JP2016187345A - 電気化学的検出装置のためのマイクロウェルの化学コーティング法 - Google Patents
電気化学的検出装置のためのマイクロウェルの化学コーティング法 Download PDFInfo
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Abstract
【解決手段】CMOS装置の上方にマイクロウェルを形成する工程を含み得る。該マイクロウェルは、底表面及び側壁を含んでよい。該方法は、該マイクロウェルの底表面に選択的に付着させるための第1の化学物質を塗布する工程と;該マイクロウェルの側壁上に金属酸化物層を形成する工程と;該マイクロウェルの側壁に選択的に付着させるための第2の化学物質を塗布する工程とを更に含んでよい。該第2の化学物質は、該第1の化学物質に対する親和性を欠いていてもよい。
【選択図】図1
Description
本願は、既に出願されている2010年8月18日出願の米国仮特許出願第61/374,676号に対する優先権の利益を主張し、参照することによりその全文を組み込むものとする。
電気化学的検出は、高感度であり、小規模であり、低コストであり、応答が早く、且つ微細加工技術に適合しているので、魅力的である。(例えば、Hughesら,Science,254:74−80(1991年)(非特許文献1);Mirら,Electrophoresis,30:3386−3397(2009年)(非特許文献2);Trojanowicz,Anal.Chim,Acta,653:36−58(2009年)(非特許文献3);及び、Xuら,Talanta,80:8−18(2009年)(非特許文献4)を参照されたい)。これら特徴によって、電流測定シグナル、電位差シグナル、又はインピーダンスシグナルに基づく様々なセンサが開発され、それを用いて化学的用途、生化学的用途、及び細胞用途のためのアレイが組立てられた。(例えば、Yeowら,Sensors and Actuators B 44:434−440(1997年)(非特許文献5);Martinoiaら,Biosensors&Bioelectronics,16:1043−1050(2001年)(非特許文献6);Hammondら,IEEE Sensors J,4:706−712(2004年)(非特許文献7);Milgrewら,Sensors and Actuators B 103:37−42(2004年)(非特許文献8);Milgrewら,Sensors and Actuators B,111−112:347−353(2005年)(非特許文献9);Hizawaら,Sensors and Actuators B,117:509−515(2006年)(非特許文献10);Heerら,Biosensors and Bioelectronics,22:2546−2553(2007年)(非特許文献11);Barbaroら,Sensors and Actuators B,118:41−46(2006年)(非特許文献12);Andersonら,Sensors and Actuators B,129:79−86(2008年)(非特許文献13);Rothbergら、米国特許出願公開第2009/0127589号(特許文献1));及びRothbergら、英国特許出願GB24611127(特許文献2))を参照されたい)。典型的に、このようなシステムにおいて、検体は、マイクロウェル(本明細書では「ウェル」とも呼ばれる)又は反応チャンバ等の閉じ込め領域のアレイにランダムに分布しており、また、試薬は、センサアレイを含むフローセルを通して前記試薬の流れを導く流体光学システムによってこのような領域に送達される。反応が生じるマイクロウェル、及び反応が生じない空ウェルは、各マイクロウェルに関連する1つ以上の電子センサによってモニタすることができる。
・N−(6−アミノヘキシル)アミノメトルトリエトキシシラン
・(メルカプトメチル)メチルジエトキシシラン
・クロロメチルトリエトキシシラン
・(イソシアナトメチル)メチルジメトキシシラン
・N−フェニルアミノメチルトリエトキシシラン
・トリエトキシシリルウンデカナル
・11−メルカプトウンデシルトリメトキシシラン
・10−ウンデセニルトリメトキシシラン
・N−(2−アミノエチル)−11−アミノウンデシルトリメトキシシラン
・11−ブロモウンデシルトリメトキシシラン
・n−オクチルトリエトキシシラン
・2−[メトキシ(ポリエチレンオキシ)プロピル]トリメトキシシラン
・3−メトキシプロピルトリメトキシシラン
・メトキシトリエチレンオキシプロピルトリシラン
・メトキシシラン
・メトキシエトキシウンデシルトリクロロシラン
・2−[メトキシ(ポリエチレンオキシ)プロピル]−トリクロロシラン
