JP7334989B2 - アナライトの検出およびそのための方法 - Google Patents
アナライトの検出およびそのための方法 Download PDFInfo
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Description
本出願は、2015年4月28日に出願された「Method and System for Identifying Cells in Blood Samples by Adding Antibodies Specific to Clusters of Differentiation」というタイトルの米国仮出願第62/153,523号の恩典を主張し、この仮出願の内容は、その全体が参照により本明細書に組み込まれる。
別段の定義がない限り、本明細書で使用される全ての技術用語および科学用語は、本発明の属する技術分野における通常の知識を有する者によって一般的に理解されるのと同じ意味を有する。本明細書で説明されるものと類似または同等の任意の方法および材料を本発明の実施または試験において用いることができるが、好ましい方法および材料が説明される。本発明の目的のために、以下の用語が以下で定義される。
本技術は、血液サンプルなどの生体サンプル中の細胞または他の成分(簡略化のため、まとめて「細胞」と呼称する)を識別および/または同定するための方法およびシステムを提供する。具体的には、方法は、細胞の特定の表面マーカーに特異的に結合する複数の抗体またはアプタマーなどの他の分子(簡略化のため、まとめて「抗体」と呼称する)と共にサンプルをインキュベートするステップを含む。本明細書で説明される方法は、1つ以上の特異性を有する1つ以上の抗体の使用を企図する。特定の表面マーカーの数およびタイプは、表面マーカーのそれぞれが特定のCDに関連するように予め選択できるか予め決定できる。さらに、サンプル(特に血液サンプル)中の抗体濃度は、計算または測定のいずれかによって決定される。一部の実施形態において、抗体濃度は、予め決定されていてよいか、既知であってよい。その後、結合した抗体から細胞を分離することによりサンプルを濾過し、濾液を生じさせる。さらに、濾液中に残っている抗体の濃度を測定する。最後に、濾過の前と後の抗体濃度を比較して、サンプル中の細胞の数および/または型を決定する。濾液には、その画分が包含されるということが理解されるであろう。
本技術はまた、検出シグナルの強度に依存してサンプル中のアナライトの濃度が決定される、免疫測定法に基づくアッセイの分析も提供する。これらの方法は一般に、生体液(例えば、血液)または非生体液などのサンプル中の抗原、抗体、タンパク質および核酸などのアナライトの検出および/または定量化に適用可能である。サンプルは単離されていてよく、精製されていてもいなくてもよい。
Claims (26)
- アッセイのシグナルのダイナミックレンジを制御するための方法であって、
サンプル中の1つ以上の標的アナライトを提供することと、
前記1つ以上の標的アナライトをコンジュゲート化結合試薬および非コンジュゲート化結合試薬の混合物と接触させることであって、前記コンジュゲート化結合試薬および前記非コンジュゲート化結合試薬が前記1つ以上の標的アナライトに対して特異的である、接触させることと、
前記1つ以上の標的アナライトと前記コンジュゲート化結合試薬および前記非コンジュゲート化結合試薬の前記混合物との間の相互作用を測定することと、
前記混合物中の前記コンジュゲート化結合試薬と前記非コンジュゲート化結合試薬の比率を調整することによってアッセイのシグナルのダイナミックレンジを制御することと、
前記1つ以上の標的アナライトと前記混合物との間の相互作用の測定の結果に基づいて、およびアッセイのシグナルのダイナミックレンジの制御に基づいて、前記サンプル中の前記1つ以上の標的アナライトを定量的に決定することと、
を含み、
前記混合物中の1つ以上のコンジュゲート化アナライトの比率の調整が計算装置によって実行され、
前記比率が、モル比、重量比および体積比ならびにそれらの任意の組み合わせからなる群より選択される、
方法。 - 前記標的アナライトのそれぞれの濃度を決定することをさらに含む、請求項1の方法。
- 1つ以上のコンジュゲート化アナライトを前記サンプルに添加することと、前記1つ以上の標的アナライトの希釈を生じさせることと、をさらに含む、請求項1または請求項2の方法。
- 1つ以上の非コンジュゲート化アナライトを前記サンプルに添加することと、前記1つ以上の標的アナライトの希釈を生じさせることと、をさらに含む、請求項1~3のいずれか1項の方法。
- 前記コンジュゲート化結合試薬または前記非コンジュゲート化結合試薬には以下のうちの1つ以上が包含される、請求項1~4のいずれか1項の方法:抗体、抗原、アプタマー、ペプチド、タンパク質、およびオリゴヌクレオチド。
- 前記コンジュゲート化結合試薬には、酵素、タンパク質、フルオロフォア、ストレプトアビジン、アビジン、抗体、抗原、アプタマーおよびオリゴヌクレオチドからなる群より選択されるコンジュゲートと連結された結合試薬が包含される、請求項1~5のいずれか1項の方法。
- 前記1つ以上の標的アナライトには以下のうちの1つ以上が包含される、請求項1~6のいずれか1項の方法:抗原、抗体、核酸、炭水化物、脂質、ペプチド、タンパク質、ポリマー、およびそれらの任意の組み合わせ。
- 前記サンプルには生体液サンプルが包含される、請求項1~7のいずれか1項の方法。
- アッセイのシグナルのダイナミックレンジを制御するための方法であって、
サンプル中の1つ以上の標的アナライトを提供することと、
