JP2019152655A - 生物学的実体を分離するための方法および装置 - Google Patents
生物学的実体を分離するための方法および装置 Download PDFInfo
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Abstract
Description
背景技術
発明の概要
本発明によって開示されるような、方法、構成要素および装置は、細胞、細菌および分子を含む生物学的実体を、ヒト血液、ヒト身体組織、ヒトの骨、ヒト体液、ヒト毛髪、他のヒト関連の生体試料ならびに制限なく動物および植物試料などから分離するために利用され得る。
第1の本発明は、流体試料内の生物学的実体を分離するための方法であって;
前記流体試料を第1の流体装置に通過させ、前記生物学的実体のサイズに基づいて、前記生物学的実体を第1のサブセットと第2のサブセットとに分離し、それにより前記生物学的実体の第1のサブセットを含む第1の試料を生成させ;
磁石を含む磁気分離装置に前記第1の試料を通過させ、磁気標識を有する生物学的実体を前記磁石によって前記第1の試料から分離し、それによって第2の試料を生成させ;
前記流体装置から前記磁気分離装置へと、前記第1の流体装置を前記磁気分離装置から流体的に分離するフローコネクターに前記第1の試料を通過させる、
段階を含む、方法である。
第2の本発明は、前記生物学的実体の前記第1のサブセットが前記生物学的実体の前記第2のサブセットよりもサイズが大きい、第1の本発明の方法である。
第3の本発明は、前記生物学的実体の前記第1のサブセットが前記生物学的実体の前記第2のサブセットよりもサイズが小さい、第1の本発明の方法である。
第4の本発明は、前記第1の流体装置内の流体チャネルを通過する前記流体試料中で生成される圧力節点によって前記第2のサブセットから前記第1のサブセットを分離し、前記流体装置に取り付けられる圧電変換器によって前記圧力節点が生成される、第1の本発明の方法である。
第5の本発明は、前記流体装置が、試料投入ポート、試料排出ポートおよびその間を接続する流体チャネルを有する流体チップであり;前記流体試料を前記投入ポートから前記排出ポートへと前記流体チャネルに通過させ;
前記磁気分離装置が試料投入端および試料排出端を有する磁気分離チャネルを含み;前記第1の試料が、前記試料投入に入り、前記試料排出端から出て;
前記流体チップ、前記フローコネクターおよび前記磁気分離チャネルが、閉鎖型の流体ラインを形成する、第1の本発明の方法である。
第6の本発明は、前記流体チャネルの前記試料排出ポートが前記フローコネクターの投入ポートに接続し、前記磁気分離チャネルの前記試料投入端が前記フローコネクターの排出ポートに接続し;第1の試料が、第1の流量で前記フローコネクターの前記投入ポートから出て、第2の流量で前記排出ポートを通過する、第5の本発明の方法である。
第7の本発明は、流体試料内の生物学的実体を分離するための方法であって;
磁石を含む磁気分離装置に前記流体試料を通過させ、磁気標識を有する生物学的実体が、前記流体試料から前記磁石によって分離され、それによって第1の試料を生成させ;
流体装置に前記第1の試料を通過させ、前記生物学的実体のサイズに基づいて、第1のサブセットおよび第2のサブセットに前記第1の試料内の前記生物学的実体を分離し、それによって、前記生物学的実体の第1のサブセットを含む第2の試料を生成させ;
前記磁気分離装置から前記流体装置へと、前記流体装置を前記磁気分離装置から流体的に分離するフローコネクターに前記第1の試料を通過させる、
段階を含む、方法である。
第8の本発明は、前記第1の試料が磁気標識を有する生物学的実体を含む、第7の本発明の方法である。
第9の本発明は、前記第1の試料が磁気標識がない生物学的実体を含む、第7の本発明の方法である。
第10の本発明は、生物学的実体を流体試料から分離するための装置であって、
長さ方向に沿って、第1の基部と、前記第1の基部よりも小さい第1の先端とを有する第1の軟磁性磁極と;前記長さ方向に沿って、第2の基部と、前記第2の基部よりも小さい第2の先端とを有する第2の軟磁性磁極と;前記長さ方向に沿って、第3の基部と前記第3の基部よりも小さい第3の先端とを有する第3の軟磁性磁極と、を含み;
