臺灣博碩士論文加值系統

摘要


量子點（QDs），膠體納米片提供許多功能，如生物標記，藥物遞送，光動力治療，納米診斷，太陽能電池和光子器件。由於顯示出高亮度發光並提供調整其尺寸和發射波長的可能性，QDs 的生物標記是當今納米材料最快的移動領域之一。

由於這種毒性和環境問題，開發CuInS2 / ZnS QDs 作為用於標記癌細胞的低毒納米材料變得重要。在這項工作中，CuInS2 / ZnS QDs 是通過熱膠體合成方法製成的。 QDs 通常被一層疏水分子覆蓋。因此，需要表面改性，例如塗覆或共軛親水或兩親分子，以將 QDs 從有機溶液轉化為水溶液用於生物應用。這裡，CuInS2 / ZnS QDs 塗覆有聚（乙二醇）甲基丙烯酸酯（PEGMA），其允許將含有極性的有機納米晶體從有機溶液轉移到水溶液中。 PEGMA 塗層的 CuInS2 / ZnS 顯示穩定的排放長達3週，並標記出具有清晰可見的紅色發光的人肝癌（HepG2）腫瘤細胞。

在本論文中，通過超聲處理的油溶性 QDs 可直接轉移到水相上，無需任何附加的表面活性劑，封端配體和表面塗層。進一步改進，顯示 CuInS2 / ZnS QDs 在直接製備而不含任何非極性溶劑的水中的分散體。最後，用水分散的 CuInS2 / ZnS QDs 染色的 HepG2 細胞共焦圖像體外評價證實轉移的 QDs 是無毒的，同時作為 HepG2 腫瘤細胞的標記試劑。

此外，證明了聚（馬來酸酐 - alt-1-十八碳烯）作為 CuInS2 / ZnS QDs 的封端配體和胺 - CuInS2 / ZnS QDs 的生物綴合的實用性。此外，還顯示了CuInS2 / ZnS QDs 在納米凝膠中的潛力的探索
关键词：CuInS2 / ZnS，量子点，超声波，肿瘤细胞
論文教授：Jia-Yaw Chang
標題：Professor of Nano Chemistry

Abstract
.
Quantum dots (QDs), which are colloidal nanocrsytals offer many functions such as biological labelling, drug delivery, photodynamic therapy, nanodiagnostic, and photonic devices. Because of displaying a bright luminescence and offering the possibility to tune their size and emission wavelength, biological labeling of QDs is one of the fastest moving field of nanomaterials today.

Due to alleged toxicity and environmental concern, developing CuInS2/ZnS QDs as low toxic nanomaterials for labeling cancer cells became important. In this work, CuInS2/ZnS QDs were made by the method of hot colloidal synthesis. QDs are usually covered by a layer of hydrophobic molecules. Thus, surface modification such as coating or conjugating hydrophilic or amphiphilic molecules is needed to convert QDs from organic to aqueous solution for biological application. Here, CuInS2/ZnS QDs was coated with Poly(ethylene glycol) methacrylate (PEGMA) which allows for transferring hydrophibically caped nanocrystals from organic to aqueous solution. The PEGMA coated CuInS2/ZnS showed stable emission for up to 3 weeks and labeled human liver carcinoma (HepG2) tumor cells with red luminescence were clearly visible.

In this thesis, CuInS2/ZnS QDs in oil phase can be directly transferred into water phase via sonication without any additional surfactant, capping ligand, or surface coating with polymers. Further improvement, CuInS2/ZnS QDs dispersion in water directly prepared without any non-polar solvent was revealed. Finally, HepG2 tumor cells confocal images stained with water-dispersed CuInS2/ZnS QDs are showing. In vitro evaluation has proven that the the transferred QDs are low-toxic along with being an efficient labelling agent to HepG2 tumor cells.

Furthermore Utility of poly(maleic anhydride-alt-1-octadecene) as capping ligand for CuInS2/ZnS QD and bioconjugation of Amine - CuInS2/ZnS QDs was demonstrated. In Addition the exploration of potential of CuInS2/ZnS QDs in nanogel was showed

Keywords : CuInS2/ZnS, Quantum Dots, Ultrasonic, tumor cells
Thesis supervisor : Jia Yaw-Chang
Title : Professor of Nano Chemistry

Table of Contents
Abstract i
Acknowledgements ii
Table of Contents iii
List of Figures v
Chapter 1 : Introduction 1
1.1 History of quantum dots synthesis. 1
1.2 Motivation and Outline 3
Chapter 2 : Theoretical Review 6
2.1 Introduction 6
2.1.1 General Introduction to Quantum Dots 6
2.1.2 Optoelectronic Properties of QDs Confined Semiconductor Nanocrystals 7
2.1.3 CuInS2/ZnS QDs in Biological Imaging Applications 8
2.1.4 Synthesis of Colloidal Quantum Dots 15
2.2 Experimental Procedures 16
2.2.1. Nanoparticle synthesis ………………………………………………………17
2.2.2. Optical Spectroscopy………………………………………………………...18
2.3 Synthesis and Characterization of CuInS2/ZnS QDs 19
2.4 Transfer of CuInS2/ZnS QDs into aqueous phase toward to drug delivery 21
2.4.1. Water Solubility of QDs………………………………………………….….21
2.4.2. Bioconjugationo of QDs…………………………………………………….25
2.4.3. Drug Delivery of QDs……………………………………………………….28
2.5 Applied and Multimodal imaging that involve CuInS2/ZnS QDs 28
2.6 Cytotoxicity 29
2.7 Ab-Initio of Nanoparticles 30
2.7.1. Continuum Model of Slab…………………………………………………….31
2.7.2 Band Gap in CuInS2/ZnS QDs 33
Chapter 3 : Results of poly(ethylene glycol) methacrylate coated CuInS2/ZnS quantum dots and their application in cell staining 35
3.1. Research Methodology………………………………………………………...37
3,2. Result and Discussion…………………………………………………………44
3,3 Summary………………………………………………………………….. 52
Chapter 4: One-step Phase Transferring Method on Preparing CuInS2/ZnS QDs Dispersion via Ultrasonic Treatment 53
4.1. Research Methodology 55
4.2. Result and Discussion 61
4.3. Summary 77
Chapter 5 : Conclusions 79
References 81
Appendix…………………………………………………………………………………94
 

References
1. Deng, D.; Chen, Y.; Cao, J.; Tian, J.; Qian, Z.; Achilefu, S.; Gu, Y., High-Quality CuInS2/ZnS Quantum Dots for In vitro and In vivo Bioimaging. Chemistry of Materials 2012, 24 (15), 3029-3037.
