JP5701896B2 - ラマン活性分子がナノ粒子二量体の接合部に位置する二量体コア−シェルナノ粒子、その用途およびその製造方法 - Google Patents
ラマン活性分子がナノ粒子二量体の接合部に位置する二量体コア−シェルナノ粒子、その用途およびその製造方法 Download PDFInfo
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Classifications
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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
- G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
- G01N33/543—Immunoassay; Biospecific binding assay; Materials therefor with an insoluble carrier for immobilising immunochemicals
- G01N33/54366—Apparatus specially adapted for solid-phase testing
- G01N33/54373—Apparatus specially adapted for solid-phase testing involving physiochemical end-point determination, e.g. wave-guides, FETS, gratings
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- C—CHEMISTRY; METALLURGY
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- C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
- C12Q1/68—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
- C12Q1/6813—Hybridisation assays
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- C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
- C12Q1/68—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
- C12Q1/6813—Hybridisation assays
- C12Q1/6827—Hybridisation assays for detection of mutation or polymorphism
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- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
- C12Q1/68—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
- C12Q1/6813—Hybridisation assays
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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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- 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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- G01N33/543—Immunoassay; Biospecific binding assay; Materials therefor with an insoluble carrier for immobilising immunochemicals
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- G01N33/54346—Nanoparticles
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- C12Q2563/00—Nucleic acid detection characterized by the use of physical, structural and functional properties
- C12Q2563/107—Nucleic acid detection characterized by the use of physical, structural and functional properties fluorescence
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- C12Q2563/00—Nucleic acid detection characterized by the use of physical, structural and functional properties
