二氧化硅包覆菁染料壳核型纳米颗粒的研究
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摘要
近年来基于二氧化硅的壳核型纳米颗粒得到迅速发展，这些纳米颗粒所选用的核材料大多数为三-(联吡啶)钌(Rubpy)、磁性材料、荧光素、罗丹明、稀土元素配合物和亚甲基蓝等染料，而且已经在生物分析的很多领域得到了广泛的应用。而壳核型纳米菁染料颗粒的研究少见报道，本论文研究了二氧化硅包覆菁染料壳核型纳米颗粒的制备和性质。
利用反相微乳液法研究了4种水溶性菁染料、Rubpy、亚甲基兰和Cy2染料在制备纳米颗粒中现象的差异，研究了Rubpy、亚甲基兰和Cy2染料纳米颗粒的透射电镜图、光谱性质、染料水洗泄漏性能等性质。结合形成纳米颗粒的反应过程，得出了能够形成稳定壳核型纳米颗粒的菁染料结构特点是：染料分子具有水溶性而且富集有正电荷。
合成了两种分子结构中带有三个正电荷的Cy3和Cy5染料各一个，染料分子通过质谱，H谱和H-H相关谱的表征。用反相微乳液法制备了菁染料纳米颗粒，粒径均一，单分散性好，平均粒径为50nm(Cy3)和60nm(Cy5)，研究了纳米颗粒和染料的光谱性质特点，探索了染料在水中浸泡的泄漏性质，发现经过48小时浸泡后，纳米颗粒仍分别保持有82％(Cy3)和64％(Cy5)的荧光强度。研究了Cy3染料和纳米颗粒的光稳定性质，经90分钟的光照后，染料荧光强度降至15％，纳米颗粒仍然保持有78％的荧光强度。
合成了分子结构中引入了APS(氨丙基三乙氧基硅烷)的Cy7染料一个，并通过质谱，H谱和H-H相关谱的表征。Cy7斯托克斯位移达到近140nm，用它制备的共价包覆壳核型菁染料纳米颗粒单分散性好，平均粒径65nm，斯托克斯位移达到120nm。在水中浸泡72小时后，纳米颗粒的荧光强度保持在96％以上，经过20min的持续照射后染料荧光强度降至33％，而纳米颗粒荧光强度仍然保持在53％，一定程度上提高了光稳定性。
Core-shell nanoparticles based on silica has been developing rapidly and opening up a promising area in new bioassay development. Among them, nanoparticles of various shapes, sizes, and compositions have been successfully used in bioimaging, labeling and sensing because of their unique properties. Most of the core-shell nanoparticles were doped with Rubpy, magnetic materials, fluorescein, rhodamine, thulium chelate etc. Unfortunately, there are few reports on Cyanine dyes doped nanoparticles, This work was concentrated on the preparation and study of the Cyanine dyes doped nanoparticles.
Difference in the preparation of four soluable cyanines, Rubpy, methlyene blue and Cy2 dyes doped into silica nanoparticles by reverse microemulsion method were studied, TEM of Rubpy, methlyene blue and Cy2, as-well as leakage experiment, spectra properties were detected. The results demonstrated that the solubility and the cation numbers containing in the Cyanine dyes are very important for those can be successfully doped into silica nanoparticles to form stable core-shell nanoparticles.
Cy3 and Cy5 with three cations in their molecules were synthesized respectively. They were characterized by NMR, MS. Both of them were successfully doped into silica nanoparticles by reverse microemulsion method, the nanoparticles were uniform and monodispersed with an average diameter of 55nm (Cy3) and 60 nm( Cy5 ). Spectra of both dyes and nanoparticles were measured, leakage experiment was also conducted by immerging the nanoparticles in water, the nanoparticles remained about 82% and 64% of fluorescence intensity, respectively. Photostability was studied by illuminating the Cy3 and Cy3-doped nanoparticles for 90 min, the fluorescence intensity of the dye decreased to 15%, while the nanoparticle remained about 78%.
Cy7 with APS in structure was synthesized, and the dye was characterized by NMR, MS. Cy7 dye has a large stokes shift about 140nm. The Cy7 doped nanoparticles were uniform and monodisperse with an average diameter of 65 nm, the stokes shift was 120nm. After immerged in water for 72h, the fluorescence intensity of the nanoparticles remained about 96%, by illuminating the Cy7doped nanoparticles for 20min, the fluorescence intensity of dye decreased to 33%, and the nanoparticles remained high intensity of about 53%, the photostablity was increased 20%.
