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- JPWO2019183608A5 JPWO2019183608A5 JP2020550666A JP2020550666A JPWO2019183608A5 JP WO2019183608 A5 JPWO2019183608 A5 JP WO2019183608A5 JP 2020550666 A JP2020550666 A JP 2020550666A JP 2020550666 A JP2020550666 A JP 2020550666A JP WO2019183608 A5 JPWO2019183608 A5 JP WO2019183608A5
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Description
本明細書に含まれる実施例及び具体例は、本発明対象が実施されうる具体的な実施形態を、限定ではなく例示として示す。言及されたように、他の実施形態が利用されたり派生したりしてよく、本開示の範囲から逸脱しない限り、構造的な、或いは論理的な置換又は変更が行われてよい。本発明対象のそのような実施形態は、本明細書においては、個別に参照されてよく、或いは、「本発明」という言い方でまとめて参照されてよく、「本発明」という言い方で参照することは、あくまで便宜上であって、本出願の範囲を、実際には２つ以上が開示されていても、いずれか１つの発明又は発明概念に自発的に限定することを意図するものではない。従って、本明細書では特定の実施形態を図示及び説明してきたが、この、示された特定の実施形態を、同じ目的を達成するように作られた任意の構成で置き換えてよい。本開示は、様々な実施形態のあらゆる翻案又は変形を包含するものである。当業者であれば、上述の説明を精査することにより、上述の複数の実施形態の組み合わせ、及び本明細書に具体的な記載がない他の実施形態が明らかになるであろう。
〔付記１〕
底面を有する本体と、
前記本体の中央開口部と、
前記底面上の乾燥試薬と、を含み、前記本体は、赤色スペクトル、青色スペクトル、及び緑色スペクトルのうちの少なくとも１つにおける励起波長及び発光波長に対して透過性を有する材料から形成されている、
を含むプラグ。
〔付記２〕
前記乾燥試薬は、前記底面のうちの、前記本体の前記中央開口部の幅より幅広な部分の上にある、付記１に記載のプラグ。
〔付記３〕
前記中央開口部の幅が、前記底面のうちの、前記乾燥試薬を収容している部分より幅広である、付記１に記載のプラグ。
〔付記４〕
前記底面に、前記乾燥試薬が入るキャビティを更に含む、付記１に記載のプラグ。
〔付記５〕
中央開口部の底部と前記プラグ本体の底部との間のプラグ厚さを更に含み、前記キャビティの深さが前記プラグ厚さの９０％未満である、付記４に記載のプラグ。
〔付記６〕
中央開口部の底部と前記プラグ本体の底部との間のプラグ厚さを更に含み、前記キャビティの深さが前記プラグ厚さの７０％未満である、付記４に記載のプラグ。
〔付記７〕
中央開口部の底部と前記プラグ本体の底部との間のプラグ厚さを更に含み、前記キャビティの深さが前記プラグ厚さの５０％未満である、付記４に記載のプラグ。
〔付記８〕
前記プラグ本体の外側エッジから前記キャビティの外周部にかけての環形を前記プラグ底面上に更に含む、付記４に記載のプラグ。
〔付記９〕
前記環形は前記キャビティの前記外周部を完全に取り囲む、付記６に記載のプラグ。
〔付記１０〕
前記キャビティは更に、前記底面に外周部を含み、前記キャビティの開始角度が前記外周部から、前記底面に対して測定され、前記開始角度は６０度以下である、付記４に記載のプラグ。
〔付記１１〕
前記キャビティは前記プラグ本体中央開口部より幅広である、付記４～８のいずれか一項に記載のプラグ。
〔付記１２〕
前記プラグ本体中央開口部は前記キャビティより幅広である、付記４～８のいずれか一項に記載のプラグ。
〔付記１３〕
前記プラグ本体底面は更に、境界のあるエリアを前記プラグ本体底面上に含み、前記乾燥試薬は前記境界のあるエリアの中にある、付記１に記載のプラグ。
〔付記１４〕
前記プラグ底面上の前記境界のあるエリアは、前記プラグ本体底面上のフィーチャによって与えられる、付記１１に記載のプラグ。
〔付記１５〕
前記フィーチャは、前記プラグ底面の上方に持ち上げられているか、前記プラグ底面に埋め込まれている、付記１２に記載のプラグ。
〔付記１６〕
前記フィーチャは湾曲断面又は矩形断面を有する、付記１３に記載のプラグ。
〔付記１７〕
前記境界のあるエリアの幅が前記本体中央開口部の幅より大きいか、前記境界のあるエリアの幅が前記本体中央開口部の幅より小さいか、前記境界のあるエリアの幅が前記本体中央開口部の幅とほぼ同じである、付記１１に記載のプラグ。
〔付記１８〕
前記プラグは研磨仕上げ又は平滑仕上げであることで、前記励起波長及び前記発光波長の透過性を促進する、付記１～１５のいずれか一項に記載のプラグ。
〔付記１９〕
前記プラグ本体上の、前記プラグ本体の前記中央開口部の周囲にフランジを更に含む、付記１～１６のいずれか一項に記載のプラグ。
〔付記２０〕
前記乾燥試薬は、核酸合成試薬、ペプチド合成試薬、ポリマー合成試薬、核酸、ヌクレオチド、核酸塩基、ヌクレオシド、ペプチド、アミノ酸、モノマー、検出試薬、触媒、又はこれらの組み合わせから成る群から選択される、付記１～１７のいずれか一項に記載のプラグ。
〔付記２１〕
前記乾燥試薬は、前記プラグ底面に付着する連続膜である、付記１～１８のいずれか一項に記載の装置。
〔付記２２〕
前記乾燥試薬は凍結乾燥試薬である、付記１～１８のいずれか一項に記載の装置。
〔付記２３〕
前記乾燥試薬は、前記プラグ底面に付着する複数の液滴を含む、付記１～１８のいずれか一項に記載の装置。
〔付記２４〕
アッセイチャンバであって、
ａ．テーパ状入口と、
ｂ．テーパ状出口と、
ｃ．底面及び中央開口部を本体に含むプラグであって、前記本体は、紫外スペクトル、青色スペクトル、緑色スペクトル、及び赤色スペクトルのうちの少なくとも１つにおける励起波長及び発光波長に対して透過性を有する材料から形成されている、前記プラグと、
ｄ．２つの湾曲境界であって、前記２つの湾曲境界と前記プラグとが一緒に前記アッセイチャンバの体積を囲むように、各湾曲境界が前記テーパ状入口から前記テーパ状出口まで延びている、前記２つの湾曲境界と、
ｅ．各湾曲境界から延びる肩部であって、前記プラグが各肩部と接触することによって、前記アッセイチャンバの境界が前記２つの湾曲境界によって与えられ、前記肩部は前記湾曲境界のそれぞれと前記プラグとから延びる、前記肩部と、
を含むアッセイチャンバ。
〔付記２５〕
前記プラグは、前記アッセイチャンバ内で前記プラグ上に乾燥試薬を有する、付記２４に記載のアッセイチャンバ。
〔付記２６〕