- C12Q2563/155—Particles of a defined size, e.g. nanoparticles
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- C12Q2565/00—Nucleic acid analysis characterised by mode or means of detection
- C12Q2565/60—Detection means characterised by use of a special device
- C12Q2565/628—Detection means characterised by use of a special device being a surface plasmon resonance spectrometer
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- C12Q2565/00—Nucleic acid analysis characterised by mode or means of detection
- C12Q2565/60—Detection means characterised by use of a special device
- C12Q2565/632—Detection means characterised by use of a special device being a surface enhanced, e.g. resonance, Raman spectrometer
Landscapes
- Health & Medical Sciences (AREA)
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- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Immunology (AREA)
- Molecular Biology (AREA)
- Organic Chemistry (AREA)
- Biochemistry (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Hematology (AREA)
- Urology & Nephrology (AREA)
- Microbiology (AREA)
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- Wood Science & Technology (AREA)
- Physics & Mathematics (AREA)
- Analytical Chemistry (AREA)
- Biotechnology (AREA)
- General Health & Medical Sciences (AREA)
- Biomedical Technology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Cell Biology (AREA)
- Biophysics (AREA)
- Pathology (AREA)
- General Physics & Mathematics (AREA)
- Medicinal Chemistry (AREA)
- Food Science & Technology (AREA)
- Genetics & Genomics (AREA)
- General Engineering & Computer Science (AREA)
- Nanotechnology (AREA)
- Investigating, Analyzing Materials By Fluorescence Or Luminescence (AREA)
- Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
- Powder Metallurgy (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Manufacture Of Metal Powder And Suspensions Thereof (AREA)
Description
ラマン活性金−銀コア−シェル二量体の合成は、ターゲットオリゴヌクレオチドが結合された金ナノ粒子およびそれに追加的に銀前駆体の量によって調節される銀シェル形成のDNA−directed bridging methodに基づいて合成した(図1)。
金ナノ粒子二量体の形成(ラマン活性分子としてCy3を使用)は、紫外線−可視光線分光法(UV−visible spectroscopy)およびHR−TEMイメージから確認した(図2)。紫外線−可視光線スペクトルは、二量体の形成後に若干の赤色変換されたスペクトルを示し、これは、Oaul Alivisatosら(Angew chem.1999.38(12)、1808)が報告した前の結果と一致する。図2(A)は、金ナノ粒子二量体の典型的なHR−TEMを示す。最小200個を分析した結果、25%の粒子がモノマーで存在し、65%が二量体で存在し、10%以下が三量体または四量体またはそれ以上の凝集体で存在した。金粒子間の粒子間距離は、HR−TEM分析による時、ca.2〜3nmであった。実際に、溶液状態(0.3PBS)におけるナノ粒子間の間隔距離は、乾燥状態よりはるかに長い〜15nmであることが予想される。