JP2019504324A - 大スケールの分子電子工学センサアレイを使用する被分析物を測定するための方法および装置 - Google Patents
大スケールの分子電子工学センサアレイを使用する被分析物を測定するための方法および装置 Download PDFInfo
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Abstract
Description
本出願は、“METHODS AND APPARATUS FOR MEASURING ANALYTES USING LARGE SCALE MOLECULAR ELECTRONICS SENSOR ARRAYS”と題する2016年1月28日に出願された米国仮特許出願番号第62/288,360号に基づく優先権を主張しており、その開示は参考として本明細書中に援用される。
本発明は、概して、バイオナノテクノロジーの分野内、より具体的には、分子電子センサの分野内にある。
センサは、特定の種類の刺激に応答して、検出可能で記録可能な状態の変化を受ける、離散システムである。好適な解釈の手段と組み合わせられたとき、センサは、他の着目システムを特性評価または定量化するために使用されることができる。本概念は、概して、図1に示される。
本開示の種々の実施形態では、集積回路半導体チップと、その上に配置された複数の分子電子センサデバイスとを含む、分子電子センサアレイチップが開示され、センサデバイスはそれぞれ、(i)ナノギャップによって分離される一対のナノスケールソース電極およびドレイン電極と、(ii)ゲート電極と、(iii)ナノギャップに跨架し、ソース電極およびドレイン電極を接続する、架橋またはプローブ分子とを含む。複数のセンサデバイスは、センサピクセルのアレイに編成される。ある側面では、センサデバイスは、架橋分子と、プローブ分子とを含み、プローブ分子は、ナノギャップに跨架する架橋分子に結合される。ある実施形態では、チップは、数百から最大で数億またはそれを上回るセンサデバイスを含んでもよい。電圧が、分子自己集合プロセスを監視および/または促進するために使用されてもよく、それによって、各架橋ならびに/もしくはプローブ分子は、各ソース電極およびドレイン電極対上に自己集合する。デバイス電圧は、連続試験のために必要とされ得るように、センサを分子前状態に復元する電圧指向リセットの使用を含む、各ソース電極およびドレイン電極対への各架橋および/またはプローブ分子の分子自己集合を監視ならびに/もしくは促進するために使用されてもよい。
本明細書の例示的実施形態の詳細な説明は、例証として例示的実施形態およびそれらの最良の様態を示す、付随する図面を参照する。これらの例示的実施形態は、当業者が本発明を実践するために十分に詳細に説明されているが、他の実施形態が実現されてもよく、本発明の精神および範囲から逸脱することなく、論理的、化学的、ならびに機械的変更が行われてもよいことを理解されたい。したがって、本明細書の詳細な説明は、限定ではなく、例証の目的のためのみに提示される。例えば、別様に記述されない限り、方法またはプロセスの説明のうちのいずれかに記載されるステップは、任意の順序で実行されてもよく、必ずしも提示される順序に限定されない。さらに、単数の任意の言及は、複数の実施形態を含み、1つを上回る構成要素またはステップの任意の言及は、単数の実施形態またはステップを含んでもよい。また、取り付けられた、固定された、接続された、または同等物の任意の言及は、恒久的、除去可能、一時的、部分的、完全、および/または任意の他の可能性として考えられる取付オプションを含んでもよい。加えて、接触なし(または類似語句)の任意の言及はまた、低減した接触または最小限の接触を含んでもよい。
図18は、付加的局所回路詳細の実施例を図示する。これらの特定の実施形態はさらに、電圧測定を行うことに先立って規定された初期電圧を設定するために使用されるリセットスイッチ/トランジスタの追加を伴って、図15および16の局所センサ回路の性能を増進する。そのようなリセットスイッチは、アクティブ化されたとき、必要に応じて任意の貯蔵された電荷を放出することによって、既知の参照レベルまで測定点における電圧をリセットする。これは、既知の参照状態を提供し、測定された信号値からのノイズまたは電圧ドリフトを識別または減算する能力を改良する。
場所iにおけるAの本期待読取り数は、配列の端部で最小であり、i=Lであり、全ての塩基の約3/4がAではない、典型的配列組成を仮定すると、(ある軽微な書き直しを伴って)ほぼ以下である。
Claims (25)
- (a)集積回路半導体チップと、
(b)その上に配置された複数の分子電子センサデバイスであって、各センサデバイスは、(i)ナノギャップによって分離される一対のナノスケールソース電極およびドレイン電極と、(ii)ゲート電極と、(iii)前記ナノギャップに跨架し、前記ソース電極およびドレイン電極を接続する、架橋またはプローブ分子とを備える、センサデバイスと、
を備え、前記センサデバイスは、センサピクセルのアレイに編成される、
分子電子センサアレイチップ。 - 各センサデバイスは、架橋およびプローブ分子を両方とも備える、請求項1に記載の分子電子センサアレイチップ。
- 前記プローブ分子は、被分析物のための結合プローブを含み、前記被分析物は、DNA、RNA、およびタンパク質のうちの少なくとも1つである、請求項1に記載の分子電子センサアレイチップ。
