JP2005186265A - 微細製作エラストマーバルブおよびポンプシステム - Google Patents
微細製作エラストマーバルブおよびポンプシステム Download PDFInfo
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Abstract
【解決手段】 エラストマー構造を製作する方法は:第一微細製作モールドが、第一エラストマー層20の底部表面に沿って延びる第一凹部を形成する第一隆起突出部を有する、工程;第二微細製作モールドが、該第二エラストマー層22の底部表面に沿って延びる、第二凹部を形成する第二隆起突出部を有する工程;該第二エラストマー層22の底部表面を、該第一エラストマー層の頂部表面上へ結合し、その結果、制御チャネル32が、該第一および第二エラストマー層20、22の間の第二凹部中に形成される工程;および平坦基板の頂部上の該第一エラストマー層20を位置決めし、その結果、フローチャネルが該第一エラストマー層と該平坦基板との間の該第一凹部中に形成される工程、を包含する。
【選択図】 図4
Description
本非仮特許出願は、2001年4月6日に出願された非仮特許出願第09/826,583号の部分継続出願である。この非仮特許出願第09/826,583号は、2000年11月28日に出願された非仮特許出願第09/724,784号の部分継続出願である。この非仮特許出願第09/724,784号は、2000年6月27日出願された非仮特許出願第09/605,520号の部分継続出願である。本特許出願は、以下の既に出願された仮特許出願の優先権を主張する:米国仮特許出願第60/141,503号(1999年6月28日出願)、米国仮特許出願第60/147,199号(1999年8月3日出願)、および米国仮特許出願第60/186,856号(2000年3月3日出願)。これらの先行の仮特許出願のテキストは、本明細書中で参考として援用される。
本明細書中に記載された仕事は、部分的に、米国国立健康研究所の付与番号HG−01642−02によって支援される。米国政府は、したがって、本発明において特定の権利を有し得る。
本発明は、微細製作された構造体と、微細製作された構造体を製作する方法とに関するものであり、また、流体速度を調整するための微細製作されたシステムに関連する。
微細流体ポンプおよび微細流体バルブを設計するにあたっての多様なアプローチが試みられてきた。残念ながら、これらアプローチの各々はそれ自体の制約を受けている。
本発明は、オン/オフバルブ、切り替えバルブ、および、ポンプのような、互いに一緒
に接着されたエラストマーの多様な層から作製された微細製作された構造体を製造し、作動させるためのシステムを明示している。本発明の構造体および方法は、流体運動を制御およびチャネリングするのに理想的なほど好適である。
マー構造を作製する。
方へ撓み可能である。
本発明は、ポンプまたはバルブとして使用できる多様な微細製作エラストマー構造体を有している。好ましいエラストマー構造体を製造する方法も明示されている。
本発明を製造する2つの具体的な方法がここに提示される。本発明がこれらの方法のうちの一方または他方による製造に限定されるものではないものと理解するべきである。むしろ、本微細構造を製造する他の好適な方法も、本方法の修正例を含めて、思量される。
図1を参照すると、第1の微細加工モールド10が提供される。微細加工モールド10は、多くの従来のシリコン処理方法によって製造され得、この方法には、フォトリソグラフィー、イオンミリング(ion−milling)、および電子線リソグラフィーが挙げられるが、これらに限定されない。
マー層20は、次いで、共に結合されて、別のエラストマー層222から構成される膜を有する一体化(すなわち、モノリシックな)エラストマー構造24を形成する。
ポンプまたはバルブとして使用することができるエラストマー構造体を製造する第2の具体的方法が、図8から図18に示された順次の工程に明示されている。
のみを残す。図15を参照すると、図示のように、エラストマー構造体45(第2のエラストマー層42とフォトレジスト44Bの第1のラインとから構成されている)および第2のフォトレジストのライン48Bの頂面の上に第3のエラストマー層50が次いで堆積され、これにより、エラストマーの構造体45と第3のエラストマー層50との間でフォトレジスト48Bの第2のラインを封入している。
微細製作は、本発明の実施態様に従って製作されたエラストマー構造の特徴のサイズを言及する。一般に少なくとも1つの寸法の微細製作された構造の変形は、微視的(すなわち1000μm以下)である少なくとも1つの寸法で、ミクロンレベルまで制御される。微細製作は、微視的レベルでの特徴寸法の作製のために設計された、フォトリソグラフィおよびスピンコーティングなどの、半導体またはMEMS製作技術を典型的には含み、少なくともいくつかの寸法の微細製作構造の寸法は、合理的に構造を解像/画像化する顕微鏡を要求する。
を含む。
る。本発明の実施態様に従った、フローチャネルの他の範囲の深さの限定的ではない列挙は、0.01から1000ミクロンであり、より好ましくは0.05から500ミクロンであり、より好ましくは0.2から250ミクロンであり、そしてより好ましくは1から100ミクロンであり、より好ましくは2から20ミクロンであり、そして最も好ましくは5から10ミクロンである。例示的なチャネル深さは、0.01μm、0.02μm、0.05μm、0.1μm、0.2μm、0.5μm、1μm、2μm、3μm、4μm、5μm、7.5μm、10μm、12.5μm、15μm、17.5μm、20μm、22.5μm、25μm、30μm、40μm、50μm、75μm、100μm、150μm、200μmおよび250μmを含む。