利用反相微乳液法研究了4种水溶性菁染料、Rubpy、亚甲基兰和Cy2染料在制备纳米颗粒中现象的差异，研究了Rubpy、亚甲基兰和Cy2染料纳米颗粒的透射电镜图、光谱性质、染料水洗泄漏性能等性质。结合形成纳米颗粒的反应过程，得出了能够形成稳定壳核型纳米颗粒的菁染料结构特点是：染料分子具有水溶性而且富集有正电荷。
合成了两种分子结构中带有三个正电荷的Cy3和Cy5染料各一个，染料分子通过质谱，H谱和H-H相关谱的表征。用反相微乳液法制备了菁染料纳米颗粒，粒径均一，单分散性好，平均粒径为50nm(Cy3)和60nm(Cy5)，研究了纳米颗粒和染料的光谱性质特点，探索了染料在水中浸泡的泄漏性质，发现经过48小时浸泡后，纳米颗粒仍分别保持有82％(Cy3)和64％(Cy5)的荧光强度。研究了Cy3染料和纳米颗粒的光稳定性质，经90分钟的光照后，染料荧光强度降至15％，纳米颗粒仍然保持有78％的荧光强度。
合成了分子结构中引入了APS(氨丙基三乙氧基硅烷)的Cy7染料一个，并通过质谱，H谱和H-H相关谱的表征。Cy7斯托克斯位移达到近140nm，用它制备的共价包覆壳核型菁染料纳米颗粒单分散性好，平均粒径65nm，斯托克斯位移达到120nm。在水中浸泡72小时后，纳米颗粒的荧光强度保持在96％以上，经过20min的持续照射后染料荧光强度降至33％，而纳米颗粒荧光强度仍然保持在53％，一定程度上提高了光稳定性。
Core-shell nanoparticles based on silica has been developing rapidly and opening up a promising area in new bioassay development. Among them, nanoparticles of various shapes, sizes, and compositions have been successfully used in bioimaging, labeling and sensing because of their unique properties. Most of the core-shell nanoparticles were doped with Rubpy, magnetic materials, fluorescein, rhodamine, thulium chelate etc. Unfortunately, there are few reports on Cyanine dyes doped nanoparticles, This work was concentrated on the preparation and study of the Cyanine dyes doped nanoparticles.
Difference in the preparation of four soluable cyanines, Rubpy, methlyene blue and Cy2 dyes doped into silica nanoparticles by reverse microemulsion method were studied, TEM of Rubpy, methlyene blue and Cy2, as-well as leakage experiment, spectra properties were detected. The results demonstrated that the solubility and the cation numbers containing in the Cyanine dyes are very important for those can be successfully doped into silica nanoparticles to form stable core-shell nanoparticles.
Cy3 and Cy5 with three cations in their molecules were synthesized respectively. They were characterized by NMR, MS. Both of them were successfully doped into silica nanoparticles by reverse microemulsion method, the nanoparticles were uniform and monodispersed with an average diameter of 55nm (Cy3) and 60 nm( Cy5 ). Spectra of both dyes and nanoparticles were measured, leakage experiment was also conducted by immerging the nanoparticles in water, the nanoparticles remained about 82% and 64% of fluorescence intensity, respectively. Photostability was studied by illuminating the Cy3 and Cy3-doped nanoparticles for 90 min, the fluorescence intensity of the dye decreased to 15%, while the nanoparticle remained about 78%.
Cy7 with APS in structure was synthesized, and the dye was characterized by NMR, MS. Cy7 dye has a large stokes shift about 140nm. The Cy7 doped nanoparticles were uniform and monodisperse with an average diameter of 65 nm, the stokes shift was 120nm. After immerged in water for 72h, the fluorescence intensity of the nanoparticles remained about 96%, by illuminating the Cy7doped nanoparticles for 20min, the fluorescence intensity of dye decreased to 33%, and the nanoparticles remained high intensity of about 53%, the photostablity was increased 20%.
引文
[1] 白春礼。纳米科技及发展前景。微纳米电子技术，2002，1(1)：2-5．
[2] 张德阳，纳米生物分析化学与分子生物学，化学工业出版社，2005．
[3] 姜忠义，成国祥，纳米生物技术，2003，化学工业出版社．
[4] J. J. Storhoff, R. Elghanian, R. C. Mucic et al. One-pot colorimetric differentiation ofpolynucleotides with single base imperfections using gold nanoparticle probes. J. Am. Chem. Soc. 1998, 120: 1959-1964.
[5] N. T. K. Thanh, Z. Rosenzweig. Development of an aggregation-based immunoassay for anti-protein A using gold nanoparticles. Anal, Chem. 2002, 74, 1624-1628.
