JPH09501489A - 分析対象物の脱着およびイオン化のための方法および装置 - Google Patents
分析対象物の脱着およびイオン化のための方法および装置Info
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- H—ELECTRICITY
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- G—PHYSICS
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- G01N33/6803—General methods of protein analysis not limited to specific proteins or families of proteins
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- Y10T436/24—Nuclear magnetic resonance, electron spin resonance or other spin effects or mass spectrometry
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- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
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- Y10T436/00—Chemistry: analytical and immunological testing
- Y10T436/25—Chemistry: analytical and immunological testing including sample preparation
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- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
- Y10T—TECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION
- Y10T436/00—Chemistry: analytical and immunological testing
- Y10T436/25—Chemistry: analytical and immunological testing including sample preparation
- Y10T436/25375—Liberation or purification of sample or separation of material from a sample [e.g., filtering, centrifuging, etc.]
- Y10T436/255—Liberation or purification of sample or separation of material from a sample [e.g., filtering, centrifuging, etc.] including use of a solid sorbent, semipermeable membrane, or liquid extraction
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Abstract
Description
Claims (1)
- 【特許請求の範囲】 1.質量分光測定によって分析対象物サンプルの分析対象物分子の質量を測定す る装置において、 分光計チューブと; 該チューブの内部を真空にする真空手段と; 該分析対象物サンプルから脱着された分析対象物分子に加速電位を付加する ための、該チューブ内に配置された電位付加手段と; 該分析対象物分子の脱着およびイオン化を速やかに行わせるために表面会合 分子と会合した該分析対象物サンプルを提示するための、該分光計チューブ内に 取り外し可能に挿入され、該表面分子がエネルギー吸収分子、親和性捕捉デバイ ス、光感作性付着分子、およびそれらの結合物で構成されるグループから選択さ れることを特徴とするサンプル提示手段と; 表面会合分子と会合した状態で該サンプル提示手段上に置かれ、それによっ て、該質量分光測定分析で消費されない少なくとも該分析対象物分子の一部が、 後で行われる化学的、生物学的、あるいは物理的分析手順に利用できるようにし ている分析対象物サンプルと; 該分析対象物サンプルから該分析対象物分子を脱着、イオン化するために、 十分なエネルギーを付与するために該分析対象物サンプルに向けられたレーザー ビームを発生するためのレーザービーム手段と;そして加速され たイオン化分析対象物分子の衝撃を検出するための、該分光計チューブと組み合 わせられた検出手段とによって構成される装置。 