JP5897780B2 - プリント回路基板上の液滴操作装置及び方法 - Google Patents
プリント回路基板上の液滴操作装置及び方法 Download PDFInfo
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Description
図1A〜1D、2A〜2B、3A〜3B、4A〜4B、及び図5を参照して、液滴操作用のPCBプロセスの基板を適応させるための必要条件をより詳細に説明する。さらに詳細に以下に説明するように、図1A〜1Dは、電極内に充填された又は非充填のビアホールを有するPCB上の厳密な同一平面配置を含む、PCBのディジタル微小流体チップ10に関する。図2A〜2Bは、電極内に充填された又は非充填のビアホールを有するPCB上の実質的な同一平面配置を含む、PCBのディジタル微小流体チップ20に関する。図3A〜3Bは、電極内に充填された又は非充填のビアホールを有するPCB上の埋め込まれた同一平面配置を含む、PCBのディジタル微小流体チップ30に関する。図4A〜4Bは、電極内に充填された又は非充填のビアホールを有するPCB上の平行な板又は2つの平面の配置を含む、PCBのディジタル微小流体チップ40に関する。また、図5は、液滴操作用のPCB上でビアホールを有する電極の密なアレイに置かれた液滴を図示する。図5は、本主題の概念を一般的に示しており、ここで、液体試料は、独立して分配され、輸送され、培養され、検出され、又は他の液滴と反応する(「ディジタル微小流体」のアプローチ」)ことのできる個別の液滴Dへディジタル化される。
上述したように、本主題の静電気の微小流体デバイスは、PCB製造用に一般に使用されるほぼいずれの基板材料にて製造可能である基板12を含む。それらの材料は、以下のものに限定されないが、FR−2、FR−4、FR−5、ポリイミド、KaptonTM、RogersTM、DuroidTM、BT、シアン酸塩エステル、及びポリテトラフルオロエチレン(PTFE)を含む。硬い、硬い可撓性、又はフレキシブルな基板は、それらのデバイスの製造に基材12として用いることができる。
PCBの最も外側の導電性の銅層は、電場により液体の液滴を操作するのに必要な駆動電極を形成するためにパターン化される。駆動電極16は、特別なアプリケーションによって、種々の形状及び形態を採ることができる。例えば、細長い電極構造は勿論、四角形の電極アレイ、円形形状の電極アレイ、六角形形状の電極アレイ、星形形状のアレイ、及び他のかみ合った又は櫛形の電極形状が使用可能である。基準電極18も、同じ導電性の層、又は同一基板(同一平面)上の別個の導電性層にパターン化することができ、又は別個の基板(2つの平面)上に設けることもできる。
PCB基板12上の導電トレースは、駆動電極16及び基準エレメント18に電気的な接続をなすために用いられる。駆動電極16又は基準エレメント18のそれぞれは、一若しくは複数の他の駆動電極16又は基準エレメント18に、同じPCB基板12上の他の電子部品、又は外部接続用のパッドに接続することができる。一つの配置では、外部接続用のパッドは、PCBのエッジに沿って提供され、また、PCBは、エッジ・カード・コネクター・ソケット28での使用に適応される(図8A〜8Bを参照)。他の配置では、パッドのアレイがPCBの表面に配置され、パッドは、バネを装荷したピン、テストクリップ、異方性導電性材料29の細片を用いて接続される(図9Aを参照)。さらに他の配置では、外部回路への接続を容易にするため、ピンヘッダー、ソケット・コネクター、又は他の個別の電子部品がPCBに接続される。
