JP5922361B2 - 活性マイクロシーブおよび生物学的応用のための方法 - Google Patents
活性マイクロシーブおよび生物学的応用のための方法 Download PDFInfo
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- JP5922361B2 JP5922361B2 JP2011196042A JP2011196042A JP5922361B2 JP 5922361 B2 JP5922361 B2 JP 5922361B2 JP 2011196042 A JP2011196042 A JP 2011196042A JP 2011196042 A JP2011196042 A JP 2011196042A JP 5922361 B2 JP5922361 B2 JP 5922361B2
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Classifications
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N15/00—Investigating characteristics of particles; Investigating permeability, pore-volume or surface-area of porous materials
- G01N15/10—Investigating individual particles
- G01N15/1031—Investigating individual particles by measuring electrical or magnetic effects
- G01N15/12—Investigating individual particles by measuring electrical or magnetic effects by observing changes in resistance or impedance across apertures when traversed by individual particles, e.g. by using the Coulter principle
- G01N15/131—Details
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B03—SEPARATION OF SOLID MATERIALS USING LIQUIDS OR USING PNEUMATIC TABLES OR JIGS; MAGNETIC OR ELECTROSTATIC SEPARATION OF SOLID MATERIALS FROM SOLID MATERIALS OR FLUIDS; SEPARATION BY HIGH-VOLTAGE ELECTRIC FIELDS
- B03C—MAGNETIC OR ELECTROSTATIC SEPARATION OF SOLID MATERIALS FROM SOLID MATERIALS OR FLUIDS; SEPARATION BY HIGH-VOLTAGE ELECTRIC FIELDS
- B03C5/00—Separating dispersed particles from liquids by electrostatic effect
- B03C5/005—Dielectrophoresis, i.e. dielectric particles migrating towards the region of highest field strength
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B03—SEPARATION OF SOLID MATERIALS USING LIQUIDS OR USING PNEUMATIC TABLES OR JIGS; MAGNETIC OR ELECTROSTATIC SEPARATION OF SOLID MATERIALS FROM SOLID MATERIALS OR FLUIDS; SEPARATION BY HIGH-VOLTAGE ELECTRIC FIELDS
- B03C—MAGNETIC OR ELECTROSTATIC SEPARATION OF SOLID MATERIALS FROM SOLID MATERIALS OR FLUIDS; SEPARATION BY HIGH-VOLTAGE ELECTRIC FIELDS
- B03C5/00—Separating dispersed particles from liquids by electrostatic effect
- B03C5/02—Separators
- B03C5/022—Non-uniform field separators
- B03C5/026—Non-uniform field separators using open-gradient differential dielectric separation, i.e. using electrodes of special shapes for non-uniform field creation, e.g. Fluid Integrated Circuit [FIC]
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12M—APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
- C12M41/00—Means for regulation, monitoring, measurement or control, e.g. flow regulation
- C12M41/30—Means for regulation, monitoring, measurement or control, e.g. flow regulation of concentration
- C12M41/36—Means for regulation, monitoring, measurement or control, e.g. flow regulation of concentration of biomass, e.g. colony counters or by turbidity measurements
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12M—APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
