WO2003060037A1 - Spheres de silice contenant des molecules de colorant fluorescent - Google Patents

Spheres de silice contenant des molecules de colorant fluorescent Download PDF

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Publication number
WO2003060037A1
WO2003060037A1 PCT/JP2001/011572 JP0111572W WO03060037A1 WO 2003060037 A1 WO2003060037 A1 WO 2003060037A1 JP 0111572 W JP0111572 W JP 0111572W WO 03060037 A1 WO03060037 A1 WO 03060037A1
Authority
WO
WIPO (PCT)
Prior art keywords
fluorescent dye
silica
dye molecule
fitc
molecule
Prior art date
Application number
PCT/JP2001/011572
Other languages
English (en)
Japanese (ja)
Inventor
Hirokazu Miyoshi
Michihiro Nakamura
Original Assignee
Techno Network Shikoku Co., Ltd.
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Techno Network Shikoku Co., Ltd. filed Critical Techno Network Shikoku Co., Ltd.
Priority to PCT/JP2001/011572 priority Critical patent/WO2003060037A1/fr
Priority to JP2003546639A priority patent/JPWO2003060037A1/ja
Priority to AU2002216422A priority patent/AU2002216422A1/en
Publication of WO2003060037A1 publication Critical patent/WO2003060037A1/fr

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C09—DYES; PAINTS; POLISHES; NATURAL RESINS; ADHESIVES; COMPOSITIONS NOT OTHERWISE PROVIDED FOR; APPLICATIONS OF MATERIALS NOT OTHERWISE PROVIDED FOR
    • C09K—MATERIALS FOR MISCELLANEOUS APPLICATIONS, NOT PROVIDED FOR ELSEWHERE
    • C09K11/00—Luminescent, e.g. electroluminescent, chemiluminescent materials
    • C09K11/06—Luminescent, e.g. electroluminescent, chemiluminescent materials containing organic luminescent materials
    • C—CHEMISTRY; METALLURGY
    • C09—DYES; PAINTS; POLISHES; NATURAL RESINS; ADHESIVES; COMPOSITIONS NOT OTHERWISE PROVIDED FOR; APPLICATIONS OF MATERIALS NOT OTHERWISE PROVIDED FOR
    • C09B—ORGANIC DYES OR CLOSELY-RELATED COMPOUNDS FOR PRODUCING DYES, e.g. PIGMENTS; MORDANTS; LAKES
    • C09B67/00—Influencing the physical, e.g. the dyeing or printing properties of dyestuffs without chemical reactions, e.g. by treating with solvents grinding or grinding assistants, coating of pigments or dyes; Process features in the making of dyestuff preparations; Dyestuff preparations of a special physical nature, e.g. tablets, films
    • C09B67/0001—Post-treatment of organic pigments or dyes
    • C09B67/0004—Coated particulate pigments or dyes
    • C09B67/0008—Coated particulate pigments or dyes with organic coatings
    • C—CHEMISTRY; METALLURGY
    • C09—DYES; PAINTS; POLISHES; NATURAL RESINS; ADHESIVES; COMPOSITIONS NOT OTHERWISE PROVIDED FOR; APPLICATIONS OF MATERIALS NOT OTHERWISE PROVIDED FOR
    • C09B—ORGANIC DYES OR CLOSELY-RELATED COMPOUNDS FOR PRODUCING DYES, e.g. PIGMENTS; MORDANTS; LAKES
    • C09B67/00—Influencing the physical, e.g. the dyeing or printing properties of dyestuffs without chemical reactions, e.g. by treating with solvents grinding or grinding assistants, coating of pigments or dyes; Process features in the making of dyestuff preparations; Dyestuff preparations of a special physical nature, e.g. tablets, films
    • C09B67/0033—Blends of pigments; Mixtured crystals; Solid solutions
    • C—CHEMISTRY; METALLURGY
    • C09—DYES; PAINTS; POLISHES; NATURAL RESINS; ADHESIVES; COMPOSITIONS NOT OTHERWISE PROVIDED FOR; APPLICATIONS OF MATERIALS NOT OTHERWISE PROVIDED FOR
    • C09K—MATERIALS FOR MISCELLANEOUS APPLICATIONS, NOT PROVIDED FOR ELSEWHERE
    • C09K2211/00—Chemical nature of organic luminescent or tenebrescent compounds
    • C09K2211/10—Non-macromolecular compounds
    • C—CHEMISTRY; METALLURGY
    • C09—DYES; PAINTS; POLISHES; NATURAL RESINS; ADHESIVES; COMPOSITIONS NOT OTHERWISE PROVIDED FOR; APPLICATIONS OF MATERIALS NOT OTHERWISE PROVIDED FOR
    • C09K—MATERIALS FOR MISCELLANEOUS APPLICATIONS, NOT PROVIDED FOR ELSEWHERE
    • C09K2211/00—Chemical nature of organic luminescent or tenebrescent compounds
    • C09K2211/10—Non-macromolecular compounds
    • C09K2211/1003—Carbocyclic compounds
    • C09K2211/1014—Carbocyclic compounds bridged by heteroatoms, e.g. N, P, Si or B