[6] J. Turkevitch, E C. Stevenson, J. Hillier. Nucleation and growth process in the synthesis of colloidal gold. Discuss.Faraday Soc. 1951, 11, 55-75.
[7] G. Frens. Controlled nucleation for the regulation of the particle size in monodisperse gold suspensions. Nature: Phys. Sci. 1973, 241, 20-22.
[8] B. O. Dabbousi, J. Rodriguez-Viejo, F. V. Mikulec, et al. (CdSe)ZnS core-shell quantum dots: synthesis and characterization of a size series of highly luminescent nanocrystallites. J. Phys. Chem. B 1997, 101, 9463-9475.
[9] H. Weller. Quantized semiconductor particles: a. novel state of matter for materials science. Adv. Mater. 1993, 5, 88-95.
[10] M. Charreyre, P. Zhang, M. A. Winnik et al. Adsorption of rhodamine 6G onto polystyrene latex particles with sulfate groups at the surface. J. Colloid. Interface Sci., 1995, 170(2): 374-382.
[11] H. Gao, Y. Zhao, S. Fu et al. Preparation of a novel polymeric fluorescent nanoparticles. Colloid Polym. Sci., 2002, 280: 653-660.
[12] S. Santra, P. Zhang, K. Wang et al. Conjugation of biomolecules with luminophore-dopes silica nanoparticles for photostable biomarkers. Anal. Chem., 2001, 73:4988-4993.
[13] M. Qhobosheane, S. Santra, P. Zhang W. Tan, Biochemically functionalized silica nanoparticles. Analyst, 2001,126:1274-1278.
[14] X. Zhao, R. Tapec, W. Tan. Ultrasensitive DNA detection using highly fluorescent bioconjugated nanoparticles, J. Am. Chem. Soc., 2003, 125:11474-11475.
[15] Qhobosheane M, Santra S, Zhang P, Tan W. Biochemically functionalized silica nanoparticles Analyst, 2001, 126:1274-1278.
[16] Santra S, Theodoropoulou N, Hebard A, Tan W. Synthesis and Characterization of Silica-Coated Iron Oxide Nanoparticles in Microemulsion. Langmuir, 2001,17:2900-2906
[17] Santra S,. Wang KM, Tan WH et al. Conjugation of Biomolecules with Luminophore-Doped Silica Nanoparticles for Photostable Biomarkers Anal Chem, 2001; 73: 4988-4993.
[18] Zhiqiang Ye, Jingli Yuan et al. Novel fluorescent europium chelate-doped silica nanoparticles: preparation, characterization and time-resolved fluorometric application Journal of Materials Chemistry, 2004, 14(5): 851-856.
[19] F. Grasset, N. Labhsetwar, J. Etourneau et al. Synthesis and Magnetic Characterization of Zinc Ferrite Nanoparticles with Different Environments: Powder, Colloidal Solution, and Zinc Ferrite-Silica Core-Shell Nanoparticles Langmuir, 2002, 18:8209-8216.
[20] Stober W, Fink A, Bohn E. Controlled growth of monodisperse silica spheres in the micron size range J Colloid Interface Sci, 1968, 26: 62-69.
[21] F. J. Arriagada , K. Osseo-Asare. Synthesis of Nanosize Silica in a Nonionic Water-in-Oil Microemulsion: Effects of the Water/Surfactant Molar Ratio and Ammonia Concentration J Colloid Interface Sci, 1999, 211: 210-220.
[22] Nynke A. M. Verhaegh, Alfons van Blaaderen. Dispersions of Rhodamine-Labeled Silica Spheres: Synthesis, Characterization, and Fluorescence Confocal Scanning Laser Microscopy Langmuir, 1994, 10: 1427-1438.
[23] Hooisweng Ow, Ulrich Wiesner. Bright and Stable Core-Shell Fluorescent Silica Nanoparticles Nano Lett.,2005, 5 (1) :113-117.
[24] S. Santra, R. Tapec, N. W. Tan. Synthesis and Characterization of Silica-Coated Iron Oxide Nanoparticles in Microemulsion: The Effect ofNonionic Surfactants Langmuir, 2001, 17: 2900-2906
[25] P. Carlos A. R. Costa, Fernando Galembeck et al. Size Dependence of St6ber Silica Nanoparticle Microchemistry J. Phys. Chem. B 2003, 107: 4747-4755.
[26] L. Levy, Y. Sahoo, E.J. Bergey et al. Nanochemistry: Synthesis and Characterization of Multifunctional Nanoclinics for Biological Applications [J].Chem. Mater Chem. Mater, 2002, 14 : 3715-3721.