チャ7602aおよび7602bは、図71Aに示されるように、複数レジスト層7604および7606のパターニングを通じて直接的に生成され得る。図71Aのモールド7600からのエラストマー物質7608の除去の際、異なる高さYおよびY’の部分7612aおよび7612bを有するフローチャネル7612をフィーチャ化する図71Bに示されるエラストマー層7610が、形成され得る。
(軟性リソグラフィー接着)
エラストマーの層20および22(または、エラストマー層42、46、および50)は、パターン化されたエラストマーの層を備えたポリマーに固有である化学的性状を利用して、一緒に化学的に結合されるのが好ましい。最も好ましくは、この結合は2種の構成要素の「付加硬化」結合を備える。
製され得る。各層は別々に硬化する。この2つの層が接触されて、そして上昇した温度において加熱されると、それらは不可逆的に結合してモノリシックエラストマー基板を形成する。
により製造されたModel ELC 500デバイスを利用して、窒素下で10分間、紫外線のもとで初期に硬化した。この組み立てられた層は、次いで追加の30分間で硬化された。反応は、Ciba−Geigy Chemicalsにより製造されたIrgacure500の0.5%vol/vol混合物により触媒された。得られたエラストマー材料は、適度な弾性およびガラスへの付着を示した。
達成され得る。エラストマー層の間の結合は、相互浸透および未硬化エラストマー層のポリマー鎖の、硬化エラストマー層のポリマー鎖との反応により生じる。エラストマー層の引き続く硬化は、エラストマー層の間の結合を作製し、そしてモノリシックエラストマー構造を作製する。
Allcockらの、Contemporary Polymer Chemistry,第二版は、一般にそのガラス転移温度と液化温度との間の温度で存在するポリマーとしてのエラストマーを記載する。エラストマー材料は、ポリマー鎖が容易に捻れ運動を行い、力に反応して骨格鎖のコイルの解きを可能にし、この骨格鎖の再コイル化により、力が存在しない場合の以前の形状を呈するために、弾性特性を示す。一般に、エラストマーは、力が適用されると変形するが、力が除去されると次にはそのもとの形状に戻る。エラストマー材料により示されるこの弾性は、ヤング率により特徴づけられ得る。約1Paと1TPaとの間、より好ましくは約10Paと100GPaとの間、より好ましくは約20Paと1GPaとの間、より好ましくは約50Paと10MPaとの間、そしてより好ましくは約100Paと1MPaとの間のヤング率を有するエラストマー材料が本発明に従って有用であるが、これらの範囲の外のヤング率を有するエラストマー材料もまた、特定の適用の必要に依存して利用され得る。
シラン架橋(型)シリコーンエラストマー(族)のようなエラストマーポリマーから製造される。しかし、本システムはこの1つの処方物のポリマー、この1つの型のポリマー、または、この族のポリマーにすら限定されず、むしろ、ほぼいかなるエラストマーのポリマーでも好適である。この微細バルブの製造の好ましい方法についての重要な要件は、エラストマーの複数の層を互いに一緒に接着する能力である。多層軟性リソグラフィーの場合、エラストマーの各層は別個に硬化されてから、互いに接着される。この設計は、互いに接着するのに十分な反応性を硬化された層が有していることを必要とする。各層が同一型のものであって、互いに結合する能力があるか、または、各層が2つの異種型のものであって、互いに結合する能力があるか、のいずれかである。別な可能性には、各層の間に接着剤を使用すること、および熱硬化性エラストマーを使用することが挙げられる。
ポリイソプレン、プリブタジエン、および、ポリクロロプレンは全てジエンのモノマーから重合化されており、それゆえ、重合化されると、1モノマーにつき1つの2重結合を有している。この2重結合はポリマーが加硫処理(本質的には、加熱処理により2重結合の間に架橋を形成するために硫黄が使用される)によりエラストマーに変換され得るようにする。これは、結合されるべき各層の不完全な加硫処理による同質多層軟性リソグラフィーを容易に可能にする。フォトレジスト封入は同様の機構により可能となる。
純正ポリイソブチレンは2重結合を有していないが、少量(約1%)のイソプレンを重合に際して含ませることにより、エラストマーとして使用するための架橋型結合される。イソプレンのモノマーはポリイソブチレンの基幹に垂下する2重結合を供与し、これを上述のように硫化することができる。
ポリ(スチレン−ブタジエン−スチレン)はリビングアニオン重合により生成され(すなわち、反応の途中で天然の連鎖終端段階は存在しない)、そのため、「生きた(living)」ポリマーの端部は硬化ポリマー中に存在し得る。これにより、このポリマーは本フォトレジスト封入システムの天然の候補となる(この場合、硬化層の頂面に注がれた液状層に未反応のモノマーが態様に存在することになる)。不完全な硬化は同質の多層軟性リソグラフィーを可能にする(A対A結合)。この化学的特性はまた、余剰のブタジエン(「A」)と結合剤とを用いて一方の層を作成し、ブタジエンを用いずに他方の層(「B」)を作成することを促進する(異種多層軟質リソグラフィーとして)。SBSは「熱硬化性エラストマー」であり、或る一定温度を越えると、このエラストマーが溶融して可塑性になる(弾性になるのとは対照的に)ことを意味しており、温度を低下させると再度、エラストマーを生じる。従って、加熱処理により各層は互いに一緒に結合することができる。