図1A−1D、2A−2B、3A−3B及び4A−4Bをさらに参照する。駆動電極16は、DC電位が駆動電極に印加されるとき、電極と導電液体との間に直流電流が流れるのを防ぐために絶縁体22によって一般的に電気的に絶縁される。電場により液滴操作が誘導されるように、AC電位が駆動電極に同様に印加されることに注目されるべきである。いかなる誘電体も用いることができるが、PCB上の銅配線を保護し、かつ電子部品が結局接合されるところのみ銅を露出するために、半田マスクは、従来のPCBプロセスで一般的に用いられる。駆動電極16を絶縁するための最も簡単なアプローチは、絶縁体22として半田マスク材料(あるいは他の誘電体)を用いることである。液体及びドライフィルムの両半田マスクは、電極絶縁体22として使用に適している。フォトイメージ可能な半田マスクは、基準エレメント18又は絶縁体22の真下の接続パッドへの電気的なアクセスを提供するために容易にパターン化することができるので、一般に好ましい。
半田マスク材料の付加層は、液体の流れをためる又は導くのに使用するウエル及びチャネル(不図示)のようなPCB表面の物理的な構造を作るために蒸着され、パターン化可能であることが構想される。
サブトラクティブ法及びアディティブ法の処理の組み合わせ
その他の実施形態では、サブトラクティブ法及びアディティブ法プロセスの組み合わせが本主題のPCB液滴操作基板を製造するために用いることができる。サブトラクティブ法は、液滴制御電極への全ての電気的なルーティング及び相互接続を形成する多層基板を製造するために用いることができる。パターン化可能な誘電体層が適用可能である。ビアは、レーザードリル又はフォトマスクによってこの誘電体にパターン化することができる。一つの実施形態では、LPIは、誘電体として用いることができる。孔に露出した電極パッドは、誘電体表面で平面にするために任意にメッキすることができる。このポイントでは、アディティブプロセスは、より小さな配線間隔を得ることができるとき、無電解の銅の堆積を用いて、全ての電極を形成するために用いることができる。
完成したデバイスは、標準のPCBプロセス及び非標準のプロセスの組み合わせを含むことができる。例えば、ワンステップの疎水性コーティングは、液滴の輸送を容易にするために完成したPCBに適用可能である。更に、誘電体としての半田マスクの使用は、絶縁されていないPCBが標準のPCBプロセスにて利用されない特別な材料で続いてコーティング可能であるような応用例では、望ましくないかもしれない。しかしながら、そのような場合において、導電性トレースを形成するための開始基板及びPCBプロセスとしてのPCBの使用は、完全なPCB互換のプロセスの利点の多く、大部分ではないにしても、をまだ提供する。
駆動電極16(例えば図1A〜1Dを参照)と同じ層に基準電極18もパターン化される実施形態では、単に駆動電極をカバーし基準電極を開かせるように、LPI半田マスクに相当数のくぼみがある場合がある。このくぼみは、液滴が基準エレメントに接触できないように、操作の信頼度に影響することがある。この場合、基準エレメントの表面がLPI半田マスク(不図示)と平面であるように、基準電極は、メッキアップすることができる。このメッキ工程は、銅又はニッケルでの表面処理の前に実行可能である。
一つの実施形態では、上述したように全ての銅の電極が形成された後、LPIコーティングは、レベル間誘電体として用いることができ、他の銅の層は、基準電極として作用するためにLPIを覆いパターン化することができる。誘電体は、また、典型的な多層構造において薄い(2ミル以下)プリプレッグPCB基板になりえ、又は、それは、最外層上で基準電極として作用する銅の特徴を持った柔軟性のある基板でありえる。この最も外側の銅の層の真下の銅の層は、駆動電極を規定する銅の特徴を有している。
その他の実施形態では、本主題のPCBは、液体の取り扱いに使用されていない領域において電子部品から成ることができるという構想が描かれる。電子部品は、電気化学の測定用の、マイクロコントローラ、リレー、高電圧マルチプレクサー、電圧変換器(電圧をステップアップするDC−DC、DC−AC、AC−DCなど)、LEDのような電気光学エレメント、フォトダイオード、光電子増倍管チューブ(PMT)、加熱エレメント、サーミスター、抵抗温度デバイス(RTDs)、及び他の電極を含むことができる。銅のトレースも、液滴のインピーダンス測定に用いることができる。抵抗加熱エレメントは、曲がりくねった銅トレースにより実現され、抵抗加熱の特徴は、銅配線の寸法に依存するだろう。一つの実施形態では、PMT又はフォトダイオードのような光学検出器を含んでいるPCBは、液滴操作PCB基板とサンドイッチを形成するために平行な板として用いることができる。他の実施形態では、標準PCBプロセスで得られる金で被覆された電極は、電気化学測定に用いることができる。