前記第1および第3の基部が第1の磁気源と接触し、前記第2の基部が前記第1の磁気源とは反対の磁極性を有する第2の磁気源と接触し;
前記流体試料が、前記長さ方向に沿ってチャネルを通って流れ;
前記第1および第3の先端が互いに向かい合っており、前記第2の先端が、前記第1および第3の先端と一致する平面からずらして置かれ、それによって前記第1の先端と前記第2および第3の先端との間に磁場が形成され;
磁気標識を有する前記生物学的実体が、前記磁場によって前記流体試料から分離される、装置である。
第11の本発明は、前記第1の磁気源が、少なくとも1個の永久磁石の第1の磁極面であり;前記第2の磁気源が、前記少なくとも1個の永久磁石の、前記第1の磁極と反対の第2の磁極面である、第10の本発明の装置である。
第12の本発明は、前記生物学的実体が、細胞、細菌、粒子、DNA、RNAおよび分子の何れかである、第10の本発明の装置である。
第13の本発明は、前記チャネルが前記第1、第2および第3の先端から離され、機械的励起手段と接触して配置され、前記機械的励起手段が前記チャネルに含有される磁気標識を有する生物学的実体の解離を引き起こす、第10の本発明の装置である。
第14の本発明は、前記機械的励起手段が、
振動を発生させるモーター;
超音波振動を発生させる圧電素子;および
前記チャネルの伸張、圧縮またはねじれを生じさせる機械的構造のうち1つを含む、第13の本発明の装置である。
第15の本発明は、前記チャネルが、可撓性材料から作られ、前記チャネルが外力により前記第1、第2および第3の先端に向かって動かされる場合、前記第1、第2および第3の先端と自動的に接触する形状に形成される、第10の本発明の装置である。
第16の本発明は、前記磁気分離装置が、少なくとも2個の軟磁性磁極を含み、前記軟磁性磁極のそれぞれが基部および先端を有し、前記先端が、前記軟磁性磁極のそれぞれに対して前記基部よりも小さい、第1および第7の本発明の方法である。
第17の本発明は、前記軟磁性磁極の1個の前記基部が第1の磁気源と接触し;残存する前記軟磁性磁極のそれぞれの前記基部が第2の磁気源と接触し;前記第1および第2の磁気源が反対の磁極性である、第16の本発明の装置である。
第18の本発明は、前記第2の試料を第2の流体装置に通過させ、前記生物学的実体のサイズに基づいて前記第2の試料内の前記生物学的実体を第3のサブセットおよび第4のサブセットに分離し、それによって前記生物学的実体の第1のサブセットを含む第1の試料を生成させる、第1の本発明の方法である。
第19の本発明は、緩衝液を前記流体試料と同時に前記第1の流体装置に通過させ;前記緩衝液および前記流体試料が前記第1の流体装置の異なる入口を通じて前記第1の流体装置内の流体チャネルに入り;前記第1の流体装置に存在する場合、前記緩衝液が、前記流体試料からの大型生物学的実体を含有するように機能する、第1の本発明の方法である。
第20の本発明は、緩衝液を前記第2の試料と同時に前記第2の流体装置に通過させ;前記緩衝液および前記第2の試料が前記第1の流体装置の異なる入口を通じて前記第2の流体装置内の流体チャネルに入り;前記第2の流体装置に存在する場合、前記緩衝液が、前記第2の試料からの大型生物学的実体を含有するように機能する、第18の本発明の方法である。。
本発明に関連する第1の発明は、流体試料内の生物学的実体を分離するための方法であって、
前記流体試料をマイクロ流体装置に通過させ、前記マイクロ流体装置に取り付けられる音響源により生成される圧力節点によって、前記生物学的実体のサイズに基づいて、前記生物学的実体を第1のサブセットと第2のサブセットとに分離し、それにより前記生物学的実体の第1のサブセットを含む第1の試料を生成させ;
磁石を含む磁気装置に前記第1の試料を通過させ、磁気標識を有する生物学的実体を前記磁石によって前記第1の試料から分離し、それによって第2の試料を生成させる、段階を含み;
前記磁気装置から前記マイクロ流体装置を流体的に分離するフローコネクターを通じて、前記第1の試料を前記マイクロ流体装置から前記磁気装置へと通過させる、