2. Sun, Y.; Song, F.; Qian, C.; Peng, K.; Sun, S.; Zhao, Y.; Bai, Z.; Tang, J.; Wu, S.; Ali, H.; Bo, F.; Zhong, H.; Jin, K.; Xu, X., High-Q Microcavity Enhanced Optical Properties of CuInS2/ZnS Colloidal Quantum Dots toward Non-Photodegradation. ACS Photonics 2017, 4 (2), 369-377.
3. Lv, G.; Guo, W.; Zhang, W.; Zhang, T.; Li, S.; Chen, S.; Eltahan, A. S.; Wang, D.; Wang, Y.; Zhang, J.; Wang, P. C.; Chang, J.; Liang, X.-J., Near-Infrared Emission CuInS/ZnS Quantum Dots: All-in-One Theranostic Nanomedicines with Intrinsic Fluorescence/Photoacoustic Imaging for Tumor Phototherapy. ACS Nano 2016, 10 (10), 9637-9645.
4. Knipe, J. M.; Peters, J. T.; Peppas, N. A., Theranostic agents for intracellular gene delivery with spatiotemporal imaging. Nano today 2013, 8 (1), 21-38.
5. Biju, V.; Itoh, T.; Ishikawa, M., Delivering quantum dots to cells: bioconjugated quantum dots for targeted and nonspecific extracellular and intracellular imaging. Chemical Society Reviews 2010, 39 (8), 3031-3056.
6. Ashenfelter, B. A.; Desireddy, A.; Yau, S. H.; Goodson III, T.; Bigioni, T. P., Fluorescence from molecular silver nanoparticles. The Journal of Physical Chemistry C 2015, 119 (35), 20728-20734.
7. Klostranec, J. M.; Chan, W. C. W., Quantum Dots in Biological and Biomedical Research: Recent Progress and Present Challenges. Advanced Materials 2006, 18 (15), 1953-1964.
8. Medintz, I. L.; Uyeda, H. T.; Goldman, E. R.; Mattoussi, H., Quantum dot bioconjugates for imaging, labelling and sensing. Nature materials 2005, 4 (6), 435.
9. Priem, B.; Tian, C.; Tang, J.; Zhao, Y.; Mulder, W. J., Fluorescent nanoparticles for the accurate detection of drug delivery. Expert opinion on drug delivery 2015, 12 (12), 1881-1894.
10. Resch-Genger, U.; Grabolle, M.; Cavaliere-Jaricot, S.; Nitschke, R.; Nann, T., Quantum dots versus organic dyes as fluorescent labels. Nature methods 2008, 5 (9), 763-775.
11. Sardar, R.; Funston, A. M.; Mulvaney, P.; Murray, R. W., Gold nanoparticles: past, present, and future. Langmuir 2009, 25 (24), 13840-13851.
12. Thakor, A.; Jokerst, J.; Zavaleta, C.; Massoud, T.; Gambhir, S., Gold nanoparticles: a revival in precious metal administration to patients. Nano letters 2011, 11 (10), 4029-4036.
13. Wang, L.; Fernández‐Terán, R.; Zhang, L.; Fernandes, D. L.; Tian, L.; Chen, H.; Tian, H., Organic Polymer Dots as Photocatalysts for Visible Light‐Driven Hydrogen Generation. Angewandte Chemie 2016, 128 (40), 12494-12498.
14. Wolfbeis, O. S., An overview of nanoparticles commonly used in fluorescent bioimaging. Chemical Society Reviews 2015, 44 (14), 4743-4768.
15. Wu, C.; Chiu, D. T., Highly fluorescent semiconducting polymer dots for biology and medicine. Angewandte Chemie International Edition 2013, 52 (11), 3086-3109.
16. Zhang, X.; Wang, Z.; Xu, C., Demonstrating the Many Possible Colors of Gold-Supported Solid Nanoparticles. Journal of Chemical Education 2014, 92 (2), 336-338.
17. Zhang, Z.; Sun, W.; Wu, P., Highly photoluminescent carbon dots derived from egg white: facile and green synthesis, photoluminescence properties, and multiple applications. ACS Sustainable Chemistry & Engineering 2015, 3 (7), 1412-1418.
18. Bonilla, C. A. M.; Kouznetsov, V. V., “Green” Quantum Dots: Basics, Green Synthesis, and Nanotechnological Applications. In Green Nanotechnology - Overview and Further Prospects, Larramendy, M. L.; Soloneski, S., Eds. InTech: Rijeka, 2016; p Ch. 07.
19. Jelinek, R., Biological Applications of Carbon-Dots. In Carbon Quantum Dots: Synthesis, Properties and Applications, Jelinek, R., Ed. Springer International Publishing: Cham, 2017; pp 47-60.
20. Volkov, Y., Quantum dots in nanomedicine: recent trends, advances and unresolved issues. Biochemical and Biophysical Research Communications 2015, 468 (3), 419-427.
21. Zhou, J.; Liu, Y.; Tang, J.; Tang, W., Surface ligands engineering of semiconductor quantum dots for chemosensory and biological applications. Materials Today.
22. Michael King, D., Imaging of metastatic melanoma. Cancer Imaging 2006, 6 (1), 204-208.
23. Delorme, S.; Krix, M., Contrast-enhanced ultrasound for examining tumor biology. Cancer Imaging 2006, 6 (1), 148-152.
24. Namasivayam, S.; Martin, D. R.; Saini, S., Imaging of liver metastases: MRI. Cancer Imaging 2007, 7 (1), 2-9.
25. Wang, M.; Liu, X.; Cao, C.; Wang, L., Highly luminescent CuInS2-ZnS nanocrystals: achieving phase transfer and nuclear homing property simultaneously through simple TTAB modification. Journal of Materials Chemistry 2012, 22 (41), 21979-21986.
26. Chen, Y.; Li, S.; Huang, L.; Pan, D., Low-cost and gram-scale synthesis of water-soluble Cu-In-S/ZnS core/shell quantum dots in an electric pressure cooker. Nanoscale 2014, 6 (3), 1295-1298.
