JP5982385B2 - 化学的検出デバイス - Google Patents
化学的検出デバイス Download PDFInfo
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- JP5982385B2 JP5982385B2 JP2013535511A JP2013535511A JP5982385B2 JP 5982385 B2 JP5982385 B2 JP 5982385B2 JP 2013535511 A JP2013535511 A JP 2013535511A JP 2013535511 A JP2013535511 A JP 2013535511A JP 5982385 B2 JP5982385 B2 JP 5982385B2
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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
- C12Q1/6869—Methods for sequencing
- C12Q1/6874—Methods for sequencing involving nucleic acid arrays, e.g. sequencing by hybridisation
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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
- C12Q1/6813—Hybridisation assays
- C12Q1/6816—Hybridisation assays characterised by the detection means
- C12Q1/6825—Nucleic acid detection involving sensors
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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
- C12Q1/6844—Nucleic acid amplification reactions
- C12Q1/6858—Allele-specific amplification
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N27/00—Investigating or analysing materials by the use of electric, electrochemical, or magnetic means
- G01N27/26—Investigating or analysing materials by the use of electric, electrochemical, or magnetic means by investigating electrochemical variables; by using electrolysis or electrophoresis
- G01N27/403—Cells and electrode assemblies
- G01N27/414—Ion-sensitive or chemical field-effect transistors, i.e. ISFETS or CHEMFETS
- G01N27/4145—Ion-sensitive or chemical field-effect transistors, i.e. ISFETS or CHEMFETS specially adapted for biomolecules, e.g. gate electrode with immobilised receptors
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N27/00—Investigating or analysing materials by the use of electric, electrochemical, or magnetic means
- G01N27/26—Investigating or analysing materials by the use of electric, electrochemical, or magnetic means by investigating electrochemical variables; by using electrolysis or electrophoresis
- G01N27/416—Systems
- G01N27/42—Measuring deposition or liberation of materials from an electrolyte; Coulometry, i.e. measuring coulomb-equivalent of material in an electrolyte
- G01N27/44—Measuring deposition or liberation of materials from an electrolyte; Coulometry, i.e. measuring coulomb-equivalent of material in an electrolyte using electrolysis to generate a reagent, e.g. for titration
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/483—Physical analysis of biological material
- G01N33/487—Physical analysis of biological material of liquid biological material
- G01N33/48707—Physical analysis of biological material of liquid biological material by electrical means
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- Chemical & Material Sciences (AREA)
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- Engineering & Computer Science (AREA)
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- Physics & Mathematics (AREA)
- Molecular Biology (AREA)
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- Wood Science & Technology (AREA)
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- General Health & Medical Sciences (AREA)
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- Bioinformatics & Cheminformatics (AREA)
- Chemical Kinetics & Catalysis (AREA)
