JP2000512744A - 標識材料を検出するシステムおよび方法 - Google Patents
標識材料を検出するシステムおよび方法Info
- Publication number
- JP2000512744A JP2000512744A JP09541141A JP54114197A JP2000512744A JP 2000512744 A JP2000512744 A JP 2000512744A JP 09541141 A JP09541141 A JP 09541141A JP 54114197 A JP54114197 A JP 54114197A JP 2000512744 A JP2000512744 A JP 2000512744A
- Authority
- JP
- Japan
- Prior art keywords
- substrate
- focusing
- excitation radiation
- scanning
- radiation
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
Classifications
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
- G01N21/62—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light
- G01N21/63—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light optically excited
- G01N21/64—Fluorescence; Phosphorescence
- G01N21/645—Specially adapted constructive features of fluorimeters
- G01N21/6452—Individual samples arranged in a regular 2D-array, e.g. multiwell plates
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- C—CHEMISTRY; METALLURGY
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- C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
- C12Q1/68—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
- C12Q1/6813—Hybridisation assays
- C12Q1/6834—Enzymatic or biochemical coupling of nucleic acids to a solid phase
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- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
- C12Q1/68—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
- C12Q1/6876—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes
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- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
- C12Q1/68—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
- C12Q1/6876—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes
- C12Q1/6883—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
- G01N21/62—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light
- G01N21/63—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light optically excited
- G01N21/64—Fluorescence; Phosphorescence
- G01N21/6428—Measuring fluorescence of fluorescent products of reactions or of fluorochrome labelled reactive substances, e.g. measuring quenching effects, using measuring "optrodes"
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
- G01N21/62—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light
- G01N21/63—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light optically excited
- G01N21/64—Fluorescence; Phosphorescence
- G01N21/645—Specially adapted constructive features of fluorimeters
- G01N21/6456—Spatial resolved fluorescence measurements; Imaging
- G01N21/6458—Fluorescence microscopy
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- G—PHYSICS
- G02—OPTICS
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- G02B21/00—Microscopes
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- G02B21/002—Scanning microscopes
- G02B21/0024—Confocal scanning microscopes (CSOMs) or confocal "macroscopes"; Accessories which are not restricted to use with CSOMs, e.g. sample holders
- G02B21/0036—Scanning details, e.g. scanning stages
- G02B21/0048—Scanning details, e.g. scanning stages scanning mirrors, e.g. rotating or galvanomirrors, MEMS mirrors
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- G—PHYSICS
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- G02B—OPTICAL ELEMENTS, SYSTEMS OR APPARATUS
- G02B21/00—Microscopes
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- G02B21/002—Scanning microscopes