27. Permadi, A.; Fahmi, M. Z.; Chen, J.-K.; Chang, J.-Y.; Cheng, C.-Y.; Wang, G.-Q.; Ou, K.-L., Preparation of poly(ethylene glycol) methacrylate coated CuInS2/ZnS quantum dots and their use in cell staining. RSC Advances 2012, 2 (14), 6018-6022.
28. Wang, M.; Chen, Z.; Cao, C., Preparation of magnetic CuInS2–ZnS nanocomposites for bioimaging. Materials Letters 2014, 120, 50-53.
29. Yu, K.; Ng, P.; Ouyang, J.; Zaman, M. B.; Abulrob, A.; Baral, T. N.; Fatehi, D.; Jakubek, Z. J.; Kingston, D.; Wu, X.; Liu, X.; Hebert, C.; Leek, D. M.; Whitfield, D. M., Low-Temperature Approach to Highly Emissive Copper Indium Sulfide Colloidal Nanocrystals and Their Bioimaging Applications. ACS Applied Materials & Interfaces 2013, 5 (8), 2870-2880.
30. Foda, M. F.; Huang, L.; Shao, F.; Han, H.-Y., Biocompatible and Highly Luminescent Near-Infrared CuInS2/ZnS Quantum Dots Embedded Silica Beads for Cancer Cell Imaging. ACS Applied Materials & Interfaces 2014, 6 (3), 2011-2017.
31. Dong, C.; Liu, Z.; Zhang, L.; Guo, W.; Li, X.; Liu, J.; Wang, H.; Chang, J., pHe-Induced Charge-Reversible NIR Fluorescence Nanoprobe for Tumor-Specific Imaging. ACS Applied Materials & Interfaces 2015, 7 (14), 7566-7575.
32. Zhao, C.; Bai, Z.; Liu, X.; Zhang, Y.; Zou, B.; Zhong, H., Small GSH-Capped CuInS2 Quantum Dots: MPA-Assisted Aqueous Phase Transfer and Bioimaging Applications. ACS Applied Materials & Interfaces 2015, 7 (32), 17623-17629.
33. Lin, B.; Yao, X.; Zhu, Y.; Shen, J.; Yang, X.; Jiang, H.; Zhang, X., Multifunctional manganese-doped core-shell quantum dots for magnetic resonance and fluorescence imaging of cancer cells. New Journal of Chemistry 2013, 37 (10), 3076-3083.
34. Lin, Z.; Fei, X.; Ma, Q.; Gao, X.; Su, X., CuInS2 quantum dots@silica near-infrared fluorescent nanoprobe for cell imaging. New Journal of Chemistry 2014, 38 (1), 90-96.
35. Shen, J.; Li, Y.; Zhu, Y.; Yang, X.; Yao, X.; Li, J.; Huang, G.; Li, C., Multifunctional gadolinium-labeled silica-coated Fe3O4 and CuInS2 nanoparticles as a platform for in vivo tri-modality magnetic resonance and fluorescence imaging. Journal of Materials Chemistry B 2015, 3 (14), 2873-2882.
36. Mandal, G.; Darragh, M.; Wang, Y. A.; Heyes, C. D., Cadmium-Free Quantum Dots as Time-Gated Bioimaging Probes in Highly-Autofluorescent Human Breast Cancer Cells. Chemical communications (Cambridge, England) 2013, 49 (6), 624-626.
37. Yong, K.-T.; Roy, I.; Hu, R.; Ding, H.; Cai, H.; Zhu, J.; Zhang, X.; Bergey, E. J.; Prasad, P. N., Synthesis of ternary CuInS2/ZnS quantum dot bioconjugates and their applications for targeted cancer bioimaging. Integrative Biology 2010, 2 (2-3), 121-129.
38. Jeong Yu, L.; Dong Heon, N.; Mi Hwa, O.; Youngsun, K.; Hyung Seok, C.; Duk Young, J.; Chan Beum, P.; Yoon Sung, N., Serum-stable quantum dot--protein hybrid nanocapsules for optical bio-imaging. Nanotechnology 2014, 25 (17), 175702.
39. Liu, Z.; Chen, N.; Dong, C.; Li, W.; Guo, W.; Wang, H.; Wang, S.; Tan, J.; Tu, Y.; Chang, J., Facile Construction of Near Infrared Fluorescence Nanoprobe with Amphiphilic Protein-Polymer Bioconjugate for Targeted Cell Imaging. ACS Applied Materials & Interfaces 2015, 7 (34), 18997-19005.
40. Arshad, A.; Chen, H.; Bai, X.; Xu, S.; Wang, L., One-Pot Aqueous Synthesis of Highly Biocompatible Near Infrared CuInS2 Quantum Dots for Target Cell Imaging. Chinese Journal of Chemistry 2016, 34 (6), 576-582.
41. Li, L.; Daou, T. J.; Texier, I.; Kim Chi, T. T.; Liem, N. Q.; Reiss, P., Highly Luminescent CuInS2/ZnS Core/Shell Nanocrystals: Cadmium-Free Quantum Dots for In Vivo Imaging. Chemistry of Materials 2009, 21 (12), 2422-2429.
42. Pons, T.; Pic, E.; Lequeux, N.; Cassette, E.; Bezdetnaya, L.; Guillemin, F.; Marchal, F.; Dubertret, B., Cadmium-Free CuInS2/ZnS Quantum Dots for Sentinel Lymph Node Imaging with Reduced Toxicity. ACS Nano 2010, 4 (5), 2531-2538.
43. Ding, K.; Jing, L.; Liu, C.; Hou, Y.; Gao, M., Magnetically engineered Cd-free quantum dots as dual-modality probes for fluorescence/magnetic resonance imaging of tumors. Biomaterials 2014, 35 (5), 1608-1617.
44. Liu, S.; Zhang, H.; Qiao, Y.; Su, X., One-pot synthesis of ternary CuInS2 quantum dots with near-infrared fluorescence in aqueous solution. RSC Advances 2012, 2 (3), 819-825.
45. Liu, L.; Hu, R.; Law, W.-C.; Roy, I.; Zhu, J.; Ye, L.; Hu, S.; Zhang, X.; Yong, K.-T., Optimizing the synthesis of red- and near-infrared CuInS2 and AgInS2 semiconductor nanocrystals for bioimaging. Analyst 2013, 138 (20), 6144-6153.
46. Gao, X.; Liu, Z.; Lin, Z.; Su, X., CuInS2 quantum dots/poly(l-glutamic acid)-drug conjugates for drug delivery and cell imaging. Analyst 2014, 139 (4), 831-836.