[27] Kluge, T, Masuda, Ushida, et al. Concentration and Molecular Weight Dependence of the Quenching of Ru(bpy)_3~(2+) by Ferricyanide in Aqueous Solutions of Synthetic Hyaluronan[J]. Macromolecules, 2000,33(2):375-381.
[28] Lin Wang, Chaoyong Yang, Weihong Tan et al. Dual-Luminophore-Doped Silica Nanoparticles for Multiplexed Signaling .Nano Lett, 2005, 5(1): 37-43.
[29] Dina Tleugabulova, Michael A. Brook, John D. Brennan et al. Optimization of Dye-Doped Silica Nanoparticles Prepared Using a Reverse Microemulsion .Langmuir, 2004, 20:8336-8342
[30] Zhiqiang Ye, Jingli Yuan, et al, Improving the Signal Sensitivity and Photostability of DNA Hybridizations on Microarrays by Using Dye-Doped Core-Shell Silica Nanoparticles..Analytical Chemistry. 2004, 76:513-518.
[31] Mingqian Tan, Jingli Yuan et al. Preparation and Time-Resolved Fluorometric Application of Luminescent Europium Nanoparticles Chemistry of Materials, 2004, 16: 2494-2498.
[32] Qisheng Huo,Jun Liu,Erica Fang et al. A New Class of Silica Cross-Linked Micellar Core-Shell Nanoparticles[J]. J. AM. CHEM. SOC. 2006, 128:6447-6453.
[33] Myung Han Lee, Eric M. Furst et al. Synthesis of monodisperse fluorescent core-shell silica particles using a modified Stober method for imaging individual particles in dense colloidal suspensions Journal of Colloid and Interface Science, 2005, 288:114-123.
[34] Ting Deng, Ji-Shan Li, Ru-Qin Yu et alreparation of Near-IR Fluorescent Nanoparticles for Fluorescence-Anisotropy-Based Immunoagglutination Assay in Whole Blood,Adv. Funct. Mater,. 2006, 16: 2147-2155.
[35] Lin Wang, Weihong Tan. Multicolor FRET Silica Nanoparticles by Single Wavelength Excitation Nano Lett., 2006, 6(1): 84-88.
[36] Xiao-xiao He, Kemin Wang, Weihong Tan. Bioconjugated Nanoparticles for DNA Protection from Cleavage J. AM. CHEM. SOC. 2003, 125 : 7168-7169.
[37] Jiaofeng Peng, Kemin Wang et al. Influence of anions on the formation and properties of chitosan-DNA nanoparticles Journal of Nanoscience and Nanotechnology, 2005, 713-717.
[38] 段菁华，王柯敏，谭蔚泓等．有机荧光染料纳米颗粒的制备及其包埋机制的研究．化学传感器，2002，22(3)：14-19．
[39] He, X. WH Tan,Kin Wang et al. J. A novel fluorescent label based on organic dye-doped silica nanoparticles for HepG liver cancer cell recognition Nanosci. Nanotechnol. 2004, 4: 585-589.
[40] S. Santra, H. Yang, D. Dutta, R.A. Mericle et al. TAT. conjugated, FITC doped silica nanoparticles for bioimaging applications Chem Commun. 2004, 24:2810-2811.
[41] A. van Blaaderen, A. Vrij, Synthesis and characterization of colloidal dispersions of fluorescent, monodisperse silica spheres Langmuir, 1992, 8:2921-2931.
[42] Nynke A. M. Verhaegh, Alfons van Blaaderen, Dispersions of Rhodamine-Labeled Silica Spheres: Synthesis, Characterization, and Fluorescence Confocal Scanning Laser Microscopy Langmuir, 1994, 10: 1427-1438.
[43] W. Lian et al. Ultrasensitive detection of biomolecules with Xuorescent dye-doped nanoparticles Analytical Biochemistry, 2004, 334, 135-144.
[44] Maria Arduini et al, Electrogenerated Chemiluminescence Sensors Using Ru(bpy)_3~(2+) Doped in Silica Nanoparticles Langmuir 2005, 21:4277-4280.
[45] Lihua Zhang, Shaojun Dong, Electrogenerated Chemiluminescence Sensors Using Ru(bpy)_3~(2+) Doped in Silica Nanoparticles Analytical chemistry, 2006, 78:5119-5120.
[46] Gang Deng, Michael A. Markowitz et al, Materials science and engineering c ,2000,11:165-172
[47] Bagwe, R. P, Hilliard, L. R.; Tan, W., Surface Modification of Silica Nanoparticles to Reduce Aggregation and Nonspecific Binding Langmuir, 2006; 22(9): 4357-4362.