ポリウレタンはジイソシアネート(A−A)とジアルコールまたはジアミン(B−B)から生成されており、かなり多様なジイソシアネートとジアルコール/アミンが存在しているので、互いに異種のポリウレタンの数は膨大である。しかし、ポリマーのA対Bの性質によりこれらは、一方の層で過剰なA−Aを利用し、他方の層で過剰なB−Bを利用することにより、丁度、RTV 615と同様に、異質多層軟性リソグラフィーについて有用となる。
シリコーンポリマーは最大級の構造的多様性を有しているように思われるが、市場で入手可能な最大数の処方物が存在しているという点では、ほぼ間違いない。RTV 615
のビニルから(Si−H)への架橋(これは異質多層軟性リソグラフィーとフォトレジスト封入の両方を可能にする)は、既に論じられているが、これは、シリコーンポリマーの化学的特性で使用されるいくつかの架橋法のうちの1つにすぎない。
上述の単純な「純正」ポリマーの使用に加えて、架橋剤を添加することもできる。いくつかの(硫化のための、垂下式2重結合を有するモノマーのような)試薬は、同質(A対A)の多層軟性リソグラフィーまたはフォトレジスト封入を可能にするのに好適であり、相補型の試薬(すなわち、垂下式2重結合を有する1つのモノマー、および垂下式Si−H群を有している別なモノマー)は、異質な(A対B)多層軟性リソグラフィーに好適である。このアプローチにおいて相補型試薬が隣接する層に添加される。
更に、クロロシラン、またはメチルシラン、エチルシラン、および、フェニルシランなどののような材料を取り込むポリマー、および例えば、ダウケミカル社のシルガード(Sylgard)182、184、186のようなポリジメチルシロキサン(PDMS)、または、UBCケミカルから販売されているエベクリル(Ebecryl)270またはIrr245のような(これらに限定されないが)脂肪族ウレタンジアクリレートを使用することもできる。
エラストマーは、同一分類の、架橋できないポリマー鎖で「ドーピング処理」し得る。例えば、RTV 615はGE SF96−50シリコーン流体で希釈し得る。これは、未硬化のエラストマーの粘性を減じる働きをし、硬化したエラストマーのヤング率を低減する。本質的に、架橋可能なポリマー鎖は「不活性な」ポリマー鎖の添加により更に離散するように分岐され、これが「希釈」と称される。ヤング率の劇的低下に伴って、RTV
615は90%までの希釈率で硬化する。
一旦、エラストマー材料が適切な形状へ成形またはエッチングされると、特定の適用に関連した操作を促進するためにこの材料を前処理することが必要であり得る。
図7Bおよび図7Hは共に、第二フローチャネルを加圧することによる第一フローチャネルの閉鎖動作を示しており、図7B(対応する図7Aにおけるフローチャネル32を破断した正面断面図)は開状態の第一フローチャネル30を示しており、図7Hは第二のフローチャネル32の加圧により閉鎖された第一のフローチャネル30を示している。
であれ、液体によるものであれ)により、膜25は下方向に撓み、それにより、フローチャネル30を通過するフローFを絞って細くする。従って、チャネル32の圧力を変動させることにより、フローチャネル30は線型作動可能なバルブ動作システムが提供されて、膜25を移動させることにより所望されるとおりにフローチャネル30が開閉され得るようになる。(例示のみを目的として、図7Gのチャネル30は「完全閉鎖」位置ではなく、「ほぼ閉鎖した」位置に示されている)。
このようなバルブがチャネル自体の屋根を移動させることにより(すなわち膜25を移動することにより)作動されるために、この技術により製造されるバルブおよびポンプは、真にゼロデッドボリュームを有し、そしてこの技術により作製されたバルブを切替えることは、バルブの動作ボリューム(例えば約100×100×10μm=100pL)にほぼ等しいデッドボリュームを有する。このようなデッドボリュームおよび移動膜により消費される領域は、ほぼ2オーダーの大きさで公知の通常の微細バルブより小さい。より小さいバルブ、およびより大きいバルブ、ならびに繰り替えバルブは、本発明において考慮され、そしてデッドボリュームの範囲の限定的でない列挙は、1aLから1μL、100aLから100nL、1fLから10nL、100fLから1nL、および1pLから100pLを含む。
(1) w=(BPb4)/(Eh3)、ここで:
w=プレートの撓み;
B=形状係数(長さ対幅およびプレートのエッジの支持に依存する);
p=付与圧力;
b=プレート幅
E=ヤング率;および
h=プレート厚み
従って、この極端に単純化された表現においてさえ、圧力に応答したエラストマー膜の撓みは:長さ、幅、および膜の厚み、膜の可撓性(ヤング率)、適用された作動力、の関数である。これらの各々のパラメータは、本発明に従った特定のエラストマーデバイスの実際の寸法および物理的組成に依存して、広く変化するために、広い範囲の膜厚および弾性、チャネル幅、および作動力が、本発明により考慮される。
二フローチャネル32のバルブ開度対付与圧力を図示する。このデバイスの膜は、約30μmの厚み、および約750kPaのヤング率を有する、General Eletric Silicones RTV 615の層により形成される。図21aおよび21bは、バルブの開度がほとんどの付与圧力の範囲にわたって実質的に直線的である程度を示す。
れ得、この膜へ付与された圧力の準瞬間移動を生じる。しかし、バルブの置換された体積が大きいか、または制御チャネルが狭いと、制御流体のより高い粘性が作動における遅延に貢献し得る。圧力移動のための最適媒体は、従って、特的の適用およびデバイス形状に依存し、そしてガス状、および液体媒体の両方が本発明により考慮される。
特定の実施態様に伴って変化する。