47. Yang, W.; Guo, W.; Gong, X.; Zhang, B.; Wang, S.; Chen, N.; Yang, W.; Tu, Y.; Fang, X.; Chang, J., Facile Synthesis of Gd–Cu–In–S/ZnS Bimodal Quantum Dots with Optimized Properties for Tumor Targeted Fluorescence/MR In Vivo Imaging. ACS Applied Materials & Interfaces 2015, 7 (33), 18759-18768.
48. Guo, W.; Sun, X.; Jacobson, O.; Yan, X.; Min, K.; Srivatsan, A.; Niu, G.; Kiesewetter, D. O.; Chang, J.; Chen, X., Intrinsically Radioactive [64Cu]CuInS/ZnS Quantum Dots for PET and Optical Imaging: Improved Radiochemical Stability and Controllable Cerenkov Luminescence. ACS Nano 2015, 9 (1), 488-495.
49. Choi, H. S.; Kim, Y.; Park, J. C.; Oh, M. H.; Jeon, D. Y.; Nam, Y. S., Highly luminescent, off-stoichiometric CuxInyS2/ZnS quantum dots for near-infrared fluorescence bio-imaging. RSC Advances 2015, 5 (54), 43449-43455.
50. Vinayagam, J.; Chen, G.-R.; Huang, T.-Y.; Ho, J.-H.; Ling, Y.-C.; Ou, K.-L.; Chang, J.-Y., Aqueous synthesis of CuInZnS/ZnS quantum dots by using dual stabilizers: A targeting nanoprobe for cell imaging. Materials Letters 2016, 173, 242-247.
51. Girma, W. M.; Fahmi, M. Z.; Permadi, A.; Abate, M. A.; Chang, J.-Y., Synthetic strategies and biomedical applications of I-III-VI ternary quantum dots. Journal of Materials Chemistry B 2017.
52. Pan, D.; Weng, D.; Wang, X.; Xiao, Q.; Chen, W.; Xu, C.; Yang, Z.; Lu, Y., Alloyed semiconductor nanocrystals with broad tunable band gaps. Chemical Communications 2009, (28), 4221-4223.
53. Nam, D.-E.; Song, W.-S.; Yang, H., Noninjection, one-pot synthesis of Cu-deficient CuInS 2/ZnS core/shell quantum dots and their fluorescent properties. Journal of colloid and interface science 2011, 361 (2), 491-496.
54. Uehara, M.; Watanabe, K.; Tajiri, Y.; Nakamura, H.; Maeda, H., Synthesis of Cu In S 2 fluorescent nanocrystals and enhancement of fluorescence by controlling crystal defect. The Journal of chemical physics 2008, 129 (13), 134709.
55. Liu, S.; Zhang, H.; Qiao, Y.; Su, X., One-pot synthesis of ternary CuInS 2 quantum dots with near-infrared fluorescence in aqueous solution. Rsc Advances 2012, 2 (3), 819-825.
56. Gardner, J. S.; Shurdha, E.; Wang, C.; Lau, L. D.; Rodriguez, R. G.; Pak, J. J., Rapid synthesis and size control of CuInS2 semi-conductor nanoparticles using microwave irradiation. Journal of Nanoparticle Research 2008, 10 (4), 633-641.
57. Li, T.-L.; Teng, H., Solution synthesis of high-quality CuInS 2 quantum dots as sensitizers for TiO 2 photoelectrodes. Journal of Materials Chemistry 2010, 20 (18), 3656-3664.
58. Chang, J.; Waclawik, E. R., Controlled synthesis of CuInS2, Cu2SnS3 and Cu2ZnSnS4 nano-structures: insight into the universal phase-selectivity mechanism. CrystEngComm 2013, 15 (28), 5612-5619.
59. Pawley, J. B., Fundamental limits in confocal microscopy. In Handbook of biological confocal microscopy, Springer: 2006; pp 20-42.
60. Yu, S.-J.; Kang, M.-W.; Chang, H.-C.; Chen, K.-M.; Yu, Y.-C., Bright fluorescent nanodiamonds: no photobleaching and low cytotoxicity. Journal of the American Chemical Society 2005, 127 (50), 17604-17605.
61. He, H.; Xie, C.; Ren, J., Nonbleaching fluorescence of gold nanoparticles and its applications in cancer cell imaging. Analytical Chemistry 2008, 80 (15), 5951-5957.
62. Tarpani, L.; Ruhlandt, D.; Latterini, L.; Haehnel, D.; Gregor, I.; Enderlein, J. r.; Chizhik, A. I., Photoactivation of Luminescent Centers in Single SiO2 Nanoparticles. Nano letters 2016, 16 (7), 4312-4316.
63. Murray, C. B.; Norris, D. J.; Bawendi, M. G., Synthesis and characterization of nearly monodisperse CdE (E = sulfur, selenium, tellurium) semiconductor nanocrystallites. Journal of the American Chemical Society 1993, 115 (19), 8706-8715.
64. Peltonen, L.; Koistinen, P.; Karjalainen, M.; Häkkinen, A.; Hirvonen, J., The effect of cosolvents on the formulation of nanoparticles from low-molecular-weight poly(I)lactide. AAPS PharmSciTech 2002, 3 (4), 52.
65. Smith, A. M.; Duan, H.; Mohs, A. M.; Nie, S., Bioconjugated Quantum Dots for In Vivo Molecular and Cellular Imaging. Advanced drug delivery reviews 2008, 60 (11), 1226-1240.
66. Booth, M.; Peel, R.; Partanen, R.; Hondow, N.; Vasilca, V.; Jeuken, L. J. C.; Critchley, K., Amphipol-encapsulated CuInS2/ZnS quantum dots with excellent colloidal stability. RSC Advances 2013, 3 (43), 20559-20566.
67. Azzazy, H. M. E.; Mansour, M. M. H.; Kazmierczak, S. C., From diagnostics to therapy: Prospects of quantum dots. Clinical Biochemistry 2007, 40 (13–14), 917-927.
68. Chang, E.; Miller, J. S.; Sun, J.; Yu, W. W.; Colvin, V. L.; Drezek, R.; West, J. L., Protease-activated quantum dot probes. Biochemical and Biophysical Research Communications 2005, 334 (4), 1317-1321.