- 前記チップは、少なくとも100個のセンサデバイスを備える、請求項1に記載の分子電子センサアレイチップ。
- 電圧が、各ソース電極およびドレイン電極対への各架橋および/またはプローブ分子の分子自己集合を監視ならびに/もしくは促進するために使用される、請求項1に記載の分子電子センサアレイチップ。
- デバイス電圧が、連続試験のために必要に応じて、前記センサを分子前状態に復元する電圧指向リセットの使用を含む、各ソース電極およびドレイン電極対への各架橋および/またはプローブ分子の分子自己集合を監視ならびに/もしくは促進するために使用される、請求項1に記載の分子電子センサアレイチップ。
- 前記プローブ分子は、酵素を含む、請求項1に記載の分子電子センサアレイチップ。
- 前記プローブ分子は、DNAハイブリダイゼーションプローブを含む、請求項1に記載の分子電子センサアレイチップ。
- 前記プローブ分子は、DNAポリメラーゼを含む、請求項1に記載の分子電子センサアレイチップ。
- 前記プローブ分子は、DNAポリメラーゼを含み、前記架橋分子は、各電極対上の特定の親和性接点に跨架する、二本鎖DNA、ペプチド、タンパク質アルファヘリックス、または天然もしくは操作されたIgG抗体を含む、請求項1に記載の分子電子センサアレイチップ。
- 各センサピクセルはさらに、各センサデバイスに接続される読出コンデンサまたは読出抵抗器を備える、請求項1に記載の分子電子センサアレイチップ。
- 各センサピクセルはさらに、トランジスタベースの出力スイッチを備える、請求項11に記載の分子電子センサアレイチップ。
- 各センサピクセルはさらに、トランジスタベースのリセットスイッチを備える、請求項12に記載の分子電子センサアレイチップ。
- 各センサピクセルはさらに、それに接続された行選択ラインおよび列読出ラインを備え、前記センサピクセルのアレイは、統合行選択・列読出アレイアーキテクチャを備え、それによって、前記行選択ラインは、前記センサピクセルを活性化させる、請求項13に記載の分子電子センサアレイチップ。
- 前記行選択ラインは、前記出力スイッチを制御する、請求項14に記載の分子電子センサアレイチップ。
- 各センサピクセルはさらに、各リセットスイッチを制御するための行リセットラインおよび列リセットラインを備える、請求項15に記載の分子電子センサアレイチップ。
- 各リセットスイッチは、各センサピクセルの前記リセットに対する直接制御を提供するため等に、前記行選択ラインおよび前記列リセットラインの組み合わせによって制御される、請求項16に記載の分子電子センサアレイチップ。
- チップに適用される複数の複製プライムDNA断片のための取り込み信号を測定するためのプロセスであって、
(a)請求項1の少なくとも1つの分子電子センサアレイチップを提供するステップと、
(b)dNTPおよび特定の塩基ターミネータの混合物を前記分子電子センサアレイチップに適用するステップと、
(c)前記DNA断片に沿って前記特定の塩基の場所を測定するステップと、
を含む、プロセス。 - 塩基反応毎に1つ、少なくとも4つの分子電子センサアレイチップが利用される、請求項18に記載のプロセス。
- デジタル断片長アッセイを行うために使用される、請求項18に記載のプロセス。
- サンプル分析のためのチップベースの分析器システムであって、
(a)請求項1に記載の少なくとも1つの分子電子センサアレイチップと、
(b)前記少なくとも1つの分子電子センサアレイチップが統合される、マザーボードと、
(c)複数の分子電子センサデバイスへの少なくとも前記サンプルの導入を制御するように構成される、液体取扱いシステムと、
(d)少なくとも1つの信号プロセッサと、
(e)CPUと、
を備える、システム。 - 前記チップベースの分析器は、マルチモダリティ生物分析器に統合され、それによって、前記サンプルからマルチモダリティ統合レポートを生成する、請求項21に記載のチップベースの分析器システム。
- ハンドヘルド、ウェアラブル、または埋込可能システムとして構成される、請求項21に記載のチップベースの分析器システム。
- 生物サンプルを分析するプロセスであって、
(a)請求項21に記載のチップベースの分析器システムを提供するステップと、
(b)対象から前記生物サンプルを収集するステップと、
(c)前記チップベースの分析器システムを通して前記生物サンプルを処理するステップであって、前記生物サンプルの分析に関連するデータを取得するステップと、
(d)前記データを記憶サーバまたはクラウドに転送するステップと、
を含む、方法。 - 前記生物サンプルは、対象に関する情報と併せて前記対象から収集され、そして前記対象に関する前記情報および前記生物サンプルの前記分析に関連する前記データの両方を備える統合レポートを生成するように分析される、請求項24に記載のプロセス。
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US20190041355A1 (en) | 2019-02-07 |
JP7280590B2 (ja) | 2023-05-24 |
EP3408220A1 (en) | 2018-12-05 |
EP3408220A4 (en) | 2019-09-04 |
KR20180105699A (ko) | 2018-09-28 |
US11624725B2 (en) | 2023-04-11 |
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