方法である。
本発明に関連する第2の発明は、前記生物学的実体の前記第1のサブセットが前記生物学的実体の前記第2のサブセットよりもサイズが大きい、本発明に関連する第1の発明の方法である。
本発明に関連する第3の発明は、前記生物学的実体の前記第1のサブセットが前記生物学的実体の前記第2のサブセットよりもサイズが小さい、本発明に関連する第1の発明の方法である。
本発明に関連する第4の発明は、前記第2の試料が磁気標識を有する生物学的実体を含む、本発明に関連する第1の発明の方法である。
本発明に関連する第5の発明は、前記第2の試料が磁気標識がない生物学的実体を含む、本発明に関連する第1の発明の方法である。
本発明に関連する第6の発明は、前記流体試料を前記マイクロ流体装置に通し、前記第1の試料を前記磁気装置に通すために、流量脈動を減少させるための流量制限器付きの蠕動ポンプが使用される、本発明に関連する第1の発明の方法である。
本発明に関連する第7の発明は、前記マイクロ流体装置が、試料投入ポート、試料排出ポートおよびその間を接続するマイクロ流体チャネルを有するマイクロ流体チップであり;前記流体試料を前記投入ポートから前記排出ポートへと前記マイクロ流体チャネルを通過させ;
前記磁気装置が試料投入端および試料排出端を有する磁気分離チャネルを含み;前記第1の試料が、前記試料投入端に入り、前記試料排出端から出て;
前記マイクロ流体チップ、前記フローコネクターおよび前記磁気分離チャネルが、閉鎖型の流体ライン中に含まれる、本発明に関連する第1の発明の方法である。
本発明に関連する第8の発明は、前記音響源が圧電変換器である、本発明に関連する第1の発明の方法である。
本発明に関連する第9の発明は、前記流体チャネルの前記試料排出ポートが前記フローコネクターの投入ポートに接続し、前記磁気分離チャネルの前記試料投入端が前記フローコネクターの排出ポートに接続し;第1の試料が、重力によって前記フローコネクターの前記投入ポートから前記排出ポートへと通過する、本発明に関連する第7の発明の方法である。
本発明に関連する第10の発明は、流体試料内の生物学的実体を分離するための方法であって、
前記流体試料を分割して複数のマクロ流体装置に通過させ、前記マイクロ流体装置のそれぞれに取り付けられる音響源により生成される音圧節点により前記マイクロ流体装置のそれぞれ内で前記生物学的実体のサイズに基づいて前記生物学的実体を第1のサブセットと第2のサブセットとに分離し、それにより、生物学的実体の前記第1のサブセットを含む前記マイクロ流体装置のそれぞれから第1の試料を生成させ;
フローコネクターに前記第1の試料を通し、前記第1の試料が第2の試料に統合し;
第2の試料を分割し、複数の磁気装置に通過させ、磁気標識を有する生物学的実体を、前記磁気装置のそれぞれに含有される磁石によって前記第2の試料から分離し、それによって第3の試料を生成させる、
段階を含む、方法である。
本発明に関連する第11の発明は、前記生物学的実体の前記第1のサブセットが前記生物学的実体の前記第2のサブセットよりもサイズが大きい、本発明に関連する第10の発明の方法である。
本発明に関連する第12の発明は、前記生物学的実体の前記第1のサブセットが前記生物学的実体の前記第2のサブセットよりもサイズが小さい、本発明に関連する第10の発明の方法である。
本発明に関連する第13の発明は、前記第3の試料が磁気標識を有する生物学的実体を含む、本発明に関連する第10の発明の方法である。
本発明に関連する第14の発明は、前記第3の試料が磁気標識がない生物学的実体を含む、本発明に関連する第10の発明の方法である。
本発明に関連する第15の発明は、前記フローコネクターが、前記複数のマイクロ流体装置を前記複数の磁気装置から流体的に分離させる、本発明に関連する第10の発明の方法である。
本発明に関連する第16の発明は、流体試料内の生物学的実体を分離するための方法であって、
磁石を含む磁気装置に前記流体試料を通過させ、前記磁石によって前記流体試料から磁気標識を有する生物学的実体を分離し、それによって第1の試料を生成させ;
