JP2021518539A - アッセイデバイス用光学反応ウェル - Google Patents
アッセイデバイス用光学反応ウェル Download PDFInfo
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- JP2021518539A JP2021518539A JP2020550666A JP2020550666A JP2021518539A JP 2021518539 A JP2021518539 A JP 2021518539A JP 2020550666 A JP2020550666 A JP 2020550666A JP 2020550666 A JP2020550666 A JP 2020550666A JP 2021518539 A JP2021518539 A JP 2021518539A
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Abstract
Description
本開示には、流体試料を流体源から複数の試料チャンバまで送達するシステム、デバイス、及び方法が含まれる。対象の実施形態によるシステムは、流体源と、複数の独立した連続的な流体経路とを含み、各流体経路は、流体源に接続された試料チャンバと、試料チャンバに接続された空気区画とを含む。流体源、試料チャンバ、及び空気区画は、流体試料を流体源から試料チャンバまで送達する為に互いに併用される。
図2A〜2Fは、一実施形態による、共通流体源からの流体試料を各試料チャンバに同時充填する過程における複数の連続した時点での図1の装置を示す。幾つかの実施形態では、本装置は、試料チャンバの充填中は、流体試料が重力に逆らって試料チャンバに移動するように方向付けられる。図1に関して上述したように、本装置の各流体経路の流体体積は異なってよい。従って、本装置の各流体経路の試料チャンバの同時充填を可能にする為に、空気体積に対する流体体積の比が本装置の各流体経路の間でほぼ同等である。
図3Aは、一実施形態による独立した流体経路310を示す。この独立した流体経路は、試料チャンバ320及び空気区画330を含む。試料チャンバは、入口導管322及びアッセイチャンバ221を含む。試料チャンバは流体体積を含む。空気区画は、空気導管332及び空気チャンバ331を含む。空気区画は空気体積を含む。
図7Aに関して上述した磁気式混合要素の動作範囲を決定する為に幾つかの別々の実験を実施した。
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
Claims (82)
- 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。 - 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、請求項1に記載のプラグ。
- 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、請求項1に記載のプラグ。
- 前記底面に、前記乾燥試薬が入るキャビティを更に含む、請求項1に記載のプラグ。
- 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、請求項4に記載のプラグ。
- 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、請求項4に記載のプラグ。
- 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、請求項4に記載のプラグ。
- 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、請求項4に記載のプラグ。
- 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、請求項6に記載のプラグ。
- 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、請求項4に記載のプラグ。
- 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、請求項4〜8のいずれか一項に記載のプラグ。
- 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、請求項4〜8のいずれか一項に記載のプラグ。
- 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、請求項1に記載のプラグ。
- 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、請求項11に記載のプラグ。
- 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、請求項12に記載のプラグ。
- 前記フィーチャは湾曲断面又は矩形断面を有する、請求項13に記載のプラグ。
- 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、請求項11に記載のプラグ。
- 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、請求項1〜15のいずれか一項に記載のプラグ。
- 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、請求項1〜16のいずれか一項に記載のプラグ。
- 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、請求項1〜17のいずれか一項に記載のプラグ。
- 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、請求項1〜18のいずれか一項に記載の装置。
- 前記乾燥試薬は凍結乾燥試薬である、請求項1〜18のいずれか一項に記載の装置。
- 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、請求項1〜18のいずれか一項に記載の装置。
- 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。 - 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、請求項24に記載のアッセイチャンバ。
- 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、請求項25に記載のアッセイチャンバ。
- 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、請求項26に記載のアッセイチャンバ。
- 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、請求項25に記載のアッセイチャンバ。
- 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、請求項24に記載のアッセイチャンバ。
- 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、請求項24に記載のアッセイチャンバ。
- 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、請求項30に記載のアッセイチャンバ。
- 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、請求項30に記載のアッセイチャンバ。
- 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、請求項24〜32のいずれか一項に記載のアッセイチャンバ。
- 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、請求項24に記載のアッセイチャンバ。
- 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、請求項34に記載のアッセイチャンバ。
- 請求項1〜23のいずれか一項に記載のようなプラグを有する、請求項24〜35のいずれか一項に記載のアッセイチャンバ。
- 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。 - 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、請求項37に記載の装置。
- 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、請求項37に記載の装置。
- 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、請求項37に記載の装置。
- 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、請求項37に記載の装置。
- 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、請求項41に記載の装置。
- 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、請求項37〜42のいずれか一項に記載のアッセイチャンバ。
- 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、請求項37に記載の装置。
- 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、請求項44に記載の装置。
- 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、請求項38に記載の装置。
- 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、請求項37〜46のいずれか一項に記載の装置。
- 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、請求項47に記載の装置。
- 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、請求項48に記載の装置。
- 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、請求項49に記載の装置。
- 請求項1〜23のいずれか一項に記載のようなプラグを有する、請求項37〜50のいずれか一項に記載の装置。
- 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。 - 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、請求項52に記載の方法。
- 前記一定圧力は、5、10、20、40、又は60psiのうちの1つである、請求項53に記載の方法。
- 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、請求項52に記載の方法。
- 圧力の各増加レベルは一定の継続時間で印加される、請求項55に記載の方法。
- 圧力の各増加レベルは一定量ずつ増やされる、請求項55に記載の方法。
- 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、請求項55に記載の方法。
- 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、請求項52に記載の方法。
- 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、請求項52又は請求項59に記載の方法。
- 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、請求項52に記載の方法。
- 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、請求項52に記載の方法。
- 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、請求項52に記載の方法。
- 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、請求項52に記載の方法。
- 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、請求項52に記載の方法。
- 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、請求項65に記載の方法。
- 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、請求項52に記載の方法。
- 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、請求項52に記載の方法。
- 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、請求項52に記載の方法。
- 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、請求項69に記載の方法。
- 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、請求項52に記載の方法。
- 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、請求項52に記載の方法。
- 前記メニスカスは前記空気チャンバ終端部に近接する、請求項72に記載の方法。
- 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、請求項52に記載の方法。
- 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、請求項52に記載の方法。
- 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、請求項52に記載の方法。
- 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、請求項74〜76のいずれか一項に記載の方法。
- 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、請求項74〜76のいずれか一項に記載の方法。
- 全ての入口導管を同時に封止するステップを更に含む、請求項77に記載の方法。
- 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、請求項77に記載の方法。
- 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、請求項80に記載の方法。
- 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、請求項74〜81のいずれか一項に記載の方法。
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