Definitions

  • the present invention relates to a fluorescent dye molecule-containing silica sphere useful as a detection system reagent.
  • Conventional technology :
  • silica spheres containing fluorescent dye molecules therein have been proposed.
  • FITC fluorescein isothiocyanate
  • APS 3-aminopropyl orthosilicate
  • quenching occurs inside the silica sphere at the highest concentration.
  • the present invention has been made in view of the above-mentioned problems of the related art, and has an object to provide a fluorescent dye molecule-containing siliceous sphere having excellent manufacturing stability and excellent performance.
  • the present inventors have conducted intensive studies in order to achieve the above object, and as a result, have found that it is extremely effective to introduce a specific compound into silica spheres containing fluorescent dye molecules, and have completed the present invention.
  • the present invention is a fluorescent dye molecule-containing siliceous sphere prepared using a fluorescent dye molecule represented by the following structural formula (1).
  • R is a substance that can have NH S in the side chain.
  • R is a substance selected from FITC (fluorescein isothiocyanate), dyes, magnetic substances and free radicals.
  • FITC fluorescein isothiocyanate
  • FI TC—CO—NH— (CH 2 ) 3 —S i— (C 2 H 5 ⁇ ) 3 ( ⁇ ) is preferred.
  • FITC represents fluorescein isothiocynate.
  • R is a substance that can have NHS in the side chain, such as other dyes such as rhodamine, magnetic substances such as iron oxide, and stable free radicals such as spin labeling agents. All included.
  • the present invention relates to the process of producing FITC-APS-silica, a silica sphere containing fluorescent dye molecules, which has been conventionally proposed.
  • FITC—NHS with NHS (N-hydroxysuccinimide ester) as the chain
  • FITC—CO— is used for its strong binding ability between the amine group of APS and the CO group of FITC-NH.S. This was prepared from APS, which significantly improved its production stability and the like.
  • the method for producing the fluorescent dye molecule-containing siliceous sphere of the present invention may be the same as that of the above-mentioned prior art. That is, a fluorosynsothiothionate or a biotin molecule having an N-hydroxysuccinimide ester in a side chain is used as a raw material, and a silane coupling agent, 3-aminopropyl orthosilicate, is used.
  • Fluorescent dye molecule-containing siliceous spheres can be manufactured using tetraorthosilicate.
  • a DMSO solution of FITC-CO-APS is added to 6 ml of water, and the ratio of 20 ml of ethanol to an aqueous solution is set to 4: 1.
  • the size of the obtained silica sphere can be freely adjusted from several nm in diameter to several hundred nm, and even to the order of m. .
  • the obtained silica spheres are purified by removing coexisting ions using a well-known ultrafiltration method, or adjusted to a desired particle size distribution.
  • the fluorescent dye molecule-containing silica spheres of the present invention can have a size of several nanometers and several tens of nanometers.
  • NHS a detection system reagent that does not easily come off when bound to proteins and is not easily quenched.
  • the conventional “FI TC_NHS” molecule has poor stability, so the number of FI TC that binds to the antibody protein is about 4 molecules, the sensitivity is low, and it can be applied only to a fixed form on a petri dish.
  • the silica spheres containing the fluorescent dye molecules of the present invention have a maximum of several thousand FITCs in the silica spheres without concentration quenching. It has an excellent effect of strong light emission and high sensitivity.
  • silica is chemically inert and easily modified, so that, for example, the surface can be made mesoporous or a specific protein can be newly added. It is possible to immobilize the receptor molecule for binding to the surface.
  • FIG. 1 is a view showing an absorption spectrum of a fluorescent dye molecule-containing siliceous sphere (A: 1st Growth, B: 2nd Growth) prepared in Example 1 in an aqueous solution.
  • FIG. 2 is a diagram showing a fluorescence decay curve of the fluorescent dye molecule-containing silica spheres (A: 1st Growth, B: 2nd Growth) prepared in Example 1.
  • FIG. 3 is a TEM photograph (X 90,000) of the fluorescent pigment molecule-containing silica sphere (1st Growth) prepared in Example 1.
  • FIG. 4 is a TEM photograph (X 15,000) of the fluorescent pigment molecule-containing silica spheres (2st Growth) prepared in Example 1.
  • a fluorescein isothiocyanate or a biotin molecule having an N-hydroxysuccinimide ester in the side chain is used as a raw material.
  • a silane coupling agent 3-aminopropyl orthosilicate
  • StSber that is, using tetraorthosilicate in a 4: 1 ethanol aqueous solution at room temperature in the air by hydrolysis and polycondensation of tetraorthosilicate in aqueous ammonia in ethanol.
  • silica spheres containing fluorescent dye molecules were produced.
  • piotin-silica particles containing a fluorescein isothiocyanate molecule were prepared, and the same observation was carried out. Similar aggregation was observed. The protein label by silica particles was confirmed.
  • FIG. 1 shows the absorption spectrum of the silica spheres containing fluorescent dye molecules (A: Ist Growth, B: 2nd Growth) prepared in Example 1 in an aqueous solution.
  • the color of the 1st Glo wt h solution was yellow with strong fluorescence, and was stable even after one month. This indicates that the solution pH at the time of sample preparation was strongly alkaline, and was present inside the silica spheres in that state.
  • a typical absorption peak was observed at 490 nm, and a scattering effect based on large particles was observed in the absorption spectrum of the second glass, in which the absorption increased toward the short wavelength side.
  • the concentration of fluorescein isothiocyanate estimated from the molecular extinction coefficient was 0.075 mM in the case of 1st Growth. Furthermore, when the fluorescence spectra were measured, both had typical fluorescence peaks.