[48] Santra et al. Fluorescence lifetime measurements to determine the core-shell nanostructure of FITC-doped silica nanoparticles: An optical approach to evaluate nanoparticle photostability Journal of Luminescence, 2006, 117 : 75-82.
[49] 李杜，何晓晓，王柯敏等，无机硅壳类纳米颗粒对细胞的毒性检测．湖南大学学报(自然科学版)2002，29(6)：1-6．
[50] Huiguang Zhu , Michael J. McShane DNA Detection Using Highly Fluorescent Bioconjugated Nanoparticles J. AM. CHEM. SOC. 2003, 125:11474-11475
[51] 段菁华，王柯敏，谭蔚泓等，新型有机荧光染料嵌合的核壳荧光纳米材料的研制．高等学校化学学报，2003，24(2)：255-259．
[52] Xichun Zhou, Jizhong Zhou. Improving the Signal Sensitivity and Photostability of DNA Hybridizations on Microarrays by Using Dye-Doped Core-Shell Silica Nanoparticles Anal Chem., 2004, 76:5302-5312.
[53] Santra S, Tapec R, Theodoropoulou N, Dobson J, Hebard Aet al. Synthesis and characterization of silica-coated iron oxide nanoparticles in microemulsion: The effect of nonionic surfactants. Langmuir 2001 ;17:2900-2906.
[54] Zhao X, Tapec-Dytioco R, Wang K, Tan W. Efficient collection of trace amounts of DNA/mRNA molecules using genomagnetic nano-capturers. Anal Chem 2003 ;75:3476-3483.
[55] Liqiu Wang, Xiaojun Peng, Fengling Song et al. New near-infrared ind0cyanines and their spectral properties in SiO2 sol-gel. Dyes and Pigments. 2004, 61: 103-107.
[56] Fengling Song, Xiaojun Peng, Erhu Lu et al. Tuning the Photoinduced Electron Transfer in Near-Infrared Heptamethine Cyanine Dyes. Tetrahedron Letters. 2005, 46:4817-4820.
[57] HoriuchiH,IshibashiS,TobitaS et al. Photodegradation Processes of Cyanine Dyes in the Film State Induced by Singlet Molecular Oxygen. J.Phys.Chem.B ;2003,107(31):7739-7746.
[58] 孙世国．铼、钉吡啶光敏染料的研究：(博士学位论文)．大连：大连理工大学，2003年．
[59] D. L. Gallaher, Jr. Johnson, M. E. Johnson et al. Development of near-infrared fluorophoric labels for the determination of fatty acids separated by capillary electrophoresis with diode laser induced fluorescence detection. Analyst, 1999, 124,1541-1546.
[60] R.C. Benson, H. Kues. Absorption and fluorescence properties of cyanine dyes .J. Chem. Eng. Data, 1977,22(4):379-383.
[61] A.C. Henry, M. Galloway, Y. Y. Davidson et al. Surface Modification of poly(methyl methacrylate) used in the fabrication of microanalytical devices. Anal. Chem. 2000, 72:5331-5337.
[62] 段菁华，王柯敏，何晓晓等．基于壳核荧光纳米颗粒的一种新型纳米pH传感器．湖南大学学报(自然科学版)．2003，30(2)：1-5．
[63] Xiaojun Peng, Fengling Song, Yunling Gao et al. Heptamethine Cyanine Dyes with a Large stokes shift and Strong Fluorescence: A Paradigm for Excited-State Intramolecular Charge Transfer. Journal of the American Chemical Society. 2005. 127: 4170-4171.
[64] Gallaher D. L,, Johnson M. E. Development of near-infrared fluorophoric labels for the determination of fatty acids separated by capillary electrophoresis with diode laser induced fluorescence detection.Analyst, 1999, 124: 1541-1546.
[65] Acar, N.; Kurzawa, J Fritz Net al. Phenothiazine-Pyrene Dyads: Photoinduced Charge Separation and Structural Relaxation in the CT State. J. Phy. Chem. A 2003, 107, 9530-9541.
[66] de Silva A. P., Gunaratne., Gunnlaugsson. T et al. Signaling Recognition Events with Fluorescent Sensors and Switches. Chem. Rev. 1997, 97(5): 1515-1566.
[2] 张德阳，纳米生物分析化学与分子生物学，化学工业出版社，2005．
[3] 姜忠义，成国祥，纳米生物技术，2003，化学工业出版社．
[4] J. J. Storhoff, R. Elghanian, R. C. Mucic et al. One-pot colorimetric differentiation ofpolynucleotides with single base imperfections using gold nanoparticle probes. J. Am. Chem. Soc. 1998, 120: 1959-1964.