されるミニチュアバルブの制約のせいで、制御信号と制御圧力反応との間にも遅延が存在する。かかる遅延をtと称し、1/e時定数をτと称すると、各値は以下のようになる。すなわち、topen=3.63ms、τopen=1.88ms、tclose=2.15ms、τclose=0.51msである。3τが開閉ごとに割り当てられるとすると、このバルブは、水溶液で充満すると、75Hzで快適に作動する。
本発明のフローチャネルは必要に応じて、それぞれの所望の応用例に依存して、異なる利点を提供する異なる断面寸法および断面形状で設計し得る。例えば、より低いフローチャネルの断面形状は、その全長に沿って、または、それを横断して延びる上部横断チャネルの下に配置された領域に、湾曲した上表面を有し得る。このような湾曲した上表面は、下記のように、バルブのシーリングを容易にする。
フローチャネルが採用される場合には、この全周辺(2×フローチャネル高さ+フローチャネル幅)が、このフローチャネルへ強制的に入らなければならない。しかし、弧状チャネルが使用される場合には、より小さい材料の周辺(半円弧状部のみ)がこのチャネルに入らなければならない。この様式で、この膜は、作動のための周辺におけるより小さい変化を要求し、従って付与された作動力により応答性となり、このチャネルをブロックする。
される。すぐ上に記載した突出部を有した実施態様、またはフローチャネルにおける凹部を有する実施態様、などのより複雑な断面形状もまた本発明により考慮される。
上述の圧力に基づく作動システムに加えて、必要に応じて静電作動システムおよび磁気作動システムも以下のように思量される。
ラックの懸濁液へ曝露することにより、エラストマー表面上のカーボンブラック(すなわちCabot Vulcan XC72R)の堆積によってもまた形成される。あるいは電極70は、導電性材料(すなわちカーボンブラックまたは微細分割粒子)でドーピングされたエラストマーから全体層20を構成することにより、形成され得る。なお、さらに代替的には、この電極は、静電堆積により、または炭素を生成する化学反応により形成され得る。本発明により実施される実験において、カーボンブラック濃度を5.6×10−16から約5×10−3(Ω−cm)−1へ増加させると、導電性を示した。動くことが要求されない低部電極72は、上述のように柔軟な電極であるか、または蒸着した金、金属プレート、またはドーピングした半導体電極などの通常の電極であり得る。
よって誘導された動電学的フローは、圧力差を生じさせ得る。
図23Aおよび図23Bは、先に(例えば、図7Aで)明示したシステムと同一の単一のオン/オフバルブの図を示している。図24Aおよび図24Bは、図23に見られるような単一のアドレス可能な複数のオン/オフバルブのから構成されているが、一緒にネットワーク化された、蠕動ポンピングシステムを示している。図25は、図24の蠕動ポンピングシステムについて、実験で達成されたポンピング流量対周波数を示すグラフである。図26Aおよび図26Bは、単一制御ラインにより制御可能である複数のフローチャネルの概略図を示している。このシステムはまた、図23の単一のアドレス可能な複数のオン/オフバルブを備え、一緒に多重化されているが、図23の構成とは異なる構成である。図27は、図23の単一のアドレス可能な複数のオン/オフバルブから構成され、共に接合またはネットワーク化され、選択されたチャネルを通る流体フローを可能にするように適合された多重化システムの概略図である。
制御ライン32Aおよび32Cを一緒に作動させ、その後、制御ライン32Aを作動させ、それに続いて制御ライン32Aおよび32Bを一緒に作動させた後、制御ライン32Bの作動が続き、その後で制御ライン32Bおよび32Cを一緒に作動させるといったパターンにより、蠕動を作動させ得る。これは連続する「101、100、110、010、011、001」のパターンに対応しており、この場合、「0」は「バルブ開」を示し、「1」は「バルブ閉」を示している。この蠕動パターンはまた、120度パターンとして知られてもいる(3つのバルブの間の作動の位相角度のことを意味する)。他の蠕動パターンも、60度のパターンおよび90度のパターンを含め、同等に可能である。
ブ7808に伝播され、チャネル7802を通じて以前にフローされた物質の方向の逆転を引き起こすことなく、別のポンピング配列のためのステージを設定する。
ると、フローチャネル30A、30B、30Eおよび30FにおけるフローF1、F2、F5およびF6を遮断する。理解されるように、1つ以上の制御ラインが同時に作動され得る。例えば、制御ライン32Aおよび32Cは同時に加圧されて、F4以外の流体の全てのフローを遮断し得る(32AはF1、F3およびF5を遮断し、32CはF1、F2、F5およびF6を遮断する)。
る。本発明のこの局面は、以下に図74と関連して示される。
マー層8112の底部表面内の凹部と下にある第二のエラストマー層8108との間に規定される。
は、複数のフローチャネル8602を規定する下部エラストマー層を含み、各フローチャネル8602は、M個の平行な分岐8602aに分割される。図81に示される特定のマルチプレクサの実施形態では、M=2である。
配することが意図される場合、第三の制御ラインセット8214の制御ライン8216aおよび8216bが作動され、第二制御ラインセット8214による信号の、第一の機能性ブロック8204および第二の機能性ブロック8206への連絡を遮断する。
図28A、図28B、図28Cおよび図28Dに例示された本発明の更なる実施態様では、フローラインに沿って配置された複数の反応チャンバのうちから別なもう1つに、流体フローを選択的に方向付けるためのシステムが提示されている。