- C12M47/00—Means for after-treatment of the produced biomass or of the fermentation or metabolic products, e.g. storage of biomass
- C12M47/04—Cell isolation or sorting
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N15/00—Investigating characteristics of particles; Investigating permeability, pore-volume or surface-area of porous materials
- G01N15/10—Investigating individual particles
- G01N15/1031—Investigating individual particles by measuring electrical or magnetic effects
- G01N15/12—Investigating individual particles by measuring electrical or magnetic effects by observing changes in resistance or impedance across apertures when traversed by individual particles, e.g. by using the Coulter principle
- G01N15/134—Devices using two or more apertures
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L2200/00—Solutions for specific problems relating to chemical or physical laboratory apparatus
- B01L2200/06—Fluid handling related problems
- B01L2200/0647—Handling flowable solids, e.g. microscopic beads, cells, particles
- B01L2200/0668—Trapping microscopic beads
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L2300/00—Additional constructional details
- B01L2300/06—Auxiliary integrated devices, integrated components
- B01L2300/0627—Sensor or part of a sensor is integrated
- B01L2300/0636—Integrated biosensor, microarrays
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L2300/00—Additional constructional details
- B01L2300/06—Auxiliary integrated devices, integrated components
- B01L2300/0627—Sensor or part of a sensor is integrated
- B01L2300/0645—Electrodes
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N15/00—Investigating characteristics of particles; Investigating permeability, pore-volume or surface-area of porous materials
- G01N15/10—Investigating individual particles
- G01N15/1031—Investigating individual particles by measuring electrical or magnetic effects
- G01N15/12—Investigating individual particles by measuring electrical or magnetic effects by observing changes in resistance or impedance across apertures when traversed by individual particles, e.g. by using the Coulter principle
- G01N2015/135—Electrodes
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
- Y10T—TECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION
- Y10T29/00—Metal working
- Y10T29/49—Method of mechanical manufacture
- Y10T29/49002—Electrical device making
- Y10T29/49117—Conductor or circuit manufacturing
- Y10T29/49124—On flat or curved insulated base, e.g., printed circuit, etc.
- Y10T29/49155—Manufacturing circuit on or in base
Landscapes
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- General Health & Medical Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Organic Chemistry (AREA)
- Zoology (AREA)
- Wood Science & Technology (AREA)
- Biochemistry (AREA)
- Biotechnology (AREA)
- Analytical Chemistry (AREA)
- Microbiology (AREA)
- Sustainable Development (AREA)
- Biomedical Technology (AREA)
- Molecular Biology (AREA)
