JP2020501107A - デジタルマイクロ流体デバイスにおける並行小滴制御のためのフィードバックシステム - Google Patents
デジタルマイクロ流体デバイスにおける並行小滴制御のためのフィードバックシステム Download PDFInfo
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Abstract
Description
本特許出願は、全体として参照により本明細書に組み入れられる、2016年8月22日に出願された米国特許仮出願第62/377,797号(「FEEDBACK SYSTEM FOR PARALLEL DROPLET CONTROL IN A DIGITAL MICROFLUIDIC DEVICE」と題する)に対する優先権を主張する。
本明細書において挙げられるすべての刊行物および特許出願は、各個の刊行物または特許出願が参照により組み入れられることが明確かつ個別に示される場合と同じ程度に、全体として参照により本明細書に組み入れられる。
デジタルマイクロフルイディクス(DMF)は、広い範囲の小型の生物学的および化学的用途のための強力な液体取り扱い技術として出現した(たとえば、Jebrail, M. J.; Bartsch, M. S.; Patel, K. D., Digital microfluidics: a versatile tool for applications in Chemistry, biology and medicine. Lab Chip 2012, 12 (14), 2452-2463(非特許文献1)を参照されたい)。DMFは、ポンプ、弁、可動部品または扱いにくい管材アセンブリを要することなく、固体、液体および刺激の強い化学物質を含む複数の試料および試薬に対して正確でかつ高度にフレキシブルなリアルタイム制御を可能にする。ナノリットルないしマイクロリットル量の別々の小滴がリザーバから疎水性絶縁体でコートされた平面に小出しされ、そこで、埋め込まれた電極アレイに一連の電位を印加することによって操作(移送、分割、統合、混合)される。たとえば、Pollack, M. G.; Fair, R. B.; Shenderov, A. D., Electrowetting-based actuation of liquid droplets for microfluidic applications. Appl. Phys. Lett. 2000, 77 (11), 1725-1726(非特許文献2);Lee, J.; Moon, H.; Fowler, J.; Schoellhammer, T.; Kim, C. J., Electrowetting and electrowetting-on dielectric for microscale liquid handling. Sens. Actuators A Phys. 2002, 95 (2-3), 259-268(非特許文献3)およびWheeler, A. R., Chemistry - Putting electrowetting to work. Science 2008, 322 (5901), 539-540(非特許文献4)を参照されたい。
概して、本明細書に記載されるものは、デジタルマイクロフルイディクス(DMF)装置のギャップ領域中の1つまたは複数の小滴、好ましくは2つ以上の小滴の位置、移動速度、蒸発速度および/またはサイズ(または他の物理的特徴)に関するフィードバックを決定提供するように構成されているデジタルマイクロフルイディクス装置(たとえばデバイスおよびシステム)である。特に、本明細書に記載されるものは、物理的特徴(サイズ、位置、移動速度、蒸発速度など)を同時にまたは同時並行的に測定するために使用され得る方法および装置である。これらの方法および装置は概して、装置の第一のプレートへの電圧印加、たとえば駆動電極に電圧を印加することによって小滴を動かすための電圧印加と、電圧印加の停止(感知回路の放電を可能にし得る)と、1つまたは複数の接地電極(たとえば1つまたは複数の第二プレート接地電極)への電圧印加との間で切り替えを行い得る。
本明細書に記載されるものは、他すべての必要な機能を実行するために特化されているチャネルベースのマイクロ流体モジュールへのおよびそこからの試料および試薬の多重化処理およびルーティングのために使用され得るデジタルマイクロフルイディクス(DMF)装置(たとえばデバイスおよびシステム)である。これらのDMF装置は、エアマトリックス(たとえばオープンエア型)、閉鎖型および/またはオイルマトリックスDMF装置ならびにそれらの使用方法であり得る。特に、本明細書に記載されるものは、小滴の性質(たとえば、装置に対する位置、小滴の移動速度、小滴の蒸発速度、小滴のサイズなど)を同時並行的に(たとえば同時に、並行的になど)決定するためのDMF装置およびそれらの使用方法である。これは、装置が、特定の駆動電極にそれぞれが接続された複数の個々の感知回路、および、駆動電極への電圧印加と、それに続く複数の駆動電極(および感知回路)とは反対側の接地電極への電圧印加とを切り替える制御装置を含み得るため、可能である。制御装置はまた、感知回路データを受け取り、結果(たとえば充電電圧データ)を所定の値または値の範囲と比較して、小滴の位置、サイズ、移動速度などを推測し得る。多様なDMF装置のいずれにも組み込まれ得る本明細書に記載される要素の配置のおかげで、結果的に得られるデータは、DMF装置の動作を制御およびモニタするための、リアルタイムフィードバックを含むフィードバックのために使用され得る。