以下に、本発明の基本的な諸特徴および種々の態様を列挙する。
[1]
化学的検出装置を製造する方法であって、
マイクロウェルが底表面及び側壁を含む、CMOS装置の上方に該マイクロウェルを形成する工程と;
該マイクロウェルの底表面に選択的に付着させるための第1の化学物質を塗布する工程と;
該マイクロウェルの側壁上に金属酸化物層を形成する工程と;
第2の化学物質が、該第1の化学物質に対する親和性を欠いている、該マイクロウェルの側壁に選択的に付着させるための該第2の化学物質を塗布する工程と
を含む、方法。
[2]
前記マイクロウェルが1つ以上の頂縁部を含み、該頂縁部もまた前記金属酸化物層によって被覆されており、該金属酸化物層が単分子層である、[1]に記載の方法。
[3]
前記金属酸化物層が、中性のPEGホスフェート又はPEGホスホネートによってコーティングされている、[2]に記載の方法。
[4]
前記金属酸化物層が、酸化ジルコニウム(ZrO 2 )の溶剤ベースの堆積物である、[2]に記載の方法。
[5]
前記第2の化学物質がシラン基を含む、[1]に記載の方法。
[6]
前記第1の化学物質が、ホスフェート、ホスホネート、カテコール、ニトロカテコール、ボロネート、フェニルボロネート、イミダゾール、シラノールを含む、[1]に記載の方法。
[7]
前記第1の化学物質がpH検知基を含む、[1]に記載の方法。
[8]
前記CMOS装置が、フローティングゲートターミナルを有する電荷敏感トランジスタを備え、且つ前記マイクロウェルの底表面が、該フローティングゲートターミナルの上にパッシベーション層を含む、[1]に記載の方法。
[9]
底表面及び側壁を有し、該底表面が、第1の化学物質によって被覆されており、該側壁が、金属酸化物層及び該金属酸化物層の上の第2の化学物質によって被覆されており、該第2の化学物質が、該第1の化学物質に対する親和性を欠いている、マイクロウェルと;
該マイクロウェルの底部の下に配置されたCMOS装置と
を備える、化学的検出装置。
[10]
前記CMOS装置が、フローティングゲートターミナルを有する電荷敏感トランジスタを備える、[9]に記載の化学的検出装置。
[11]
前記マイクロウェルの底部が、前記フローティングゲートターミナルの上にパッシベーション層を含む、[10]に記載の化学的検出装置。
[12]
前記パッシベーション層が、1層以上の他の金属酸化物層の上にある金属酸化物層である、[11]に記載の化学的検出装置。
[13]
前記第1の化学物質が、ホスフェート、ホスホネート、カテコール、ニトロカテコール、ボロネート、フェニルボロネート、イミダゾール、シラノールを含む、[9]に記載の化学的検出装置。
[14]
前記第1の化学物質がpH検知基を含む、[9]に記載の化学的検出装置。
[15]
前記マイクロウェルがSiO 2 側壁を有する、[9]に記載の化学的検出装置。
[16]
前記側壁を被覆している金属酸化物層が単分子層である、[9]に記載の化学的検出装置。
[17]
前記マイクロウェルの頂縁部もまた、前記金属酸化物層によって被覆されている、[16]に記載の化学的検出装置。
[18]
前記金属酸化物層が、1つの酸化ジルコニウム(ZrO 2 )の溶剤ベースの堆積物である、[17]に記載の化学的検出装置。
[19]
前記第2の化学物質が、中性のPEGホスフェート又はPEGホスホネートである、[9]に記載の化学的検出装置。
[20]
マイクロウェルが、底表面及び側壁を含み、且つ該マイクロウェルが、複数の検体が付着している固相支持体を受容するように構成される、CMOS装置の上方に該マイクロウェルを形成する工程と;
該マイクロウェルの底表面に選択的に付着させるための第1の化学物質を塗布する工程と;
該マイクロウェルの側壁上に金属酸化物層を形成する工程と;
第2の化学物質が、該第1の化学物質に対する親和性を欠いており、該CMOS装置が、該マイクロウェルの底表面における電荷を検知するように構成され、該電荷が、該複数の検体との少なくとも1つの化学反応によって生成される1つ以上の副産物に起因し、該1つ以上の副産物が、該第2の化学物質に起因して該マイクロウェルの側壁に対する親和性を欠いている、該マイクロウェルの側壁に選択的に付着させるための該第2の化学物質を塗布する工程と
を含む、方法。
[21]
前記第1の化学物質が、前記固相支持体を受容する前に正に帯電して、該固相支持体の堆積を促進する、[20]に記載の方法。
[22]
前記固相支持体が、マイクロ粒子、ナノ粒子、ビーズ、固体、及び、ゲルを含む多孔体のうちの1つである、[20]に記載の方法。
[23]
前記複数の検体が、DNAサンプルの複数のコピーである、[20]に記載の方法。
Claims (23)
- 化学的検出装置を製造する方法であって、