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Engineering & Computer Science (AREA)
  • Materials Engineering (AREA)
  • Investigating Or Analysing Materials By The Use Of Chemical Reactions (AREA)

Abstract

L'invention concerne des sphères de silice contenant des molécules de colorant fluorescent, remarquables non seulement quant à leur stabilité de production, mais également quant à leurs propriétés d'emploi. Les sphères de silice sont préparées avec des molécules de colorant fluorescent représentées par la formule développée suivante (1) R-CO-NH-(CH2)3-Si-(C2H5O)3, dans laquelle R désigne une substance capable de porter un NHS dans une chaîne latérale, par exemple, FITC (isothiocyanate de fluorescéine).
PCT/JP2001/011572 2001-12-27 2001-12-27 Spheres de silice contenant des molecules de colorant fluorescent WO2003060037A1 (fr)

Priority Applications (3)

Application Number Priority Date Filing Date Title
PCT/JP2001/011572 WO2003060037A1 (fr) 2001-12-27 2001-12-27 Spheres de silice contenant des molecules de colorant fluorescent
JP2003546639A JPWO2003060037A1 (ja) 2001-12-27 2001-12-27 蛍光色素分子含有シリカ球
AU2002216422A AU2002216422A1 (en) 2001-12-27 2001-12-27 Silica sphere containing fluorescent dye molecule

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
PCT/JP2001/011572 WO2003060037A1 (fr) 2001-12-27 2001-12-27 Spheres de silice contenant des molecules de colorant fluorescent

Publications (1)

Publication Number Publication Date
WO2003060037A1 true WO2003060037A1 (fr) 2003-07-24

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Application Number Title Priority Date Filing Date
PCT/JP2001/011572 WO2003060037A1 (fr) 2001-12-27 2001-12-27 Spheres de silice contenant des molecules de colorant fluorescent

Country Status (3)

Country Link
JP (1) JPWO2003060037A1 (fr)
AU (1) AU2002216422A1 (fr)
WO (1) WO2003060037A1 (fr)