リバースストリームフィードバックシステムは、電極パッド上の小滴の存在に依存する電圧値を報告する。計測用信号が送られるとき通過する電極パッドを小滴が占有している場合、コンデンサはより多く充電され、報告される電圧は、エアギャップを通して計測用信号が送られる、小滴が存在しない場合よりも、有意に高くなる。これは、2つの媒質、すなわち空気と水の伝導率の差による。
Claims (26)
- 複数の駆動電極を有する第一のプレート;
1つまたは複数の接地電極を有し、該第一のプレートからギャップによって向かい側に離間している、第二のプレート;
電圧源;
複数の感知回路であって、該複数の感知回路からの感知回路が各駆動電極に電気的に接続されており、各感知回路が、該感知回路の充電回路中のコンデンサの充電電圧を検出するように構成されている、複数の感知回路;および
該電圧源からの電圧を該第一のプレートおよび該第二のプレートに交互に印加するように構成された制御装置であって、該第一のプレートへの電圧の印加が、該ギャップ内で1つまたは複数の小滴を動かすために該複数の駆動電極からの1つまたは複数の駆動電極に電圧を印加することを含み、該第二のプレートへの電圧の印加が、該1つまたは複数の接地電極に電圧を印加することを含み、さらに、該制御装置が、該第二のプレートへの電圧の印加時に該感知回路それぞれからの入力に基づいて該複数の駆動電極に対する1つまたは複数の小滴の位置を並行的に感知するように構成されている、制御装置
を含む、並行小滴検出を備えたデジタルマイクロ流体(DMF)装置。 - 複数の感知回路の各感知回路が充電回路、放電回路およびアナログ-デジタル変換器を含む、請求項1記載の装置。
- 複数の感知回路の各感知回路が充電回路、放電回路およびアナログ-デジタル変換器(ADC)を含み、さらに、該放電回路がトランジスタおよび接地を含む、請求項1記載の装置。
- 複数の感知回路の各感知回路が充電回路、放電回路およびアナログ-デジタル変換器(ADC)を含み、さらに、該充電回路がコンデンサおよびダイオードを含む、請求項1記載の装置。
- 複数の感知回路の各感知回路が充電回路、放電回路およびアナログ-デジタル変換器(ADC)を含み、さらに、該ADCが、該充電回路の充電電圧を検出するように構成されている、請求項1記載の装置。
- 複数の感知回路の各感知回路が充電回路、放電回路およびアナログ-デジタル変換器(ADC)を含み、さらに、制御装置が、該放電回路、次いで該充電回路を順次アクティブ化するように、および該複数の感知回路のすべての感知回路に関して並行的に該ADCから該充電回路の充電電圧を受け取るように構成されている、請求項1記載の装置。
- 電圧源と1つまたは複数の接地電極と複数の駆動電極との間に接続されたフォワード/リバーススイッチをさらに含み、制御装置が、該フォワード/リバーススイッチを作動させて、第一のプレートへの電圧印加と第二のプレートへの電圧印加とを切り替えるように構成されている、請求項1記載の装置。
- 複数の電極スイッチをさらに含み、該複数の電極スイッチからの各電極スイッチが、複数の駆動電極のうちの1つの駆動電極に接続されており、かつスイッチ制御装置を介して制御装置によって制御されて、電圧源からの電圧を該駆動電極に印加する、請求項1記載の装置。
- 電圧電源が高電圧電源を含む、請求項1記載の装置。
- 制御装置が、複数の感知回路のそれぞれによって感知された電圧をしきい電圧値と比較して、複数の駆動電極に対する1つまたは複数の小滴の位置を決定するように構成されている、請求項1記載の装置。
- 制御装置が、複数の感知回路のそれぞれによって感知された電圧を所定の電圧値または電圧値の範囲と比較して、1つまたは複数の小滴のサイズを決定するように構成されている、請求項1記載の装置。
- 第一の疎水性層を有する第一のプレート;
第二の疎水性層を有する第二のプレート;
該第一のプレート中の複数の駆動電極;
該第二のプレート中の1つまたは複数の接地電極;
電圧源;
該電圧源と該1つまたは複数の接地電極と該複数の駆動電極との間に接続されており、該電圧源と、該1つもしくは複数の接地電極または該複数の駆動電極のいずれかとの間の接続を切り替えるように構成された、フォワード/リバーススイッチ;
複数の電極スイッチであって、該複数の電極スイッチからの電極スイッチが、該フォワード/リバーススイッチと該複数の駆動電極の各駆動電極との間に接続されており、該電圧源から該電極への電圧の印加を可能にするように構成されている、複数の電極スイッチ;
複数の感知回路であって、該複数の感知回路からの感知回路が、該フォワード/リバーススイッチと各駆動電極との間に接続された該電極スイッチと、各電極との間に接続されている、複数の感知回路;および