前記プラグ上のキャビティが前記肩部のそれぞれの間に位置し、前記乾燥試薬は前記キャビティ内にある、付記２５に記載のアッセイチャンバ。
〔付記２７〕
前記湾曲境界又は前記肩部の一部分が、前記キャビティの外周部に合致する形状になっている、付記２６に記載のアッセイチャンバ。
〔付記２８〕
前記プラグ上の前記乾燥試薬は前記肩部のそれぞれの間に位置する、付記２５に記載のアッセイチャンバ。
〔付記２９〕
前記プラグ本体の前記底部の平らな一部分が前記肩部に接触する、付記２４に記載のアッセイチャンバ。
〔付記３０〕
前記アッセイチャンバの前記体積を調節する為に、前記肩部のそれぞれの高さが使用される、付記２４に記載のアッセイチャンバ。
〔付記３１〕
前記肩部のそれぞれの前記高さは１００マイクロメートル以上である、付記３０に記載のアッセイチャンバ。
〔付記３２〕
前記肩部のそれぞれの前記高さは、前記２つの湾曲境界の、離隔距離が最大になった時点での互いからの距離を超えない、付記３０に記載のアッセイチャンバ。
〔付記３３〕
前記肩部は、前記テーパ状入口から前記テーパ状出口にかけて前記アッセイチャンバの湾曲境界全体を保持する形状になっている、付記２４～３２のいずれか一項に記載のアッセイチャンバ。
〔付記３４〕
前記２つの湾曲境界及び前記肩部はモノリシック基板に形成されている、付記２４に記載のアッセイチャンバ。
〔付記３５〕
前記モノリシック基板の表面に接着された膜を更に含み、前記膜は前記アッセイチャンバの１つの壁を形成する、付記３４に記載のアッセイチャンバ。
〔付記３６〕
付記１～２３のいずれか一項に記載のようなプラグを有する、付記２４～３５のいずれか一項に記載のアッセイチャンバ。
〔付記３７〕
ａ．共通流体経路と、
ｂ．前記共通流体経路に接続された、複数の独立した連続的な流体経路であって、独立した連続的な各流体経路は、
ｉ．アッセイチャンバと、
ｉｉ．空気区画と、
を含み、
１．前記アッセイチャンバは前記共通流体経路に接続されており、前記アッセイチャンバの流体体積の一部が、乾燥試薬をプラグ上に有する前記プラグによって定義されており、
２．前記空気区画は、空気体積を有していて、前記アッセイチャンバを介して前記共通流体経路につながっており、
前記複数の独立した連続的な流体経路の各流体経路は、前記アッセイチャンバと前記共通流体源との接続を含まない閉鎖系であり、各アッセイチャンバは更に、を含む、
前記複数の独立した連続的な流体経路と、
ｃ．両側テーパ状チャンバであって、
ｉｉｉ．前記流体経路の入口導管の終端部と流体連通しているテーパ状入口と、
ｉｖ．前記空気区画の終端部と流体連通しているテーパ状出口と、
ｖ．２つの湾曲境界であって、前記２つの湾曲境界が一緒に前記アッセイチャンバの体積を囲むように、各湾曲境界が前記テーパ状入口から前記テーパ状出口まで延びている、前記２つの湾曲境界と、
を含む前記両側テーパ状チャンバと、
ｄ．各湾曲境界から延びる肩部であって、前記プラグが各肩部と接触することによって、前記アッセイチャンバの境界が前記２つの湾曲境界によって与えられ、前記肩部は前記湾曲境界のそれぞれと前記プラグとから延びる、前記肩部と、
を含む装置。
〔付記３８〕
前記プラグ上のキャビティが前記肩部のそれぞれの間に位置し、前記乾燥試薬は前記キャビティ内にある、付記３７に記載の装置。
〔付記３９〕
前記プラグ上の乾燥試薬が前記肩部のそれぞれの間に位置する、付記３７に記載の装置。
〔付記４０〕
前記プラグ本体の前記底部の平らな一部分が前記肩部に接触する、付記３７に記載の装置。
〔付記４１〕
前記アッセイチャンバの前記体積を調節する為に、前記肩部のそれぞれの高さが使用される、付記３７に記載の装置。
〔付記４２〕
前記肩部のそれぞれの前記高さは１００マイクロメートル以上である、付記４１に記載の装置。
〔付記４３〕
前記肩部は、前記テーパ状入口から前記テーパ状出口にかけて前記アッセイチャンバの湾曲境界全体を保持する形状になっている、付記３７～４２のいずれか一項に記載のアッセイチャンバ。
〔付記４４〕
前記２つの湾曲境界はモノリシック基板に形成されている、付記３７に記載の装置。
〔付記４５〕
前記プラグの前記本体はある深さで前記アッセイチャンバの前記モノリシック基板内に突出しており、前記プラグの前記本体が前記アッセイチャンバの前記モノリシック基板内に突出する前記深さを変化させることによって、前記アッセイチャンバ体積を変化させることが容易に可能である、付記４４に記載の装置。
〔付記４６〕
前記湾曲境界又は前記肩部の一部分が、前記キャビティの外周部に合致する形状になっている、付記３８に記載の装置。
〔付記４７〕
前記装置の少なくとも一部分の表面に接着された第１の膜を更に含み、前記第１の膜は、前記装置の１つ以上のチャンバ、区画、又は導管の１つの壁を形成する、付記３７～４６のいずれか一項に記載の装置。
〔付記４８〕
前記第１の膜に接着された第２の膜を更に含み、前記第２の膜は前記第１の膜より融解温度が高い、付記４７に記載の装置。
〔付記４９〕
前記第１の膜又は前記第２の膜を使用して前記流体経路のそれぞれに形成された熱カシメ領域を更に含み、前記熱カシメ領域は、前記共通流体経路を前記アッセイチャンバ及び前記空気チャンバから封鎖する、付記４８に記載の装置。
〔付記５０〕
前記複数の独立した連続的な流体経路のそれぞれの中に持ち上がったプラットフォームを更に含み、前記持ち上がったプラットフォームは前記アッセイチャンバの入口と前記共通流体経路との間に位置し、前記熱カシメ領域は、前記持ち上がったプラットフォームの一部分を使用して形成される、付記４９に記載の装置。
〔付記５１〕
付記１～２３のいずれか一項に記載のようなプラグを有する、付記３７～５０のいずれか一項に記載の装置。
〔付記５２〕
複数の試料チャンバの同時充填を行う方法であって、
ａ．共通流体経路内の流体試料を加圧するステップと、
ｂ．前記共通流体経路から複数の入口導管に前記流体試料を導入するステップと、
ｃ．前記入口導管のそれぞれに沿って前記入口導管のそれぞれの入口導管終端部に向けて前記流体試料を流すステップであって、各入口導管は試料チャンバに接続されている、前記ステップと、
ｄ．各試料チャンバのテーパ状入口部分に沿って前記流体試料を流すステップと、
ｅ．各試料チャンバ内で肩部のペアに隣接する前記流体試料をプラグに沿って流すステップと、
ｆ．前記流体試料を各試料チャンバのテーパ状出口部分に沿って空気区画終端部に向けて流すステップと、
ｇ．各入口導管及び各試料チャンバに収容されていた気体を、各空気区画終端部と連通している空気チャンバ内へと押し退けるステップと、
を含む方法。
〔付記５３〕
前記流体試料を加圧する前記ステップは一定圧力で実施される、付記５２に記載の方法。
〔付記５４〕
前記一定圧力は、５、１０、２０、４０、又は６０ｐｓｉのうちの１つである、付記５３に記載の方法。
〔付記５５〕