また、増幅されたSERS信号を作るために、ナノ粒子間の間隔距離を減らすため、銀ナノ粒子が既存に知られた改質方法(Chem.Comm.2008、J.Phys.Chem.B2004、108、5882−5888)によってナノメートルで調節しながら、金ナノ粒子二量体の表面に導入した(実施例1参照)。〜3nm〜10nmの銀シェルの厚さを有する金−銀コア−シェルモノマー(図2(C)の1a、1b)も、類似の条件で精製されたプローブB溶液(30nmのAuNP)から合成した。各溶液の紫外線−可視光線スペクトル(図2(B))は、銀シェルの厚さに応じて〜400nmのプラズモン共鳴ピークで区別された。図2(C)は、個別の金−銀コア−シェルヘテロ二量体のHR−TEMイメージを示し、直径26nm−36nm(図2(C)−2)、30nm−40nm(図2(C)−3)、40nm−50nm(図2(C)−3)の2つのコア−シェルナノ粒子の球形および銀シェルの厚さを示す。2つのナノ粒子の間には1nm以下の狭い隙間がある。図2(C)−1a、1bはさらに、個別の金−銀コア−シェルモノマーのHR−TEMイメージを示し、直径40nm(シェルの厚さ=5nm、図2(C)−1a)、50nm(シェルの厚さ=10nm、図2(C)−1b)の各ナノ粒子の球形および銀シェルの厚さを示す。
図3(A)は、代表的なコア−シェルモノマーおよびヘテロ二量体ナノ構造(ラマン活性分子としてCy3を使用)の拡大されたAMF(atomic force micrograph)イメージ(1μm×1μm)を示す。形状および直径は、HR−TEM分析結果と一致した。図3(B)は、SERSスペクトルが、図3(A)で指示された単一粒子に対するAFMイメージによって校正されたことを示す。コア−シェルモノマー構造にはホットスポットがなく、また、たった1つのCy3分子のみが存在するため、銀シェルの厚さが5nm(図3(A)−1)または10nm(図3(A)−2)の金−銀コア−シェルモノマーはSERS信号が検出されなかった。銀シェルがない金二量体または1nm以下の間隔距離を有する金二量体もSERS信号が検出されなかった。これは、514.5nmのレーザ励起条件下の電磁的増大が不足するからである。シェルの厚さが薄い(3nm未満)図3(A)−4の場合、同様に入射レーザパワー(〜200μM)を高めた場合にも信号が検出されなかった。この結果は、非常に薄い銀レイヤー(layer)は、十分な電磁的増大を生産することができないことを示す。一方、シェルの厚さが〜5nmの図3(A)−5の場合には、1つのCy3がナノ粒子間の接合部(junction)に位置する単一金−銀コア−シェル二量体から検出した相対的に高いSERS信号が現れた。低い強度(intensity)にもかかわらず、514.5nmのレーザ励起(excitation)での指紋スペクトル(fingerprint spectra)である1470および1580cm−1においてCy3の特徴的なピークが現れた。低い強度(intensity)は、単一分子SERS研究(science1997.275(5203)、1102、Phys rev lett1997、78(9)、1667、Nano lett2006、6(1)2173、Nano lett DOI:10.1021/ni803621x)で用いたパワー強度(intensity)に比べた時、比較的低いレーザパワー(100μW)およびホットスポット部位内でたった1つの分子に影響を与える。また、金ナノ粒子上で改質されたオリゴヌクレオチドのような他種からのシグナルを測定した。図3(C)は、凝集された銀コロイドにおいて、Cy3改質されたオリゴヌクレオチド(5−HS−(CH2)6−A10−PEG18−ATCCTTATCAATATTAAA−Cy3−3’、1nM、赤い線)のSERSスペクトルを、Cy3−フリーオリゴヌクレオチド(5−HS−(CH2)6−A10−PEG18−ATCCTTATCAATATTAAA−3’、1nM、黒い線)のSERSスペクトルと比較した結果を示す。図3(C)(黒い線)のSERSスペクトルは、アデニン塩基(A10がスペーサー配列として用いられた)がリッチであることにより、アデニンモード(734cm−1、1320cm−1)が優位にあることと、他の塩基よりも増大していることを示す(JACS、2008、130(16)、5523)。また、他のDNA塩基に対してこれまで報告された最も低い検出限界がマイクロモル以下(sub−micromolar)の範囲であることも重要である(JACS、2006、128、15580)。しかし、図3(C)のSERSスペクトル(赤い線)は、Cy3分子で発生した信号である1470cm−1、1580cm−1における相対的に高い信号を示す(Ananl chem.2004、76、412−417)。しかし、ラマン強度および時間によるスペクトル位置変動(spectral positions fluctuate with time)、およびスペクトルが各二量体ごとに異なって観察される(J.Phys.Chem.B2002、106、8096)。したがって、スペクトルパターンは、既存に報告されたのと完全には符合しない。銀シェルの厚さに関係なく、実験条件下で金−銀コア−シェルモノマーでの検出可能なSERS信号の不在は、二量体構造の接合部に位置するCy構造のみが1470および1580cm−1においてSERSピークを誘導することを確認させる。シェルの厚さが〜10nmにおけるコア−シェル二量体のラマンスペクトル(図3(A)−6)は、1480cm−1における他のCy−3関連ピークとともに、734cm−1、1320cm−1におけるアデニンモードが優位にあることを示す。他のナノ粒子に対するラマン散乱強度は、実験ごとに一定の形式(form)を維持しない。厚い銀シェルは、適切でない電磁的増強をもたらすCy3分子をカバーすることができる。