該フォワード/リバーススイッチと、スイッチ制御装置を介した該複数の電極スイッチとを制御して、該フォワード/リバーススイッチが該電圧源を該複数の電極に接続するとき該第一のプレートと該第二のプレートとの間のギャップ内で1つまたは複数の小滴を動かすように構成され、さらに、該フォワード/リバーススイッチが該電圧源を該1つまたは複数の接地電極に接続するとき該感知回路それぞれからの入力に基づいて該複数の駆動電極に対する1つまたは複数の小滴の位置を決定するように構成された、制御装置
を含む、並行小滴検出を備えたデジタルマイクロ流体(DMF)装置。 - デジタルマイクロフルイディクス(DMF)装置において複数の小滴の位置を同時に決定する方法であって、
第一のプレートと第二のプレートとの間のギャップ内で1つまたは複数の小滴を動かすために該第一のプレート中の複数の駆動電極に電圧を印加する工程;
該第二のプレート中の1つまたは複数の接地電極に電圧を印加する工程;
該1つまたは複数の接地電極に電圧を印加しながら、複数の感知回路において充電電圧を同時並行的に感知する工程であって、各駆動電極が該複数の感知回路からの別個の感知回路と関連付けられている、工程;および
感知された該充電電圧に基づいて、該複数の駆動電極に対する該1つまたは複数の小滴の位置を決定する工程
を含む方法。 - 複数の駆動電極に電圧を印加する工程および1つまたは複数の接地電極に電圧を印加する工程が、同じ高電圧源からの電圧を印加することを含む、請求項13記載の方法。
- 複数の駆動電極に電圧を印加する工程が、隣接する駆動電極に順次に電圧を印加することを含む、請求項13記載の方法。
- 1つまたは複数の小滴の決定された位置に基づいて複数の駆動電極のうちの1つまたは複数に電圧を再び印加する工程をさらに含む、請求項13記載の方法。
- 第二のプレート中の1つまたは複数の接地電極に電圧を印加する工程が、第一のプレート中の駆動電極に電圧を印加せずに、該1つまたは複数の接地電極に電圧を印加することを含む、請求項13記載の方法。
- 1つまたは複数の接地電極に電圧を印加する前に、第一のプレート中の各感知回路において電圧を放電する工程をさらに含む、請求項13記載の方法。
- 1つまたは複数の接地電極に電圧を印加しているとき、第一のプレート中の複数の感知回路の各感知回路中のコンデンサを充電する工程をさらに含む、請求項13記載の方法。
- 1つまたは複数の接地電極に電圧を印加する前に各感知回路において電圧を放電し、次いで、該1つまたは複数の接地電極に電圧を印加しているとき、該複数の感知回路の各感知回路中のコンデンサを充電する工程をさらに含む、請求項13記載の方法。
- 1つまたは複数の小滴の位置を決定する工程が、感知された充電電圧を所定の値または値の範囲と比較して、小滴が駆動電極上にあるかまたは駆動電極に隣接しているかを決定することを含む、請求項13記載の方法。
- 1つまたは複数の小滴の位置を決定する工程が、感知された充電電圧を所定のしきい電圧値と比較して、小滴が駆動電極上にあるかまたは駆動電極に隣接しているかを決定することを含む、請求項13記載の方法。
- 感知された充電電圧に基づいて1つまたは複数の小滴のサイズを決定する工程をさらに含む、請求項13記載の方法。
- 1つまたは複数の小滴の決定された位置に基づいて小滴の動きを修正する工程をさらに含む、請求項13記載の方法。
- 感知された充電電圧に基づいて蒸発速度を決定する工程をさらに含む、請求項13記載の方法。
- デジタルマイクロフルイディクス(DMF)装置において複数の小滴のサイズまたは位置を同時に決定する方法であって、
第一のプレートと第二のプレートとの間のギャップ内で1つまたは複数の小滴を動かすために該第一のプレート中の複数の駆動電極に電圧を印加する工程;
該第一のプレート中の該複数の駆動電極に電圧を印加していないとき、複数の感知回路の各感知回路において電圧を放電する工程であって、各駆動電極が該複数の感知回路からの別個の感知回路と関連付けられている、工程;
該電圧を放電したのち、該第二のプレート中の1つまたは複数の接地電極に電圧を印加する工程;
該1つまたは複数の接地電極に電圧を印加しながら、各感知回路において充電電圧を同時並行的に感知する工程;および
感知された該充電電圧に基づいて、該複数の駆動電極に対する該1つまたは複数の小滴のサイズまたは位置を決定する工程
を含む方法。
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EP3500660A1 (en) | 2019-06-26 |
US10596572B2 (en) | 2020-03-24 |
CA3034064A1 (en) | 2018-03-01 |
EP3500660A4 (en) | 2020-03-04 |
WO2018039281A1 (en) | 2018-03-01 |
US11298700B2 (en) | 2022-04-12 |
US20200254458A1 (en) | 2020-08-13 |
CN109715781A (zh) | 2019-05-03 |
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