前記流体を加圧する前記ステップは更に、前記流体試料を一連の増加する圧力レベルで加圧することを含む、付記５２に記載の方法。
〔付記５６〕
圧力の各増加レベルは一定の継続時間で印加される、付記５５に記載の方法。
〔付記５７〕
圧力の各増加レベルは一定量ずつ増やされる、付記５５に記載の方法。
〔付記５８〕
前記流体試料を加圧する前記ステップにより、低い圧力レベルから高い圧力レベルにかけての一連の圧力レベルが印加される、付記５５に記載の方法。
〔付記５９〕
使用時に、前記空気チャンバが試料チャンバの上方にあり、その為、前記流体試料を前記試料チャンバのテーパ状出口部分に沿って空気区画終端部に向けて流す前記ステップ、並びに各入口導管に収容されていた気体を押し退ける前記ステップは、重力に逆らって実施される、付記５２に記載の方法。
〔付記６０〕
使用時には、前記複数の試料チャンバの方向付けが、前記複数の試料チャンバのうちの特定の試料チャンバに関連付けられた各空気チャンバが前記試料チャンバの上方に位置付けられるように行われる、付記５２又は付記５９に記載の方法。
〔付記６１〕
前記流体試料を前記装置の各流体経路の前記試料チャンバに流入させることにより、前記流体経路内の気体が前記流体経路の前記空気区画に向かって圧縮される、付記５２に記載の方法。
〔付記６２〕
前記空気区画のそれぞれの内圧が前記共通流体経路に印加されている圧力と等しくなった時点で、流体試料を加圧する前記ステップの間に達した圧力を保持するステップを更に含む、付記５２に記載の方法。
〔付記６３〕
気体を押し退ける前記ステップの間に各空気区画の内圧を高めるステップと、前記共通流体経路に印加されている圧力が各空気区画の内圧と等しくなった時点で前記内圧を高めることを停止するステップと、を更に含む、付記５２に記載の方法。
〔付記６４〕
前記空気区画のそれぞれの前記内圧が前記共通流体経路に印加されている圧力と等しくなった時点で、前記試料を流す前記ステップのそれぞれを停止するステップを更に含む、付記５２に記載の方法。
〔付記６５〕
前記複数の試料チャンバのうちの少なくとも２つの試料チャンバの体積が異なる、付記５２に記載の方法。
〔付記６６〕
前記共通流体経路から前記複数の試料チャンバの各試料チャンバに入る流量が前記試料チャンバの流体体積に比例し、少なくとも２つの異なる流量がある、付記６５に記載の方法。
〔付記６７〕
前記複数の試料チャンバの各試料チャンバの同時充填を行うステップを更に含む、付記５２に記載の方法。
〔付記６８〕
前記流体試料を前記テーパ状入口に沿って流す前記ステップの途中又は後に、前記流体試料を前記試料チャンバ内の分岐する２つの湾曲境界に沿って流すステップを更に含む、付記５２に記載の方法。
〔付記６９〕
前記流体試料を前記肩部ペアに沿って流す前記ステップの後又は途中に、前記流体試料を前記試料チャンバ内の収斂する２つの湾曲境界に沿って流すステップを更に含む、付記５２に記載の方法。
〔付記７０〕
前記２つの湾曲境界の収斂によって、前記流体試料のメニスカスの前面先導部における流体前進速度が低下し、これによって、前記流体試料が前記テーパ状出口に達した時点で、前記流体試料の前記メニスカスは前記アッセイチャンバの最大寸法に関してほぼ対称であり、これによって、充填中の前記アッセイチャンバ内での気泡のトラッピングが最小限に抑えられる、付記６９に記載の方法。
〔付記７１〕
各試料チャンバにおいてメニスカスを前記空気チャンバ終端部に近接して位置させるステップを更に含む、付記５２に記載の方法。
〔付記７２〕
前記流体試料内で形成された１つ以上の気泡を前記試料チャンバ内の前記流体試料のメニスカスに近接して位置させる為に、前記ステップのうちの１つ以上を実施することを更に含む、付記５２に記載の方法。
〔付記７３〕
前記メニスカスは前記空気チャンバ終端部に近接する、付記７２に記載の方法。
〔付記７４〕
前記共通流体経路内の流体試料を加圧する前記ステップを実施する間は前記複数の入口導管のそれぞれを封止するステップを更に含む、付記５２に記載の方法。
〔付記７５〕
前記試料チャンバのテーパ状部分に沿って前記流体試料を流す前記ステップを停止した時点で、前記複数の入口導管のそれぞれを封止するステップを更に含む、付記５２に記載の方法。
〔付記７６〕
前記共通流体経路から前記入口導管のそれぞれに沿って前記流体試料を流す前記ステップを停止した時点で、前記複数の入口導管のそれぞれを封止するステップを更に含む、付記５２に記載の方法。
〔付記７７〕
封止する前記ステップは、前記入口導管の閉鎖された部分を熱カシメするステップを更に含む、付記７４～７６のいずれか一項に記載の方法。
〔付記７８〕
第１の膜の、前記入口導管のそれぞれに近接する部分を加熱するステップと、前記第１の膜を溶融して前記入口導管の前記それぞれを封鎖するステップと、を更に含む、付記７４～７６のいずれか一項に記載の方法。
〔付記７９〕
全ての入口導管を同時に封止するステップを更に含む、付記７７に記載の方法。
〔付記８０〕
前記第１の膜によって前記入口導管から隔てられている第２の膜を、溶融することなく加熱するステップを更に含む、付記７７に記載の方法。
〔付記８１〕
前記第２の膜を溶融することなく、前記入口導管の一部分を前記第１の膜の一部分に融着させるステップを更に含む、付記８０に記載の方法。
〔付記８２〕
前記入口導管のそれぞれを封止した後、第１の膜又は第２の膜の一部分が、前記入口導管のそれぞれに形成された持ち上がったプラットフォームに融着される、付記７４～８１のいずれか一項に記載の方法。
参照符号一覧
アイテム 最後の２桁
装置 ００
共通流体源 ０１
モノリシック基板 ０２
熱カシメ ０３
持ち上がったプラットフォーム ０５
独立した流体経路 １０
第１の膜 １２
第２の膜 １４
試料チャンバ ２０
アッセイチャンバ ２１
入口導管 ２２
入口導管終端部 ２３
空気区画 ３０
空気チャンバ ３１
空気導管 ３２
空気区画終端部 ３３
両側テーパ状チャンバ ４０
テーパ状入口 ４１
テーパ状出口 ４２
両側テーパ状チャンバの中心点 ４３
第１の湾曲境界 ４４
第２の湾曲境界 ４５
第１の湾曲境界中点 ４６
第２の湾曲境界中点 ４７
最大寸法 ４８
空気 ５０
凹部 ５２
流体試料 ６０
メニスカス ６１
前面先導部 ６２
プラグ ７０
プラグ本体 ７１
プラグキャップ ７２
プラグキャップのフランジ ７３
プラグキャップの内部キャビティ ７４
乾燥試薬 ７５
プラグ底面 ７６
中央開口部 ７７
中央開口部の側壁 ７８
中央開口部の底部 ７９
平らな環形 ８０
磁気式混合要素 ８１
外部磁石 ８２
モータ ８３
被加熱要素 ８４
プラグ厚さ ８５
開始角度 ８６
凸状フィーチャ ８７
凹状フィーチャ ８８
肩部高さ ９２
肩部 ９５
アッセイチャンバ体積 ９６
支持リング／凸状環形 ９７
モノリシック基板のプラグ用開口部 ９８