シェルの厚さが〜5nmである大部分のコア−シェル二量体ナノ粒子(ラマン活性分子としてCy3を使用)は、図4(A)、(B)に示すように、単一粒子から検出可能なSERSを示した。入射レーザ光(incident laser light)が二量体の粒子間軸に正確に偏光されないことを考慮すれば(図4(A)−1、2、3、4、5)、垂直的に偏光化された各二量体ナノ粒子は、検出可能なSERS信号を示す。しかし、図5(C)は、1470cm−1において小さいピークのみを示すが、これは、二量体の発生(orientation)が入射管に略垂直であるからである。したがって、シェルの厚さが最適化されたこれらのコア−シェル二量体ナノ構造が単一DNAの検出に高度に適用可能なホットスポット構造であり得ることを発見した。
Claims (28)
- 表面にオリゴヌクレオチドが結合された金または銀コア(core)と、前記コアを取り囲む金または銀シェル(shell)とからなるコア−シェルナノ粒子2つの接合部にラマン活性分子が位置し、前記2つのナノ粒子がオリゴヌクレオチドを介して連結された構造を有することを特徴とするナノ粒子二量体。
- それぞれのナノ粒子は、オリゴヌクレオチドの一方の末端がコアの表面に結合され、前記オリゴヌクレオチドの一部は、シェルの外部に露出していることを特徴とする請求項1に記載のナノ粒子二量体。
- 前記それぞれのナノ粒子の表面に結合されたオリゴヌクレオチドは、保護オリゴヌクレオチドおよびターゲット捕捉オリゴヌクレオチドを含むことを特徴とする請求項2に記載のナノ粒子二量体。
- 前記2つのナノ粒子の表面に結合されたターゲット捕捉オリゴヌクレオチドは、ターゲットオリゴヌクレオチドと混成化をなしていることを特徴とする請求項3に記載のナノ粒子二量体。
- 前記オリゴヌクレオチドは、チオール基、アミン基およびアルコール基からなる群より選択されるいずれか1つの表面結合官能基で金ナノ粒子、銀ナノ粒子の表面に結合されていることを特徴とする請求項1に記載のナノ粒子二量体。
- 前記オリゴヌクレオチドは、前記表面結合官能基とオリゴヌクレオチドとの間にスペーサー配列を含むことを特徴とする請求項5に記載のナノ粒子二量体。
- 前記ナノ粒子二量体は、
i)金コアおよび銀シェルからなるコア−シェルナノ粒子2つが連結されたナノ粒子二量体と、
ii)銀コアおよび金シェルからなるコア−シェルナノ粒子2つが連結されたナノ粒子二量体と、
iii)金コアおよび金シェルからなるコア−シェルナノ粒子2つが連結されたナノ粒子二量体と、
iv)銀コアおよび銀シェルからなるコア−シェルナノ粒子2つが連結されたナノ粒子二量体と、
v)金コアおよび銀シェルからなるコア−シェルナノ粒子と、銀コアおよび金シェルからなるコア−シェルナノ粒子とが連結されたナノ粒子二量体とからなる群より選択されるものであることを特徴とする請求項1に記載のナノ粒子二量体。 - 前記コアの直径は、5〜300nmであることを特徴とする請求項1に記載のナノ粒子二量体。
- 前記コアの直径は、10〜40nmであることを特徴とする請求項8に記載のナノ粒子二量体。
- 前記シェルの厚さは、1〜300nmであることを特徴とする請求項1に記載のナノ粒子二量体。
- 前記シェルの厚さは、1〜20nmであることを特徴とする請求項10に記載のナノ粒子二量体。
- 前記ラマン活性分子は、FAM、Dabcyl、TRIT(テトラメチルローダミンイソチオール)、NBD(7−ニトロベンズ−2−1,3−ジアゾール)、テキサスレッド(Texas Red)染料、フタル酸、テレフタル酸、イソフタル酸、クレシルファーストバイオレット、クレシルブルーバイオレット、ブリリアント(brilliant)クレシルブルー、パラ−アミノ安息香酸、エリトロシン、ビオチン、ジゴキシゲニン(digoxigenin)、5−カルボキシ−4’,5’−ジクロロ−2’,7’−ジメトキシフルオレセイン、5−カルボキシ−2’,4’,5’,7’−テトラクロロフルオレセイン、5−カルボキシフルオレセイン、5−カルボキシローダミン、6−カルボキシローダミン、6−カルボキシテトラメチルアミノフタロシアニン、アゾメチン、シアニン、キサンチン、スクシニルフルオレセイン、アミノアクリジン、量子ドット、炭素ナノチューブ、炭素同素体、シアン化物、チオール、塩素、臭素、メチル、リン、硫黄およびシアニン染料(Cy3、Cy3.5、Cy5)、ローダミン(Rhodamine)からなる群より選択されるものであることを特徴とする請求項1に記載のナノ粒子二量体。
- 前記ラマン活性分子は、有機蛍光分子であることを特徴とする請求項1に記載のナノ粒子二量体。
- 請求項1に記載のナノ粒子二量体の表面またはコアの表面に、検出しようとする分析物を認識できるバイオ分子が機能化されていることを特徴とするナノ粒子二量体。
- 前記検出しようとする分析物は、アミノ酸、ペプチド、ポリペプチド、蛋白質、グリコプロテイン、リポプロテイン、ヌクレオシド、ヌクレオチド、オリゴヌクレオチド、核酸、糖、炭水化物、オリゴサッカリド、ポリサッカリド、脂肪酸、脂質、ホルモン、代謝産物、サイトカイン、ケモカイン、受容体、神経伝達物質、抗原、アレルゲン、抗体、基質、代謝産物、補助因子、抑制剤、薬物、薬学物、営養物、プリオン、毒素、毒物、爆発物、殺虫剤、化学無機剤、生体有害性製剤、放射線同位元素、ビタミン、ヘテロ環芳香族化合物、発癌物質、突然変異誘発要因、痲酔剤、アンフェタミン、バルビツレート、幻覚剤、廃棄物または汚染物であることを特徴とする請求項14に記載のナノ粒子二量体。
- 前記バイオ分子は、抗体、抗体断片、受容体蛋白質、結合蛋白質、酵素、抑制剤蛋白質、細胞癒着蛋白質、オリゴヌクレオチド、ポリヌクレオチド、核酸またはアプタマーであることを特徴とする請求項14に記載のナノ粒子二量体。
