JP4448142B2 - 分析チップ及びその分析チップの分子の構造と機能を測定するための使用方法 - Google Patents
分析チップ及びその分析チップの分子の構造と機能を測定するための使用方法 Download PDFInfo
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Classifications
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- 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
- G01N33/68—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B82—NANOTECHNOLOGY
- B82Y—SPECIFIC USES OR APPLICATIONS OF NANOSTRUCTURES; MEASUREMENT OR ANALYSIS OF NANOSTRUCTURES; MANUFACTURE OR TREATMENT OF NANOSTRUCTURES
- B82Y5/00—Nanobiotechnology or nanomedicine, e.g. protein engineering or drug delivery
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- 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
- G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
- G01N33/543—Immunoassay; Biospecific binding assay; Materials therefor with an insoluble carrier for immobilising immunochemicals
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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
- G01N33/68—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids
- G01N33/6803—General methods of protein analysis not limited to specific proteins or families of proteins
- G01N33/6845—Methods of identifying protein-protein interactions in protein mixtures
Description
a)複数のナノ細孔を備えたナノ細孔基板と、
b)当該のナノ細孔基板と合致する複数のナノ細孔を備えた、当該のナノ細孔基板上に積層された好適なほぼ平坦な支持層と、
c)当該の支持層上に積層されて、複数のナノ細孔を覆っており、その結果測定のために生物学的効果層の両側からナノ細孔にアクセス可能となっている、少なくとも一つの非脂質分子又は機能分子を収容することが可能な生物学的効果層と、
を有する分析チップによって達成される。
a)分子を含む流動体を流動体の生物学的効果層の片側に適用して、この分子を結合させて、非脂質分子と相互作用させること
b)分析チップのシス側又はトランス側での物理的又は化学的な変化を測定することにより、この流動体の生物学的効果層でのエフェクター結合により誘発された非脂質分子の反応と結合分子の相互作用の両方又は一方を観察すること
従って、前述した分析チップは、この発明にもとづき、スクリーニング対象の医薬品化合物候補に反応する膜タンパク質の機能性全体に関する医薬品開発プロセスで使用することができる。例えば、蛍光消滅に対しては生物学的効果層のシス側で、或いはpH、K+ 、Na+ 濃度の変化の測定、少さい体積での放射能又は色素の測定に対してはトランス側で、結合を観察することができる。
Claims (19)
- 非脂質分子の機能性及び分子との相互作用を調査するための分析チップ(2)であって、
a)複数のナノ細孔(8)を備えたナノ細孔基板(28)と、
b)当該のナノ細孔基板(28)の当該のナノ細孔と合致する複数のナノ細孔(8)を備えた、当該のナノ細孔基板(28)上に積層された平坦な支持層(6)と、
c)当該の支持層(6)上に積層されて、複数のナノ細孔(8)を覆っており、その結果測定のために生物学的効果層(4)の両側からナノ細孔(8)にアクセス可能となっている、少なくとも一つの非脂質分子又は機能分子を収容することが可能な生物学的効果層(4)と、
を有する分析チップ。 - 支持層(6)の表面が、活性化された疎水性又は親水性シラン又はその他の成分などによって化学的に修正されて、支持促進層(9)となっていることを特徴とする請求項1に記載の分析チップ。
- 当該の支持層(6)を、窒化ケイ素(Si3N4)の層と二酸化ケイ素(SiO2)の層から成るグループから選定することと、当該の基板(28)を、ケイ素と炭素を含む材料、ポリマー、金属、誘電体、ガラス、セラミックから成るグループから選定することを特徴とする請求項1又は2に記載の分析チップ。