The examples and specific examples included in the present specification show specific embodiments in which the subject of the present invention can be carried out, without limitation, as examples. As mentioned, other embodiments may be utilized or derived, and structural or logical substitutions or modifications may be made without departing from the scope of the present disclosure. Such embodiments of the subject matter of the present invention may be referred to individually in the present specification, or may be collectively referred to by the term "invention", and may be referred to by the term "invention". Is for convenience only and is not intended to voluntarily limit the scope of the present application to any one invention or invention concept, even if two or more are actually disclosed. Accordingly, although specific embodiments have been illustrated and described herein, this particular embodiment may be replaced with any configuration designed to achieve the same purpose. The present disclosure embraces any adaptation or modification of the various embodiments. Those skilled in the art will discover combinations of the plurality of embodiments described above, as well as other embodiments not specifically described herein, by scrutinizing the above description.
[Appendix 1]
The main body with the bottom and
The central opening of the main body and
The body comprises a drying reagent on the bottom surface, and the body is formed of a material that is transparent to the excitation and emission wavelengths in at least one of a red spectrum, a blue spectrum, and a green spectrum.
Plug including.
[Appendix 2]
The plug according to Appendix 1, wherein the drying reagent is on a portion of the bottom surface that is wider than the width of the central opening of the main body.
[Appendix 3]
The plug according to Appendix 1, wherein the width of the central opening is wider than the portion of the bottom surface containing the drying reagent.
[Appendix 4]
The plug according to Appendix 1, further comprising a cavity in the bottom surface for containing the drying reagent.
[Appendix 5]
The plug according to Appendix 4, further comprising a plug thickness between the bottom of the central opening and the bottom of the plug body, the depth of the cavity being less than 90% of the plug thickness.
[Appendix 6]
The plug according to Appendix 4, further comprising a plug thickness between the bottom of the central opening and the bottom of the plug body, the depth of the cavity being less than 70% of the plug thickness.
[Appendix 7]
The plug according to Appendix 4, further comprising a plug thickness between the bottom of the central opening and the bottom of the plug body, the depth of the cavity being less than 50% of the plug thickness.
[Appendix 8]
The plug according to Appendix 4, further comprising a ring shape from the outer edge of the plug body to the outer peripheral portion of the cavity on the bottom surface of the plug.
