JP5894272B2 - 液滴アクチュエーターにおける試薬保存 - Google Patents
液滴アクチュエーターにおける試薬保存 Download PDFInfo
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Description
本発明は、米国保健福祉省により付与されたHG004354に基づく政府の援助を受けてなされたものである。米国政府は本発明に一定の権利を有する。
液滴アクチュエーターは、通常、液滴操作を行うための表面または間隙を形成するように構成された1つ以上の基板を含む。1つ以上の基板は液滴操作を行うための液滴操作表面または間隙をなし、液滴操作を行うために配置された電極を含んでいてもよい。液滴操作基板または基板間の液滴操作間隙は、液滴を形成する液体と混和しない充填流体で被覆または充填されていてもよい。
以下の用語は、本明細書では以下に示された意味を有する。
ポリエーテルエーテルケトン;液晶ポリマー;シクロオレフィンコポリマー(COC);シクロオレフィンポリマー(COP);アラミド;THERMOUNT(登録商標)不織布アラミド補強材(DE、Wilmington、DuPont社から入手可能);NOMEX(登録商標)ブランド繊維(DE、Wilmington、DuPont社から入手可能);および紙。種々の材料についても、基板の誘電体部材としての使用に適している。例としては以下のものを含む:PARYLENE(商標)C(特にガラス上)およびPARYLENE(商標)N(TX、Katy、Parylene Coating Services社から入手可能)等の蒸着した誘電体;TEFLON(登録商標)AFコーティング;サイトップ;TAIYO(商標)PSR4000シリーズ、TAIYO(商標)PSRおよびAUSシリーズのような液体光画像形成可能なソルダーマスク(NV、Carson City、Taiyo America社から入手可能)(熱制御を含む用途に良好な熱特性)、およびPROBIMER(商標)8165(熱制御を含む用途に良好な熱特性)(CA、Los Angels、Huntsman Advanced Materials Americas社から入手可能)等のソルダーマスク;VACREL(登録商標)乾燥フィルムソルダーマスク系(DE、Wilmington、DuPont社から入手可能)等の乾燥フィルムソルダーマスク;ポリイミドフィルム(例えば、KAPTON(登録商標)ポリイミドフィルム、DE、Wilmington、DuPont社から入手可能)等のフィルム誘電体、ポリエチレン、およびフルオロポリマー(例えば、FEP)、ポリテトラフルオロエチレン;ポリエステル;ポリエチレンナフタレート;シクロオレフィンコポリマー(COC);シクロオレフィンポリマー(COP);上で列挙した他のPCB基板材料のいずれか;ブラックマトリックス樹脂;およびポリプロピレン。液滴輸送の電圧と周波数は、個別の測定手順で用いられる試薬の性能によって選択してもよい。設計パラメーターは異なっていてもよく、例えば、アクチュエーターのリザーバの数と配置、独立した電極接続の数、異なるリザーバの大きさ(体積)、磁石/ビーズ洗浄ゾーンの配置、電極サイズ、電極間の間隔、および間隙高さ(頂部基板と底部基板の間)は、個別の試薬、手順、液滴体積等の使用のために異なっていてもよい。いくつかの場合、本発明の基板は、溶液中のポリもしくはパーフルオロ化合物または重合性単量体等の化合物を使用した、堆積または原位置合成等により、低界面エネルギー材料または化学的性質により誘導体化させてもよい。例としては、浸漬またはスプレーコーティング用のTEFLON(登録商標)AFコーティングおよびFLUOROPEL(登録商標)コーティング、ならびにプラズマ化学気相成長法(PECVD)用の他のフッ素化された単量体が挙げられる。加えて、いくつかの場合、液滴操作表面の一部または全部は、PCB基板からのバックグラウンド蛍光発光等のバックグラウンドのノイズを低減する物質で被覆されていてもよい。例えば、ノイズ低減コーティングは、日本の東レ株式会社から入手可能なブラックマトリックス樹脂等のブラックマトリックス樹脂を含んでもよい。液滴アクチュエーターの電極は、通常、コントローラーまたはプロセッサーにより制御され、コントローラーまたはプロセッサーは、それ自体、システムの一部として設けられ、処理機能と同様に、データおよびソフトウェアストレージならびに入力および出力機能を含んでいてもよい。試薬は、液滴アクチュエーター上であって、液滴操作間隙内、または、液滴操作間隙に流体的に結合したリザーバ内に供給されてもよい。試薬は、液滴等の液体形態でもよく、または試薬は、液滴操作間隙内または液滴操作間隙に流体的に結合したリザーバ内で再構成可能な形態で供給されてもよい。再構成可能な試薬は、通常、再構成のために液体と組み合わせることができる。本発明での使用に好適な再構成可能な試薬の例として、Meathrelらによる2010年6月1日に特許された題名「Disintegratable films for diagnostic devices」の米国特許第7,727,466号明細書に記載された試薬が挙げられる。