- 前記ナノ粒子二量体は、無機物で全体がコーティングされていることを特徴とする請求項1に記載のナノ粒子二量体。
- 前記無機物は、シリカであることを特徴とする請求項17に記載のナノ粒子二量体。
- 1)表面が保護オリゴヌクレオチドおよびターゲット捕捉オリゴヌクレオチドで結合されたコアAと、表面が保護オリゴヌクレオチドおよびラマン活性分子が末端に結合されたターゲット捕捉オリゴヌクレオチドで結合されたコアBとをそれぞれ製造するステップと、
2)前記製造されたコアAおよびコアBにターゲットオリゴヌクレオチドを処理して混成化させることにより、二量体を形成するステップと、
3)前記コアAおよびコアBの表面にそれぞれシェルを導入するステップとを含むことを特徴とする請求項1に記載のナノ粒子二量体の製造方法。 - 前記ステップ1)でコアAとコアBとをそれぞれ製造した後、コアAとコアBのターゲット捕捉オリゴヌクレオチドと相補的な配列を有する磁性マイクロ粒子と混成化反応を進行し、コアAとコアBからターゲット捕捉オリゴヌクレオチドが結合されたナノ粒子のみを分離する過程をさらに含むことを特徴とする請求項19に記載のナノ二量体の製造方法。
- 前記シェルの導入は、コアからなる二量体とシェル前駆体を、還元剤および安定化剤の存在下で反応させることによって行われることを特徴とする請求項19に記載の方法。
- 1)請求項1〜18のいずれか1項に記載のナノ粒子二量体を製造するステップと、
2)前記ナノ粒子二量体の表面またはコアの表面に、検出しようとする分析物を認識できるバイオ分子を機能化するステップと、
3)前記ナノ粒子二量体を、1つ以上の分析物を含むサンプルに露出させるステップと、
4)レーザ励起(excitation)およびラマン分光法を用いて1つ以上の分析物を検出および確認するステップとを含むことを特徴とする分析物の検出方法。 - 1)請求項1〜18のいずれか1項に記載のナノ粒子二量体を製造するステップと、
2)前記ナノ粒子二量体の表面またはコアの表面に、検出しようとする核酸に相補的なバイオ分子を機能化するステップと、
3)試料から核酸を抽出、精製、および増幅させるステップと、
4)前記増幅された核酸の特定配列にコア−シェルナノ粒子二量体を反応させて混成化を行うステップと、
5)前記ナノ粒子二量体が結合された核酸にラマン分光を行うステップとを含むことを特徴とする核酸の検出方法。 - 前記核酸の検出方法は、疾病の診断のための核酸の検出方法であることを特徴とする請求項23に記載の核酸の検出方法。
- 前記核酸の検出方法は、単一塩基多型性(SNP)の検出方法であることを特徴とする請求項23に記載の核酸の検出方法。
- 前記ラマン分光法が、表面増強ラマン分光法(SERS)、表面増強共鳴ラマン分光法(SERRS)ハイパーラマンおよび/または非干渉性反ストークスラマン分光法(CARS)であることを特徴とする請求項22に記載の分析物の検出方法。
- 前記核酸は、遺伝子、ウイルスRNAおよびDNA、バクテリアDNA、カビDNA、哺乳動物DNA、cDNA、mRNA、RNAおよびDNA断片、オリゴヌクレオチド、合成オリゴヌクレオチド、改質されたオリゴヌクレオチド、単鎖および二本鎖核酸、自然的および合成核酸であることを特徴とする請求項23に記載の核酸の検出方法。
- 請求項1〜18のいずれか1項に記載のナノ粒子二量体を含むことを特徴とする分析物検出用キット。
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CN102442638A (zh) * | 2011-09-15 | 2012-05-09 | 王利兵 | 一种具有手性信号的不对称金纳米粒子二聚体的制备方法 |
US9518986B2 (en) * | 2011-11-02 | 2016-12-13 | University Of Cape Town | Method of detecting and/or quantifying an analyte in a biological sample |
CN102556959B (zh) * | 2011-12-30 | 2014-04-16 | 中国科学院苏州纳米技术与纳米仿生研究所 | 一种金属纳米颗粒二聚体的制备方法 |
CN102590174A (zh) * | 2012-02-14 | 2012-07-18 | 厦门大学 | 用Fe3O4@Au核壳纳米探针检测生物分子的方法 |
US20130295563A1 (en) | 2012-05-04 | 2013-11-07 | Snu R&Db Foundation | Nanoparticles in the shape of nanosnowman with a head part and a body part, a preparation method thereof and a detection method using the same |
KR101387357B1 (ko) * | 2012-07-09 | 2014-04-21 | 인텔렉추얼디스커버리 주식회사 | 양자점 및 양자점 나노 복합체의 형성 방법 및 이를 포함하는 백색 발광 소자 |
WO2014022330A2 (en) * | 2012-07-31 | 2014-02-06 | Northwestern University | Dispersible surface-enhanced raman scattering nanosheets |