[Appendix 9]
The plug according to Appendix 6, wherein the ring shape completely surrounds the outer peripheral portion of the cavity.
[Appendix 10]
The plug according to Appendix 4, wherein the cavity further includes an outer peripheral portion in the bottom surface, the starting angle of the cavity is measured from the outer peripheral portion to the bottom surface, and the starting angle is 60 degrees or less.
[Appendix 11]
The plug according to any one of Supplementary note 4 to 8, wherein the cavity is wider than the central opening of the plug body.
[Appendix 12]
The plug according to any one of Supplementary note 4 to 8, wherein the central opening of the plug body is wider than the cavity.
[Appendix 13]
The plug according to Appendix 1, wherein the bottom surface of the plug body further includes an area having a boundary on the bottom surface of the plug body, and the drying reagent is in the area having the boundary.
[Appendix 14]
The plug according to Appendix 11, wherein the bordered area on the bottom of the plug is provided by a feature on the bottom of the plug body.
[Appendix 15]
The plug according to Appendix 12, wherein the feature is lifted above the bottom of the plug or embedded in the bottom of the plug.
[Appendix 16]
The plug according to Appendix 13, wherein the feature has a curved or rectangular cross section.
[Appendix 17]
Whether the width of the area with the boundary is larger than the width of the central opening of the main body, the width of the area with the boundary is smaller than the width of the central opening of the main body, or the width of the area with the boundary is the central opening of the main body. The plug according to Appendix 11, which has almost the same width as the portion.
[Appendix 18]
The plug according to any one of Supplementary note 1 to 15, wherein the plug has a polished finish or a smooth finish to promote the transparency of the excitation wavelength and the emission wavelength.
[Appendix 19]
The plug according to any one of Supplementary note 1 to 16, further comprising a flange around the central opening of the plug body on the plug body.
[Appendix 20]
The drying reagent is selected from the group consisting of a nucleic acid synthesis reagent, a peptide synthesis reagent, a polymer synthesis reagent, a nucleic acid, a nucleotide, a nucleic acid base, a nucleoside, a peptide, an amino acid, a monomer, a detection reagent, a catalyst, or a combination thereof. The plug according to any one of 1 to 17.
[Appendix 21]
The apparatus according to any one of Supplementary note 1 to 18, wherein the drying reagent is a continuous film adhering to the bottom surface of the plug.
[Appendix 22]
The apparatus according to any one of Supplementary note 1 to 18, wherein the drying reagent is a freeze-drying reagent.
[Appendix 23]
The apparatus according to any one of Supplementary note 1 to 18, wherein the drying reagent contains a plurality of droplets adhering to the bottom surface of the plug.
[Appendix 24]
It ’s an assay chamber.
a. With a tapered entrance,
b. With a tapered exit,
c. A plug that includes a bottom surface and a central opening in the body, the body of which is transparent to the excitation and emission wavelengths in at least one of the ultraviolet, blue, green, and red spectra. With the plug, which is formed from
d. The two curved boundaries, wherein each curved boundary extends from the tapered inlet to the tapered outlet so that the two curved boundaries and the plug together enclose the volume of the assay chamber. With two curved boundaries,
e. A shoulder extending from each curved boundary, the contact of the plug with each shoulder provides the boundary of the assay chamber by the two curved boundaries, the shoulder being each of the curved boundaries and the plug. With the shoulder extending from
Assay chamber containing.
[Appendix 25]
The assay chamber according to Appendix 24, wherein the plug has a drying reagent on the plug in the assay chamber.
[Appendix 26]
The assay chamber according to Appendix 25, wherein the cavity on the plug is located between each of the shoulders and the drying reagent is in the cavity.
[Appendix 27]
26. The assay chamber according to Appendix 26, wherein the curved boundary or a portion of the shoulder is shaped to match the outer periphery of the cavity.
[Appendix 28]
25. The assay chamber according to Appendix 25, wherein the drying reagent on the plug is located between each of the shoulders.
[Appendix 29]
24. The assay chamber according to Appendix 24, wherein the flat portion of the bottom of the plug body contacts the shoulder.
[Appendix 30]
24. The assay chamber according to Appendix 24, wherein the height of each of the shoulders is used to adjust the volume of the assay chamber.
[Appendix 31]
30. The assay chamber according to Appendix 30, wherein the height of each of the shoulders is 100 micrometers or more.
[Appendix 32]
The assay chamber according to Appendix 30, wherein the height of each of the shoulders does not exceed the distance of the two curved boundaries from each other at the time of maximum separation.
[Appendix 33]
The assay chamber according to any one of Supplementary note 24 to 32, wherein the shoulder portion is shaped to hold the entire curved boundary of the assay chamber from the tapered inlet to the tapered outlet.
[Appendix 34]
The assay chamber according to Appendix 24, wherein the two curved boundaries and the shoulder are formed on a monolithic substrate.
[Appendix 35]
The assay chamber according to Appendix 34, further comprising a membrane adhered to the surface of the monolithic substrate, wherein the membrane forms one wall of the assay chamber.
[Appendix 36]
The assay chamber according to any one of Supplementary Provisions 24 to 35, which has a plug as described in any one of Supplementary note 1 to 23.
[Appendix 37]
a. Common fluid path and
b. A plurality of independent continuous fluid paths connected to the common fluid path, and each independent continuous fluid path is
i. Assay chamber and
ii. Air compartment and
Including
1. 1. The assay chamber is connected to the common fluid pathway, and a portion of the fluid volume of the assay chamber is defined by the plug having a desiccant on the plug.
2. 2. The air compartment has an air volume and is connected to the common fluid path through the assay chamber.
Each fluid pathway of the plurality of independent continuous fluid pathways is a closed system that does not include a connection between the assay chamber and the common fluid source, and each assay chamber further comprises.
With the plurality of independent continuous fluid paths,
c. It is a tapered chamber on both sides,
iii. A tapered inlet that communicates with the end of the inlet conduit of the fluid path,
iv. A tapered outlet that communicates with the end of the air compartment,
v. With the two curved boundaries, each of which extends from the tapered inlet to the tapered outlet so that the two curved boundaries surround the volume of the assay chamber together. ,
With the tapered chambers on both sides, including
d. A shoulder extending from each curved boundary, the contact of the plug with each shoulder provides the boundary of the assay chamber by the two curved boundaries, the shoulder being each of the curved boundaries and the plug. With the shoulder extending from
Equipment including.