PCB上の機械的に空けられた孔は、他の表面へ基板を付着又は固定するために一般的に用いられる。本主題のPCB微小流体的チップにおいて、それらのあけられた孔は、PCB基板の表面へ、又はその表面からの液体の追加及び除去のための流体の入口/出口ポートとして作用するために使用可能であるということが構想される。それはさらに、これらのあけられた孔は、次のものに限定されないが、フレキシブルなチューブ、注射器、ピペット、ガラス毛細管、経静脈ライン、あるいはマイクロダイアリシス管腔を含む液体源と結びあわされることができるということが構想される。これらのチューブにおける液体は、圧力又は他のいずれの手段によって駆動することができる。管からの液体の連続的な流れは、流れから直接に、又はPCB上の中間の貯蔵部を通って液滴に離散化可能なそれらのドリル孔を通してPCBにインターフェース連結可能である。
一般に、本主題の装置上で移動された液滴は、PCBを備える一つ又は両方の板を有するサンドイッチ構造における水平面内で操作される。その他の実施形態では、PCB上に空けられた孔は、鉛直面においてサンドイッチ構造から離れた液滴を抽出するために使用可能である。液滴は、様々な方法で孔を通して抽出することができる。サンドイッチ構造に閉じこめられた液滴と大きな孔との間の圧力差を利用する一つの方法では、孔の真下にまさに位置決めすることにより、液滴は、液滴の半径よりも大きな直径を有する孔を通って無抵抗で押すことができる。他の板がサンドイッチ構造に加えられ、液滴が、電位を印加することにより新しく形成されたサンドイッチ構造へ一つのサンドイッチ構造から引っ張られる場合、電気的な手段によって液滴を抽出することができる。この場合、抽出過程を単純化するために、サンドイッチ構造は、同一平面のPCB基板と電極を有する他の基板との間に形成することができる。これらの両方の板が平行板の配置を形成している間、液滴は、同一平面のPCB基板のみに接触し、及び、平面から離れて液滴を静電気的に引っ張るために電位が一方の基板に印加されるとき、一方の基板上へ垂直に移動するだろう。液滴は、また、他の板上に型押しをするために重力で垂直に移動可能である。液滴のかかる垂直動作のための応用は、DNA又はタンパク質の型押し応用を含んでいる。かかる孔から引き出された液滴は、また、吸光度測定用の経路長を増すために、及び別の層に輸送を可能にする他のサンドイッチ構造内へ輸送するために使用可能である。
多くの生化学的反応は、本主題に示されるように、PCB基板上の液体の操作によって行なうことができる。ここに示されるように、本主題は、光学的な、電気的な検出手段により試料液内の目標分析物を検出するための装置を提供する。試料液は、次のものに限定されないが、体液(次のものに限定されないが、哺乳類サンプル、特に人間のサンプルが好ましく、事実上いずれかの有機体の血液、汗、涙、尿、血漿、血清、リンパ液、唾液、肛門及び膣の分泌物、***); 食物及び環境上のサンプル(次のものに限定されないが、空気、農産物、水、及び土壌のサンプル); 細菌戦争薬剤サンプル; 研究サンプル; 浄化されたゲノムのDNA、RNA、タンパク質、細胞などのような浄化されたサンプル; 及び生のサンプル(バクテリア、ビールス、菌類など)を含むかなり多くの品目を有することができる。ここに示されるようなPCB基板上で行なうことができる分析のタイプは、サンドイッチ及び均質の配置を含む、酵素の分析、等温での又は熱循環によるDNA増幅、免疫アッセイ、及び光学的な及び電気的な検出手段を備えた細胞に基づく分析を含む。生理学のサンプル中で測定された分析物は、代謝物質、電解質、ガス、タンパク質、ホルモン、サイトカイニン、ペプチド、DNA及びRNAを含んでいる。