2.分析対象物分子の質量を質量分光測定するための方法において、 分析対象物分子と結合するための手段を有する親和性捕捉デバイスでプロー ブ端表面にサンプル提示表面を誘導するステップと; 該誘導されたプローブ端表面を、該分析対象物分子をそこに結合させるため に該分析対象物分子に露出させるステップと; そこに結合した該分析対象物分子と共に該誘導されたプローブ端を飛行時間 質量分光計の一端に置いて、真空化し、電場を発生させてその分光計内部に加速 電位を形成させるステップと; 該先端からの該分析対象物分子のイオンを脱着するために、ひとつ、あるい は複数のレーザーパルスで上記分光計内部で、該誘導されたプローブ端面に結合 した上記分析対象物分子の少なくとも一部に衝撃を与えるステップと; 該質量分光計内部での飛行時間によってそれらイオンの質量を検出するステ ップと;そして それら検出された質量を表示するステップ とで構成された方法。 3.上記方法において、さらに、脱着およびイオン化補助マトリックス材料を、 該親和性捕捉デバイスと会合する該プローブ端面に適用するステップで構成され た請求項2記載の方法。 4.上記方法において、さらに、該質量分光計から該プローブ端面を除去するス テップと; 脱着されていない該分析対象物分子の該一部に化学的、生物学的手順を行い 、脱着されていない該分析対象物分子の該一部の組成を変更するステップと; 該変更された分析対象物分子により該プローブ端面を再挿入するステップと ;そして 続いて質量分光測定分析を行い、該変更された分析対象物分子の分子量を判 定するステップ とで構成された請求項3記載の方法。 5.上記方法において、該親和性捕捉デバイスが該プローブ端の該面に化学的に 結合されることを特徴とする請求項2記載の方法。 6.上記方法において、該親和性捕捉デバイスが該プローブ端の該面に物理的に 接合されることを特徴とする請求項2記載の方法。 7.上記方法において、該親和性捕捉デバイスが、該分析対象物分子に化学的に 結合するために改良されることを特徴とする請求項2記載の方法。 8.上記方法において、該親和性捕捉デバイスが、該分析 対象物分子に生物学的に接合するために収良されることを特徴とする請求項2記 載の方法。 9.上記方法において、該分析対象物分子が生分子で、該親和性試薬が、分化さ れていない生物学的サンプルから該生分子を選択的に分離するために改良される ことを特徴とする請求項2記載の方法。 10.上記方法において、該マトリックス材料が、弱酸性から強塩基性pHの範囲に あることを特徴とする請求項3記載の方法。 11.上記方法において、該マトリックス材料が、6.0以上のpHを有することを特 徴とする請求項3記載の方法。 12.上記方法において、該プローブ端の該面が、電気的に絶縁された材料で形成 されることを特徴とする請求項2記載の方法。 13.上記分析対象物分子の脱着およびイオン化を速やかに行わせるために、エネ ルギー吸収物質を該分析対象物分子と組み合わせて用いるレーザー脱着/イオン 化、飛行時間質量分光計によって分析対象物の質量を測定する方法において、 上記エネルギー吸収物質の表面上、あるいはその上方に上記分析対象物分子 を提示し、その場合、該質量分光測定分析で脱着されない少なくとも上記分析対 象物分子の1部が後で行われる分析手順で化学的に利用できることを特徴とする 改良。 14.分析対象物分子の脱着およびイオン化を速やかに行わせるための装置におい て、 サンプル提示面と; エネルギー吸収分子、親和性捕捉デバイス、光感作性付着分子、およびそれ らの組み合わせで構成されるグループから選択される表面会合分子で、該サンプ ル提示表面と会合しており、該分析対象物分子と結合するための手段を有してい る表面会合分子 とで構成される装置。 15.上記装置において、該サンプル提示表面が、飛行時間質量分光測定アナライ ザーに使用されるプローブ端の表面で構成されていることを特徴とする請求項14 記載の装置。 16.上記装置において、該親和性捕捉デバイスまたは光感作性付着分子が該サン プル提示表面に化学的に結合することを特徴とする請求項14記載の装置。 17.上記装置において、該親和性捕捉デバイスが該サンプル提示表面に物理的に 接合することを特徴とする請求項14記載の装置。 18.上記装置において、該親和性捕捉デバイスまたは光感作性付着分子が該分析 対象物分子に化学的に結合することを特徴とする請求項14記載の装置。 19.上記装置において、該親和性捕捉デバイスが該分析対象物分子に生物学的に 接合することを特徴とする請求項 14記載の装置。 20.上記装置において、該分析対象物分子が生分子で、該親和性捕捉デバイスま たは光感作性付着分子が、分化されていない生体サンプルから該生分子を選択的 に分離するために改良されることを特徴とする請求項14記載の装置。 21.