[5] N. T. K. Thanh, Z. Rosenzweig. Development of an aggregation-based immunoassay for anti-protein A using gold nanoparticles. Anal, Chem. 2002, 74, 1624-1628.
[6] J. Turkevitch, E C. Stevenson, J. Hillier. Nucleation and growth process in the synthesis of colloidal gold. Discuss.Faraday Soc. 1951, 11, 55-75.
[7] G. Frens. Controlled nucleation for the regulation of the particle size in monodisperse gold suspensions. Nature: Phys. Sci. 1973, 241, 20-22.
[8] B. O. Dabbousi, J. Rodriguez-Viejo, F. V. Mikulec, et al. (CdSe)ZnS core-shell quantum dots: synthesis and characterization of a size series of highly luminescent nanocrystallites. J. Phys. Chem. B 1997, 101, 9463-9475.
[9] H. Weller. Quantized semiconductor particles: a. novel state of matter for materials science. Adv. Mater. 1993, 5, 88-95.
[10] M. Charreyre, P. Zhang, M. A. Winnik et al. Adsorption of rhodamine 6G onto polystyrene latex particles with sulfate groups at the surface. J. Colloid. Interface Sci., 1995, 170(2): 374-382.
[11] H. Gao, Y. Zhao, S. Fu et al. Preparation of a novel polymeric fluorescent nanoparticles. Colloid Polym. Sci., 2002, 280: 653-660.
[12] S. Santra, P. Zhang, K. Wang et al. Conjugation of biomolecules with luminophore-dopes silica nanoparticles for photostable biomarkers. Anal. Chem., 2001, 73:4988-4993.
[13] M. Qhobosheane, S. Santra, P. Zhang W. Tan, Biochemically functionalized silica nanoparticles. Analyst, 2001,126:1274-1278.
[14] X. Zhao, R. Tapec, W. Tan. Ultrasensitive DNA detection using highly fluorescent bioconjugated nanoparticles, J. Am. Chem. Soc., 2003, 125:11474-11475.
[15] Qhobosheane M, Santra S, Zhang P, Tan W. Biochemically functionalized silica nanoparticles Analyst, 2001, 126:1274-1278.
[16] Santra S, Theodoropoulou N, Hebard A, Tan W. Synthesis and Characterization of Silica-Coated Iron Oxide Nanoparticles in Microemulsion. Langmuir, 2001,17:2900-2906
[17] Santra S,. Wang KM, Tan WH et al. Conjugation of Biomolecules with Luminophore-Doped Silica Nanoparticles for Photostable Biomarkers Anal Chem, 2001; 73: 4988-4993.
[18] Zhiqiang Ye, Jingli Yuan et al. Novel fluorescent europium chelate-doped silica nanoparticles: preparation, characterization and time-resolved fluorometric application Journal of Materials Chemistry, 2004, 14(5): 851-856.
[19] F. Grasset, N. Labhsetwar, J. Etourneau et al. Synthesis and Magnetic Characterization of Zinc Ferrite Nanoparticles with Different Environments: Powder, Colloidal Solution, and Zinc Ferrite-Silica Core-Shell Nanoparticles Langmuir, 2002, 18:8209-8216.
[20] Stober W, Fink A, Bohn E. Controlled growth of monodisperse silica spheres in the micron size range J Colloid Interface Sci, 1968, 26: 62-69.
[21] F. J. Arriagada , K. Osseo-Asare. Synthesis of Nanosize Silica in a Nonionic Water-in-Oil Microemulsion: Effects of the Water/Surfactant Molar Ratio and Ammonia Concentration J Colloid Interface Sci, 1999, 211: 210-220.
[22] Nynke A. M. Verhaegh, Alfons van Blaaderen. Dispersions of Rhodamine-Labeled Silica Spheres: Synthesis, Characterization, and Fluorescence Confocal Scanning Laser Microscopy Langmuir, 1994, 10: 1427-1438.
[23] Hooisweng Ow, Ulrich Wiesner. Bright and Stable Core-Shell Fluorescent Silica Nanoparticles Nano Lett.,2005, 5 (1) :113-117.
[24] S. Santra, R. Tapec, N. W. Tan. Synthesis and Characterization of Silica-Coated Iron Oxide Nanoparticles in Microemulsion: The Effect ofNonionic Surfactants Langmuir, 2001, 17: 2900-2906
[25] P. Carlos A. R. Costa, Fernando Galembeck et al. Size Dependence of St6ber Silica Nanoparticle Microchemistry J. Phys. Chem. B 2003, 107: 4747-4755.
