JP2020525769A - マイクロ流体分析装置 - Google Patents
マイクロ流体分析装置 Download PDFInfo
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- JP2020525769A JP2020525769A JP2019570912A JP2019570912A JP2020525769A JP 2020525769 A JP2020525769 A JP 2020525769A JP 2019570912 A JP2019570912 A JP 2019570912A JP 2019570912 A JP2019570912 A JP 2019570912A JP 2020525769 A JP2020525769 A JP 2020525769A
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Abstract
Description
核酸分析物が付着する付着部位を含む第1区域と、
前記付着部位をわたって第1流動媒体を流すことによって核酸を漸進的に核酸構成ヌクレオシド三リン酸に加ピロリン酸分解する第1経路と、
前記付着部位周りからのヌクレオシド三リン酸を除去する第2経路と、
前記第2経路において、水不混和性キャリアの水性微小液滴からなる第2媒体を生み出す手段と、
光学的に媒介されるエレクトロウェッティングを用いて前記微小液滴を操作する微小液滴操作区域であり、前記微小液滴操作区域は、
第1複合壁であり、
第1透明基板、
前記第1透明基板上の、70〜250nmの厚さを有する第1透明導体層、
前記第1透明導体層上の、300〜1000nmの厚さを有し、400〜1000nmの波長範囲の電磁照射によって活性化される光活性層、及び
前記第1透明導体層上の、120〜160nmの厚さを有する第1誘電体層
を含む第1複合壁と、
第2複合壁であり、
第2透明基板、
前記第2基板上の、70〜250nmの厚さを有する第2導体層、及び
任意に、前記第2導体層上の、25〜50nmの厚さを有する第2誘電体層
を含む第2複合壁と、
からなり、前記第1誘電体層及び第2誘電体層の露出面は、10μm未満の間隔で配置されて、微小液滴を含むように適合されるマイクロ流体空間を画定する、微小液滴操作区域と、
前記第1複合壁及び第2複合壁にわたって、前記第1透明導体層及び第2導体層を接続する電位差を供給する交流電源と、
前記光活性層に衝突させて、前記第1誘電体層の表面上の対応する第1一過性エレクトロウェッティング箇所を誘起するように適合される光励起層のバンドギャップより高いエネルギを有する少なくとも1つの第1電磁放射源と、
前記第1一過性エレクトロウェッティング箇所の配置を変えることにより、少なくとも1つの第1エレクトロウェッティング経路を生成し、前記第1エレクトロウェッティング経路に沿って前記微小液滴を移動させることができるように、前記光活性層上での電磁照射の衝突点を操作する手段と、
前記微小液滴操作区域の下流に配置され、又は前記微小液滴操作区域と一体の、検出区域と、
前記検出区域で前記微小液滴に衝突するように適合される第2電磁放射源、及び前記微小液滴から放射される前記蛍光又はラマン散乱を検出する検出器を備える蛍光又はラマン散乱検出システムと、
を備える、核酸分析物を調査する装置が提供される。
水性加ピロリン酸分解媒体を、第1経路に配置される付着部位に固定される分析物と接触させて、これにより前記分析物を漸進的に前記分析物の構成ヌクレオシド三リン酸に加ピロリン酸分解するステップと、
第2水性媒体の形をとるヌクレオシド三リン酸を、前記付着部位周りから、第2マイクロ流体経路を経て除去するステップと、
不混和性キャリア媒体内の前記第2水性媒体に由来する微小液滴を、光学的に媒介されるエレクトロウェッティング装置を用いて操作するステップと、
電磁放射源によって各微小液滴に照射するときに、各微小液滴において放出されるフルオロフォアに由来する蛍光を検出するステップと、
を含む、
ポリヌクレオチド分析物を調査する方法であり、
前記エレクトロウェッティング装置は、
第1複合壁であり、第1透明基板、第1透明基板上の、70〜250nmの厚さを有する第1透明導体層、第1透明導体層上の、300〜1000nmの厚さを有し、400〜1000nmの波長範囲の電磁照射によって活性化される光活性層、及び第1透明導体層上の、120〜160nmの厚さを有する第1誘電体層からなる第1複合壁と、