る。図30を参照すると、制御ライン32Aまたは32Dのいずれかまたは両方が減圧されて、側方向通路35を通る(互いに平行なフローチャネル30Aと30Bとの間の)流体フローが可能となる。本発明のこの局面では、制御ライン32Cおよび32Dの加圧が、35Aと35Bとの間のフローチャネル30Aを遮断し、横方向通路35Bも遮断する。このように、フローF1として入ったフローがフローチャネル30Aおよび35Aを通って連続的に移動し、フローF4としてフローチャネル30Bを出る。
なお別の新規な実施態様においては、流体通路は、2つの垂直な方向のうちのいずれかに選択的に指向して流れ得る。このような「切換え可能なフローアレイ」システムの1例は、図31A〜31Dに与えられる。図31Aは、エラストマー(または他の任意の適切な基質)の第一層90の底面図を示し、この第一層の底部表面は、固体ポスト92のアレイにより規定されるフローチャネルグリッドを形成する凹部のパターンを有し、このポストのそれぞれの周囲を、フローチャネルが通過する。
本発明のエラストマーバルブ構造はまた、生体ポリマー合成(例えば、オリゴヌクレオチド、タンパク質、ペプチド、DNAなどの合成)に使用され得る。好ましい局面においては、このような生体ポリマー合成システムは、一体化されたシステムを含み得、このシステムは、容器のアレイ、特定の容器からのフローを選択するための流体論理(本発明による)、合成が実施されるチャネルまたは容器のアレイ、および選択された試薬が流入するチャネルを決定するための流体論理(これもまた本発明による)を含む。このようなシ
ステム200の1例を、以下のように、図32に示す。
506をパターン化して、マスクされた領域3508を覆い、曝露されたマスクされていない領域3510を残す工程を示す。図35Cは、マスクされていない領域3510においてエッチングブロッキング層3504を除去する溶媒に曝露する工程を示す。
下部エラストマー層8704および上部エラストマー層8708それぞれの両方を通じて堅い中空部材8714をパンチングすることによって形成され得る。再度、下部エラストマー層8704のフローチャネル側8704aからこのコア形成プロセスを開始することにより、フローチャネル8702を有する第二のビアの正しい整列を保証する。
本発明のモノリシック微細製作エラストマーバルブおよびポンプの有利な応用は、多数である。従って、本発明は、その特定の応用または使用のいずれにも限定されない。好ましい局面においては、本発明の以下の使用および応用が考慮される。
本発明の微細製作ポンプおよびバルブはまた、細胞の選別およびDNAのサイジングのための、フローサイトメーターにおいて使用され得る。サイズに基づく物体の選別は、多くの技術分野において非常に有用である。
スであって、粒子と溶質との間の電気的相互作用よりはむしろ、流体フローの機械的制御に依存する、デバイスが必要とされる。
放射線3640の吸収または放出が、次いで、検出器3644により検出される。
半導体ガスフロー制御のため(特に、少量のガスが正確に測定される、エピタキシャル応用のため)のシステムもまた、本発明により考慮される。例えば、半導体デバイスの製造の間に、固体材料が、化学蒸着(CVD)を利用して半導体基板の頂部に堆積される。これは、この基板をガス前駆体材料の混合物に曝露し、これによってこれらのガスを反応させ、生成物をこの基板の頂部に結晶化させることによって、達成される。
記載される本発明の実施態様は、ここまでは、全体がエラストマー材料で構成された構造の操作に関するが、本発明は、このタイプの構造に限定されない。具体的には、エラストマー構造を、シリコンに基づく従来の半導体構造と組み合わせることは、本発明の範囲内である。
程、このエラストマーを硬化させる工程、形成したエラストマーをモールドから除去する工程、および導電性ドーパントを形成したエラストマーの表面領域に導入する工程により、形成され得る。あるいは、図7C〜7Gに関して上に記載したように、第一エラストマー層3822は、エラストマー材料がチャネル壁の高さと同じ高さになるように、エラストマー材料を交差チャネルを有するモールドに挿入し、次いで別個のドープしたエラストマー層を既存のエラストマー材料と結合して頂部表面に膜を形成することによって、エラストマーの2つの層から形成され得る。
記載したばかりの微細ミラーアレイ構造は、入射光の反射を制御する。しかし、本発明は、反射の制御に限定されない。本発明のさらに別の実施態様は、レンズおよびフィルタ
ー構造を作製するために、入射光の屈折の正確な制御の実施を可能とする。
された、不均一に間隔を空け、流体で満たされた、直列のフローチャネル4108に遭遇する。これらのそれぞれの流体/エラストマー領域に存在する物質の光学特性が異なる結果として、入射光の部分は均一には屈折されず、相互作用して干渉パターンを形成する。ちょうど記載した様式の屈折性構造のスタックは、入射光の、さらにより複雑で特殊化された屈折を達成し得る。
上記図7Bおよび図7Hは、エラストマー膜が、第1の緩和位置からフローチャネルがブロックされている第2の作動位置へと移動可能であるバルブ構造を示す。しかし、本発明は、この特定のバルブ構成に限定されない。
本発明のさらなる適用において、エラストマー構造は、物質の分離を実行するために利用され得る。図43は、このようなデバイスの1つの実施態様を示す。
質および用いられる特定のクロマトグラフィー技術に依存する。エラストマー分離構造は、種々のクロマトグラフィー技術を用いる使用に適切であり、これには、ゲル排除、ゲル浸透、イオン交換、逆相、疎水性相互作用、アフィニティークロマトグラフィー、急速タンパク質(fast protein)液体クロマトグラフィー(FPLC)、および高速液体クロマトグラフィー(HPLC)の全ての形式が挙げられるがこれらに限定されない。HPLCに利用される高い圧力は、ウレタン、ジシクロペンタジエンまたは他のエラストマーの組合せの使用を必要とし得る。