- 当該の基板の厚さとナノ細孔(8)の直径は、その比率が0.25〜5の範囲となるように選定されることを特徴とする請求項1から3までのいずれか一つに記載の分析チップ。
- 当該の基板の厚さとナノ細孔(8)の直径は、その比率が0.75〜2の範囲となるように選定されることを特徴とする請求項1から3までのいずれか一つに記載の分析チップ。
- ナノ細孔(8)の直径が、50〜2000nmの範囲にあることを特徴とする請求項4又は5に記載の分析チップ。
- ナノ細孔(8)の直径が、100〜2000nmの範囲にあることを特徴とする請求項4又は5に記載の分析チップ。
- 当該のナノ細孔は、全体の面積が1×10−6mm2〜10mm2である自立した窒化ケイ素膜(29)上の1×10−6mm2〜1mm2の範囲の面積を持つ複数のナノ細孔列区域内に配置されていることを特徴とする請求項1から7までのいずれか一つに記載の分析チップ。
- 当該のナノ細孔(8)の相互の間隔が、それらのナノ細孔の直径の0.5〜5倍の範囲にあることを特徴とする請求項1から8までのいずれか一つに記載の分析チップ。
- 当該のナノ細孔(8)の相互の間隔が、それらのナノ細孔の直径の0.8〜2倍の範囲にあることを特徴とする請求項1から8までのいずれか一つに記載の分析チップ。
- 当該の生物学的効果層が、原核細胞又は真核細胞から単離された生物膜であるか、或いは脂質小胞の準備とその後の融合とによって形成された脂質二重層であるか、又は超分子集合体の機能層であることを特徴とする請求項1から10までのいずれか一つに記載の分析チップ。
- 当該の非脂質分子が、真核細胞や原核細胞などの自然源から得られたものであることを特徴とする請求項1から11までのいずれか一つに記載の分析チップ。
- 当該の非脂質分子が、合成品であることを特徴とする請求項12に記載の分析チップ。
- 当該の生体膜と脂質二重層の両方が、非脂質分子と機能分子(3)の両方又は一方の少なくとも一つを有し、その際機能分子(3)が、組換えDNA又はRNA技術を用いて作られたものであることを特徴とする請求項11に記載の分析チップ。
- 当該の生物学的効果層が、少なくとも一つの無傷の生細胞から作られていることを特徴とする請求項11に記載の分析チップ。
- 請求項1から15までのいずれか一つに記載の分析チップの生物学的効果層(4)に組み込まれた非脂質分子又は機能分子(3)の機能性を分析する方法であって、
a)結合化合物(14,22)を含む流動体を流動体の生物学的効果層の片側に適用して、この結合化合物(14,22)を非脂質分子と相互作用させることと、
b)分析チップ(2)のシス側又はトランス側での物理的又は化学的な変化を測定することにより、この流動体の生物学的効果層でのエフェクター結合(14,22)により誘発された非脂質分子(3)の反応と結合分子(13)の相互作用の両方又は一方を観察することと、
を有する方法。 - 請求項16に記載された方法において、スクリーニング対象の医薬品候補をアゴニスト部位(15)又はアロステリック部位(23)で膜タンパク質(3)と結合させた際の結合に対する膜タンパク質(3,13)の機能性に関する医薬品開発プロセスに本方法を使用することを特徴とする方法。
- 請求項16に記載された方法において、ローカルプローブ顕微鏡法を用いて、或いは蛍光、イオン、電流、放射能、機械的な信号を測定して、細胞及び細胞群を造影するための膜タンパク質の準備に本方法を使用することを特徴とする方法。
- 請求項16に記載された方法において、マイクロ流動体システムの一部としてのサブミリリットルからマイクロリットルの範囲の体積を持つ二つの区画が、任意選択としてタンパク質を組み込まれた生物学的効果層によって分離されており、タンパク質が、膜貫通型か、内在性であるか、ペプチドにより付着されているか、脂質アンカーに付着されているか、脂質二重層(4)に非共有結合されているかであり、これらの二つの区画間の分子プロセスを巨視的に調査又は検出するための用途に本方法を使用することを特徴とする方法。
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WO2013154750A1 (en) * | 2012-04-10 | 2013-10-17 | The Trustees Of Columbia Unversity In The City Of New York | Systems and methods for biological ion channel interfaces |
CN102414555B (zh) * | 2009-03-26 | 2016-05-04 | 波士顿大学董事会 | 在两液体间的薄固态界面上成像的方法 |
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JP5325735B2 (ja) * | 2009-10-05 | 2013-10-23 | エスケー化研株式会社 | 塗膜形成方法 |
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