KR101538218B1 (ko) * | 2012-08-24 | 2015-07-22 | 한양대학교 에리카산학협력단 | 표면―증강 라만 산란에 기초한 고속 및 고감도 미량 분석용 유무기 나노섬유 복합체 기판 및 이의 제조방법 |
GB2505401A (en) * | 2012-08-31 | 2014-03-05 | Uni Heidelberg | Transferring nanoparticles into eukaryotic cells |
US10322194B2 (en) | 2012-08-31 | 2019-06-18 | Sloan-Kettering Institute For Cancer Research | Particles, methods and uses thereof |
US9410007B2 (en) | 2012-09-27 | 2016-08-09 | Rhodia Operations | Process for making silver nanostructures and copolymer useful in such process |
CN102914646B (zh) * | 2012-11-16 | 2014-08-20 | 湖南大学 | 基于表面等离子体耦合效应的均相多组分免疫分析方法 |
CN105073142B (zh) | 2012-12-19 | 2019-12-10 | 索隆-基特林癌症研究协会 | 多模态粒子、其方法和用途 |
CN103074327B (zh) * | 2013-01-11 | 2015-05-06 | 东南大学 | 三角银纳米片在分离单链dna中的应用 |
EP2958481A4 (en) | 2013-02-20 | 2017-03-08 | Sloan-Kettering Institute for Cancer Research | Wide field raman imaging apparatus and associated methods |
WO2014134338A1 (en) * | 2013-03-01 | 2014-09-04 | Arizona Board Of Regents, A Body Corporate Of The State Of Arizona, Acting For And On Behalf Of Arizona State University | Oligonucleotide functionalized quantum dots |
CN103192089B (zh) * | 2013-03-13 | 2015-04-22 | 江南大学 | 基于聚合酶链反应的大小金二聚体-金核壳结构组装产物手性研究的方法 |
CN103212705B (zh) * | 2013-03-13 | 2015-06-10 | 江南大学 | 基于聚合酶链反应的金-金核壳结构二聚体的手性研究的方法 |
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KR101484743B1 (ko) | 2013-08-13 | 2015-01-26 | 고려대학교 산학협력단 | 생체분자를 기반으로 하는 금속 나노구조물의 제조방법 |
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US10912947B2 (en) | 2014-03-04 | 2021-02-09 | Memorial Sloan Kettering Cancer Center | Systems and methods for treatment of disease via application of mechanical force by controlled rotation of nanoparticles inside cells |
KR101597894B1 (ko) * | 2014-05-20 | 2016-02-26 | 서울대학교산학협력단 | 금속증강형광용 코어-쉘 나노 복합체 |
WO2016018896A1 (en) | 2014-07-28 | 2016-02-04 | Memorial Sloan Kettering Cancer Center | Metal(loid) chalcogen nanoparticles as universal binders for medical isotopes |
CN104280542B (zh) * | 2014-10-21 | 2016-06-08 | 基蛋生物科技股份有限公司 | 基于金属增强发光及纳米粒子标记放大的双增强化学发光免疫分析法 |
EP3259286A4 (en) * | 2015-02-19 | 2018-07-11 | Ionica Sciences | Reagents and methods for detecting infectious diseases |
CN104923777A (zh) * | 2015-03-18 | 2015-09-23 | 华南理工大学 | 一种高耐盐性金属纳米粒子组装体及其制备方法 |
CN104914087B (zh) * | 2015-05-18 | 2018-05-04 | 上海交通大学 | 一种多层核壳结构的表面增强拉曼探针及制备方法 |
WO2016187588A1 (en) * | 2015-05-21 | 2016-11-24 | Lamdagen Corporation | Plasmonic nanoparticles and lspr-based assays |
CN104897645B (zh) * | 2015-06-08 | 2018-01-09 | 江南大学 | 一种基于金银纳米粒子二聚体拉曼信号检测叶酸的方法 |