その他の実施形態では、液滴の高さと同じオーダーの厚さを有する銅トレースは、液滴が同じ基板上のトレースと絶縁体で覆われているトレースとの間に含まれるように、使用可能である。液滴は、それに垂直よりもむしろ基板平面に主に適用される電場によって作動される。同一平面上の配置と異なり、液滴が、同一平面上の駆動及び基準電極及び平行板の配置に置かれるところで、液滴が、基板上の駆動電極と平行基板上の共通の基準電極との間にはさまれる場合、この構造において、液滴は、同一平面上の駆動と基準電極との間にはさまれる。
本主題の一般的な実施形態及びプロセスが上述されたが、微小体積の液体試料を操作する装置の製造のより詳しい実施形態を以下に述べる。ここで上記装置は、プリント回路基板を備える。
ここに示されるような電場を媒介とした液滴マニピュレーター用の2層単一基板設計が、市販のエレクトロニクスPCBメーカーに提出されテストされ、実験が行なわれた。設計は、大きな液体体積から液滴分配用の電極形状を特定化することはもちろん、液滴の輸送及び混合用の異なる制御電極形状のアレイからなる。電極は、PCB表面上の銅と同じ層にパターン化された導電性トレースによって接点パッドに接続される。必要なところでは、トレースは、制御電極から離れた位置で従来のビアを用いて基板の2つの側面間に経路が定められる。いくつかの異なったチップ設計及び相互接続案がテストされた。
図14のB、Dは、開いたシステム(同一平面)における液滴に関して、液滴輸送及び混合をそれぞれ図示する。混合は、8Hzのスイッチング周波数で行なわれ、2つの2.5μlの「閉じ込められた」液滴に関して5秒以内で完成され、そして「開いた」システムにおける2つの6μlの液滴に関して1.8秒以内に完成される。したがって、開いた(同一平面)システムで観察された混合速度(単位時間当たりの体積)は、閉じ込められたシステム(2つの平面)の場合のほぼ7倍大きい。この改善された混合は、液滴がより薄くなるとき循環が悪化すると以前に示されたように、より厚い液滴内で経験された増加した循環に起因することがある。
以下にリストされた参考文献は、ここで使用された方法論、技術、及び/又はプロセスに関する補足、説明、バックグランドの提供、又は教示をそれらが行う範囲まで参考としてここに編入される。この出願内で参照された全ての引用特許文献及び刊行物は、参考としてここに明確に編入される。
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Claims (19)
- エレクトロウェッティング方式の技術により、電極のアレイを含む基板上で、分離した流れの液滴を電気的に操作するためのディジタル微小流体プロセッサ装置であって、
(a)第1側面及び第2側面を有するプリント回路基板と、
(b)上記プリント回路基板の第1側面に配置された、エレクトロウェッティング方式の技術による液滴操作のための電極のアレイであって、上記液滴操作は、上記電極のアレイにより規定される経路に沿う液滴輸送を含む、上記電極のアレイと、
(c)上記プリント回路基板の第1側面に配置されかつ上記電極のアレイをカバーするためにパターン化された誘電体層と、
(d)上記電極のアレイの連続作動を動的に作成しそれにより上記プリント回路基板の第1側面に配置された液滴が、エレクトロウェッティング方式の技術により電気的に操作される電極セレクターと、
を備え、
上記プリント回路基板は、それに形成され上記プリント回路基板の第1側面から上記プリント回路基板の第2側面に延在する複数の基板開口を備え、上記電極のアレイのそれぞれの電極は、電極開口を備え、上記電極開口の一つは、前記ディジタル微小流体プロセッサ装置を通じて複数のビアホールを形成するための上記複数の基板開口の一つに配列される、装置。 - 上記ビアホールは、誘電体物質で満たされる、請求項1記載の装置。
- 上記ビアホールは、樹脂で満たされる、請求項1記載の装置。