本発明は、液滴アクチュエーター上の測定試薬の保存および再構成(例えば、試薬回収)の方法を提供する。一実施形態において、本発明は、液滴アクチュエーターの固体表面上で1つ以上の測定試薬を乾燥させる方法を提供する。別の実施形態において、本発明は、液滴アクチュエーター上で1つ以上の液体試薬を保存する方法を提供する。さらに別の実施形態において、本発明は、デジタルマイクロ流体液体処理手順を用いて、1つ以上の乾燥した測定試薬を液滴アクチュエーターの固体表面から回収する方法を提供する。乾燥した試薬および表面は充填流体、例えばシリコーンオイルなどで被覆されてもよい。
本発明は、液滴アクチュエーター上で試薬を保存および再構成(すなわち、試薬回収)する方法を提供する。化学試薬(例えば、サンプル調製試薬、免疫測定試薬、およびRT-qPCR試薬)を固体表面で維持および保存するための利用可能な試薬乾燥技術を選択して液滴アクチュエーター上での使用に適応させてもよい。デジタルマイクロ流体液体処理手順を用いて乾燥試薬を回収してもよい。液体試薬(例えば、オイル充填流体、再水和バッファー、および特定測定試薬)もまた液滴アクチュエーター上で保存してもよく、再構成に先立ち、これをもって前述の試薬を被覆してもよい。試薬は、リザーバ内でまたは、液滴操作間隙または表面に続く流路内で乾燥させてもよい。試薬は、液滴操作表面、例えば液滴アクチュエーターの疎水性表面上で乾燥させてもよい。
1.液滴アクチュエーターの表面上に、1つ以上の試薬を含む水滴を堆積(付着)させる行程、
2.前記液滴を乾燥させて、液滴アクチュエーターの表面上に乾燥した組成物を生成する工程、
3.前記乾燥組成物をオイル充填流体で被覆する工程、および
4.前記オイル充填流体内の第2の水滴(すなわち、再水和液滴)を輸送して前記乾燥組成物に接触させ、それにより1つ以上の乾燥試薬を再懸濁させる工程。
固体表面上の試薬流体を乾燥させる既存の技術を選択し、液滴アクチュエーターでの使用に適応させてもよい。一例において、オイル充填液滴アクチュエーター内の乾燥試薬を効率的に回収するために試薬乾燥技術を選択してもよい。別の例において、測定および/または液滴操作を実質的に阻害しないよう、試薬安定剤および/または保護化合物を選択してもよい。さらに別の例において、試薬乾燥技術は、異なる環境条件(例えば、運送温度、湿度等)において長期間安定性(有効期間)をもたらすよう選択してもよい。場合によっては、試薬液滴が非常に小さいために、特別な乾燥技術を必要としない。さらに別の例において、使用者の操作を不要とするため、試薬を再構成するための分配操作を自動化してもよい。
本発明の試薬再構成方法は、乾燥試薬の回収にデジタルマイクロ流体液体処理手順を用いる。一実施形態において、本発明の方法は、乾燥試薬液滴を回収するための水滴の操作に、エレクトロウェッティングを媒介した液滴操作を用いる。重要なことは、本発明者が、オイルを通過して乾燥試薬に接触するよう液滴を輸送することにより、乾燥試薬をオイル充填流体で被覆し、実質的に完全に再構成することが可能であることを発見したということである。
液滴アクチュエーターにおいて、特定の他の試薬とともに再構成バッファーを液体状で保存してもよい。1つ以上の物理的構造物および/または要素を液滴アクチュエーター内に組み入れて液体試薬の格納に用いてもよい。一例において、物理的構造物および/または要素は、運送時に液体試薬を格納できるよう選択してもよい。大量の試薬流体、例えば洗浄バッファーを、独立したリザーバ(例えば、頂部基板上のリザーバ)内に保存してもよい。液体保存に適当な試薬は、有効期間研究に基づいて選択することができる。