69. Fan, H.; Leve, E. W.; Scullin, C.; Gabaldon, J.; Tallant, D.; Bunge, S.; Boyle, T.; Wilson, M. C.; Brinker, C. J., Surfactant-Assisted Synthesis of Water-Soluble and Biocompatible Semiconductor Quantum Dot Micelles. Nano Letters 2005, 5 (4), 645-648.
70. Jana, N. R., Design and development of quantum dots and other nanoparticles based cellular imaging probe. Physical Chemistry Chemical Physics 2011, 13 (2), 385-396.
71. Mulvaney, P.; Liz-Marzan, L. M.; Giersig, M.; Ung, T., Silica encapsulation of quantum dots and metal clusters. Journal of Materials Chemistry 2000, 10 (6), 1259-1270.
72. Tomczak, N.; Jańczewski, D.; Tagit, O.; Han, M.-Y.; Vancso, G. J., Surface Engineering of Quantum Dots with Designer Ligands. In Surface Design: Applications in Bioscience and Nanotechnology, Wiley-VCH Verlag GmbH & Co. KGaA: 2009; pp 341-361.
73. Liu, S.; Shi, F.; Zhao, X.; Chen, L.; Su, X., 3-Aminophenyl boronic acid-functionalized CuInS2 quantum dots as a near-infrared fluorescence probe for the determination of dopamine. Biosensors and Bioelectronics 2013, 47, 379-384.
74. Barichard, A.; Galstian, T.; Israëli, Y., Influence of CdSe/ZnS Quantum Dots in the Polymerization Process and in the Grating Recording in Acrylate Materials. The Journal of Physical Chemistry B 2010, 114 (46), 14807-14814.
75. Matsuoka, S.-i.; Kikuno, T.; Takagi, K.; Suzuki, M., Poly(ethylene glycol)-induced acceleration of free radical polymerization of methyl methacrylate: effects of highly viscous solvent and kinetic study. Polym J 2010, 42 (5), 368-374.
76. Yu, Q.; Zeng, F.; Zhu, S., Atom Transfer Radical Polymerization of Poly(ethylene glycol) Dimethacrylate. Macromolecules 2001, 34 (6), 1612-1618.
77. Zrazhevskiy, P.; Sena, M.; Gao, X., Designing multifunctional quantum dots for bioimaging, detection, and drug delivery. Chemical Society Reviews 2010, 39 (11), 4326-4354.
78. Lin, C.-A. J.; Lee, C.-H.; Hsieh, J.-T.; Wang, H.-H.; Li, J. K.; Shen, J.-L.; Chan, W.-H.; Yeh, H.-I.; Chang, W. H., Synthesis of fluorescent metallic nanoclusters toward biomedical application: recent progress and present challenges. J Med Biol Eng 2009, 29 (6), 276-283.
79. Huo, Q., A perspective on bioconjugated nanoparticles and quantum dots. Colloids and Surfaces B: Biointerfaces 2007, 59 (1), 1-10.
80. Zhou, J.; Yang, Y.; Zhang, C.-y., Toward biocompatible semiconductor quantum dots: from biosynthesis and bioconjugation to biomedical application. Chemical reviews 2015, 115 (21), 11669-11717.
81. Chakraborty, A.; Jana, N. R., Clathrin to lipid raft-endocytosis via controlled surface chemistry and efficient perinuclear targeting of nanoparticle. J. Phys. Chem. Lett 2015, 6 (18), 3688-3697.
82. Ruedas-Rama, M. J.; Walters, J. D.; Orte, A.; Hall, E. A., Fluorescent nanoparticles for intracellular sensing: a review. Analytica chimica acta 2012, 751, 1-23.
83. Liu, Y.; Solomon, M.; Achilefu, S., Perspectives and potential applications of nanomedicine in breast and prostate cancer. Medicinal research reviews 2013, 33 (1), 3-32.
84. Ozalp, V. C.; Eyidogan, F.; Oktem, H. A., Aptamer-gated nanoparticles for smart drug delivery. Pharmaceuticals 2011, 4 (8), 1137-1157.
85. Ahmed, E. M., Hydrogel: Preparation, characterization, and applications: A review. Journal of advanced research 2015, 6 (2), 105-121.
86. Koetting, M. C.; Peters, J. T.; Steichen, S. D.; Peppas, N. A., Stimulus-responsive hydrogels: Theory, modern advances, and applications. Materials Science and Engineering: R: Reports 2015, 93, 1-49.
87. Sahiner, N.; Sel, K.; Meral, K.; Onganer, Y.; Butun, S.; Ozay, O.; Silan, C., Hydrogel templated CdS quantum dots synthesis and their characterization. Colloids and Surfaces A: Physicochemical and Engineering Aspects 2011, 389 (1), 6-11.
88. Zhang, X.; Ding, S.; Cao, S.; Zhu, A.; Shi, G., Functional surface engineering of quantum dot hydrogels for selective fluorescence imaging of extracellular lactate release. Biosensors and Bioelectronics 2016, 80, 315-322.
89. Saha, S.; Das, G.; Thote, J.; Banerjee, R., Photocatalytic metal–organic framework from CdS quantum dot incubated luminescent metallohydrogel. Journal of the American Chemical Society 2014, 136 (42), 14845-14851.
90. Hardman, R., A Toxicologic Review of Quantum Dots: Toxicity Depends on Physicochemical and Environmental Factors. Environmental Health Perspectives 2006, 114 (2), 165-172.
91. Michalet, X.; Pinaud, F. F.; Bentolila, L. A.; Tsay, J. M.; Doose, S.; Li, J. J.; Sundaresan, G.; Wu, A. M.; Gambhir, S. S.; Weiss, S., Quantum Dots for Live Cells, in Vivo Imaging, and Diagnostics. Science (New York, N.Y.) 2005, 307 (5709), 538-544.
92. Booth, M.; Brown, A. P.; Evans, S. D.; Critchley, K., Determining the Concentration of CuInS2 Quantum Dots from the Size-Dependent Molar Extinction Coefficient. Chemistry of Materials 2012, 24 (11), 2064-2070.
93. Qin, L.; Li, D.; Zhang, Z.; Wang, K.; Ding, H.; Xie, R.; Yang, W., The determination of extinction coefficient of CuInS2, and ZnCuInS3 multinary nanocrystals. Nanoscale 2012, 4 (20), 6360-6364.