前記第1の試料をマイクロ流体装置に通過させ、前記マイクロ流体装置に取り付けられる音響源により生成される圧力節点によって前記生物学的実体のサイズに基づいて、前記第1の試料内の前記生物学的実体を第1のサブセットと第2のサブセットとに分離し、それにより前記生物学的実体の第1のサブセットを含む第2の試料を生成させ;
前記マイクロ流体装置を前記磁気装置から流体的に分離するフローコネクターを通って前記第1の試料を前記磁気装置から前記マイクロ流体装置へ通過させる、
段階を含む、方法である。
本発明に関連する第17の発明は、前記第1の試料が磁気標識を有する生物学的実体を含む、本発明に関連する第16の発明の方法である。
本発明に関連する第18の発明は、前記第1の試料が磁気標識がない生物学的実体を含む、本発明に関連する第16の発明の方法である。
本発明に関連する第19の発明は、前記生物学的実体の前記第1のサブセットが前記生物学的実体の前記第2のサブセットよりもサイズが大きい、本発明に関連する第16の発明の方法である。
本発明に関連する第20の発明は、前記生物学的実体の前記第1のサブセットが前記生物学的実体の前記第2のサブセットよりもサイズが小さい、本発明に関連する第16の発明の方法である。
発明の詳細な説明
Claims (20)
- 流体試料内の生物学的実体を分離するための方法であって;
前記流体試料を第1の流体装置に通過させ、前記生物学的実体のサイズに基づいて、前記生物学的実体を第1のサブセットと第2のサブセットとに分離し、それにより前記生物学的実体の第1のサブセットを含む第1の試料を生成させ;
磁石を含む磁気分離装置に前記第1の試料を通過させ、磁気標識を有する生物学的実体を前記磁石によって前記第1の試料から分離し、それによって第2の試料を生成させ;
前記流体装置から前記磁気分離装置へと、前記第1の流体装置を前記磁気分離装置から流体的に分離するフローコネクターに前記第1の試料を通過させる、
段階を含む、方法。 - 前記生物学的実体の前記第1のサブセットが前記生物学的実体の前記第2のサブセットよりもサイズが大きい、請求項1に記載の方法。
- 前記生物学的実体の前記第1のサブセットが前記生物学的実体の前記第2のサブセットよりもサイズが小さい、請求項1に記載の方法。
- 前記第1の流体装置内の流体チャネルを通過する前記流体試料中で生成される圧力節点によって前記第2のサブセットから前記第1のサブセットを分離し、前記流体装置に取り付けられる圧電変換器によって前記圧力節点が生成される、請求項1に記載の方法。
- 前記流体装置が、試料投入ポート、試料排出ポートおよびその間を接続する流体チャネルを有する流体チップであり;前記流体試料を前記投入ポートから前記排出ポートへと前記流体チャネルに通過させ;
前記磁気分離装置が試料投入端および試料排出端を有する磁気分離チャネルを含み;前記第1の試料が、前記試料投入に入り、前記試料排出端から出て;
前記流体チップ、前記フローコネクターおよび前記磁気分離チャネルが、閉鎖型の流体ラインを形成する、請求項1に記載の方法。 - 前記流体チャネルの前記試料排出ポートが前記フローコネクターの投入ポートに接続し、前記磁気分離チャネルの前記試料投入端が前記フローコネクターの排出ポートに接続し;第1の試料が、第1の流量で前記フローコネクターの前記投入ポートから出て、第2の流量で前記排出ポートを通過する、請求項5に記載の方法。
- 流体試料内の生物学的実体を分離するための方法であって;
磁石を含む磁気分離装置に前記流体試料を通過させ、磁気標識を有する生物学的実体が、前記流体試料から前記磁石によって分離され、それによって第1の試料を生成させ;
流体装置に前記第1の試料を通過させ、前記生物学的実体のサイズに基づいて、第1のサブセットおよび第2のサブセットに前記第1の試料内の前記生物学的実体を分離し、それによって、前記生物学的実体の第1のサブセットを含む第2の試料を生成させ;
前記磁気分離装置から前記流体装置へと、前記流体装置を前記磁気分離装置から流体的に分離するフローコネクターに前記第1の試料を通過させる、
段階を含む、方法。 - 前記第1の試料が磁気標識を有する生物学的実体を含む、請求項7に記載の方法。