[Appendix 38]
37. The apparatus of Appendix 37, wherein the cavity on the plug is located between each of the shoulders and the drying reagent is in the cavity.
[Appendix 39]
37. The apparatus of Appendix 37, wherein the desiccant on the plug is located between each of the shoulders.
[Appendix 40]
37. The device of Appendix 37, wherein a flat portion of the bottom of the plug body contacts the shoulder.
[Appendix 41]
37. The device of Appendix 37, wherein the height of each of the shoulders is used to adjust the volume of the assay chamber.
[Appendix 42]
The device according to Appendix 41, wherein the height of each of the shoulders is 100 micrometers or more.
[Appendix 43]
The assay chamber according to any one of Supplementary note 37 to 42, wherein the shoulder portion is shaped to hold the entire curved boundary of the assay chamber from the tapered inlet to the tapered outlet.
[Appendix 44]
The device according to Appendix 37, wherein the two curved boundaries are formed on a monolithic substrate.
[Appendix 45]
The body of the plug projects at a certain depth into the monolithic substrate of the assay chamber, and by varying the depth at which the body of the plug projects into the monolithic substrate of the assay chamber. 44. The device of Appendix 44, wherein the assay chamber volume can be easily varied.
[Appendix 46]
The device according to Appendix 38, wherein the curved boundary or a part of the shoulder portion has a shape that matches the outer peripheral portion of the cavity.
[Appendix 47]
It further comprises a first membrane adhered to the surface of at least a portion of the device, wherein the first membrane forms one wall of one or more chambers, compartments, or conduits of the device, Appendix 37-. The apparatus according to any one of 46.
[Appendix 48]
47. The apparatus of Appendix 47, further comprising a second membrane adhered to the first membrane, wherein the second membrane has a higher melting temperature than the first membrane.
[Appendix 49]
Further comprising a thermal caulking region formed in each of the fluid pathways using the first membrane or the second membrane, the thermal caulking region extends the common fluid pathway from the assay chamber and the air chamber. The device according to Appendix 48, which is to be closed.
[Appendix 50]
The lifted platform further comprises a platform lifted within each of the plurality of independent continuous fluid pathways, the lifted platform located between the inlet of the assay chamber and the common fluid pathway, the thermal caulking region. The device according to Appendix 49, which is formed using a portion of the lifted platform.
[Appendix 51]
The device according to any one of the appendices 37 to 50, which has a plug as described in any one of the appendices 1 to 23.
[Appendix 52]
It is a method of simultaneous filling of multiple sample chambers.
a. The step of pressurizing the fluid sample in the common fluid path,
b. The step of introducing the fluid sample from the common fluid path into a plurality of inlet conduits,
c. A step of flowing the fluid sample along each of the inlet conduits towards the respective inlet conduit termination of the inlet conduit, wherein each inlet conduit is connected to a sample chamber.
d. A step of flowing the fluid sample along the tapered inlet portion of each sample chamber,
e. The step of flowing the fluid sample adjacent to the shoulder pair in each sample chamber along the plug,
f. A step of flowing the fluid sample toward the end of the air compartment along the tapered outlet portion of each sample chamber.
g. A step of pushing the gas contained in each inlet conduit and each sample chamber into the air chamber communicating with the end of each air compartment.
How to include.
[Appendix 53]
52. The method of Appendix 52, wherein the step of pressurizing the fluid sample is performed at a constant pressure.
[Appendix 54]
The method according to Appendix 53, wherein the constant pressure is one of 5, 10, 20, 40, or 60 psi.
[Appendix 55]
25. The method of Appendix 52, wherein the step of pressurizing the fluid further comprises pressurizing the fluid sample at a series of increasing pressure levels.
[Appendix 56]
The method of Appendix 55, wherein each increasing level of pressure is applied over a fixed duration.
[Appendix 57]
The method of Appendix 55, wherein each increase level of pressure is increased by a constant amount.
[Appendix 58]
55. The method of Appendix 55, wherein the step of pressurizing the fluid sample applies a series of pressure levels from a low pressure level to a high pressure level.
[Appendix 59]
In use, the air chamber is above the sample chamber and is therefore accommodated in the step, as well as in each inlet conduit, which allows the fluid sample to flow along the tapered outlet portion of the sample chamber towards the end of the air compartment. The method according to Appendix 52, wherein the step of pushing away the existing gas is carried out against gravity.
[Appendix 60]
In use, the orientation of the plurality of sample chambers is performed such that each air chamber associated with a particular sample chamber of the plurality of sample chambers is located above the sample chamber, appendix 52 or appendix. 59.
[Appendix 61]
52. The method of Appendix 52, wherein by allowing the fluid sample to flow into the sample chamber of each fluid path of the apparatus, the gas in the fluid path is compressed towards the air compartment of the fluid path.
[Appendix 62]
Addendum 52 further comprises a step of retaining the pressure reached during the step of pressurizing the fluid sample when the internal pressure of each of the air compartments becomes equal to the pressure applied to the common fluid path. the method of.
[Appendix 63]
A step of increasing the internal pressure of each air compartment during the step of pushing away the gas, and a step of stopping increasing the internal pressure when the pressure applied to the common fluid path becomes equal to the internal pressure of each air compartment. The method according to Appendix 52, further comprising.
[Appendix 64]
52. The method of Appendix 52, further comprising stopping each of the steps of flowing the sample when the internal pressure of each of the air compartments becomes equal to the pressure applied to the common fluid path.
[Appendix 65]
52. The method of Appendix 52, wherein at least two of the plurality of sample chambers have different volumes.
[Appendix 66]
65. The method of Appendix 65, wherein the flow rate from the common fluid path into each sample chamber of the plurality of sample chambers is proportional to the fluid volume of the sample chamber and there are at least two different flow rates.
[Appendix 67]
52. The method of Appendix 52, further comprising the step of simultaneously filling each sample chamber of the plurality of sample chambers.
