JP2016505140A - 複数の所定の線に沿って対象試料を結合可能となるように平面導波路の外表面を用意する方法および平面導波路 - Google Patents
複数の所定の線に沿って対象試料を結合可能となるように平面導波路の外表面を用意する方法および平面導波路 Download PDFInfo
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- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
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Abstract
Description
Claims (16)
- 対象試料を複数の所定の線(4)に沿って結合可能となるように、平面導波路(1)の外表面(11)を用意する方法であって、
− リンカー分子(2)を付着させるよう構成された外表面(11)を有する平面導波路(1)を準備するステップと、
− 少なくとも1組の複数のリンカー分子(2,5;2)を前記外表面(11)に順次接触させるステップであって、当該少なくとも1組の複数のリンカー分子(2,5;2)は各組ごとに集合してリンカー分子(2,5;2)の個別レイヤーを形成し、複数の個別レイヤーが、前記平面導波路(1)の前記外表面(11)上に一層ずつ積層され、各リンカー分子(2,5;2)は官能基(22,52;22)および頭部基(21,51;21)を有し、前記頭部基(21,51;21)は、前記平面導波路(1)の前記外表面(11)または一層手前のレイヤーのリンカー分子(2)の官能基(22)に付着可能で、最上層レイヤーのリンカー分子(5;2)の官能基(52;22)は光解離性保護基(3)に結合して、当該光解離性保護基(3)に結合した最上層レイヤーの各官能基(52;22)が他の分子の相補的官能基を付着不能である、ステップと、
− 複数の所定の線(4)に沿って配置された最上層レイヤーの光解離性保護基(3)を所定の波長の光で露光して、当該露光された光解離性保護基(3)を前記官能基(52;22)から除去し、他の分子の相補的官能基を付着可能にするステップと
を有する方法。 - 前記少なくとも1組の複数のリンカー分子(2,5)を順次接触させるステップは、複数のリンカー分子(2,5)2組のみを接触させることからなり、当該2組のリンカー分子(2,5)は、集まって、前記平面導波路(1)の前記外表面(11)上に、リンカー分子(2,5)の2層の別個のレイヤーを積層形成することを特徴とする請求項1に記載の方法。
- − 対象試料(8)を結合可能な捕獲分子(6)の相補的官能基を、複数の所定の線(4)に沿って配置されたリンカー分子の最上層の官能基(52)に付着させるステップと、
− 前記複数の所定の線(4)の間に配置された光解離性保護基(3)を、前記所定の波長の光で露光して、当該露光された光解離性保護基(3)を前記官能基(52)から除去し、それらの官能基(52)が前記他の分子の相補的官能基を付着させることができるようにするステップと、
− 前記捕獲分子(6)が結合することができる対象試料(8)には結合することができない修飾された捕獲分子(7)の相補的官能基を、前記複数の所定の線(4)の間に配置された前記官能基(52)に付着させるステップと
をさらに有する請求項1または2に記載の方法。 - 前記少なくとも1組の複数のリンカー分子(2)を順次接触させるステップは、複数のリンカー分子(2)を1組のみ接触させることからなることを特徴とする請求項1に記載の方法。
- 他の組の複数のリンカー分子の頭部基を、前記複数の所定の線(4)に沿って配置された前記一層手前のレイヤーのリンカー分子(2)の官能基(22)に付着させるステップを有し、当該他の組の複数のリンカー分子(5)に属するリンカー分子(5)の官能基(52)は、光解離性保護基(3)と結合していないので、他の分子の相補的官能基を付着させることが可能であることを特徴とする請求項1、2、または4に記載の方法。
- − 捕獲分子(6)の相補的官能基を、前記複数の所定の線(4)に沿って配置された前記他の組の複数のリンカー分子(5)に属するリンカー分子(5)の官能基(52)に付着させるステップと、
− 前記複数の所定の線(4)の間に配置された光解離性保護基(3)を、所定の波長の光で露光して、当該露光した光解離性保護基(3)を前記官能基(22)から除去し、当該官能基(22)を他の分子の相補的官能基を付着させるようにするステップと、
− さらに他の組の複数のリンカー分子(5)の相補的官能基を、前記複数の所定の線(4)の間に配置されている前記一層手前のレイヤーのリンカー分子(2)の官能基(22)に付着させるステップであって、前記さらに他の組の複数のリンカー分子(5)に属するリンカー分子(5)の官能基(52)は、光解離性保護基(3)とは結合していないので、他の分子の相補的官能基を付着可能である、ステップと、
− 修飾された捕獲分子(7)の相補的官能基を、前記複数の所定の線(4)の間に配置された前記他の組の複数のリンカー分子(5)に属するリンカー分子(5)の官能基(52)に付着させるステップと