[26] L. Levy, Y. Sahoo, E.J. Bergey et al. Nanochemistry: Synthesis and Characterization of Multifunctional Nanoclinics for Biological Applications [J].Chem. Mater Chem. Mater, 2002, 14 : 3715-3721.
[27] Kluge, T, Masuda, Ushida, et al. Concentration and Molecular Weight Dependence of the Quenching of Ru(bpy)_3~(2+) by Ferricyanide in Aqueous Solutions of Synthetic Hyaluronan[J]. Macromolecules, 2000,33(2):375-381.
[28] Lin Wang, Chaoyong Yang, Weihong Tan et al. Dual-Luminophore-Doped Silica Nanoparticles for Multiplexed Signaling .Nano Lett, 2005, 5(1): 37-43.
[29] Dina Tleugabulova, Michael A. Brook, John D. Brennan et al. Optimization of Dye-Doped Silica Nanoparticles Prepared Using a Reverse Microemulsion .Langmuir, 2004, 20:8336-8342
[30] Zhiqiang Ye, Jingli Yuan, et al, Improving the Signal Sensitivity and Photostability of DNA Hybridizations on Microarrays by Using Dye-Doped Core-Shell Silica Nanoparticles..Analytical Chemistry. 2004, 76:513-518.
[31] Mingqian Tan, Jingli Yuan et al. Preparation and Time-Resolved Fluorometric Application of Luminescent Europium Nanoparticles Chemistry of Materials, 2004, 16: 2494-2498.
[32] Qisheng Huo,Jun Liu,Erica Fang et al. A New Class of Silica Cross-Linked Micellar Core-Shell Nanoparticles[J]. J. AM. CHEM. SOC. 2006, 128:6447-6453.
[33] Myung Han Lee, Eric M. Furst et al. Synthesis of monodisperse fluorescent core-shell silica particles using a modified Stober method for imaging individual particles in dense colloidal suspensions Journal of Colloid and Interface Science, 2005, 288:114-123.
[34] Ting Deng, Ji-Shan Li, Ru-Qin Yu et alreparation of Near-IR Fluorescent Nanoparticles for Fluorescence-Anisotropy-Based Immunoagglutination Assay in Whole Blood,Adv. Funct. Mater,. 2006, 16: 2147-2155.
[35] Lin Wang, Weihong Tan. Multicolor FRET Silica Nanoparticles by Single Wavelength Excitation Nano Lett., 2006, 6(1): 84-88.
[36] Xiao-xiao He, Kemin Wang, Weihong Tan. Bioconjugated Nanoparticles for DNA Protection from Cleavage J. AM. CHEM. SOC. 2003, 125 : 7168-7169.
[37] Jiaofeng Peng, Kemin Wang et al. Influence of anions on the formation and properties of chitosan-DNA nanoparticles Journal of Nanoscience and Nanotechnology, 2005, 713-717.
[38] 段菁华，王柯敏，谭蔚泓等．有机荧光染料纳米颗粒的制备及其包埋机制的研究．化学传感器，2002，22(3)：14-19．
[39] He, X. WH Tan,Kin Wang et al. J. A novel fluorescent label based on organic dye-doped silica nanoparticles for HepG liver cancer cell recognition Nanosci. Nanotechnol. 2004, 4: 585-589.
[40] S. Santra, H. Yang, D. Dutta, R.A. Mericle et al. TAT. conjugated, FITC doped silica nanoparticles for bioimaging applications Chem Commun. 2004, 24:2810-2811.
[41] A. van Blaaderen, A. Vrij, Synthesis and characterization of colloidal dispersions of fluorescent, monodisperse silica spheres Langmuir, 1992, 8:2921-2931.
[42] Nynke A. M. Verhaegh, Alfons van Blaaderen, Dispersions of Rhodamine-Labeled Silica Spheres: Synthesis, Characterization, and Fluorescence Confocal Scanning Laser Microscopy Langmuir, 1994, 10: 1427-1438.
[43] W. Lian et al. Ultrasensitive detection of biomolecules with Xuorescent dye-doped nanoparticles Analytical Biochemistry, 2004, 334, 135-144.
[44] Maria Arduini et al, Electrogenerated Chemiluminescence Sensors Using Ru(bpy)_3~(2+) Doped in Silica Nanoparticles Langmuir 2005, 21:4277-4280.
[45] Lihua Zhang, Shaojun Dong, Electrogenerated Chemiluminescence Sensors Using Ru(bpy)_3~(2+) Doped in Silica Nanoparticles Analytical chemistry, 2006, 78:5119-5120.