[Appendix 68]
52. The method of Appendix 52, further comprising flowing the fluid sample along two bifurcated curved boundaries in the sample chamber during or after the step of flowing the fluid sample along the tapered inlet.
[Appendix 69]
52. The method of Appendix 52, further comprising flowing the fluid sample along two convergent curved boundaries in the sample chamber after or in the middle of the step of flowing the fluid sample along the shoulder pair. ..
[Appendix 70]
Convergence of the two curved boundaries slows the fluid advance speed at the frontal lead of the meniscus of the fluid sample, thereby causing the meniscus of the fluid sample to reach the tapered outlet. The method of Appendix 69, which is substantially symmetrical with respect to the maximum dimensions of the assay chamber, thereby minimizing trapping of air bubbles in the assay chamber during filling.
[Appendix 71]
52. The method of Appendix 52, further comprising locating the meniscus in each sample chamber in close proximity to the end of the air chamber.
[Appendix 72]
Addendum, further comprising performing one or more of the steps to position one or more bubbles formed in the fluid sample close to the meniscus of the fluid sample in the sample chamber. 52.
[Appendix 73]
72. The method of Appendix 72, wherein the meniscus is in close proximity to the end of the air chamber.
[Appendix 74]
52. The method of Appendix 52, further comprising sealing each of the plurality of inlet conduits while performing the step of pressurizing a fluid sample in the common fluid path.
[Appendix 75]
52. The method of Appendix 52, further comprising sealing each of the plurality of inlet conduits when the step of flowing the fluid sample along the tapered portion of the sample chamber is stopped.
[Appendix 76]
52. The method of Appendix 52, further comprising sealing each of the plurality of inlet conduits when the step of flowing the fluid sample from the common fluid path along each of the inlet conduits is stopped.
[Appendix 77]
The method according to any one of Supplementary note 74-76, wherein the sealing step further comprises a step of heat caulking the closed portion of the inlet conduit.
[Appendix 78]
Addendum 74-76 further comprises heating a portion of the first membrane close to each of the inlet conduits and melting the first membrane to seal each of the inlet conduits. The method described in any one of the above.
[Appendix 79]
The method of Appendix 77, further comprising the step of sealing all inlet conduits simultaneously.
[Appendix 80]
77. The method of Appendix 77, further comprising heating the second membrane, which is separated from the inlet conduit by the first membrane, without melting.
[Appendix 81]
80. The method of Appendix 80, further comprising the step of fusing a portion of the inlet conduit to the portion of the first membrane without melting the second membrane.
[Appendix 82]
Any one of Appendix 74-81, after sealing each of the inlet conduits, the first membrane or a portion of the second membrane is fused to the lifted platform formed on each of the inlet conduits. The method described in the section.
Reference code list Item Last 2-digit device 00
Common fluid source 01
Monolithic board 02
Heat caulking 03
Lifted platform 05
Independent fluid path 10
First film 12
Second membrane 14
Sample chamber 20
Assay chamber 21
Inlet conduit 22
Inlet conduit end 23
Air compartment 30
Air chamber 31
Air conduit 32
Air compartment end 33
Both sides tapered chamber 40
Tapered entrance 41
Tapered outlet 42
Center point of tapered chambers on both sides 43
First curved boundary 44
Second curved boundary 45
First curved boundary midpoint 46
Second curved boundary midpoint 47
Maximum dimensions 48
Air 50
Recess 52
Fluid sample 60
Meniscus 61
Front lead part 62
Plug 70
Plug body 71
Plug cap 72
Plug cap flange 73
Internal cavity of plug cap 74
Dry reagent 75
Plug bottom 76
Central opening 77
Side wall of central opening 78
Bottom of central opening 79
Flat annelid 80
Magnetic mixing element 81
External magnet 82
Motor 83
Heated element 84
Plug thickness 85
Starting angle 86
Convex feature 87
Concave feature 88
Shoulder height 92
Shoulder 95
Assay chamber volume 96
Support ring / convex annelid 97
Monolithic board plug opening 98
Claims (27)
（ａ）共通流体源と、 (A) Common fluid source and
（ｂ）複数の独立した連続的な流体経路であって、独立した連続的な各流体経路は、 (B) A plurality of independent continuous fluid paths, and each independent continuous fluid path is
（ｉ）前記共通流体源に接続された試料チャンバであって、前記試料チャンバは流体体積を含み、アッセイチャンバと入口導管とを備え、前記アッセイチャンバはアッセイチャンバ体積を含み、前記入口導管は前記共通流体源と前記アッセイチャンバとを接続する、前記試料チャンバと、 (I) A sample chamber connected to the common fluid source, wherein the sample chamber contains a fluid volume and comprises an assay chamber and an inlet conduit, the assay chamber contains an assay chamber volume, and the inlet conduit is said. The sample chamber, which connects the common fluid source and the assay chamber,
（ｉｉ）前記試料チャンバに接続された空気区画であって、前記空気区画は空気体積を含む、前記空気区画と、 (Ii) An air compartment connected to the sample chamber, wherein the air compartment comprises an air volume.
を含む、前記流体経路と、 Including the fluid path and
（ｃ）前記装置の少なくとも一部分の表面に接着された第１の膜であって、前記第１の膜が各流体経路の入口導管の１つの壁を形成している、前記第１の膜と、 (C) A first membrane adhered to the surface of at least a portion of the device, wherein the first membrane forms one wall of an inlet conduit for each fluid path. ,
（ｄ）前記第１の膜に接着された第２の膜であって、前記第２の膜は前記第１の膜よりも高い溶融温度を含む、前記第２の膜と、 (D) A second film adhered to the first film, wherein the second film contains a melting temperature higher than that of the first film, and the second film.
を備え、 Equipped with
前記試料チャンバと前記共通流体源との間の接続部を除いて、各流体経路は閉鎖系であり、前記空気体積に対する前記流体体積の比は、前記複数の流体経路の各流体経路についてほぼ同等である、 Except for the connection between the sample chamber and the common fluid source, each fluid path is a closed system, and the ratio of the fluid volume to the air volume is approximately the same for each fluid path of the plurality of fluid paths. Is,
装置。 Device.