を有することを特徴とする請求項5に記載の方法。 - 前記複数の所定の線(4)に沿って配置された光解離性保護基(3)を露光するステップが第1の照射線量で実行され、前記複数の所定の線(4)の間に配置された光解離性保護基(3)を露光するステップが第2の照射線量で実行され、前記第1の照射線量は前記第2の照射線量とは異なることを特徴とする請求項3から請求項6のいずれか一項に記載の方法。
- 前記第1の照射線量と前記第2の照射線量が10ジュール/cm2未満であることを特徴とする請求項7に記載の方法。
- 前記複数の所定の線(4)に沿って配置された光解離性保護基(3)を露光するステップは、
− 第1屈折率n1を有する複数の突出部(91)を有する位相マスク(9)を前記光解離性保護基(3)に近接させて配置するステップであって、該第1屈折率n1は、前記位相マスク(9)と前記平面導波路(1)の前記外表面(11)との間に配置された媒質の第2屈折率n2とは異なる、ステップと、
− 前記所定の波長の光を、前記複数の所定の線(4)に沿って配置された光解離性保護基(3)を露光するための前記位相マスク(9)を通過させるステップと
を有することを特徴とする先行する請求項のいずれか一項に記載の方法。 - 前記頭部基(21)が前記外表面(11)に付着する前記複数のリンカー分子(2)が、集まって、厚みが0.5nmから10nmの個別のレイヤーを形成することを特徴とする先行する請求項のいずれか一項に記載の方法。
- 前記頭部基(21)が前記外表面(11)に付着する前記複数のリンカー分子(2)が、集まって、リンカー分子(2)の単分子層を形成することを特徴とする先行する請求項のいずれか一項に記載の方法。
- 前記頭部基(51)が前記一層手前のレイヤーのリンカー分子(2)の官能基(22)に付着する複数のリンカー分子(5)が、集まって、厚みが10nmから200nmの最上層の個別のレイヤーを形成することを特徴とする先行する請求項のいずれか一項に記載の方法。
- 前記複数の所定の線(4)は、前記平面導波路(1)の前記外表面(11)における、それぞれ面積が25μm2より大きい少なくとも2つの離れた回折スポット(41)に配置されており、前記複数の所定の線(4)は、隣接する線(4)間の距離が1.5μm未満、特に1μm未満であることを特徴とする先行する請求項のいずれか一項に記載の方法。
- 複数の所定の線(4)に沿って対象試料を結合可能となるように用意された外表面(11)を備えた平面導波路(1)であって、前記複数の所定の線(4)は、前記外表面(11)における、それぞれ面積が25μm2より大きい少なくとも2つの離れた回折スポット(41)に配置されており、複数の所定の線(4)は、隣接する線(4)間の距離が1.5μm未満、特に1μm未満であることを特徴とする平面導波路(1)。
- 前記複数の所定の線(4)が、光カプラーを通って前記平面度波路(1)内に結合される光の伝播方向において、隣接する所定の線(4)間の距離が前記光の伝播方向に向かうにつれて狭くなるように配置され、もしくは前記光の伝播方向に対して角度をつけて配置されていることを特徴とする請求項14に記載の平面導波路(1)。
- 請求項14または請求項15に記載の平面導波路(1)、および複数の所定の線(4)に沿って対象試料を結合可能な前記平面導波路(1)の外表面(11)を用意するための位相マスク(9)を有するキット。
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ES2671951T3 (es) | 2018-06-11 |
US9405069B2 (en) | 2016-08-02 |
HK1211698A1 (en) | 2016-05-27 |
BR112015016590B1 (pt) | 2023-01-10 |
EP2946210A1 (en) | 2015-11-25 |
EP2946210B1 (en) | 2018-04-11 |
BR112015016590A2 (pt) | 2017-07-11 |
CA2897890A1 (en) | 2014-07-24 |
KR20150105473A (ko) | 2015-09-16 |
JP6358476B2 (ja) | 2018-07-18 |
PL2946210T3 (pl) | 2018-09-28 |
US20150338579A1 (en) | 2015-11-26 |
RU2015134553A (ru) | 2017-02-22 |
CA2897890C (en) | 2022-08-23 |
WO2014111521A1 (en) | 2014-07-24 |
EP2757374A1 (en) | 2014-07-23 |
CN104937417A (zh) | 2015-09-23 |
TR201806853T4 (tr) | 2018-06-21 |
RU2674696C2 (ru) | 2018-12-12 |
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