94. Yuan, X.; Zhao, J.; Jing, P.; Zhang, W.; Li, H.; Zhang, L.; Zhong, X.; Masumoto, Y., Size- and Composition-Dependent Energy Transfer from Charge Transporting Materials to ZnCuInS Quantum Dots. The Journal of Physical Chemistry C 2012, 116 (22), 11973-11979.
95. Cho, S. J.; Maysinger, D.; Jain, M.; Röder, B.; Hackbarth, S.; Winnik, F. M., Long-Term Exposure to CdTe Quantum Dots Causes Functional Impairments in Live Cells. Langmuir 2007, 23 (4), 1974-1980.
96. Zhang, T.; Stilwell, J. L.; Gerion, D.; Ding, L.; Elboudwarej, O.; Cooke, P. A.; Gray, J. W.; Alivisatos, A. P.; Chen, F. F., Cellular Effect of High Doses of Silica-Coated Quantum Dot Profiled with High Throughput Gene Expression Analysis and High Content Cellomics Measurements. Nano Letters 2006, 6 (4), 800-808.
97. Walling, M. A.; Novak, J. A.; Shepard, J. R. E., Quantum Dots for Live Cell and In Vivo Imaging. International Journal of Molecular Sciences 2009, 10 (2), 441-491.
98. Derfus, A. M.; Chan, W. C. W.; Bhatia, S. N., Probing the Cytotoxicity of Semiconductor Quantum Dots. Nano Letters 2004, 4 (1), 11-18.
99. Lewinski, N.; Colvin, V.; Drezek, R., Cytotoxicity of Nanoparticles. Small 2008, 4 (1), 26-49.
100. Hauck, T. S.; Anderson, R. E.; Fischer, H. C.; Newbigging, S.; Chan, W. C. W., In vivo Quantum-Dot Toxicity Assessment. Small 2010, 6 (1), 138-144.
101. Nel, A.; Xia, T.; Mädler, L.; Li, N., Toxic Potential of Materials at the Nanolevel. Science 2006, 311 (5761), 622.
102. Helgaker;, T.; Jorgensen;, P.; Olsen, J., Molecular Electronic-Structure Theory. Wiley: England, 2000; Vol. 2.
103. Izadi, S.; Anandakrishnan, R.; Onufriev, A. V., Building Water Models: A Different Approach. The Journal of Physical Chemistry Letters 2014, 5 (21), 3863-3871.
104. Akdas, T.; Haderlein, M.; Walter, J.; Apeleo Zubiri, B.; Spiecker, E.; Peukert, W., Continuous synthesis of CuInS2 quantum dots. RSC Advances 2017, 7 (17), 10057-10063.
105. Sun, C.; Gardner, J. S.; Shurdha, E.; Margulieux, K. R.; Westover, R. D.; Lau, L.; Long, G.; Bajracharya, C.; Wang, C.; Thurber, A.; Punnoose, A.; Rodriguez, R. G.; Pak, J. J., A High-Yield Synthesis of Chalcopyrite CuIn Nanoparticles with Exceptional Size Control. Journal of Nanomaterials 2009, 2009, 7.
106. Tomasi, J.; Mennucci, B.; Cammi, R., Quantum Mechanical Continuum Solvation Models. Chemical Reviews 2005, 105 (8), 2999-3094.
107. Kittel, C., Introduction to solid state physics. Wiley: 2013.
108. Krug, H. F.; Wick, P., Nanotoxicology: An Interdisciplinary Challenge. Angewandte Chemie International Edition 2011, 50 (6), 1260-1278.
109. Soenen, S. J.; Rivera-Gil, P.; Montenegro, J.-M.; Parak, W. J.; De Smedt, S. C.; Braeckmans, K., Cellular toxicity of inorganic nanoparticles: Common aspects and guidelines for improved nanotoxicity evaluation. Nano Today 2011, 6 (5), 446-465.
110. Zhao, F.; Zhao, Y.; Liu, Y.; Chang, X.; Chen, C.; Zhao, Y., Cellular Uptake, Intracellular Trafficking, and Cytotoxicity of Nanomaterials. Small 2011, 7 (10), 1322-1337.
111. Jamieson, T.; Bakhshi, R.; Petrova, D.; Pocock, R.; Imani, M.; Seifalian, A. M., Biological applications of quantum dots. Biomaterials 2007, 28 (31), 4717-4732.
112. Li, L.; Pandey, A.; Werder, D. J.; Khanal, B. P.; Pietryga, J. M.; Klimov, V. I., Efficient Synthesis of Highly Luminescent Copper Indium Sulfide-Based Core/Shell Nanocrystals with Surprisingly Long-Lived Emission. Journal of the American Chemical Society 2011, 133 (5), 1176-1179.
113. Ma, Q.; Su, X., Near-infrared quantum dots: synthesis, functionalization and analytical applications. Analyst 2010, 135 (8), 1867-1877.
114. Xie, R.; Rutherford, M.; Peng, X., Formation of High-Quality I−III−VI Semiconductor Nanocrystals by Tuning Relative Reactivity of Cationic Precursors. Journal of the American Chemical Society 2009, 131 (15), 5691-5697.
115. Lees, E. E.; Nguyen, T.-L.; Clayton, A. H. A.; Mulvaney, P., The Preparation of Colloidally Stable, Water-Soluble, Biocompatible, Semiconductor Nanocrystals with a Small Hydrodynamic Diameter. ACS Nano 2009, 3 (5), 1121-1128.
116. Basiruddin, S. K.; Saha, A.; Pradhan, N.; Jana, N. R., Advances in Coating Chemistry in Deriving Soluble Functional Nanoparticle. The Journal of Physical Chemistry C 2010, 114 (25), 11009-11017.
117. Hsu, J.-C.; Huang, C.-C.; Ou, K.-L.; Lu, N.; Mai, F.-D.; Chen, J.-K.; Chang, J.-Y., Silica nanohybrids integrated with CuInS2/ZnS quantum dots and magnetite nanocrystals: multifunctional agents for dual-modality imaging and drug delivery. Journal of Materials Chemistry 2011, 21 (48), 19257-19266.
118. Hoshino, A.; Hanaki, K.-i.; Suzuki, K.; Yamamoto, K., Applications of T-lymphoma labeled with fluorescent quantum dots to cell tracing markers in mouse body. Biochemical and Biophysical Research Communications 2004, 314 (1), 46-53.