- G02B21/0024—Confocal scanning microscopes (CSOMs) or confocal "macroscopes"; Accessories which are not restricted to use with CSOMs, e.g. sample holders
- G02B21/0052—Optical details of the image generation
- G02B21/0072—Optical details of the image generation details concerning resolution or correction, including general design of CSOM objectives
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- G—PHYSICS
- G02—OPTICS
- G02B—OPTICAL ELEMENTS, SYSTEMS OR APPARATUS
- G02B21/00—Microscopes
- G02B21/0004—Microscopes specially adapted for specific applications
- G02B21/002—Scanning microscopes
- G02B21/0024—Confocal scanning microscopes (CSOMs) or confocal "macroscopes"; Accessories which are not restricted to use with CSOMs, e.g. sample holders
- G02B21/0052—Optical details of the image generation
- G02B21/0076—Optical details of the image generation arrangements using fluorescence or luminescence
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- G—PHYSICS
- G02—OPTICS
- G02B—OPTICAL ELEMENTS, SYSTEMS OR APPARATUS
- G02B21/00—Microscopes
- G02B21/0004—Microscopes specially adapted for specific applications
- G02B21/002—Scanning microscopes
- G02B21/0024—Confocal scanning microscopes (CSOMs) or confocal "macroscopes"; Accessories which are not restricted to use with CSOMs, e.g. sample holders
- G02B21/008—Details of detection or image processing, including general computer control
- G02B21/0084—Details of detection or image processing, including general computer control time-scale detection, e.g. strobed, ultra-fast, heterodyne detection
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
- B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
- B01J2219/00277—Apparatus
- B01J2219/00497—Features relating to the solid phase supports
- B01J2219/00527—Sheets
- B01J2219/00529—DNA chips
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- B01J2219/00614—Delimitation of the attachment areas
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- B—PERFORMING OPERATIONS; TRANSPORTING
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- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
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- B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
- B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
- B01J2219/00583—Features relative to the processes being carried out
- B01J2219/00603—Making arrays on substantially continuous surfaces
- B01J2219/00659—Two-dimensional arrays
Abstract
Description
Claims (1)
- 【特許請求の範囲】 1.基板の表面上のマークされた領域を検出するシステムであって、 励起放射源と、 該励起放射源からの放射を該基板の該表面の選択領域上にフォーカシングさせ る焦点システムであって、フォーカスされたスポット径に対する走査フィールド 径の比が約2000より大きく且つ開口数が約0.2よりも大きい対物レンズを 含むフォーカシングシステムと、 該基板の該表面にわたって少なくとも5画像ライン/秒の速度で該フォーカス された励起放射を走査する放射指向システム(radiation direction system)と、 該励起放射に応答して該基板の該表面からの発光を検出する検出器であって、 該対物レンズが該発光を受けて該発光を該検出器に伝送する、検出器と、 該検出された発光の量を、該発光が発せられた該基板の該表面上の位置の関数 として記録するデータ取得システム(data acquisition system)と、 を備えた、システム。 2.前記フォーカシングシステムのフォーカスされたスポット径に対する走査フ ィールド径の比は3000より大きい、請求項1に記載のシステム。 3.前記フォーカシングシステムのフォーカスされたスポット径に対する走査フ ィールド径の比は4000より大きい、請求項1に記載のシステム。 4.前記フォーカシングシステムは、前記励起放射を直径約10μm未満のスポ ットにフォーカスさせる、請求項1に記載のシステム。 5.前記フォーカシングシステムは、前記励起放射を前記基板の前記表面上にお いて直径約5μm未満のスポットにフォーカスさせる、請求項1に記載のシステ ム。 6.前記フォーカシングシステムは、前記励起放射を前記基板の前記表面上にお いて直径約3μmのスポットにフォーカスさせる、請求項1に記載のシステム。 7.前記走査フィールド径は約10mmより大きい、請求項1に記載のシステム 。 8.前記走査フィールド径は約14mmである、請求項1に記載のシステム。 9.前記開口数は約0.25より大きい、請求項1に記載のシステム。 10.前記フォーカシングシステムはアクロマチックである、請求項1に記載の システム。 11.前記放射指向システムは、前記基板にわたって少なくとも10画像ライン /秒の速度でスポットを走査させ得る、請求項1に記載のシステム。 12.前記放射指向システムは、前記基板にわたって少なくとも30画像ライン /秒の速度でスポットを走査させ得る、請求項1に記載のシステム。 13.前記放射指向システムは角振動ミラー(angularly oscillating mirror)ま たは回転多面ミラー(rotating polyhedral mirror)を含む、請求項1に記載のシ ステム。 