CN105158125B (zh) * | 2015-06-11 | 2018-01-05 | 东南大学 | 一种端粒长度测量方法 |
EP3317035A1 (en) | 2015-07-01 | 2018-05-09 | Memorial Sloan Kettering Cancer Center | Anisotropic particles, methods and uses thereof |
WO2017007291A1 (ko) * | 2015-07-09 | 2017-01-12 | 서울대학교산학협력단 | 표면 증강 라만 산란 입자를 이용한 핵산 분자 검출 방법 |
CN104940956B (zh) * | 2015-07-09 | 2017-12-29 | 中国科学院宁波材料技术与工程研究所 | 一种核壳结构的复合纳米材料及其制法和应用 |
KR101802386B1 (ko) * | 2015-12-11 | 2017-11-30 | 재단법인 대구경북첨단의료산업진흥재단 | 표면증강라만산란(sers) 나노입자, 이의 제조 방법 및 이의 응용 |
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CN106111974B (zh) * | 2016-07-26 | 2017-11-28 | 江南大学 | 一种金银核壳粒子‑金纳米棒自组装结构的制备方法及应用 |
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KR102202503B1 (ko) * | 2018-01-10 | 2021-01-14 | 서울대학교 산학협력단 | 탈합금화 기반의 플라즈모닉 내부 나노갭 나노입자, 이의 제조방법 및 이의 용도 |
US20220364162A1 (en) * | 2018-08-14 | 2022-11-17 | Korea University Research And Business Foundation | Method for synthesizing single metal nanobridged structure and method for manufacturing dna point mutation detection sensor by using same |
KR102300360B1 (ko) * | 2018-08-14 | 2021-09-09 | 고려대학교 산학협력단 | 단일 금속 나노 브릿지 구조의 합성 방법 및 이를 이용한 dna 점돌연변이 검출 센서 제작 방법 |
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KR102190796B1 (ko) | 2019-02-12 | 2020-12-14 | 건국대학교 산학협력단 | Sers 신호를 내부표준 신호로 포함하는 다층 코어-쉘 입자 및 이를 이용한 표적 분석물의 검출방법 |
KR102202505B1 (ko) * | 2019-06-10 | 2021-01-14 | 서울대학교 산학협력단 | Dna 혼성화에 의해 형성된 계층적 구조의 금속나노큐브 조립체를 이용하는 표면증강라만산란에 의한 표적 물질 검출방법 |
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KR102246335B1 (ko) * | 2019-09-05 | 2021-04-29 | 한국표준과학연구원 | 표면 증강 라만 산란을 이용한 검출 대상 물질 검출 장치 및 방법 |
CN112229828B (zh) * | 2020-08-11 | 2021-04-06 | 嘉兴学院 | 高选择性捕捉苏丹染料的sers活性基底及其制备方法 |
WO2022182126A1 (ko) * | 2021-02-23 | 2022-09-01 | 모던밸류 주식회사 | 타겟 핵산의 라만 검출을 위한 핵산 기반 자가조립 복합체 및 이의 용도 |
CN113249698B (zh) * | 2021-04-23 | 2023-04-28 | 杭州电子科技大学 | 一种多层纳米帽-星耦合周期性阵列及其制备方法 |
CN113267628A (zh) * | 2021-04-25 | 2021-08-17 | 南通大学 | 一种***sp10蛋白检测试纸条及定量检测方法 |
US20230061881A1 (en) * | 2021-08-25 | 2023-03-02 | The United States Of America, As Represented By The Secretary Of The Navy | Measurement Device with Tunable Two-Dimensional Material for Environment Characterization |
CN114438215A (zh) * | 2022-04-02 | 2022-05-06 | 山东中医药大学 | 一种基于dna超支化自组装检测肺癌标志物的sers探针和试剂盒 |
CN114624225B (zh) * | 2022-05-16 | 2022-07-29 | 南京邮电大学 | 膜蛋白二聚态原位检测试剂盒及其应用 |
