側面図が断面で示される。プラテン10は、多数の貫通孔12のキャリヤであり、貫通孔はプラテン10の一方の面14から反対側の面16までプラテンを横断し、本発明の実施形態により分析くぼみ又は空所(即ち、マイクロウエル)を構成する。貫通孔12は、直円柱の形状又はその代わりに長方形の断面を有し得る。しかし、他の形状の貫通孔は、本発明の範囲内である。本明細書及び添付された請求の範囲で用いられるように「プラテン」の用語は、実質的に平行な平面を有する構造体であって、横の寸法が実質的に平行な平面間で構造体の厚さを実質的に超えるものを指す。
本発明の実施形態により用いられる寸法規模に関して、貫通孔12の直径に対する軸の縦横比が1より大きいところでは、貫通孔空所の物質流体動力学の支配において粘性力が慣性力を支配し得る。結果的に、貫通孔12をサンプル流体18で装填するために毛管作用が用いられ得る。図4を参照すると、貫通孔空所を装填する2つの面が、サンプル挿入装置30に関して記載されている。貫通孔マイクロ空所12は両側で開放されているので、液体の流入及びこの液体に置き換えられてしまう空気の流出に関して、単一開口しか有しない先行技術の空所構造体で起こるように、空所ヘ液体を挿入しても、挿入と同時に、液体で置き換えられてしまう空気を、入って来る流体中に貫流させる必要はない。ポート33を介して貯水器34内へ挿入される液体32は、既に述べた通り、懸濁液の形で細胞又は他の粒子を含み得る。プラテン10の面を横切る方向36に沿って加えられる力により液体32内へプラテン10を駆り立てるように、液体32は、並列衝撃により貫通孔マイクロ空所12(図1)内へ強制挿入され得る。横のピストン力は、軸38を介するか若しくは機械工学で知られる他の任意の方法で加えられ得る。
それぞれのマイクロ空所の液状サンプルを維持するために、液体の蒸発は避けられなければならない。蒸発を防ぐ1方法は、湿度100%の周囲の大気環境を与えることである。本発明の実施形態により、蒸発を抑制するために実施し得る数ある方法の中では、例えば、各種のアルコールのような高分子量流体をマイクロ空所の各端に導入し、それによって液体サンプルの蒸発を避けるために分子単層又は他の薄い層を形成し得ることである。
本発明が適用される用途に依存して、第1液状サンプルと次に加えられる検体との反応結果は、生物学又は生物化学技術の当事者に知られた広範な方法で読み出され得る。読出しシステムは、特定の反応が起こってしまったかどうかを決めるために、アドレスを用いてアクセス可能なマイクロ空所内のサンプルの検査を可能にする各種のタガント(taggants)を用い得る。幾つかの反応は光学的に検査され得る。即ち、比色定量又は蛍光光度計方法若しくはラマンスペクトル方法を含む共鳴又は比共鳴散乱方法が限定なしに含まれる。
図8を参照すると、本発明の有利な実施形態によると、例えば、可撓性重合物質であり得るプラテン10は、光学的光源72及び検出器アレイ74を含む光学的検査システムを通り過ぎる方向70に運ばれる。液状のサンプルは、貫通孔12内に装入されかつ特定された指示が期待される周期間に列76が光学的に検査されるように、関連した反応回数によって制御されるレートで前進する。
図9を参照すると、液状サンプルを調製し、混合し又は希釈する本発明の実施形態により行われる処理(工程)を見越して、互いに隣接される第1プラテン90及び第2プラテン92の一部断面図が示される。プラテン90の貫通孔12は、幾つかの特定されたサブセットの貫通孔12を横切って同一であるか又はプラテン全部につき同一の液状サンプルが装入されてしまっているように示される。液体サンプル94は、概略的に示されるように、溶媒98内の溶液として細胞又は他の標的96を含み得る。
本発明の実施形態により本明細書に記載された多孔プラテンは、例えば、同一系統の細胞サンプルを実験室に出荷するために用いられ得る。この用途では、細胞又は他の生物的サンプルは、水溶液又は他の液状懸濁液にして本発明の貫通孔空所内に導入され得る。液状キャリヤは、その後蒸発され、細胞又は他の生物的サンプルが、複数の貫通孔空所の煙突形コーティングを形成することを可能にする。その後サンプルは、続いて濡らすことによって再懸濁され、さらなる検体が導入され得る。
10 プラテン
12 貫通穴
18 第1サンプル
Claims (9)
- 壁を有する1組の複数の円筒形貫通孔を有するプラテンを用意する段階であって、該プラテンは親水性材料でできた内層部と該内層部の両側にある疎水性材料でできた2層の外層部を具備することを特徴とする、段階と
液状キャリヤに懸濁させた生物的サンプルを該貫通孔に装入する段階と、
該生物的サンプルが該貫通孔の壁上に堆積させるために該液状キャリヤを蒸発させる段階と、
から成る生物的サンプル運搬方法。 - 第1組の複数の液状サンプルの構成要素と第2組の複数の液状サンプルの構成要素との複数の組合せで構成要素を調製する方法であって、
貫通孔を有する第1多孔プラテンと、貫通孔を有する第2多孔プラテンとを用意する段階であって、該プラテンは親水性材料でできた内層部と該内層部の両側にある疎水性材料でできた2層の外層部を具備することを特徴とする、段階と、
第1多孔プラテンの該貫通孔に第1組の液状サンプルを装入する段階と、