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- General Physics & Mathematics (AREA)
- Electrochemistry (AREA)
- Spectroscopy & Molecular Physics (AREA)
- Microelectronics & Electronic Packaging (AREA)
- Biomedical Technology (AREA)
- Hematology (AREA)
- Urology & Nephrology (AREA)
- Food Science & Technology (AREA)
- Medicinal Chemistry (AREA)
- Apparatus Associated With Microorganisms And Enzymes (AREA)
- Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
- Investigating Or Analyzing Materials By The Use Of Electric Means (AREA)
Description
典型的なシステムのブロック図が図1に示される。検体の濃度(検体がサンプルにないゼロ濃度を含む)を含む流体サンプルは、検体の濃度をアナログ電気信号に変換するISFETの化学的検出表面に接している。変換器は化学信号をアナログ信号に変換する。変換器は振動信号の入力部に接続される。化学信号および振動信号は組み合わせて振動出力信号を生成する。変換器がCMOSインバータのISFET形成部分を含む場合、変換器は、示されるようなパルス出力信号を生成するために電源をオンおよびオフするであろう。アナログ化学信号は、位相ずれまたはパルス幅が変わるように、出力信号を調節するのに貢献する。この変化は化学的濃度を表す。その後、時間−デジタルコンバータまたは位相復調器は、パルス信号を復号し、デジタル信号を出力する。振動入力信号からの寄与は、正味の化学的寄与を残すために差し引かれることができる。これらの信号はあらかじめ処理され、メモリに保存されてもよい。時間−デジタルコンバータは、以下に記載されるタイプであってもよい:Jianjun Yu et al, 12−Bit Vernier Ring Time−to−Digital Converter in 0.13 um CMOS Technology, IEEE JOURNAL OF SOLID−STATE CIRCUITS, VOL. 45, NO. 4, April 2010、または、 Gordon W. Roberts, A Brief Introduction to Time−to−Digital Digital−to−Time Converters, IEEE TRANSACTIONS ON CIRCUITS AND SYSTEMS II: EXPRESS BRIEFS, VOL. 57, NO. 3, March 2010。
遺伝子検査の分野で、核酸(DNAとRNAのような)の1つ以上のヌクレオチドを同定することが望ましい。典型的には、核酸の一本鎖は、核酸上のある点が同定されるまで、または、該点を含んで、プローブによってアニール処理される。ヌクレオチドは、鎖を伸張するために、プローブの3’末端へと組み込まれるようになるであろう。この組み込み反応は、適切に処理された検出表面を備えたISFETによって検知可能な水素イオンを放出すると示されてきた。例えば、該表面は、窒化ケイ素、二酸化ケイ素、タンタル酸化物、または、水素イオンに対して感度を有すると示されたそれ以外のものであってもよい。
核酸中の単一のヌクレオチド塩基の同定に対する延長として、数十から数百のヌクレオチド塩基の配列を同定することが望ましい。
6塩基長のDNAに基づいたシミュレーション結果が図4で示され、ここで、グラフは、(a)反応時間全体(16秒)にわたる4つのセンサーの各々での塩基の呼び出し順序と塩基の伸長、および、(b)1つの反応全体(2秒)における各々のセンサーに関する振動基準信号と変調出力信号とを示す。
−ISFETの新しい構造形態を使用することによって、単一の検出ピクセルのためのトランジスタの合計数は、2まで減らすことができる(選択トランジスタを含む)。
−アナログ処理回路は必要ない。
上述の通り、ひとつの実施形態において、システムへの化学的入力は、当初のイオン濃度が出力信号を変調するために作用するように制御された化学信号によって変えられてもよい。組み合わされた化学信号は、(a)緩衝液中のイオン濃度を検査するために、および(b)トランジスタの電気的な動作点(閾値下、線形、飽和)を検査するために、ある範囲にわたって掃引(sweep)され得る。前者は、当初のイオン濃度が、任意の小さな変化が緩衝液によりマスキングされるような緩衝能内であるときに有用である。後者は、上述のように、当初のイオン濃度により変調された幅の出力パルスを生成するために、インバータで操作され得る。2つの効果は、追加の滴定液がイオン濃度の作動点を緩衝能以上に引き上げ、インバータの切り換え点も越えるように組み合わされ得る。
(I1−I2)=ΔI=T2−T1
Claims (7)
- 第1の電気的出力信号を提供するための、および、電気的入力信号を受け取るように配される変換器であって、第1の電気出力信号をオン状態とオフ状態の間で切り替える変換器と、
化学的入力信号を受け取るために、変換器につながれた化学的検出表面と、
変換器の切り換え点を変えるためにかつ第1の期間の間、前記第1の電気的出力信号をオンに、第2の期間の間オフに切り換えるために、前記化学的入力信号を振動させるための信号発生器と
を備える、ことを特徴とする装置。 - 信号発生器は、化学的検出表面によって検知されたイオンの濃度に影響を及ぼす化学薬品を放出または吸着するように配された滴定電極を含む、ことを特徴とする請求項1に記載の装置。
- 信号発生器は、滴定電極に振動電流を提供するために制御装置をさらに含む、ことを特徴とする請求項2に記載の装置。
- 前記変換器は、CMOSインバータを形成するために、第2のタイプの第2のトランジスタに接続された第1のタイプの第1のトランジスタを含む、ことを特徴とする請求項1乃至3のいずれかに記載の装置。
- 前記第1の電気的出力信号を受け取る復調器をさらに含み、
前記復調器は、化学的入力信号の量を表す第2のデジタル出力信号を提供する、ことを特徴とする請求項1乃至4のいずれかに記載の装置。 - 第2のデジタル出力信号に接続されたエンコーダをさらに含み、
前記エンコーダは、2ビットのバイナリーコードを含む第3の出力信号を提供するように配される、ことを特徴とする請求項5に記載の装置。 - 複数の装置を備えるアレイであって、該複数の装置の各々が請求項1乃至6のいずれかに記載の装置であり、前記第1の電気的出力信号が復調される装置を選択するために、各装置に接続されたマルチプレクサーを含む、ことを特徴とする請求項1乃至6のいずれかに記載の装置。
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
GBGB1018224.4A GB201018224D0 (en) | 2010-10-28 | 2010-10-28 | Chemical sensing device |
GB1018224.4 | 2010-10-28 | ||
PCT/GB2011/052105 WO2012056247A1 (en) | 2010-10-28 | 2011-10-28 | Chemical sensing device |
Related Child Applications (1)