[46] Gang Deng, Michael A. Markowitz et al, Materials science and engineering c ,2000,11:165-172
[47] Bagwe, R. P, Hilliard, L. R.; Tan, W., Surface Modification of Silica Nanoparticles to Reduce Aggregation and Nonspecific Binding Langmuir, 2006; 22(9): 4357-4362.
[48] Santra et al. Fluorescence lifetime measurements to determine the core-shell nanostructure of FITC-doped silica nanoparticles: An optical approach to evaluate nanoparticle photostability Journal of Luminescence, 2006, 117 : 75-82.
[49] 李杜，何晓晓，王柯敏等，无机硅壳类纳米颗粒对细胞的毒性检测．湖南大学学报(自然科学版)2002，29(6)：1-6．
[50] Huiguang Zhu , Michael J. McShane DNA Detection Using Highly Fluorescent Bioconjugated Nanoparticles J. AM. CHEM. SOC. 2003, 125:11474-11475
[51] 段菁华，王柯敏，谭蔚泓等，新型有机荧光染料嵌合的核壳荧光纳米材料的研制．高等学校化学学报，2003，24(2)：255-259．
[52] Xichun Zhou, Jizhong Zhou. Improving the Signal Sensitivity and Photostability of DNA Hybridizations on Microarrays by Using Dye-Doped Core-Shell Silica Nanoparticles Anal Chem., 2004, 76:5302-5312.
[53] Santra S, Tapec R, Theodoropoulou N, Dobson J, Hebard Aet al. Synthesis and characterization of silica-coated iron oxide nanoparticles in microemulsion: The effect of nonionic surfactants. Langmuir 2001 ;17:2900-2906.
[54] Zhao X, Tapec-Dytioco R, Wang K, Tan W. Efficient collection of trace amounts of DNA/mRNA molecules using genomagnetic nano-capturers. Anal Chem 2003 ;75:3476-3483.
[55] Liqiu Wang, Xiaojun Peng, Fengling Song et al. New near-infrared ind0cyanines and their spectral properties in SiO2 sol-gel. Dyes and Pigments. 2004, 61: 103-107.
[56] Fengling Song, Xiaojun Peng, Erhu Lu et al. Tuning the Photoinduced Electron Transfer in Near-Infrared Heptamethine Cyanine Dyes. Tetrahedron Letters. 2005, 46:4817-4820.
[57] HoriuchiH,IshibashiS,TobitaS et al. Photodegradation Processes of Cyanine Dyes in the Film State Induced by Singlet Molecular Oxygen. J.Phys.Chem.B ;2003,107(31):7739-7746.
[58] 孙世国．铼、钉吡啶光敏染料的研究：(博士学位论文)．大连：大连理工大学，2003年．
[59] D. L. Gallaher, Jr. Johnson, M. E. Johnson et al. Development of near-infrared fluorophoric labels for the determination of fatty acids separated by capillary electrophoresis with diode laser induced fluorescence detection. Analyst, 1999, 124,1541-1546.
[60] R.C. Benson, H. Kues. Absorption and fluorescence properties of cyanine dyes .J. Chem. Eng. Data, 1977,22(4):379-383.
[61] A.C. Henry, M. Galloway, Y. Y. Davidson et al. Surface Modification of poly(methyl methacrylate) used in the fabrication of microanalytical devices. Anal. Chem. 2000, 72:5331-5337.
[62] 段菁华，王柯敏，何晓晓等．基于壳核荧光纳米颗粒的一种新型纳米pH传感器．湖南大学学报(自然科学版)．2003，30(2)：1-5．
[63] Xiaojun Peng, Fengling Song, Yunling Gao et al. Heptamethine Cyanine Dyes with a Large stokes shift and Strong Fluorescence: A Paradigm for Excited-State Intramolecular Charge Transfer. Journal of the American Chemical Society. 2005. 127: 4170-4171.
[64] Gallaher D. L,, Johnson M. E. Development of near-infrared fluorophoric labels for the determination of fatty acids separated by capillary electrophoresis with diode laser induced fluorescence detection.Analyst, 1999, 124: 1541-1546.
[65] Acar, N.; Kurzawa, J Fritz Net al. Phenothiazine-Pyrene Dyads: Photoinduced Charge Separation and Structural Relaxation in the CT State. J. Phy. Chem. A 2003, 107, 9530-9541.
[66] de Silva A. P., Gunaratne., Gunnlaugsson. T et al. Signaling Recognition Events with Fluorescent Sensors and Switches. Chem. Rev. 1997, 97(5): 1515-1566.