119. McNamee, C. E.; Yamamoto, S.; Higashitani, K., Effect of the Physicochemical Properties of Poly(Ethylene Glycol) Brushes on their Binding to Cells. Biophysical Journal 2007, 93 (1), 324-334.
120. Dabbousi, B. O.; Rodriguez-Viejo, J.; Mikulec, F. V.; Heine, J. R.; Mattoussi, H.; Ober, R.; Jensen, K. F.; Bawendi, M. G., (CdSe)ZnS Core−Shell Quantum Dots:  Synthesis and Characterization of a Size Series of Highly Luminescent Nanocrystallites. The Journal of Physical Chemistry B 1997, 101 (46), 9463-9475.
121. Yang, Y. Q.; Zheng, L. S.; Guo, X. D.; Qian, Y.; Zhang, L. J., pH-Sensitive Micelles Self-Assembled from Amphiphilic Copolymer Brush for Delivery of Poorly Water-Soluble Drugs. Biomacromolecules 2011, 12 (1), 116-122.
122. Qin, Z.; Chen, Y.; Zhou, W.; He, X.; Bai, F.; Wan, M., Synthesis and properties of polymer brushes composed of poly(diphenylacetylene) main chain and poly(ethylene glycol) side chains. European Polymer Journal 2008, 44 (11), 3732-3740.
123. Liu, Y.; Wang, W.; Hu, W.; Lu, Z.; Zhou, X.; Li, C. M., Highly sensitive poly[glycidyl methacrylate-co-poly(ethylene glycol) methacrylate] brush-based flow-through microarray immunoassay device. Biomedical Microdevices 2011, 13 (4), 769-777.
124. Jon, S.; Seong, J.; Khademhosseini, A.; Tran, T.-N. T.; Laibinis, P. E.; Langer, R., Construction of Nonbiofouling Surfaces by Polymeric Self-Assembled Monolayers. Langmuir 2003, 19 (24), 9989-9993.
125. Hussain, H.; Mya, K. Y.; He, C., Self-Assembly of Brush-Like Poly[poly(ethylene glycol) methyl ether methacrylate] Synthesized via Aqueous Atom Transfer Radical Polymerization. Langmuir 2008, 24 (23), 13279-13286.
126. Chiag, Y.-C.; Chang, Y.; Chen, W.-Y.; Ruaan, R.-c., Biofouling Resistance of Ultrafiltration Membranes Controlled by Surface Self-Assembled Coating with PEGylated Copolymers. Langmuir 2012, 28 (2), 1399-1407.
127. Han, R.; Yu, M.; Zheng, Q.; Wang, L.; Hong, Y.; Sha, Y., A Facile Synthesis of Small-Sized, Highly Photoluminescent, and Monodisperse CdSeS QD/SiO2 for Live Cell Imaging. Langmuir 2009, 25 (20), 12250-12255.
128. Graf, C.; Dembski, S.; Hofmann, A.; Rühl, E., A General Method for the Controlled Embedding of Nanoparticles in Silica Colloids. Langmuir 2006, 22 (13), 5604-5610.
129. Darbandi, M.; Thomann, R.; Nann, T., Single Quantum Dots in Silica Spheres by Microemulsion Synthesis. Chemistry of Materials 2005, 17 (23), 5720-5725.
130. Qu, L.; Peng, X., Control of Photoluminescence Properties of CdSe Nanocrystals in Growth. Journal of the American Chemical Society 2002, 124 (9), 2049-2055.
131. Manna, L.; Scher, E. C.; Li, L.-S.; Alivisatos, A. P., Epitaxial Growth and Photochemical Annealing of Graded CdS/ZnS Shells on Colloidal CdSe Nanorods. Journal of the American Chemical Society 2002, 124 (24), 7136-7145.
132. Ivanov, S. A.; Piryatinski, A.; Nanda, J.; Tretiak, S.; Zavadil, K. R.; Wallace, W. O.; Werder, D.; Klimov, V. I., Type-II Core/Shell CdS/ZnSe Nanocrystals:  Synthesis, Electronic Structures, and Spectroscopic Properties. Journal of the American Chemical Society 2007, 129 (38), 11708-11719.
133. Bagaria, H. G.; Kini, G. C.; Wong, M. S., Electrolyte Solutions Improve Nanoparticle Transfer from Oil to Water. The Journal of Physical Chemistry C 2010, 114 (47), 19901-19907.
134. Gedanken, A., Using sonochemistry for the fabrication of nanomaterials. Ultrasonics Sonochemistry 2004, 11 (2), 47-55.
135. Zhu, J. J.; Xu, S.; Wang, H.; Zhu, J. M.; Chen, H. Y., Sonochemical Synthesis of CdSe Hollow Spherical Assemblies Via an In-Situ Template Route. Advanced Materials 2003, 15 (2), 156-159.
136. Vinatoru, M.; Bartha, E.; Badea, F.; Luche, J. L., Sonochemical and thermal redox reactions of triphenylmethane and triphenylmethyl carbinol in nitrobenzene. Ultrasonics Sonochemistry 1998, 5 (1), 27-31.
137. Suslick, K. S.; Gawienowski, J. J.; Schubert, P. F.; Wang, H. H., Sonochemistry in non-aqueous liquids. Ultrasonics 1984, 22 (1), 33-36.
138. Margulis, M. A., Fundamental problems of sonochemistry and cavitation. Ultrasonics Sonochemistry 1994, 1 (2), S87-S90.
139. Dang, F.; Enomoto, N.; Hojo, J.; Enpuku, K., Sonochemical synthesis of monodispersed magnetite nanoparticles by using an ethanol–water mixed solvent. Ultrasonics Sonochemistry 2009, 16 (5), 649-654.
140. Dalvi, S. V.; Dave, R. N., Analysis of nucleation kinetics of poorly water-soluble drugs in presence of ultrasound and hydroxypropyl methyl cellulose during antisolvent precipitation. International Journal of Pharmaceutics 2010, 387 (1–2), 172-179.
141. Doktycz, S. J.; Suslick, K. S., "The Effects of Ultrasound on Solids" in Advances in Sonochemistry. T.J., M. JAI Press: New York, 1990; Vol. 1, p 247.
142. Vogel, A.; Lauterborn, W.; Timm, R., Optical and acoustic investigations of the dynamics of laser-produced cavitation bubbles near a solid boundary. Journal of Fluid Mechanics 2006, 206, 299-338.
143. Zeiger, B. W.; Suslick, K. S., Sonofragmentation of Molecular Crystals. Journal of the American Chemical Society 2011, 133 (37), 14530-14533.