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JP2016142766A Division JP6449198B2 (ja) | 2010-10-28 | 2016-07-20 | 化学的検出デバイス |
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JP2014508915A JP2014508915A (ja) | 2014-04-10 |
JP5982385B2 true JP5982385B2 (ja) | 2016-08-31 |
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JP2013535511A Active JP5982385B2 (ja) | 2010-10-28 | 2011-10-28 | 化学的検出デバイス |
JP2016142766A Active JP6449198B2 (ja) | 2010-10-28 | 2016-07-20 | 化学的検出デバイス |
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US (3) | US9683260B2 (ja) |
EP (2) | EP3258257A1 (ja) |
JP (2) | JP5982385B2 (ja) |
CN (1) | CN103189741B (ja) |
CA (1) | CA2811701C (ja) |
ES (1) | ES2649064T3 (ja) |
GB (2) | GB201018224D0 (ja) |
WO (1) | WO2012056247A1 (ja) |
Families Citing this family (6)
Publication number | Priority date | Publication date | Assignee | Title |
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US9702846B2 (en) | 2013-11-08 | 2017-07-11 | Taiwan Semiconductor Manufacturing Company, Ltd. | Biosensor device and related method |
JP6239665B2 (ja) | 2016-03-16 | 2017-11-29 | 株式会社東芝 | 半導体装置 |
JP7231963B2 (ja) * | 2017-02-21 | 2023-03-02 | 国立大学法人山形大学 | 電気化学計測装置 |
CN110208676A (zh) * | 2019-05-20 | 2019-09-06 | 西北工业大学 | 前端读出集成电路的等效噪声电荷测试电路及测试方法 |
CN112880401A (zh) * | 2019-11-29 | 2021-06-01 | 科德尔科股份公司 | 用于测量熔炼炉中白金属中铜的百分比的系统 |
US11614421B2 (en) | 2020-05-08 | 2023-03-28 | Taiwan Semiconductor Manufacturing Company Ltd. | BioFET system |
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2010
- 2010-10-28 GB GBGB1018224.4A patent/GB201018224D0/en not_active Ceased
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2011
- 2011-10-28 CN CN201180052589.4A patent/CN103189741B/zh active Active
- 2011-10-28 EP EP17183237.1A patent/EP3258257A1/en not_active Withdrawn
- 2011-10-28 JP JP2013535511A patent/JP5982385B2/ja active Active
- 2011-10-28 WO PCT/GB2011/052105 patent/WO2012056247A1/en active Application Filing
- 2011-10-28 CA CA2811701A patent/CA2811701C/en active Active
- 2011-10-28 EP EP11782200.7A patent/EP2633296B1/en active Active
- 2011-10-28 GB GB1118666.5A patent/GB2485068B/en active Active
- 2011-10-28 ES ES11782200.7T patent/ES2649064T3/es active Active
- 2011-10-28 US US13/881,986 patent/US9683260B2/en active Active
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2016
- 2016-07-20 JP JP2016142766A patent/JP6449198B2/ja active Active
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- 2017-05-15 US US15/594,994 patent/US10144964B2/en active Active
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Also Published As
Publication number | Publication date |
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JP6449198B2 (ja) | 2019-01-09 |
JP2017006132A (ja) | 2017-01-12 |
CA2811701A1 (en) | 2012-05-03 |
US20170321272A1 (en) | 2017-11-09 |
CA2811701C (en) | 2014-07-22 |
US20190040463A1 (en) | 2019-02-07 |
EP2633296B1 (en) | 2017-10-11 |
JP2014508915A (ja) | 2014-04-10 |
GB2485068A (en) | 2012-05-02 |
ES2649064T3 (es) | 2018-01-09 |
EP3258257A1 (en) | 2017-12-20 |
GB2485068B (en) | 2013-03-13 |
GB201118666D0 (en) | 2011-12-14 |
EP2633296A1 (en) | 2013-09-04 |
GB201018224D0 (en) | 2010-12-15 |
US20130252828A1 (en) | 2013-09-26 |
US9683260B2 (en) | 2017-06-20 |
CN103189741B (zh) | 2016-09-07 |
US10144964B2 (en) | 2018-12-04 |
CN103189741A (zh) | 2013-07-03 |
WO2012056247A1 (en) | 2012-05-03 |
US10697011B2 (en) | 2020-06-30 |
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