- 前記第1の試料が磁気標識がない生物学的実体を含む、請求項7に記載の方法。
- 生物学的実体を流体試料から分離するための装置であって、
長さ方向に沿って、第1の基部と、前記第1の基部よりも小さい第1の先端とを有する第1の軟磁性磁極と;前記長さ方向に沿って、第2の基部と、前記第2の基部よりも小さい第2の先端とを有する第2の軟磁性磁極と;前記長さ方向に沿って、第3の基部と前記第3の基部よりも小さい第3の先端とを有する第3の軟磁性磁極と、を含み;
前記第1および第3の基部が第1の磁気源と接触し、前記第2の基部が前記第1の磁気源とは反対の磁極性を有する第2の磁気源と接触し;
前記流体試料が、前記長さ方向に沿ってチャネルを通って流れ;
前記第1および第3の先端が互いに向かい合っており、前記第2の先端が、前記第1および第3の先端と一致する平面からずらして置かれ、それによって前記第1の先端と前記第2および第3の先端との間に磁場が形成され;
磁気標識を有する前記生物学的実体が、前記磁場によって前記流体試料から分離される、装置。 - 前記第1の磁気源が、少なくとも1個の永久磁石の第1の磁極面であり;前記第2の磁気源が、前記少なくとも1個の永久磁石の、前記第1の磁極と反対の第2の磁極面である、請求項10に記載の装置。
- 前記生物学的実体が、細胞、細菌、粒子、DNA、RNAおよび分子の何れかである、請求項10に記載の装置。
- 前記チャネルが前記第1、第2および第3の先端から離され、機械的励起手段と接触して配置され、前記機械的励起手段が前記チャネルに含有される磁気標識を有する生物学的実体の解離を引き起こす、請求項10に記載の装置。
- 前記機械的励起手段が、
振動を発生させるモーター;
超音波振動を発生させる圧電素子;および
前記チャネルの伸張、圧縮またはねじれを生じさせる機械的構造のうち1つを含む、請求項13に記載の装置。 - 前記チャネルが、可撓性材料から作られ、前記チャネルが外力により前記第1、第2および第3の先端に向かって動かされる場合、前記第1、第2および第3の先端と自動的に接触する形状に形成される、請求項10に記載の装置。
- 前記磁気分離装置が、少なくとも2個の軟磁性磁極を含み、前記軟磁性磁極のそれぞれが基部および先端を有し、前記先端が、前記軟磁性磁極のそれぞれに対して前記基部よりも小さい、請求項1および7に記載の方法。
- 前記軟磁性磁極の1個の前記基部が第1の磁気源と接触し;残存する前記軟磁性磁極のそれぞれの前記基部が第2の磁気源と接触し;前記第1および第2の磁気源が反対の磁極性である、請求項16に記載の装置。
- 前記第2の試料を第2の流体装置に通過させ、前記生物学的実体のサイズに基づいて前記第2の試料内の前記生物学的実体を第3のサブセットおよび第4のサブセットに分離し、それによって前記生物学的実体の第1のサブセットを含む第1の試料を生成させる、請求項1に記載の方法。
- 緩衝液を前記流体試料と同時に前記第1の流体装置に通過させ;前記緩衝液および前記流体試料が前記第1の流体装置の異なる入口を通じて前記第1の流体装置内の流体チャネルに入り;前記第1の流体装置に存在する場合、前記緩衝液が、前記流体試料からの大型生物学的実体を含有するように機能する、請求項1に記載の方法。
- 緩衝液を前記第2の試料と同時に前記第2の流体装置に通過させ;前記緩衝液および前記第2の試料が前記第1の流体装置の異なる入口を通じて前記第2の流体装置内の流体チャネルに入り;前記第2の流体装置に存在する場合、前記緩衝液が、前記第2の試料からの大型生物学的実体を含有するように機能する、請求項18に記載の方法。。
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US20190270092A1 (en) | 2019-09-05 |
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US20200001298A1 (en) | 2020-01-02 |
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