第2複合壁であり、第2基板、第2基板上の、70〜250nmの厚さを有する第2透明導体層、及び任意に、第2導体層上の、25〜50nmの厚さを有する第2誘電体層からなる第2複合壁と、
前記第1複合壁及び第2複合壁にわたって、前記第1透明導体層及び第2透明導体層を接続する電位差を供給する交流電源と、
前記光活性層に衝突させて、前記第1誘電体層の表面上の対応する一過性エレクトロウェッティング箇所を誘起するように適合される光励起層のバンドギャップより高いエネルギを有する少なくとも1つの電磁放射源と、
前記一過性エレクトロウェッティング箇所の配置を変えることにより、少なくとも1つの第1エレクトロウェッティング経路を生成し、前記第1エレクトロウェッティング経路に沿って微小液滴を移動させることができるように、前記光活性層上での電磁照射の衝突点を操作する手段と、
を備え、
前記第1誘電体層及び第2誘電体層の露出面は、10μm未満の間隔で配置されて、前記微小液滴を含むように適合されるマイクロ流体空間を画定し、
前記微小液滴は、操作時のある時点において、ヌクレオシド三リン酸の一部又は全部をさらに含み、
オリゴヌクレオチド捕捉システムは、不使用状態では蛍光を発しない蛍光プローブと、蛍光状態において使用される前記オリゴヌクレオチド捕捉システムから前記フルオロフォアを放出させることができる、ポリメラーゼ並びに任意にリガーゼ及びエキソヌクレアーゼ及び/又はエンドヌクレアーゼとからなる、
方法が提供される。
Claims (16)
- 核酸分析物が付着する付着部位を含む第1区域と、
前記付着部位をわたって第1流動媒体を流すことによって核酸を漸進的に核酸構成ヌクレオシド三リン酸に加ピロリン酸分解する第1経路と、
前記付着部位周りからのヌクレオシド三リン酸に関する第2経路と、
前記第2経路において、水不混和性キャリアの水性微小液滴からなる第2媒体を生み出す手段と、
光学的に媒介されるエレクトロウェッティングを用いて前記微小液滴を操作する微小液滴操作区域であり、前記微小液滴操作区域は、
第1複合壁であり、
第1透明基板、
前記第1透明基板上の、70〜250nmの厚さを有する第1透明導体層、
前記第1透明導体層上の、300〜1000nmの厚さを有し、400〜1000nmの波長範囲の電磁照射によって活性化される光活性層、及び
前記第1透明導体層上の、120〜160nmの厚さを有する第1誘電体層
を含む第1複合壁と、
第2複合壁であり、
第2基板、
前記第2基板上の、70〜250nmの厚さを有する第2導体層、及び
前記第2導体層上の、120〜1600nmの厚さを有する第2誘電体層
を含む第2複合壁と、
からなり、前記第1誘電体層及び第2誘電体層の露出面は、10μm未満の間隔で配置されて、微小液滴を含むように適合されるマイクロ流体空間を画定する、微小液滴操作区域と、
前記第1複合壁及び第2複合壁にわたって、前記第1透明導体層及び第2導体層を接続する電圧を供給する交流電源と、
前記光活性層に衝突させて、前記第1誘電体層の表面上の対応する第1一過性エレクトロウェッティング箇所を誘起するように適合される光励起層のバンドギャップより高いエネルギを有する少なくとも1つの第1電磁放射源と、
前記一過性エレクトロウェッティング箇所の配置を変えることにより、少なくとも1つの第1エレクトロウェッティング経路を生成し、前記第1エレクトロウェッティング経路に沿って前記微小液滴を移動させることができるように、前記光活性層上での電磁照射の衝突点を操作する手段と、
前記微小液滴操作区域の下流に配置され、又は前記微小液滴操作区域と一体の、検出区域と、
前記検出区域で前記微小液滴に衝突するように適合される第2電磁放射源、及び前記微小液滴から放射される蛍光又はラマン散乱を検出する検出器を備える蛍光又はラマン散乱検出システムと、
を備える、核酸分析物を調査する装置。 - 前記検出区域がエレクトロウェッティング箇所のアレイを含むことを特徴とする、請求項1に記載の装置。
- 前記検出区域が、前記微小液滴が通過する毛細管のブロックを含み、
第2電磁放射の衝突点がマイクロ流体チャンネルの出口であることを特徴とする、請求項1に記載の装置。 - ビードがある領域に固定され、別個の微小液滴が前記領域上で順次動かされ、各液滴が前記ビードをある期間の間濡らし、前記期間後、前記領域が前記ビードを乾かす又は部分的に乾かすことを特徴とする、請求項1に記載の装置。
- 前記ビードにわたって動かされる水性微小液滴が、一時的に前記水性微小液滴と接触するときに、前記ビード上でデオキシリボ核酸の加ピロリン酸分解が起きることを特徴とする、請求項4と請求項1〜3の何れか一項とに記載の装置。