144. Madigan, N. A.; Hagan, C. R. S.; Zhang, H.; Coury, L. A., Effects of sonication on electrode surfaces and metal particles. Ultrasonics Sonochemistry 1996, 3 (3), S239-S247.
145. Jafari, V.; Allahverdi, A.; Vafaei, M., Ultrasound-assisted synthesis of colloidal nanosilica from silica fume: Effect of sonication time on the properties of product. Advanced Powder Technology 2014, 25 (5), 1571-1577.
146. Luque de Castro, M. D.; Priego-Capote, F., Ultrasound-assisted preparation of liquid samples. Talanta 2007, 72 (2), 321-334.
147. Haldorai, Y.; Nguyen, V. H.; Shim, J.-J., Synthesis of polyaniline/Q-CdSe composite via ultrasonically assisted dynamic inverse emulsion polymerization. Colloid and Polymer Science 2011, 289 (7), 849-854.
148. Cheng, Q.; Debnath, S.; Gregan, E.; Byrne, H. J., Ultrasound-Assisted SWNTs Dispersion: Effects of Sonication Parameters and Solvent Properties. The Journal of Physical Chemistry C 2010, 114 (19), 8821-8827.
149. Nann, T., Phase-transfer of CdSe@ZnS quantum dots using amphiphilic hyperbranched polyethylenimine. Chemical Communications 2005, (13), 1735-1736.
150. Niemann, B.; Veit, P.; Sundmacher, K., Nanoparticle Precipitation in Reverse Microemulsions:  Particle Formation Dynamics and Tailoring of Particle Size Distributions. Langmuir 2008, 24 (8), 4320-4328.
151. Entezari, M. H.; Ghows, N., Micro-emulsion under ultrasound facilitates the fast synthesis of quantum dots of CdS at low temperature. Ultrasonics Sonochemistry 2011, 18 (1), 127-134.
152. Ghows, N.; Entezari, M. H., Fast and easy synthesis of core–shell nanocrystal (CdS/TiO2) at low temperature by micro-emulsion under ultrasound. Ultrasonics Sonochemistry 2011, 18 (2), 629-634.
153. Shi, L.; Pei, C.; Li, Q., Ordered arrays of shape tunable CuInS2 nanostructures, from nanotubes to nano test tubes and nanowires. Nanoscale 2010, 2 (10), 2126-2130.
154. Kruszynska, M.; Borchert, H.; Parisi, J.; Kolny-Olesiak, J., Synthesis and Shape Control of CuInS2 Nanoparticles. Journal of the American Chemical Society 2010, 132 (45), 15976-15986.
155. Mathey, K., Implicit solvation model for density-functional study of nanocrystal surfaces and reaction pathways. The Journal of Chemical Physics 2014, 140 (8), 084106.
156. Chang, J.-Y.; Cheng, C.-Y., Facile one-pot synthesis of copper sulfide-metal chalcogenide anisotropic heteronanostructures in a noncoordinating solvent. Chemical Communications 2011, 47 (32), 9089-9091.
157. Belenguer, A. M.; Lampronti, G. I.; Cruz-Cabeza, A. J.; Hunter, C. A.; Sanders, J. K. M., Solvation and surface effects on polymorph stabilities at the nanoscale. Chemical Science 2016, 7 (11), 6617-6627.
158. Vasconcelos, T.; Sarmento, B.; Costa, P., Solid dispersions as strategy to improve oral bioavailability of poor water soluble drugs. Drug discovery today 2007, 12 (23), 1068-1075.
159. Chiou, W. L.; Riegelman, S., Pharmaceutical applications of solid dispersion systems. Journal of pharmaceutical sciences 1971, 60 (9), 1281-1302.
160. Mejia, J.; Valembois, V.; Piret, J.-P.; Tichelaar, F.; van Huis, M.; Masereel, B.; Toussaint, O.; Delhalle, J.; Mekhalif, Z.; Lucas, S., Are stirring and sonication pre-dispersion methods equivalent for in vitro toxicology evaluation of SiC and TiC? Journal of Nanoparticle Research 2012, 14 (4), 815.
161. Suslick, K. S.; Price, G., J., Applications of ultrasound to materials chemistry. Annual Review of Materials Science 1999, 29, 295-326.
162. Reddy, S.; Fogler, H., Emulsion stability of acoustically formed emulsions. The Journal of Physical Chemistry 1980, 84 (12), 1570-1575.
163. Ren, C.; Zhang, J.; Chen, M.; Yang, Z., Self-assembling small molecules for the detection of important analytes. Chemical Society Reviews 2014, 43 (21), 7257-7266.
164. Tang, F.; Wang, C.; Wang, J.; Wang, X.; Li, L., Fluorescent Organic Nanoparticles with Enhanced Fluorescence by Self-Aggregation and their Application to Cellular Imaging. ACS Applied Materials & Interfaces 2014, 6 (20), 18337-18343.
165. Yang, Y.; Wang, X.; Cui, Q.; Cao, Q.; Li, L., Self-Assembly of Fluorescent Organic Nanoparticles for Iron(III) Sensing and Cellular Imaging. ACS Applied Materials & Interfaces 2016, 8 (11), 7440-7448.
166. Pilotek, S.; Tabellion, F.; Schär, S.; Steingröver, K., Dispersing Nanoparticles–The Key to Application.
167. Bihari, P.; Vippola, M.; Schultes, S.; Praetner, M.; Khandoga, A. G.; Reichel, C. A.; Coester, C.; Tuomi, T.; Rehberg, M.; Krombach, F., Optimized dispersion of nanoparticles for biological in vitro and in vivo studies. Particle and Fibre Toxicology 2008, 5 (1), 14.
168. Walling, M. A.; Novak, J. A.; Shepard, J. R., Quantum dots for live cell and in vivo imaging. International journal of molecular sciences 2009, 10 (2), 441-491.
169. Yu, K.; Zaman, B.; Singh, S.; Wang, D.; Ripmeester, J. A., The effect of dispersion media on photoluminescence of colloidal CdSe nanocrystals synthesized from TOP. Chemistry of materials 2005, 17 (10), 2552-2561.
170. Acevedo, D.; Abruna, H. D., Electron-transfer study and solvent effects on the formal potential of a redox-active self-assembling monolayer. The Journal of Physical Chemistry 1991, 95 (23), 9590-9594.