上記装置が、さらに、該親和性捕捉デバイスまたは光感作性付着分子と会合 した状態でサンプル提示表面に置かれたマトリックス材料によって構成されるこ とを特徴とする請求項14記載の装置。 22.上記装置において、該マトリックス材料が弱酸性から強塩基性pHの範囲にあ ることを特徴とする請求項21記載の装置。 23.上記方法において、該マトリックス材料が、6.0以上のpHを有することを特 徴とする請求項21記載の方法。 24.上記方法において、該サンプル提示表面が、電気的に絶縁された材料で形成 されることを特徴とする請求項14記載の方法。 25.サンプル提示表面上に分析対象物分子を捕捉し、後で行なわれる分析のため に該サンプル提示表面から該捕捉された分析対象物分子を脱着/イオン化させる 方法において、該分析対象物分子と結合するための手段を有する親和性捕捉装置 あるいは光感作性付着分子で該サンプル提示表面を誘導させるステップと; 該誘導されたサンプル提示表面を該分析対象物分子を含んでいるサンプルに 露出するステップと; 該親和性捕捉デバイス、あるいは光感作性付着分子によって該誘導されたサ ンプル提示表面上に該分析対象物分子を捕捉するステップと;そして 該分析対象物分子を、該親和性捕捉デバイスあるいは光感作性付着分子によ って該誘導されたサンプル提示表面に結合されたままの状態で、エネルギーまた は光源に露出させて、少なくとも該分析対象物分子の1部を該表面から脱着させ るステップ とで構成される方法。 26.分析のために分析対象物分子を提示する表面を作成する方法において、該分 析対象物を支持する該表面上に基板を配置するステップと; 該分析対象物と選択的に結合するための手段を有する親和性捕捉デバイスま たは光感作性付着分子によって、該基板を誘導するステップと;そして 該親和性捕捉デバイスまたは光感作性付着分子と結合した該分析対象物分子 を検出する手段とで構成される方法。 27.上記方法において、検出材料を該表面に適用するステップを追加して構成さ れることを特徴とする請求項26記載の方法。 28.上記方法において、そのような材料が蛍光性の種によ り構成されていることを特徴とする請求項27記載の方法。 29.上記方法において、そのような検出材料が酵素性の種により構成されている ことを特徴とする請求項27記載の方法。 30.上記方法が、そのような検出材料が放射性の種により構成されている点をさ らに有していることを特徴とする請求項27記載の方法。 31.上記方法が、そのような検出材料が発光性の種により構成されている点をさ らに有していることを特徴とする請求項27記載の方法。 32.上記方法が、該親和性捕捉デバイスまたは光感作性付着分子に結合する状態 で該サンプル提示表面に脱着/イオン化補助材料を置くステップをさらに有する ことを特徴とする請求項27記載の方法。 33.上記方法において、該エネルギー源がレーザーにより構成されていることを 特徴とする請求項25記載の方法。 34.上記方法において、親和性捕捉デバイスが使われ、また該エネルギー源がイ オン源により構成されていることを特徴とする請求項25記載の方法。 35.上記方法において、該分析対象物分子の一部が、該サンプル提示表面を該エ ネルギー源に露出させた後で、該サンプル提示表面に結合されるようにすること を特徴とする請求項25記載の方法。 36.上記方法が、さらに、該誘導されたサンプル提示表面 に結合させようとする分析対象物分子の少なくとも一部を、化学的、生物学的、 または物理的反応によって、改良された分析対象物分子に変換し、該分析対象物 分子が、該親和性捕捉デバイスまたは光感作性付着分子によって該誘導されたサ ンプル提示表面に結合されるようにするステップと;そして 該改良された分析対象物分子の少なくとも一部を該表面から脱着させるため に、該改良された分析対象物分子をエネルギー源に露出させるステップ とで構成されることを特徴とする請求項35記載の方法。 37.完全な分析対象物をガス状に脱着することを促すサンプルプローブが、 サンプル提示表面と;そして サンプル提示表面と会合するエネルギー吸収分子 とで構成され、該サンプルプローブがエネルギー源に影響されるときに、該サ ンプルプローブが、エネルギー吸収分子上、その上方、またはその間に位置する 完全な分析対象物分子の脱着を促すサンプルプローブ。 38.上記サンプルプローブにおいて、エネルギー吸収分子が、桂皮酸、桂皮酸ブ ロマイド、2,5−ジヒドロキシ安息香酸、そして、α−シアノ−4−ヒドロキ シ桂皮酸で構成されるグループから選ばれることを特徴とする請求項37記載のサ ンプルプローブ。 39.上記サンプルプローブにおいて、上記サンプル提示表 面が、有機重合体や自然生体高分子などの、ガラスと、セラミック、テフロン被 覆された磁気材料とで構成されるグループから選ばれることを特徴とする請求項 37記載のサンプルプローブ。 40.