- General Engineering & Computer Science (AREA)
- Genetics & Genomics (AREA)
- Physics & Mathematics (AREA)
- Pathology (AREA)
- Immunology (AREA)
- General Physics & Mathematics (AREA)
- Dispersion Chemistry (AREA)
- Microelectronics & Electronic Packaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Electrochemistry (AREA)
- Cell Biology (AREA)
- Investigating Or Analyzing Materials By The Use Of Electric Means (AREA)
- Apparatus Associated With Microorganisms And Enzymes (AREA)
- Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
- Investigating Or Analysing Biological Materials (AREA)
Description
ホールと、
ホールと電気的に結合した電極であって、基板に内蔵され、または基板上に配置された少なくとも1つの電極と、
前記基板内に集積され、少なくとも1つの電極および複数の相互接続部の少なくとも1つに作動可能に接続された少なくとも1つのトランジスタとを備える。
基板を取得することと、
前記基板上に、複数のトランジスタを備えるトランジスタ層を設けることと、
前記基板上に、少なくとも1つのトランジスタにそれぞれ作動可能に接続した複数の電極を備える電極層を設けることと、
前記基板内に、少なくとも1つの電極にそれぞれ電気的に結合した複数のホールを設けることとを含む。
活性シーブデバイス(1)内に、前記生物検体を含む媒質を導入することと、
該活性シーブデバイスを用いて前記生物検体を分離することと、
前記トランジスタを駆動することによって、前記分離した生物検体上で測定を実施することと、
前記測定に従って、標的とする生物検体を特定することとを含む。
それぞれがホール2と、
ホール2と電気的に結合した少なくとも1つの電極3と、
基板7内に集積され、少なくとも1つの電極3、および、例えば動作させ、または測定するための電気回路に少なくとも1つの電極3を相互接続させるための複数の相互接続部4の少なくとも1つに作動可能に接続した少なくとも1つのトランジスタ(図24には図示していない)とを備える。隣接するセグメント250間の、実質的に直交する間隔D1,D2は、対応する方向のセグメント250の寸法に対して、例えば少なくとも20%、例えば約半分の割合を有するであろう。隣接する領域10の、実質的に直交する間隔D3、D4は、対応する寸法の領域10の寸法と、ほとんど同じであり、例えばその80%〜120%であろう。
Claims (15)
- 生物検体を分析するための活性シーブデバイスであって、前記デバイスは、前記生物検体の検体粒子を支持するための基板を備え、該基板は、複数の相互接続部および複数の領域を有し、各領域は、
ホールと、
前記ホールの周りに設けられた2つの電極と、
前記基板に埋め込まれ、前記2つの電極のそれぞれおよび前記複数の相互接続部の少なくとも1つに動作可能に接続された少なくとも1つのトランジスタと、
前記基板の表面に対して略垂直な方向に延び、前記2つの電極をそれぞれ前記トランジスタに接続する導電性経路とを備える活性シーブデバイス。 - 前記トランジスタは、前記2つの電極のそれぞれおよび前記複数の相互接続部の少なくとも1つとの間にスイッチを構成する請求項1記載の活性シーブデバイス。
- 前記2つの電極は、前記検体粒子のインピーダンスを測定するように構成された請求項1記載の活性シーブデバイス。
- マルチプレクサ、アナログ−デジタル変換器、デジタル−アナログ変換器、処理ユニット、高速フーリエ変換装置、および通信制御装置、ならびに/または他のデジタル回路をさらに備える請求項1記載の活性シーブデバイス。
- 前記各領域は、前記ホールに隣接配置された先細り形状の誘導エレメントをさらに備える請求項1記載の活性シーブデバイス。
- 前記複数の領域は、前記基板の正平面部分を形成するように配置した請求項1記載の活性シーブデバイス。
- 前記2つの電極を駆動して磁気的操作または電気的操作を実施することによりマルチパラメータ分離を可能にするための駆動手段をさらに備える請求項1記載の活性シーブデバイス。
- 細胞を計数し、動作させ、および/または溶解させることに適合した制御装置をさらに備える請求項1記載の活性シーブデバイス。
- 光学的に細胞にアドレスするための手段をさらに備える請求項1記載の活性シーブデバイス。
- 所定のコンポーネントについて、結合特性を化学的に変更することに適合した表面層をさらに備える請求項1記載の活性シーブデバイス。
- 生物検体を分析するための活性シーブデバイスを製造するための方法であって、
前記生物検体の検体粒子を支持するための基板を取得することと、
前記基板上に、複数のトランジスタを備えるトランジスタ層を設けることと、
前記基板上に、それぞれが少なくとも1つのトランジスタと動作可能に接続した複数の電極を備える電極層を設けることと、
前記基板の表面に対して略垂直な方向に延びる導電性経路を設け、前記2つの電極をそれぞれ前記トランジスタに接続することと、
前記基板内に、それぞれ前記2つの電極と電気的に結合した複数のホールを設けることとを含む方法。 - 直流電流に対して大きいインピーダンスを有する不動態材料から成る少なくとも1つの層を付加することをさらに含み、
前記不動態材料は、SiO 2 、SiN、Ta 2 O 5 、パリレン、SU8、テフロンおよびポリアミドから成る群から選択される請求項11記載の方法。 - 前記基板の上部に、少なくとも1つの先細り形状の誘導エレメントを設けることをさらに含む請求項11記載の方法。
- 請求項1から10のいずれか1項に記載の活性シーブデバイスを用いて生物検体を分析するための方法であって、
前記生物検体を含む媒質を、前記活性シーブデバイスに導入することと、
前記活性シーブデバイスを用いて前記生物検体を分離することと、
前記トランジスタを駆動することによって、前記分離した生物検体上で測定を実施することと、
前記測定に従って、標的とした生物検体を特定することとを含む方法。 - 前記標的とした生物検体を計数し、動作させ、かつ/または溶解させ、下流側でポリメラーゼ連鎖反応を実施することをさらに含む請求項14記載の方法。
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