本発明の方法は、HIVの混合(すなわち、サンプル応答)サンプル調製および多重検出のためのポイントオブケア(POC)診断装置を提供するよう用いられる。この例において、サンプル調製、HIV抗体の免疫測定、およびHIVウイルス負荷を測定するRT−PCRのための乾燥試薬を液滴アクチュエーター上で保存することができる。液体試薬、例えば、洗浄バッファーおよびオイル充填流体もまた液滴アクチュエーター上で保存することができる。
本発明の様々な態様を、方法、システム、コンピューターで読み取り可能な媒体、および/またはコンピュータープログラム製品として実施してもよいことが理解されるだろう。本発明の態様は、ハードウェアの実施形態、ソフトウェアの実施形態(ファームウェア、常駐ソフトウェア、マイクロコード等を含む)、または通常、本明細書で「回路」、「モジュール」または「システム」として言及する全てのソフトウェアおよびハードウェアの態様を組み合わせた実施形態を取り得る。さらに、本発明の方法は、コンピューターで使用可能なストレージ媒体でのコンピュータープログラムプロダクトの形態を取ってもよく、当該媒体は、当該媒体で実施される、コンピューターで使用可能なプログラムコードを有する。
上述した、実施形態の詳細な説明は、添付の図面を参照し、当該図面は、本発明の特定の実施形態を表す。異なる構造および動作を含む他の実施形態は本発明の範囲から逸脱しない。用語「本発明」等は、本明細書で説明した出願人の発明の多くの代替態様または実施形態のいくつかの特定の例を参照して用いられ、その使用または不使用は出願人の発明の範囲または特許請求の範囲を限定することを意図しない。本明細書は、読者の便宜のみのために章で分割されている。見出しは、発明の範囲を限定するものとして解釈すべきでない。定義は本発明の記載の一部として意図されている。本発明の範囲を逸脱することなく本発明の様々な詳細を変更してもよいことが理解されるだろう。さらに、上述の記載は説明のみのためのものであり、限定を目的としたものではない。
Claims (11)
- 1つ以上の試薬を含む液滴を提供する方法であって、
(a)1つ以上の試薬を含む第1の液滴を表面に付着させる工程と、
(b)前記第1の液滴を乾燥させて、前記1つ以上の試薬を含む表面上に乾燥組成物を生成させる工程と、
(c)前記乾燥組成物をオイルで被覆する工程と、
(d)前記オイル中の第2の液滴を前記乾燥組成物に接触させ、それにより1つ以上の試薬を再懸濁させる工程と、
を含み、
前記表面が電極を含み、前記乾燥組成物が前記電極の上に配置され、
前記電極が、電極アレイの構成要素であり、
前記電極アレイが、前記表面上で液滴操作を行うよう構成され、
工程(d)がエレクトロウェッティング液滴操作で媒介される、
方法。 - 前記第1の液滴がさらに、液滴アクチュエーターにおける乾燥測定試薬の保存および放出制御のための安定化剤を含む、請求項1に記載の方法。
- 前記安定化剤が糖を含む、請求項2に記載の方法。
- 前記糖が、デキストラン、スクロース、およびトレハロースからなる群より選択される請求項3に記載の方法。
- 前記安定化剤がポリマーを含む、請求項2〜4のいずれか1項に記載の方法。
- 前記第1の液滴が界面活性剤を含む、請求項1〜5のいずれかに記載の方法。
- 前記第2の液滴が界面活性剤を含む、請求項1〜6のいずれかに記載の方法。
- 前記表面が疎水性である、請求項1〜7のいずれかに記載の方法。
- 前記第2の液滴にパルス印加する工程をさらに含む、請求項1〜8のいずれかに記載の方法。
- 前記パルス印加が、電極により媒介される、請求項9に記載の方法。
- 前記パルス印加が、エレクトロウェッティングで媒介される、請求項10に記載の方法。
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AU2012279420A1 (en) | 2014-01-30 |
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CN103733059B (zh) | 2016-04-06 |
CA2840949A1 (en) | 2013-01-10 |
KR20140064771A (ko) | 2014-05-28 |
EP2729792A4 (en) | 2015-03-18 |
EP2729792A2 (en) | 2014-05-14 |
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WO2013006312A2 (en) | 2013-01-10 |
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