前記1つ以上の標的アナライトを少なくとも1つの結合試薬を含む混合物と接触させることであって、前記結合試薬が前記1つ以上の標的アナライトに対して特異的である、接触させることと、
前記1つ以上の標的アナライトと前記混合物との間の相互作用を測定することと、
1つ以上のコンジュゲート化アナライトを前記サンプルに添加して前記1つ以上の標的アナライトの希釈を生じさせることと、
前記混合物中の前記1つ以上のコンジュゲート化アナライトの比率を調整することによってアッセイのシグナルのダイナミックレンジを制御することと、
前記1つ以上の標的アナライトと前記混合物との間の相互作用の測定の結果に基づいて、およびアッセイのシグナルのダイナミックレンジの制御に基づいて、前記サンプル中の前記1つ以上の標的アナライトを定量的に決定することと、
を含み、
前記混合物中の1つ以上のコンジュゲート化アナライトの比率の調整が計算装置によって実行され、
前記比率が、モル比、重量比および体積比ならびにそれらの任意の組み合わせからなる群より選択される、
方法。 - 前記少なくとも1つの結合試薬には非コンジュゲート化結合試薬が包含される、請求項9の方法。
- 前記非コンジュゲート化結合試薬には以下のうちの1つ以上が包含される、請求項10の方法:抗体、抗原、アプタマー、ペプチド、タンパク質、およびオリゴヌクレオチド。
- 前記少なくとも1つの結合試薬にはコンジュゲート化結合試薬が包含される、請求項9~11のいずれか1項の方法。
- 前記コンジュゲート化結合試薬には以下のうちの1つ以上が包含される、請求項12の方法:抗体、抗原、アプタマー、ペプチド、タンパク質、およびオリゴヌクレオチド。
- 前記コンジュゲート化結合試薬には、酵素、タンパク質、フルオロフォア、ストレプトアビジン、アビジン、抗体、抗原、アプタマーおよびオリゴヌクレオチドからなる群より選択されるコンジュゲートと連結された結合試薬が包含される、請求項12または13の方法。
- 1つ以上の非コンジュゲート化アナライトを前記サンプルに添加することと、前記1つ以上の標的アナライトの希釈を生じさせることと、をさらに含む、請求項9~14のいずれか1項の方法。
- 前記1つ以上の標的アナライトには以下のうちの1つ以上が包含される、請求項9~15のいずれか1項の方法:抗原、抗体、核酸、炭水化物、脂質、ペプチド、タンパク質、ポリマー、およびそれらの任意の組み合わせ。
- 前記サンプルには生体液サンプルが包含される、請求項9~16のいずれか1項の方法。
- アッセイのシグナルのダイナミックレンジを制御するための方法であって、
(i)サンプル中の1つ以上の標的アナライトを提供することと、
(ii)前記1つ以上の標的アナライトを少なくとも1つの結合試薬を含む混合物と接触させることであって、前記結合試薬が前記1つ以上の標的アナライトに対して特異的である、接触させることと、
(iii)前記1つ以上の標的アナライトと前記混合物との間の相互作用を測定することと、
(iv)1つ以上の改変アナライトを前記サンプルに添加することと、
(v)前記混合物中の前記1つ以上の改変アナライトの比率を調整することによってアッセイのシグナルのダイナミックレンジを制御することと、
を含む方法。 - 前記1つ以上の改変アナライトには、前記1つ以上の標的アナライト内の構造と同じ構造を有する分子が包含される、請求項18の方法。
- 前記1つ以上の改変アナライトには、前記標的アナライトのうちの少なくとも1つのサブユニットが包含される、請求項18の方法。
- 1つ以上のコンジュゲート化アナライトを前記サンプルに添加して前記1つ以上の標的アナライトの希釈を生じさせるステップをさらに含んでもよい、請求項18の方法。
- 前記少なくとも1つの結合試薬には、非コンジュゲート化結合試薬またはコンジュゲート化結合試薬が包含される、請求項18の方法。
- アッセイのシグナルのダイナミックレンジを制御するためのシステムであって、
サンプル中の1つ以上の標的アナライトを提供して前記1つ以上の標的アナライトをコンジュゲート化結合試薬および非コンジュゲート化結合試薬の混合物と接触させるための容器であって、前記コンジュゲート化結合試薬および前記非コンジュゲート化結合試薬が前記1つ以上の標的アナライトに対して特異的である、容器と、
前記1つ以上の標的アナライトと前記コンジュゲート化結合試薬および前記非コンジュゲート化結合試薬の前記混合物との間の相互作用を測定するように構成されたセンサーと、
前記サンプル中の前記コンジュゲート化結合試薬と前記非コンジュゲート化結合試薬の比率を調整することによってアッセイのシグナルのダイナミックレンジを制御するように構成された制御器と、
を含むシステム。 - 前記標的アナライトのそれぞれの濃度を決定するように構成された分析装置をさらに含む、請求項23のシステム。
- 前記センサーには、以下のうちの1つ以上が包含されてもよい、請求項23のシステム:比色センサー、蛍光センサー、測光センサーおよび分光測定装置。
- 前記分析装置は、前記センサーに動作可能に接続された計算装置を含んでもよい、請求項24のシステム。
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JP7153494B2 (ja) * | 2018-07-27 | 2022-10-14 | シスメックス株式会社 | 生体粒子の測定方法、非特異シグナルの検出方法、生体粒子測定方法及び生体粒子を検出するための試薬キット |
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US20210405033A1 (en) | 2021-12-30 |
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