完全な分析対象物をガス状に脱着することを促すサンプルプローブが、 サンプル提示表面と;そして 該サンプル・プローブがエネルギー源に影響されるときに、該サンプルプロ ーブが、完全な分析対象物分子がガス状に変化することを促す、サンプル提示表 面と会合するエネルギー吸収分子 とで構成されるサンプルプローブ。 41.上記サンプルプローブにおいて、上記親和性捕捉デバイスが、金属イオン、 蛋白質と、ペプチド、免疫グロブリン、核酸、炭水化物、レシチン、染料、還元 剤およびそれらの結合物とで構成されたグループから選ばれることを特徴とする 請求項40記載のサンプルプローブ。 42.上記サンプルプローブにおいて、上記サンプル提示表面が、有機重合体や自 然生体高分子などの、ガラスと、セラミック、テフロン被覆された磁気材料とで 構成されるグループから選ばれることを特徴とする請求項40記載のサンプルプロ ーブ。 43.完全な分析対象物の脱着をガス状へ促すためのサンプルプローブが、 サンプル提示表面と;そして 親和性捕捉デバイスと、エネルギー吸収分子と、該サンプル提示表面と会合 した光感作性付着分子とで構成されるグループから選ばれた少なくとも2つの異 なる分子とで構成され、分析対象物が該サンプルプローブと会合するときに、し かも該サンプルプローブがエネルギー源に影響されるときは、該サンプルプロー ブが分析対象物のガス状への変化を促すサンプルプローブ。 44.上記サンプルプローブにおいて、上記分析対象物が、エネルギー源によって 影響された後の混合物から選択的に脱着することを特徴とする請求項43記載のサ ンプルプローブ。 45.完全な分析対象物の、ガス状への分化、脱着を促すためのサンプルプローブ が、 サンプル提示表面と;そして サンプル提示表面と会合する少なくとも2つの異なる親和性捕捉デバイスと で構成され、該サンプルプローブがエネルギー源に影響されるときに、該サンプ ルプローブが、該分析対象物分子と会合する親和性捕捉デバイスによって異なる 量で、分析対象物分子のガス状への変化を促すサンプルプローブ。 46.上記サンプルプローブにおいて、上記親和性捕捉デバイスが所定の配列で並 べられていることを特徴とする請求項45記載のサンプルプローブ。 47.上記サンプルプローブにおいて、上記配列が複数の異なる分析対象物を吸収 することを特徴とする請求項46記載のサンプルプローブ。 48.分析対象物の量を計るためのサンプルプローブを有する上記装置において、 親和性捕捉デバイスの位置と量が、吸収された分析対象物の量を決定することを 特徴とする請求項40記載の装置。 49.上記装置において、その結合が選択的であることを特徴とする請求項2,14 ,21記載の装置。 50.上記装置において、その結合が非選択的であることを特徴とする請求項2, 14,21記載の装置。 51.上記方法において、その結合が選択的であることを特徴とする請求項3,4 ,25記載の方法。 52.上記方法において、その結合が非選択的であることを特徴とする請求項3, 4,25記載の方法。 53.上記サンプルプローブにおいて、その結合が非選択的であることを特徴とす る請求項40,41,43または45記載の方法。 54.上記サンプルプローブにおいて、その結合が選択的であることを特徴とする 請求項40,41,43または45記載の方法。 55.完全な分析対象物のガス状への脱着を促すためのサンプルプローブが、 サンプル提示表面と;そして 表面会合分子とで構成され、該表面会合分子が、エネルギー吸収分子機能と 親和性捕捉デバイス機能と両方機能することが可能なサンプルプローブ。 56.完全な分析対象物のガス状への脱着を促すためのサンプルプローブが、 サンプル提示表面と;そして 該表面会合分子が少なくとも2つの結合部位を有し、少なくとも1つの結合 部位はサンプル提示表面に結合し、少なくとも1つの結合部位は分析対象物と結 合することが可能であり、また上記分析対象物結合部位が光感作性である表面会 合分子 とで構成されるサンプルプローブ。 57.分析対象物分子の質量を測定するための質量分光測定方法において、 光感作性付着分子(PAM)が少なくとも2つの結合部位を有し、1つの結 合部位が上記サンプル提示表面と結合し、少なくとも1つの結合部位が分析対象 物分子と結合可能であるPAMを有するプローブ端面上にサンプル提示表面を誘 導するステップと; 該誘導されたプローブ端面を、該分析対象物分子をそこに結合させるために 該分析対象物分子に露出させるステップと; そこに結合した該分析対象物分子と共に上記誘導されたプローブ端面を飛行 時間質量分光計の一端に置いて、 真空化し、電場を発生させてその分光計内部に加速電位を形成させるステップと ; 該先端からの分析対象物分子のイオンを脱着するために、ひとつ、あるいは 複数のレーザーパルスで上記分光計内部で、該誘導されたプローブ端面に結合し た上記分析対象物分子の少なくとも1部に衝撃を与えるステップと; 該質量分光内部での飛行時間によってそれらイオンの質量を検出するステッ プと;そして それら検出された質量を表示するステップ とで構成された方法。 