第2多孔プラテンの該貫通孔に第2組の液状サンプルを装入する段階と、
第1多孔プラテンの該貫通孔を第2多孔プラテンの該貫通孔と正しく合わせる段階と、
前記第1組の液状サンプルを前記第2組の液状サンプルと結合させる段階と、
から成る複数の化合物調製方法。 - 前記結合させる段階が、前記第1組サンプルを前記第2多孔プラテン内に慣性力により射出することを含む、請求項2の方法。
- 互いに平行な第1平坦面及び第2平坦面を有する第1プラテンに設けた複数の貫通孔内に第1組の液状サンプルを装入する段階であって、該プラテンは親水性材料でできた内層部と該内層部の両側にある疎水性材料でできた2層の外層部を具備することを特徴とする、段階と、
互いに平行な第1平坦面及び第2平坦面を有する第2プラテンに設けた複数の貫通孔内に第2組の液状サンプルを装入する段階と、
前記第1組の少なくとも1つの貫通孔が前記第2組の少なくとも1つの貫通孔と正しく合うように、前記第1プラテンの該第1平坦面を前記第2プラテンの該第2平坦面と接触させて配置させる段階と、
から成る複数の液状サンプルを混合させる方法。 - 前記接触させて配置させる段階が行われると同時に前記第1液状サンプルの溶液濃度が希釈されるように、前記第1組の液状サンプルが溶媒で溶解する溶質を含み、第2組の液状サンプルが溶媒を含む、請求項4の方法。
- 前記第1組の液状サンプルの液体を前記第2組の液状サンプルの液体と混合する段階をさらに含む、請求項5の方法。
- 前記混合する段階は、光学的手段で前記液体内に乱流を生じさせる段階を含む、請求項6の方法。
- 前記混合する段階は、音響的手段で前記液体内に乱流を生じさせる段階を含む、請求項6の方法。
- 前記混合する段階は、機械的手段で前記液体内に乱流を生じさせる段階を含む、請求項6の方法。
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- 1999-01-05 DE DE69942697T patent/DE69942697D1/de not_active Expired - Lifetime
- 1999-01-05 ES ES06075151T patent/ES2350702T3/es not_active Expired - Lifetime
- 1999-01-05 JP JP2000527355A patent/JP4271371B2/ja not_active Expired - Lifetime
- 1999-01-05 CA CA 2316912 patent/CA2316912C/en not_active Expired - Lifetime
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Also Published As
Publication number | Publication date |
---|---|
ATE477850T1 (de) | 2010-09-15 |
US6387331B1 (en) | 2002-05-14 |
DE69942697D1 (de) | 2010-09-30 |
EP2286918B1 (en) | 2014-10-01 |
ATE322341T1 (de) | 2006-04-15 |
EP1051259A1 (en) | 2000-11-15 |
DE69930726D1 (de) | 2006-05-18 |
JP2008139319A (ja) | 2008-06-19 |
US20150126412A1 (en) | 2015-05-07 |
AU2102699A (en) | 1999-07-26 |
JP2002500373A (ja) | 2002-01-08 |
EP1051259B1 (en) | 2006-04-05 |
EP1714699A1 (en) | 2006-10-25 |
JP2009244271A (ja) | 2009-10-22 |
US20170028376A9 (en) | 2017-02-02 |
JP4271371B2 (ja) | 2009-06-03 |
CA2316912C (en) | 2009-09-15 |
WO1999034920A1 (en) | 1999-07-15 |
EP1714699B1 (en) | 2010-08-18 |
JP4448166B2 (ja) | 2010-04-07 |
US20150298089A1 (en) | 2015-10-22 |
US20040171166A1 (en) | 2004-09-02 |
ES2350702T3 (es) | 2011-01-26 |
EP2286918A1 (en) | 2011-02-23 |
CA2316912A1 (en) | 1999-07-15 |
DE69930726T2 (de) | 2007-01-25 |
US6743633B1 (en) | 2004-06-01 |
US20110065590A1 (en) | 2011-03-17 |
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