Cited By (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2006514708A (ja) * 2002-11-26 2006-05-11 コーネル リサーチ ファウンデーション，インコーポレーティッド シリカ系蛍光ナノ粒子
JP2006300930A (ja) * 2005-03-22 2006-11-02 Univ Of Tokushima 蛍光材料及びｘ線増感基板
EP2062946A1 (fr) * 2007-08-13 2009-05-27 Procter & Gamble International Operations SA. Particules chargées de colorant
WO2009072657A1 (fr) * 2007-12-06 2009-06-11 The University Of Tokushima Particules de silice nanofonctionnelles et leur procédé de fabrication
US8168095B2 (en) 2007-08-13 2012-05-01 The Procter & Gamble Company Spray-drying process for the manufacture of dye-loaded particles
JP2012532211A (ja) * 2009-06-30 2012-12-13 スリーエム イノベイティブ プロパティズ カンパニー ナノ粒子を用いる蛍光が改善された透明蛍光構造体、その製造方法、及び使用
CN103904804A (zh) * 2012-12-28 2014-07-02 上海微电子装备有限公司 用于电机绕组的线圈单元及应用该线圈单元的平面电机
CN106118636A (zh) * 2016-06-27 2016-11-16 高大元 一种荧光氧化硅纳米颗粒的制备方法
CN110964341A (zh) * 2019-11-29 2020-04-07 安徽捷融数据科技有限公司 一种用于棉制品的高水洗牢度天然染料的制备方法

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4918200A (en) * 1984-07-16 1990-04-17 Huls America Inc. Chromogenic and fluorogenic silanes and using the same
WO1991007087A1 (fr) * 1989-11-13 1991-05-30 Affymax Technologies N.V. Immobilisation adressable dans l'espace d'anti-ligands sur des surfaces

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4918200A (en) * 1984-07-16 1990-04-17 Huls America Inc. Chromogenic and fluorogenic silanes and using the same
WO1991007087A1 (fr) * 1989-11-13 1991-05-30 Affymax Technologies N.V. Immobilisation adressable dans l'espace d'anti-ligands sur des surfaces

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
IMHOF A. ET AL.: "Spectroscopy of fluorescein (FITC) dyed colloidal silica spheres", J. PHYS. CHEM. B, vol. 103, 1999, pages 1408 - 1415, XP002909427 *
LOBNIK ALEKSANDRA ET AL.: "pH optical sensors based on sol-gels: Chemical doping versus covalent immobilization", ANALYTICA CHIMICA ACTA, vol. 367, 1998, pages 159 - 165, XP002909428 *

Cited By (13)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2014133893A (ja) * 2002-11-26 2014-07-24 Cornell Research Foundation Inc シリカ系蛍光ナノ粒子
JP2006514708A (ja) * 2002-11-26 2006-05-11 コーネル リサーチ ファウンデーション，インコーポレーティッド シリカ系蛍光ナノ粒子
JP2010070768A (ja) * 2002-11-26 2010-04-02 Cornell Research Foundation Inc シリカ系蛍光ナノ粒子
JP2011052228A (ja) * 2002-11-26 2011-03-17 Cornell Research Foundation Inc シリカ系蛍光ナノ粒子
JP2006300930A (ja) * 2005-03-22 2006-11-02 Univ Of Tokushima 蛍光材料及びｘ線増感基板
EP2062946A1 (fr) * 2007-08-13 2009-05-27 Procter & Gamble International Operations SA. Particules chargées de colorant
WO2009022307A3 (fr) * 2007-08-13 2009-12-17 Procter & Gamble International Operations Sa Particules chargées de colorant
US8168095B2 (en) 2007-08-13 2012-05-01 The Procter & Gamble Company Spray-drying process for the manufacture of dye-loaded particles
WO2009072657A1 (fr) * 2007-12-06 2009-06-11 The University Of Tokushima Particules de silice nanofonctionnelles et leur procédé de fabrication
JP2012532211A (ja) * 2009-06-30 2012-12-13 スリーエム イノベイティブ プロパティズ カンパニー ナノ粒子を用いる蛍光が改善された透明蛍光構造体、その製造方法、及び使用
CN103904804A (zh) * 2012-12-28 2014-07-02 上海微电子装备有限公司 用于电机绕组的线圈单元及应用该线圈单元的平面电机
CN106118636A (zh) * 2016-06-27 2016-11-16 高大元 一种荧光氧化硅纳米颗粒的制备方法
CN110964341A (zh) * 2019-11-29 2020-04-07 安徽捷融数据科技有限公司 一种用于棉制品的高水洗牢度天然染料的制备方法

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JPWO2003060037A1 (ja) 2005-05-19
AU2002216422A1 (en) 2003-07-30

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