- 前記付着部位が、前記核酸分析物が付着するビードを受けるように適合されることを特徴とする、請求項1〜5の何れか一項に記載の装置。
- 前記第1区域の上流に、ビードを調製する調製区域を更に備え、
前記ビードは第2エレクトロウェッティング経路によって前記調製区域から前記第1区域まで移動することを特徴とする、請求項1〜6の何れか一項に記載の装置。 - 前記第2エレクトロウェッティング経路が、誘電体被覆電極及び/又は誘電体被覆光活性層に対応する第2エレクトロウェッティング箇所からなることを特徴とする、請求項7に記載の装置。
- 前記第1複合壁及び第2複合壁がそれぞれ、前記第1誘電体層及び前記第2誘電体層上に、第1防汚層及び第2防汚層を更に備えることを特徴とする、請求項1〜8の何れか一項に記載の装置。
- マイクロ流体空間が、前記第1複合壁及び第2複合壁に取り付けられるスペーサによって更に画定されることを特徴とする、請求項1〜9のいずれか一項に記載の装置。
- マイクロ流体空間が、2μm〜8μmの深さを有することを特徴とする、請求項1〜10のいずれか一項に記載の装置。
- 互いに付随して走る複数の第1エレクトロウェッティング経路を更に含むことを特徴とする、請求項1〜11のいずれか一項に記載の装置。
- 前記第1エレクトロウェッティング経路と交差して、少なくとも1つの微小液滴合流箇所を作るように適合される、複数の第3エレクトロウェッティング経路を更に備えることを特徴とする、請求項12に記載の装置。
- 連続的流体の一連供給チャンネルが、前記微小液滴操作区域のインタフェースとなり、前記連続的流体の一連供給チャンネルを用いて、その後液滴化され操作される投入試薬を供給することを特徴とする、請求項1〜13の何れか一項に記載の装置。
- 前記光活性層上での前記電磁照射の前記衝突点を操作する前記手段が、前記第1エレクトロウェッティング経路、第2エレクトロウェッティング経路及び第3エレクトロウェッティング経路のいずれか又はすべてを生み出し、経路における、それぞれの微小液滴の、他のすべての微小液滴に対する移動を同期させる、マイクロプロセッサを備えることを特徴とする、請求項1〜14の何れか一項に記載の装置。
- 請求項1〜15の何れか一項に記載の装置を、天然又は合成起源のデオキシリボ核酸又はリボ核酸のシーケンサに対して使用する方法。
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CA3067105A1 (en) | 2018-12-27 |
CN113967488B (zh) | 2024-02-06 |
KR20240051316A (ko) | 2024-04-19 |
US11318472B2 (en) | 2022-05-03 |
CN110769936B (zh) | 2022-07-08 |
EP3943192A1 (en) | 2022-01-26 |
SG11201912290XA (en) | 2020-01-30 |
EP3641935B1 (en) | 2021-09-08 |
KR20200019716A (ko) | 2020-02-24 |
IL271545B1 (en) | 2023-05-01 |
IL271545B2 (en) | 2023-09-01 |
BR112019027770A2 (pt) | 2020-07-07 |
AU2023204199A1 (en) | 2023-07-20 |
AU2018288533A1 (en) | 2020-02-06 |
JP7257341B2 (ja) | 2023-04-13 |
AU2018288533B2 (en) | 2023-07-13 |
SG10202109873XA (en) | 2021-10-28 |
CN113967488A (zh) | 2022-01-25 |
US20220219173A1 (en) | 2022-07-14 |
CN110769936A (zh) | 2020-02-07 |
WO2018234446A1 (en) | 2018-12-27 |
EP3641935A1 (en) | 2020-04-29 |
US20200197941A1 (en) | 2020-06-25 |
IL271545A (en) | 2020-02-27 |
KR102657042B1 (ko) | 2024-04-12 |
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