58.上記方法において、さらに、脱着/イオン化補助マトリックス材料を、該P AMと会合した該プローブ端面に適用するステップを有することを特徴とする請 求項57記載の方法。 59.上記方法において、さらに、 該質量分光計から該プローブ端面を取り除くステップと; 脱着していない該分析対象物分子の該1部上で、化学的、生物学的、または 物理的な手順を行い、脱着していない該分析対象物分子の該一部の組成を変更す るステップと; 上記の上で該変更された分析対象物分子を有する該プローブ端面を再挿入す るステップと;そして 続いて質量分光測定分析を行い、該変更された分析対象物分子の分子量を決 定するステップ とで構成される方法。 60.上記方法において、該PAMが該プローブ端の該面に化学的に結合すること を特徴とする請求項57記載の方法。 61.上記方法において、該PAMが該分析対象物分子に化学的に結合し、また上 記PAMと上記分析対象物分子との間の該結合が壊れ、上記分析対象物分子が光 によって放出されることを特徴とする請求項57記載の方法。 62.上記方法において、該分析対象物分子が生分子で、また該PAMが分化され ていない生物学的サンプルから該生分子を選択的に分離するために改良されるこ とを特徴とする請求項57記載の方法。 63.上記方法において、該マトリックス材料が弱酸性から強塩基pHの範囲にある ことを特徴とする請求項58記載の方法。 64.上記方法において、該マトリックス材料が6.0以上のpHを有することを特徴 とする請求項58記載の方法。 65.上記方法において、該プローブ端の該面が電気的に絶縁された材料で形成さ れることを特徴とする請求項57記載の方法。 66.上記分析対象物分子の脱着およびイオン化を速やかに行わせるために、光感 作性付着分子(PAM)が該分析対象物分子と組み合わせて用いるレーザー脱着 /イオン 化、飛行時間質量分光測定によって分析対象物分子の質量を測定する方法におい て、 上記PAMの表面上、あるいはその情報に上記分析対象物分子を提示し、そ の場合、該質量分光測定分析で脱着されない少なくとも上記分析対象物分子の1 部が後で行われる分析手順で化学的に利用できることを特徴とする改良。 67.完全な分析対象物のガス状への分化脱着を促すためのサンプル・プローブが 、 サンプル提示表面と; 該サンプル提示表面と会合した少なくとも2つの異なる光感作性付着分子と で構成され、該サンプルプローブがエネルギー源に影響されるとき、該分析対象 物分子と会合した光感作性付着分子により異なる量で、該サンプルプローブが分 析対象物分子のガス状への変更を促すサンプルプローブ。 68.上記サンプルプローブにおいて、上記光感作性付着分子が所定の配列で並ん でいることを特徴とする請求項67記載のサンプルプローブ。 69.上記サンプルブロープにおいて、上記配列が、複数の異なる分析対象物を選 択的に吸収することを特徴とする請求項68記載のサンプルプローブ。 70.完全な分析対象物のガス状への脱着を促すためのサンプルプローブが、 サンプル提示表面と;そして 該サンプル提示表面と会合した該光感作性付着分子とで構成され、該サンプ ルプローブがエネルギー源に影響されるとき、該サンプルプローブが完全な分析 対象物分子のガス状への変化を促すサンプルプローブ。 71.分析対象物の量を計るための上記装置において、光感作性付着分子の位置と 量が、吸収された分析対象物の量を決定する装置。 72.生体高分子の配列決定のための方法が、 エネルギー吸収分子と、親和性捕捉デバイスと、光感作性付着分子と、それ らの結合物とで構成されるグループから選ばれた表面選択分子を有するサンプル 提示表面を持つプローブ端面に、生体高分子分析対象物を結合するステップと; 質量分光測定分析において、生体高分子の少なくとも1部がプローブ端から 脱着しない生体高分子分析対象物を脱着するステップと; 上記プローブ端にまだ結合している上記生体高分子・分析対象物を変更して 脱着した結果を分析するステップと;そして 分析、修飾のステップを繰り返すことが 上記生体高分子の配列が決定されるまで、脱着、分析修飾を繰り返すステッ プ で構成される方法。 73.上記方法において、上記生体高分子が、蛋白質と、RNAと、DNAと、炭 水化物とで構成されるグループから選ばれることを特徴とする請求項72記載の方 法。
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JP2002104978A (ja) * | 2000-09-25 | 2002-04-10 | Fujirebio Inc | パルボウイルスの除去方法及び精製方法 |
JP4706093B2 (ja) * | 2000-09-25 | 2011-06-22 | 富士レビオ株式会社 | パルボウイルスの除去方法及び精製方法 |
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