14.前記基板が搭載される並進ステージをさらに備え、該並進ステージは前記 対物レンズの光学軸に垂直な少なくとも1つの寸法方向(dimension)に可動であ る、請求項1に記載のシステム。 15.前記基板の前記表面を前記フォーカシングシステムの焦点面に配置するオ ートフォーカスシステムをさらに備えた、請求項1に記載のシステム。 16.前記基板が搭載される並進ステージをさらに備え、該並進ステージは前記 フォーカシングシステムの光学軸に平行な少なくとも1つの寸法方向および該フ ォーカシングシステムの該光学軸に垂直な少なくとも1つの寸法方向に可動であ る、請求項1に記載のシステム。 17.集光システムをさらに備え、該集光システムは、 前記基板の前記表面から発光された蛍光を集光し、該基板の該表面から反射し た励起放射を集光する集光光学系と、 該発光された蛍光を該基板の該表面から反射した励起放射から分離し、該蛍光 を共焦ピンホールを通してフォーカスさせる分離光学系(separation optics)と 、 該蛍光に応答して、該共焦ピンホールを通ってフォーカスした該蛍光の量を記 録するレコーダと、 を備えている、請求項1に記載のシステム。 18.前記基板の前記表面は、該表面上にある複数の異なる既知の位置において 、複数の互いに異なるポリマーシーケンス(polymer sequences)を含む、請求項 1に記載のシステム。 19.前記異なるポリマーシーケンスのそれぞれは、幅または長さ寸法の少なく とも一方が約50μm未満であるフィーチャー内に含まれる、請求項18に記載 のシステム。 20.信号を処理および格納して、これにより、サンプルの2次元画像を生成す るプロセッサをさらに備えた、請求項1に記載のシステム。 21.サンプルが載った少なくとも第1の表面を有する前記基板を固定化する本 体をさらに備え、該本体は、 搭載面と、 該搭載面内のキャビティ(cavity)であって、該第1の表面が該搭載面に結合し て該キャビティを封止し、該サンプルは該キャビティと流体連通しており(in fl uid communication)、該キャビティは光吸収材料を含む底面を有する、キャビテ ィと、 該キャビティと連通した入口および出口であって、該サンプルに接触するため に該キャビティ内へと流れる流体は該入口を通って流れ、該キャビティから流出 する流体は該出口を通って流れる、入口および出口と、 該キャビティ内の温度を制御する温度制御装置と、 を備えている、請求項1に記載のシステム。 22.前記温度制御装置は熱電冷却器を含む、請求項21に記載のシステム。 23.基板の表面上のマークされた領域を検出するシステムであって、 励起放射源と、 該励起放射を該基板の該表面上で直径5μm未満のスポットにフォーカスさせ る第1の焦点光学系であって、対物レンズを含む焦点光学系と、 該スポットを該基板の該表面にわたって直線的に走査させる往復放射指向シス テムであって、該スポットの移動距離は少なくとも10mmである、往復放射指 向システムと、 該基板の該表面からの発光を該基板の該表面から反射した該励起放射から分離 する光学トレインであって、該対物レンズを含む光学トレインと、 該基板の該表面を該第1の焦点光学系の焦点面に自動的に配置するオートフォ ーカスシステムと、 を備えた、システム。 24.前記光学トレインは、前記基板の前記表面から発光された蛍光を該基板の 該表面から反射した前記励起放射から分離するダイクロイックビームスプリッタ を含む、請求項23に記載のシステム。 25.前記オートフォーカスシステムは、 前記基板の前記表面から反射した前記励起放射を共焦ピンホールを通してフォ トダイオード上にフォーカシングする第2の焦点光学系と、 該基板が搭載される並進ステージであって、該基板を該第1の焦点光学系の焦 点面へと動かすために、該第1の焦点光学系の光学軸に平行な方向に可動である 並進ステージと、 を備えている、請求項23に記載のシステム。 26.前記励起放射に応答して前記基板の前記表面からの発光を検出する検出器 と、該検出された発光量を、該発光が発せられた該基板の該表面上の位置の関数 として記録するデータ取得システムとをさらに備えた、請求項23に記載のシス テム。 27.それぞれ異なる既知のロケーションにおいて基板の表面上に固定化された 複数の異なるポリマーシーケンスを有するポリマーアレイを走査し、これにより 、該アレイ上のどのポリマーシーケンスが標的分子と結合しているかを特定する 方法であって、 対物レンズを用いて励起放射源を該基板の該表面上にフォーカスさせる工程と 、 該基板の該表面にわたって少なくとも約5画像ライン/秒の速度で該励起放射 を走査させる工程と、 該対物レンズを用いて、該励起放射に応答して該基板の該表面からの発光を集 光する工程と、 該基板の該表面上の位置の関数として該発光を記録する工程であって、該位置 が標的分子と結合した該アレイ上の該ポリマーシーケンスを示す、工程と、 を包含する、方法。 28.前記ポリマーアレイは、異なる既知のロケーションにおいて前記基板の前 記表面上に固定化された複数の異なるオリゴヌクレオチドシーケンスを含む、請 求項27に記載の方法。 29.前記励起放射源を直径約3μmのスポットにフォーカスさせる工程と、前 記基板上で少なくとも14mmにわたって直線方向に該スポットを走査させる工 程とをさらに包含する、請求項27に記載の方法。 30.前記基板を本体上に固定化する工程と、 第1の波長を有する電磁放射源からの励起放射で該基板上の前記サンプルを励 起する工程と、 該励起放射に応答して第2の波長を有する応答放射を検出する工程であって、 該応答放射は前記複数の領域の画像を表す、工程と、 該サンプル上の次の複数の領域を励起する工程と、 該応答放射を処理および格納して、これにより、該サンプルの2次元画像を生 成する工程と、 該サンプルを該励起放射の焦点面にオートフォーカスする工程と、 をさらに包含する、請求項27に記載の方法。 31.前記本体は上にキャビティのある搭載面を備え、前記基板は、前記サンプ ルが前記反応チャンバと流体連通するように該搭載面上に固定化され、該反応チ ャンバは、該反応チャンバ内におよび該反応チャンバを通して、流体を流すため の入口および出口を備えている、請求項30に記載の方法。 32.前記本体は、前記キャビティ内の温度を制御するための温度制御装置をさ らに備えている、請求項31に記載の方法。 33.前記励起放射を前記基板の前記表面にわたって少なくとも約10画像ライ ン/秒の速度で走査させる、請求項27に記載の方法。 34.前記励起放射を前記基板の前記表面にわたって少なくとも約30画像ライ ン/秒の速度で走査させる、請求項27に記載の方法。
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JP2016031234A (ja) * | 2014-07-25 | 2016-03-07 | 高電工業株式会社 | 検体検査装置 |
JP2020514823A (ja) * | 2017-03-15 | 2020-05-21 | ユニベルシテ ドゥ ボルドー | ターゲット上に粒子を堆積するための装置および方法 |
Also Published As
Publication number | Publication date |
---|---|
US6597000B2 (en) | 2003-07-22 |
US5981956A (en) | 1999-11-09 |
WO1997043611A1 (en) | 1997-11-20 |
EP0902885A4 (en) | 2006-09-27 |
US20020185610A1 (en) | 2002-12-12 |
US6207960B1 (en) | 2001-03-27 |
US20010030290A1 (en) | 2001-10-18 |
EP0902885A1 (en) | 1999-03-24 |
JP2006258821A (ja) | 2006-09-28 |
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