本発明のさらなる適用において、エラストマー構造は、生物または他の生物学的材料を操作するために利用され得る。図44A〜44Dは、本発明に従う細胞ペン構造の1つの実施態様の平面図を示す。
らく図36に関係する上記のような選別構造によってロードされる。図44B〜44Cは、1)近接したペン4404aおよび4404bのいずれかの側のバルブ4406を開くこと、2)細胞CおよびGを置き換えるために水平フローチャネル4402aをポンプすること、次いで3)細胞Cを除去するために、垂直フローチャネル4402bをポンプすることによって、個別に貯蔵された細胞Cにアクセスすること、および取り除くことを示す。図44Dは、第2の細胞Gが、水平フローチャネル4402aを通して液体のフローの方向を逆向きにすることによって細胞ペンアレイ4400中のその前の位置の中に移動されて戻されることを示す。
記載された細胞ペン以外の機能を行うために用いられ得る。例えば、クロスフローチャネルアーキテクチャは、用途を最大にする際に利用され得る。
本発明のなおさらなる適用において、エラストマー構造は、電子工学の分野にしばしば用いられる発振器回路に類似する圧力発振器構造を作製するために利用され得る。図47は、このような圧力発振器構造の1つの実施態様の平面図を示す。
先の記載は、制御チャネルが上に配置され、かつ下にあるフローチャネルからエラストマー膜に介入することによって分離される微細製作されたエラストマーバルブ構造に焦点を当てるが、本発明は、この構成に限定されない。図48Aおよび48Bは、本発明の1つの実施態様に従う側面作動バルブ構造の1つの実施態様の平面図を示す。
以下は、本発明のさらなる局面を表す:本発明のバルブおよびポンプは、薬物送達に(例えば、移植用薬物送達デバイスにおいて);生物学的流体のサンプリングに(例えば、サンプル間にスペーサー流体の栓を備えるカラムに連続してサンプルを貯蔵することによって)使用され得、ここでこのサンプルは、異なる貯蔵容器中に流され得るか、または適切なセンサ(単数または複数)に直接的に通され得る。このような流体サンプリングデバイスはまた、患者の身体において実行され得る。
のプローブに対して多くの通路を作製し得る。このようなデバイスは、サンプルに、代わりの相補性プローブに結合する機会を与えるが、通常は、非相補性プローブ上に存在して、消耗される。このようなループ状フローシステムの利点は、このシステムが必要とするサンプル容量を減少させ、それによってアッセイの感度を増加させることである。
以下は、本発明のさらなる局面を表す:エラストマー構造の微細製作されたチャネル内の流体の流れを制御する湾曲可能な膜の使用;微細製作された可動部を備える微細製作されたエラストマーデバイスを作製するエラストマー層の使用;および微細製作されたバルブまたはポンプを作製するエラストマー材料の使用。
ラストマーブロックの膜部分によって分離される第1および第2の微細製作された凹部)で形成されたエラストマーブロックを提供すること、ならびに膜部分が第1および第2の凹部のうちの一方に湾曲されるように、膜部分に作動力を印加することを包含する。
上述の図1〜図7および図8〜図18は、それぞれ、本発明によるエラストマー構造を製作する多層ソフトリソグラフィおよびカプセル化方法の実施形態を示す。しかしながら、これらの製作方法は、例示にすぎず、エラストマー構造を生成するためにこれらの技術の変形が用いられ得る。
402は、接触するようにそれぞれ配置される。あるいは、図51は、エラストマー層の配向を示し、ここで、凹部を有する面5500および5502は、接触するように配置されるので、凹部は、構造の両側に配置される。このようなエラストマー構造5512は、互いに交差するチャネル5504および5506を生成するように、基板5508と5510とにはさまれ得る。
図38のマイクロミラーアレイ構造との関連ですでに議論されたように、本発明の製作されたエラストマー構造は、複合構造を生成するために非エラストマー材料と組み合わされ得る。このような複合構造の製作は、ここで、さらに詳細に議論される。
またはチャンバといった受動機能(passive feature)を有する硬質の基板を含み得る。しかしながら、本発明は、このアプローチに限定されず、下に位置する硬質の基板は、凹部を有するエラストマーコンポーネントと相互作用する能動機能(active feature)を有し得る。
ラストマーコンポーネントに形成する工程と、材料を凹部内に配置する工程と、能動デバイスを含む実質的に平坦な非エラストマーコンポーネントを形成する工程と、エラストマーコンポーネントを非エラストマーコンポーネントに対してシールして能動デバイスが膜部分および材料のうちの少なくとも1つと相互作用し得るようにする工程とを包含する。
エラストマー構造の潜在的に有用な特性は、気体透過性である。具体的には、エラストマー材料は、特定の気体の種類の拡散を可能にし得、他方、液体の拡散を防止する。この特性は、小さい体積の流体を操作する際に非常に有用であり得る。
る。
複数のハイスループットスクリーニングおよび診断の用途は、反応チャンバ内に異なった試液の正確な組み合わせを必要とする。流体のフローを確実にするために、微小流動デバイスのチャネルをプライム化することが必要とされる場合、サンプルを導入する前に、混合溶液が反応チャンバの内容物によって希釈または汚染されないことを保証するのは困難であり得る。
ラストマー層6302は、制御チャネル(図示せず)と流体をやり取りする制御チャンバ6306を含む。制御チャンバ6306は上に位置し、膜6310によって第2のエラストマー層6304のデッドエンド反応チャンバ6308から分離される。第2のエラストマー層6304は、さらに、デッドエンド反応チャンバ6308に通じるフローチャネル6312を含む。上述のように、第1の反応物Xは、圧力下でデッドエンド反応チャンバ6308に導入され得る