Family Cites Families (18)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2001006257A1 (en) * | 1999-07-16 | 2001-01-25 | Wm. Marsh Rice University | Metal nanoshells for biosensing applications |
ATE487136T1 (de) * | 2000-03-28 | 2010-11-15 | Nanosphere Inc | Nanopartikel mit gebundenen oligonukleotiden und verwendungen derselben |
US7238472B2 (en) * | 2001-05-25 | 2007-07-03 | Nanosphere, Inc. | Non-alloying core shell nanoparticles |
US20030211488A1 (en) * | 2002-05-07 | 2003-11-13 | Northwestern University | Nanoparticle probs with Raman spectrocopic fingerprints for analyte detection |
GB0216197D0 (en) * | 2002-07-12 | 2002-08-21 | Univ Strathclyde | Serrs active particles |
US7361821B2 (en) * | 2002-09-20 | 2008-04-22 | Intel Corporation | Controlled alignment of nanobarcodes encoding specific information for scanning probe microscopy (SPM) reading |
US20080076119A9 (en) | 2003-12-29 | 2008-03-27 | Lei Sun | Composite organic inorganic nanoclusters |
US7361410B2 (en) | 2003-12-29 | 2008-04-22 | Intel Corporation | External modification of composite organic inorganic nanoclusters comprising raman active organic compound |
US7381529B2 (en) * | 2003-12-31 | 2008-06-03 | Intel Corporation | Methods and compositions for detecting nucleic acids using scanning probe microscopy and nanocodes |
AU2005246415B8 (en) * | 2004-05-19 | 2011-09-01 | Vp Holding, Llc | Optical sensor with layered plasmon structure for enhanced detection of chemical groups by SERS |
CN1285737C (zh) * | 2004-08-03 | 2006-11-22 | 湖南大学 | 硅壳纳米颗粒检测sars病毒基因组片断的方法 |
US7485471B1 (en) * | 2004-12-17 | 2009-02-03 | Intel Corporation | Detection of enhanced multiplex signals by surface enhanced Raman spectroscopy |
JP2007225576A (ja) * | 2006-02-27 | 2007-09-06 | Canon Inc | 検出試薬、検出素子、および検出方法 |
DE602007008716D1 (de) * | 2006-05-03 | 2010-10-07 | Univ California | Nachweis von protease und protease-aktivität mithi |
US20090280188A1 (en) * | 2006-06-23 | 2009-11-12 | Northwestern University | Asymmetric functionalizated nanoparticles and methods of use |
EP1992938A1 (en) * | 2007-05-14 | 2008-11-19 | Koninklijke Philips Electronics N.V. | Improved methods of SE(R)RS detection using multiple labels |
WO2009113674A1 (ja) * | 2008-03-14 | 2009-09-17 | 学校法人北里研究所 | 膀胱癌の診断 |
KR101153748B1 (ko) * | 2008-05-07 | 2012-06-14 | 재단법인서울대학교산학협력재단 | 바이오센서로 유용한 새로운 형태의 금/은 코어쉘 복합체 |
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IL220294A (en) | 2017-01-31 |
WO2011071343A2 (ko) | 2011-06-16 |
CA2783788A1 (en) | 2011-06-16 |
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