- 上記樹脂は、導電性のエポキシ樹脂又は光学的に透明なエポキシ樹脂である、請求項3記載の装置。
- 上記プリント回路基板は、上記電極のアレイの電極の少なくとも一つに隣接した少なくとも一つの液滴入口ポートを形成する、請求項1記載の装置。
- 少なくとも一つの上記液滴入口ポートは、可撓管、注射器、ピペット、外部流体ポンプ、ガラス毛細管、経静脈ライン、及びマイクロダイアリシス管腔から成るグループから選択された液体流源と連通する、請求項5記載の装置。
- 上記プリント回路基板は、上記電極のアレイの電極の少なくとも一つに隣接した少なくとも一つの液滴出口ポートを形成する、請求項5記載の装置。
- 少なくとも一つの上記液滴出口ポートは、可撓管、注射器、ピペット、外部流体ポンプ、ガラス毛細管、経静脈ライン、及びマイクロダイアリシス管腔から成るグループから選択された液体流源と連通する、請求項7記載の装置。
- 上記誘電体層は、半田マスク材料、スピンオン材料、ディップコート可能材料、ブラシ又はスプレー被覆可能な材料、蒸着可能な材料、又はスパッタ可能な材料である、請求項1記載の装置。
- 上記半田マスク材料は、液体のフォトイメージ可能な半田マスク(LPI)、及びドライフィルム半田マスク(DFSS)から成るグループから選択される、請求項9記載の装置。
- 上記プリント回路基板に接続される電子部品をさらに備え、該電子部品は、マイクロコントローラ、リレー、高電圧マルチプレクサー、電圧変換器、発光ダイオード(LED)、フォトダイオード、光電子増倍管チューブ(PMT)、加熱エレメント、サーミスター、抵抗温度デバイス(RTDs)、及び電気化学測定電極からなるグループから選択される、請求項1記載の装置。
- 上記電極のアレイは、駆動電極のアレイを含み、
共通の基準電位に設定可能であり、上記駆動電極のアレイに対して少なくとも実質的に同一平面に配置される一若しくは複数の基準エレメントのアレイをさらに備える、請求項1から11のいずれか一項に記載の装置。 - 上記基準エレメントのアレイは、細長い構造のグリッドを備える、請求項12記載の装置。
- 上記細長い構造のグリッドの高さは、上記プリント回路基板の第1側面に配置された液滴の高さと少なくとも等しい、請求項13記載の装置。
- 上記電極のアレイは、駆動電極のアレイを含み、
細長い基準エレメントであって、該基準エレメントと上記プリント回路基板の第1側面との間にスペースを形成するための距離により上記プリント回路基板の第1側面に実質的に平行でかつ上記プリント回路基板の第1側面から離れて間隔をあけられ、上記距離は、上記スペースに配置される液滴を含むのに十分なものである、基準エレメントをさらに備える、請求項1から11のいずれか一項に記載の装置。 - 上記細長い基準エレメントは、一つ若しくは複数のワイヤーのアレイである、請求項15記載の装置。
- 上記細長い基準エレメントは、板である、請求項15記載の装置。
- 上記基準エレメント板は、上記プリント回路基板の第1側面に面する板表面を備え、該板表面は疎水性である、請求項17記載の装置。
- 上記プリント回路基板は、第1プリント回路基板を含み、
上記装置は、
(a)第1側面及び第2側面を有する第2プリント回路基板であって、上記第2プリント回路基板の第2側面と上記第1プリント回路基板の第1側面との間にスペースを形成するための距離により上記第1プリント回路基板と実質的に平行でありかつ上記第1プリント回路基板から離れて間隔をあけられ、上記距離は上記スペースに配置される液滴を含むのに十分なものである、第2プリント回路基板と、
(b)上記第2プリント回路基板の第2側面に配置される駆動電極のアレイ及び一若しくは複数の基準エレメントのアレイと、をさらに備え、
上記電極セレクターは、上記電極のアレイの連続作動を動的に作成しそれにより上記第1プリント回路基板の第1側面及び上記第2プリント回路基板の第2側面に配置された液滴が電気的に操作される、請求項1に記載の装置。
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