図58Bは、制御チャンバ6306内の圧力の増加の結果を示す。具体的には、制御チャンバ圧力が増加すると、膜6310を下方に向かって屈曲させて反応チャンバ6308に入れ、反応チャンバ6308の有効体積を体積Vだけ低減する。これは、次に、反応チャンバ6308から反応物の等価な体積Vを排除し、従って、第1の反応物Xの体積がフローチャネル6312から出力される。制御チャンバ6306において増加する圧力とフローチャネル6312から出力される材料の体積との完全な相関関係が、正確に較正され得る。
上述のように、本発明による微細加工されたエラストマーデバイスの実施形態は、混合および反応の目的で、極めて正確に流体を計量することを可能にする。しかしながら、流体体積の計量についての正確な制御は、さらに、タンパク質等の分子の結晶化を促進するために用いられ得る。
び高圧を付与して膜が撓んでチャンバに入るようにすることによって環境に対して再シールされ得る。再シールは、再結晶化がほぼ数日単位または数週間単位で生じることが要求され得る場合に必要であり得る。チャンバの目視検査によって高品質の結晶の存在が明らかになった場合、結晶は、使い捨てエラストマーシステムのチャンバから物理的に除去され得る。
上述のように、本発明による微細加工されたエラストマーデバイスの特定の実施形態は、流体のフローを制御するために圧力を利用する。従って、これらの硬化を強化するために付与された圧力の増幅を可能にする構造をデバイス内に含むことが有用であり得る。
p2/p1=圧力増幅率である。
等式(2)は、増幅構造それ自体の弾力性による近似値であり、これは、通常、増幅効果を低減する作用をする。
従来の流体ハンドリングデバイスにおける潜在的に有用な1つの構造は、導管を通る流体が1方向にのみ流れることを可能にするチェックバルブである。図61Aおよび図61Bは、本発明の実施形態による微細加工された逆流防止弁構造の平面図および断面図のそれぞれを示す。微細加工構造6600は、エラストマー6604に形成されたフローチャネル6602を含む。フローチャネル6602の左部分6602aおよび右部分6602bは、逆流防止弁6606を通じて流体を互いにやり取りする。
2Aにおいて、第1のミクロ機械加工されたシリコンモールド6620は、第1の凹部6624を規定する第1のパターニングされたフォトレジスト層6622を用いて形成される。第1の凹部は、次に、フローチャネルの底部シール部分6626を規定する。図62Bにおいて、エラストマーは、モールド6620上に流し込まれ、かつ凝固され、従って、第1の成型されたピース6625の除去は、隆起した底部シール部分6626を生成する。図62Cにおいて、第2のミクロ機械加工されたシリコンモールド6630は、第2の凹部6634を規定する第2のパターニングされたフォトレジスト層6632を用いて形成され、この第2の凹部は、次に、フローチャネルの天井およびフラップを規定する。図62Dにおいて、エラストマーは、第2のモールド6630上に流し込まれ、かつ硬化され、従って、第2の成型されたピース6636の除去は、突き出したフラップ6608を含む。図62Eにおいて、第1の成型ピース6625および第2の成型ピース6636は、貼り合せられて、介在フローチャネル6602および逆流防止弁6606を生成する。
流体素子は、流れる流体を媒体を有する信号として利用する、およびこれらの信号の改変(スイッチング、増幅)の流体力学の特性を活用する技術に関する。流体素子は、エレクトロニクスと類似であり、電子の流れが信号保有媒体として用いられ、電磁特性は、信号のスイッチングおよび増幅のために利用される。
スを通って流れる流体を制御するために、通常、流圧よりも大きい圧力を制御することを必要とする。しかしながら、本発明による圧力増幅器を用いて、流体回路の制御チャネルおよびフローチャネル内の圧力は、ほぼ同じ大きさであり得る。
の部分から規定され、第2の撓めることが可能な膜は、第2の凹部と第3凹部との間の第2のエラストマー層の部分から規定される。
ラストマー層の膜部分は、並行するチャネルの拡大された部分と、下に位置する並行な分岐との間に規定され、膜部分は、並行なブランチを流れる流体を制御するように、並行な分岐になるように撓めることが可能である。
Microfluidic Systems in Poly(dimethlsiloxane)」、Analytical Chemistry、70(23):4974〜4984ページ(1998年)は、成型された非エラストマー層をチャネルおよびリザーバを有するエラストマー層のひな型を迅速に作成するための原型として利用する微小流動素子のシステムを提示する。
for Integration with Fluid−Handling Systems」Proceedings of Transducers ’95、the 8th International Conference on Solid−State Sensors and Actuators,and EurosensorsIX(スゥエーデン、1995年6月)vol.2、284〜286ページは、空気圧で駆動されてフローチャネルを閉じることができるシリコンプランジャ構造を支持する可動エラストマー部分を備える微小流動素子ポンプ構造を記載する。Fahrenbergらによる「A Microvalve System Fabricated by Thermoplastic Molding」Journal of Micromechanics and Microengineering、vol.5、no.2(1995年6月)169〜171ページは、ポリイミド膜を含むバルブの熱空気圧駆動を記載する。