前記両側テーパ状チャンバは、 The tapered chambers on both sides are
前記流体経路の前記入口導管の終端部と流体連通しているテーパ状入口と、 A tapered inlet that communicates with the end of the inlet conduit of the fluid path,
前記空気区画の終端部と流体連通しているテーパ状出口であって、前記テーパ状入口と前記テーパ状出口は、前記アッセイチャンバ体積の最大寸法だけ離れている、前記テーパ状出口と、 A tapered outlet that communicates fluid with the end of the air compartment, wherein the tapered inlet and the tapered outlet are separated by the maximum dimension of the assay chamber volume.
２つの湾曲境界であって、各湾曲境界は前記テーパ状入口から前記テーパ状出口まで延びており、前記２つの湾曲境界は一緒に前記アッセイチャンバ体積を囲み、各湾曲境界は中点を含み、前記２つの湾曲境界が前記中点から前記テーパ状入口に向かって、並びに前記中点から前記テーパ状出口に向かって湾曲するにつれて、前記２つの湾曲境界の間の距離が短くなっていく、前記２つの湾曲境界と、 Two curved boundaries, each curved boundary extending from the tapered inlet to the tapered exit, the two curved boundaries together enclosing the assay chamber volume, and each curved boundary containing a midpoint. As the two curved boundaries bend from the midpoint towards the tapered inlet and from the midpoint towards the tapered exit, the distance between the two curved boundaries becomes shorter. Two curved boundaries and
を含む、請求項１に記載の装置。 The apparatus according to claim 1.
請求項１に記載の装置を提供するステップであって、前記共通流体源は流体試料を含み、各独立した連続した流体経路は気体を含む、ステップと、 A step of providing the apparatus of claim 1, wherein the common fluid source comprises a fluid sample and each independent continuous fluid path comprises a gas.
前記共通流体源内の前記流体試料に供給圧力を印加することにより、前記流体試料を前記入口導管を介して各流体経路の前記試料チャンバに強制的に送り込むステップであって、前記流体試料を前記試料チャンバまで流して、前記流体経路内の前記気体を前記流体経路の前記空気区画に向かって圧縮することにより、前記空気区画の内圧を高め、前記空気区画の前記内圧が前記供給圧力に等しいとき、前記流体試料が前記共通流体源から前記流体経路に流れるのを停止する、ステップと、 A step of forcibly feeding the fluid sample into the sample chamber of each fluid path through the inlet conduit by applying a supply pressure to the fluid sample in the common fluid source, wherein the fluid sample is referred to the sample. When the internal pressure of the air compartment is increased by flowing to a chamber and compressing the gas in the fluid path towards the air compartment of the fluid passage, the internal pressure of the air compartment is equal to the supply pressure. A step of stopping the fluid sample from flowing from the common fluid source into the fluid path.
を含む方法。 How to include.
前記両側テーパ状チャンバは、 The tapered chambers on both sides are
前記流体経路の前記入口導管の終端部と流体連通しているテーパ状入口と、 A tapered inlet that communicates with the end of the inlet conduit of the fluid path,
前記空気区画の終端部と流体連通しているテーパ状出口であって、前記テーパ状入口と前記テーパ状出口は、前記アッセイチャンバ体積の最大寸法だけ離れている、前記テーパ状出口と、 A tapered outlet that communicates fluid with the end of the air compartment, wherein the tapered inlet and the tapered outlet are separated by the maximum dimension of the assay chamber volume.
２つの湾曲境界であって、各湾曲境界は前記テーパ状入口から前記テーパ状出口まで延びており、前記２つの湾曲境界は一緒に前記アッセイチャンバ体積を囲み、各湾曲境界は中点を含み、前記２つの湾曲境界が前記中点から前記テーパ状入口に向かって、並びに前記中点から前記テーパ状出口に向かって湾曲するにつれて、前記２つの湾曲境界の間の距離が短くなっていく、前記２つの湾曲境界と、 Two curved boundaries, each curved boundary extending from the tapered inlet to the tapered exit, the two curved boundaries together enclosing the assay chamber volume, and each curved boundary containing a midpoint. As the two curved boundaries bend from the midpoint towards the tapered inlet and from the midpoint towards the tapered exit, the distance between the two curved boundaries becomes shorter. Two curved boundaries and
を含む、請求項１５に記載の方法。 15. The method of claim 15.
アッセイチャンバであって、前記アッセイチャンバは、モノリシック基板に形成された第１の境界表面と、プラグで形成された第２の境界表面とを含み、前記プラグは、本体とキャップを含み、前記本体は、ある深さで前記モノリシック基板内に突出しており、前記プラグの前記キャップは、前記アッセイチャンバの前記第２の境界表面を形成することにより、前記アッセイチャンバの体積を囲む、前記アッセイチャンバと、 An assay chamber, the assay chamber comprising a first boundary surface formed on a monolithic substrate and a second boundary surface formed by a plug, the plug comprising a body and a cap, said body. Projecting into the monolithic substrate at a certain depth, the cap of the plug encloses the volume of the assay chamber by forming the second boundary surface of the assay chamber with the assay chamber. ,
前記プラグ前記のキャップに形成された内部キャビティに含まれる１つ以上の乾燥試薬と、 The plug One or more drying reagents contained in the internal cavity formed in the cap and
前記アッセイチャンバ体積で旋回を引き起こすことが可能なように構成された磁気式混合要素と、 With a magnetic mixing element configured to be capable of causing swirl in the assay chamber volume,
を含む装置。 Equipment including.
請求項２５に記載の装置を提供するステップと、 The step of providing the apparatus according to claim 25,
前記アッセイチャンバに流体を充填するステップと、 The step of filling the assay chamber with fluid and
前記アッセイチャンバの外側の磁石を回転させて前記磁気式混合要素の旋回を引き起こすことにより、前記試薬を前記流体内で可溶化するステップと、 A step of solubilizing the reagent in the fluid by rotating a magnet outside the assay chamber to cause swirling of the magnetic mixing element.
を含む方法。 How to include.
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| US16/027,749 US10618047B2 (en) | 2018-03-22 | 2018-07-05 | Reaction well for assay device |
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