マイクロウェルが底表面及び側壁を含む、CMOS装置の上方に該マイクロウェルを形成する工程と;
該マイクロウェルの底表面に選択的に付着させるための第1の化学物質を塗布する工程と;
該マイクロウェルの側壁上に金属酸化物層を形成する工程と;
第2の化学物質が、該第1の化学物質に対する親和性を欠いている、該マイクロウェルの側壁に選択的に付着させるための該第2の化学物質を塗布する工程と
を含む、方法。 - 前記マイクロウェルが1つ以上の頂縁部を含み、該頂縁部もまた前記金属酸化物層によって被覆されており、該金属酸化物層が単分子層である、請求項1に記載の方法。
- 前記金属酸化物層が、中性のPEGホスフェート又はPEGホスホネートによってコーティングされている、請求項2に記載の方法。
- 前記金属酸化物層が、酸化ジルコニウム(ZrO2)の溶剤ベースの堆積物である、請求項2に記載の方法。
- 前記第2の化学物質がシラン基を含む、請求項1に記載の方法。
- 前記第1の化学物質が、ホスフェート、ホスホネート、カテコール、ニトロカテコール、ボロネート、フェニルボロネート、イミダゾール、シラノールを含む、請求項1に記載の方法。
- 前記第1の化学物質がpH検知基を含む、請求項1に記載の方法。
- 前記CMOS装置が、フローティングゲートターミナルを有する電荷敏感トランジスタを備え、且つ前記マイクロウェルの底表面が、該フローティングゲートターミナルの上にパッシベーション層を含む、請求項1に記載の方法。
- 底表面及び側壁を有し、該底表面が、第1の化学物質によって被覆されており、該側壁が、金属酸化物層及び該金属酸化物層の上の第2の化学物質によって被覆されており、該第2の化学物質が、該第1の化学物質に対する親和性を欠いている、マイクロウェルと;
該マイクロウェルの底部の下に配置されたCMOS装置と
を備える、化学的検出装置。 - 前記CMOS装置が、フローティングゲートターミナルを有する電荷敏感トランジスタを備える、請求項9に記載の化学的検出装置。
- 前記マイクロウェルの底部が、前記フローティングゲートターミナルの上にパッシベーション層を含む、請求項10に記載の化学的検出装置。
- 前記パッシベーション層が、1層以上の他の金属酸化物層の上にある金属酸化物層である、請求項11に記載の化学的検出装置。
- 前記第1の化学物質が、ホスフェート、ホスホネート、カテコール、ニトロカテコール、ボロネート、フェニルボロネート、イミダゾール、シラノールを含む、請求項9に記載の化学的検出装置。
- 前記第1の化学物質がpH検知基を含む、請求項9に記載の化学的検出装置。
- 前記マイクロウェルがSiO2側壁を有する、請求項9に記載の化学的検出装置。
- 前記側壁を被覆している金属酸化物層が単分子層である、請求項9に記載の化学的検出装置。
- 前記マイクロウェルの頂縁部もまた、前記金属酸化物層によって被覆されている、請求項16に記載の化学的検出装置。
- 前記金属酸化物層が、1つの酸化ジルコニウム(ZrO2)の溶剤ベースの堆積物である、請求項17に記載の化学的検出装置。
- 前記第2の化学物質が、中性のPEGホスフェート又はPEGホスホネートである、請求項9に記載の化学的検出装置。
- マイクロウェルが、底表面及び側壁を含み、且つ該マイクロウェルが、複数の検体が付着している固相支持体を受容するように構成される、CMOS装置の上方に該マイクロウェルを形成する工程と;
該マイクロウェルの底表面に選択的に付着させるための第1の化学物質を塗布する工程と;
該マイクロウェルの側壁上に金属酸化物層を形成する工程と;
第2の化学物質が、該第1の化学物質に対する親和性を欠いており、該CMOS装置が、該マイクロウェルの底表面における電荷を検知するように構成され、該電荷が、該複数の検体との少なくとも1つの化学反応によって生成される1つ以上の副産物に起因し、該1つ以上の副産物が、該第2の化学物質に起因して該マイクロウェルの側壁に対する親和性を欠いている、該マイクロウェルの側壁に選択的に付着させるための該第2の化学物質を塗布する工程と
を含む、方法。 - 前記第1の化学物質が、前記固相支持体を受容する前に正に帯電して、該固相支持体の堆積を促進する、請求項20に記載の方法。
- 前記固相支持体が、マイクロ粒子、ナノ粒子、ビーズ、固体、及び、ゲルを含む多孔体のうちの1つである、請求項20に記載の方法。
- 前記複数の検体が、DNAサンプルの複数のコピーである、請求項20に記載の方法。
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JP5959516B2 (ja) | 2016-08-02 |
JP6126274B2 (ja) | 2017-05-10 |
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