10th Annual Workshop of Micro Electro Mechanical Systems(日本、1997年1月)114〜118ページは
、エッチングによって実質的に除去された非エラストマー(Si/SiN)架橋に対して硬化されたシリコーン膜を硬化することによるミクロ流体バルブ構造の製作を記載する。Shojiらによる「Smallest Dead Volume Microvalves for Integrated Chemical analyzing Sys
tems」Proceedings of Transducers’91、the 1991 International Conference on Solid−State Sensors and Actuators(サンフランシスコ、1991年6月)1052〜1055ページは、駆動される圧電により駆動される重合化された負のフォトレジスト材料の膜を有する微小流動素子バルブ構造を記載する。
of Transducers’97、the 1997 International conference on Solid−State Sensors and Actuators(シカゴ、1997年)、vol.1、361〜364ページは、非エラストマー膜の駆動を利用する微細加工されたバルブ構造との関連でのポリイミドチェックバルブの使用を記載する。Olssonらによる「Simulation Studies of Diffuser and Nozzle Elements for Valve−less Micropumps」Proceedings of Transducers’97、the 1997 International Conference on Solid−State Sensors and actuators(シカゴ、1007年6月)vol.2、1039〜1042ページは、後で射出成型プラスチックポンプおよびバルブ構造を製作するために利用される、電気めっきされたニッケルモールドを形成するためのシリコンモールドの使用を記載する。
Claims (1)
- 微細流体構造であって
下にある基板と、
該基板の上にある第一エラストマー層であって、該第一エラストマー層は、底部表面に第一凹部を有する、第一エラストマー層と、
該第一エラストマー層の上にある第二エラストマー層であって、該第二エラストマー層は、底部表面にアーチ形の天井を有する第二凹部を有する第二エラストマー層と、
該第一凹部と該第二凹部との間に規定された該第一エラストマー層の膜部であって、該膜部は、該アーチ形の天井に沿って天井を密閉するために上方の第二凹部に湾曲可能であることを含む微細流体構造。
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Cited By (4)
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JP2018522206A (ja) * | 2015-04-30 | 2018-08-09 | オルフィディア リミテッド | マイクロ流体バルブおよびマイクロ流体デバイス |
JP2021060118A (ja) * | 2015-04-30 | 2021-04-15 | オルフィディア リミテッド | マイクロ流体バルブおよびマイクロ流体デバイス |
JP7311156B2 (ja) | 2015-04-30 | 2023-07-19 | オルフィディア リミテッド | マイクロ流体バルブおよびマイクロ流体デバイス |
JP2018517576A (ja) * | 2015-05-13 | 2018-07-05 | ベルキン ビーブイBerkin B.V. | バルブユニットを備える流体流動装置、および、その製造方法 |
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US10155250B2 (en) | 2018-12-18 |
US7766055B2 (en) | 2010-08-03 |
EP1345551A2 (en) | 2003-09-24 |
US20080277005A1 (en) | 2008-11-13 |
US6899137B2 (en) | 2005-05-31 |
US20050166980A1 (en) | 2005-08-04 |
AU2002228664A1 (en) | 2002-06-11 |
US20080173365A1 (en) | 2008-07-24 |
US20020029814A1 (en) | 2002-03-14 |
EP1345551B1 (en) | 2009-04-01 |
US20170001195A1 (en) | 2017-01-05 |
US8104497B2 (en) | 2012-01-31 |
US20080236669A1 (en) | 2008-10-02 |
US7754010B2 (en) | 2010-07-13 |
WO2002043615A2 (en) | 2002-06-06 |
US7216671B2 (en) | 2007-05-15 |
JP2004526578A (ja) | 2004-09-02 |
US8656958B2 (en) | 2014-02-25 |
US20080220216A1 (en) | 2008-09-11 |
US20090151422A1 (en) | 2009-06-18 |
US20150276089A1 (en) | 2015-10-01 |
WO2002043615A3 (en) | 2003-03-13 |
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