| 研究生: |
梁世欣 Liang, Shih-shin |
|---|---|
| 論文名稱: |
整體性層析材料與微裝置的製造與其在生化分析上的應用 Fabrication and Application of Monolithic Chromatographic Materials and Microdevices for Bioanalysis |
| 指導教授: |
陳淑慧
Chen, Shu-Hui |
| 學位類別: |
博士 Doctor |
| 系所名稱: |
理學院 - 化學系 Department of Chemistry |
| 論文出版年: | 2009 |
| 畢業學年度: | 97 |
| 語文別: | 英文 |
| 論文頁數: | 123 |
| 中文關鍵詞: | 光聚合高分子 、層析材料 、吸附金屬親和層析 、固相微萃取 、二氧化鈦 、多孔性 、乳化作用 |
| 外文關鍵詞: | immobilized metal ion affinity chromatography (I, titanium dioxide (TiO2), Porogenic, photo-polymerization, chromatography material, emulsification, solid phase micro-extraction (SPME) |
| 相關次數: | 點閱:202 下載:1 |
| 分享至: |
| 查詢本校圖書館目錄 查詢臺灣博碩士論文知識加值系統 勘誤回報 |
本論文的中心思想在於整體性材料,配合兩種方法形成多孔性結構,再進行生物分析的應用。
第一個方法:照光高分子的單體在多孔性溶劑的作用之下,形成多孔性膠體製成去鹽濃縮的吸管尖。在此方法中,照光高分的單體與多孔性溶劑混合,並包埋靜相粒子形成整體性連續床。在光聚合之後,高分子的多孔性結構被固定在吸管尖端,並進行微萃取。靜相粒子,如:碳十八或奈米尺寸的二氧化鈦,被包埋在微萃取吸管尖,再進行樣品去鹽或磷酸化胜肽濃度的提升。除此之外,消化酵素,諸如:胰蛋白酶,也可以固定其上以進行蛋白質體研究的消化動作,但是,此方法受限於過小的孔洞尺寸,其所造成操作流體時的背壓。
第二個方法:利用乳化反應(油/水)技術,形成多孔性結構。乳化現象整合層析材料與紫外光催化的照光高分子化,可以包覆多樣的萃取粒子。使用此方法,乳化吸管尖具有大於二十微米的孔洞尺寸,能夠形成易於操作的吸管尖。與市售吸管尖如EasyTips 大約0.4-2 毫克消化胜肽的吸附值相比,乳化吸管尖可以吸附約3-3.5 毫克。所增加的吸附值主因是因為在整體性材料中增加多條流通管道所致,除此之外,操作的平衡時間也由EasyTips 的六百秒,縮短為六十秒。乳化反應能夠發展為水/油/水與油/水/油的技術,並利用適當官能基共價鍵結酵素分子。進行線上分析是藉由整合兩種固定連續床—胰蛋白酶酵素與碳十八去鹽的連續床。
許多的應用,諸如:蛋白質鑑定、磷酸根胜肽的偵測與藥物分子的分子的演示,都是透過本論文提及的微萃取吸管尖進行,而滿意的結果則是未來發展的憑藉。
Monolithic material is the main theme in this research and two methods were developed to form porous structures for bioanalysis applications.
The first method is to apply porogenic solvent to form monolithic tips for sample desalting and concentration. In this method, the monomers of photo-polymer were mixed with porogenic solvent and encapsulating particles to form monolithic beds. After photo-polymerization, polymeric porous structure was formed and fixed on pipette tips for
micro-extraction. Reversed phase C18 and nano-scaled titanium dioxide particles were encapsulated to prepare extraction tips for sample desalting and phosphopeptide
enrichment. Alternatively, digestion enzyme, such as trypsin, was immobilized for sample digestion in proteomics research. This method, however, is limited by the back
pressure due to small pore sizes.
The second method is to apply emulsification technique for forming porous structure using water-in-oil (O/W) technique. Emulsification can be integrated with
chromatographic materials and photo-polymerization by UV light to encapsulate various extraction particles. Using this method, EmulsionTips with a pore size as large as
20 μmcan be formed and thus the flow can be easily manipulated by a pipetter. The loadingcapacity for commercial tips such as EasyTips, is around 0.4-2 micrograms of total protein degest, and the loading capacity is around 3-3.5 micrograms of total protein digest for EmulsionTips. The increased loading capacity was due to the increased number of assessable flow-paths within the monolithic material. Furthermore, the equilibration time
was also reduced due to multiple paths: 600 seconds for EasyTips and 60 seconds for EmulsionTips. Emulsification can also be extended to water/oil/water (W/O/W) and
oil/water/oil (O/W/O) technique for covalent enzyme immobilization by exposing proper functional groups. On-line processing by combining two immobilized beds such as
trypsin enzyme bed and C18 desalting bed was also demonstrated.
Several applications such as protein identification, phosphopeptide detection and drug analysis were demonstrated using the micro extraction tips reported here and all showed satisfactory results, which warrant future developments.
1. Kawasaki, H.; Takeda, Y.; Arakawa, R., Mass spectrometric analysis for high molecular weight synthetic polymers using ultrasonic degradation and the mechanism of degradation. Anal Chem 2007, 79, (11), 4182-4187.
2. Wilkins, J. A.; Xiang, R.; Horvath, C., Selective enrichment of low-abundance peptides in complex mixtures by elution-modified displacement chromatography and their identification by electrospray ionization mass spectrometry. Anal Chem 2002, 74, (16), 3933-3941.
3. Anari, M. R.; Sanchez, R. I.; Bakhtiar, R.; Franklin, R. B.; Baillie, T. A., Integration of knowledge-based metabolic predictions with liquid chromatography data-dependent tandem mass spectrometry for drug metabolism studies: application to studies on the biotransformation of indinavir. Anal Chem 2004, 76, (3), 823-832.
4. Kertesz, V.; Van Berkel, G. J.; Vavrek, M.; Koeplinger, K. A.; Schneider, B. B.; Covey, T. R., Comparison of drug distribution images from whole-body thin tissue sections obtained using desorption electrospray ionization tandem mass spectrometry and autoradiography. Anal Chem 2008, 80, (13), 5168-5177.
5. Matta, A.; DeSouza, L. V.; Shukla, N. K.; Gupta, S. D.; Ralhan, R.; Siu, K. W., Prognostic significance of head-and-neck cancer biomarkers previously discovered and identified using iTRAQ-labeling and multidimensional liquid chromatography-tandem mass spectrometry. J Proteome Res 2008, 7, (5), 2078-2087.
6. Fenn, J. B.; Mann, M.; Meng, C. K.; Wong, S. F.; Whitehouse, C. M., Electrospray ionization for mass spectrometry of large biomolecules. Science 1989, 246, (4926), 64-71.
7. Hillenkamp, F.; Karas, M., Mass spectrometry of peptides and proteins by matrix-assisted ultraviolet laser desorption/ionization. Methods Enzymol 1990, 193, 280-295.
8. McLachlin, D. T.; Chait, B. T., Analysis of phosphorylated proteins and peptides by mass spectrometry. Curr Opin Chem Biol 2001, 5, (5), 591-602.
9. Minakuchi, H.; Nakanishi, K.; Soga, N.; Ishizuka, N.; Tanaka, N., Octadecylsilylated porous silica rods as separation media for reversed-phase liquid chromatography. Analytical Chemistry 1996, 68, (19), 3498-3501.
10. Yu, C.; Davey, M. H.; Svec, F.; Frechet, J. M., Monolithic porous polymer for on-chip solid-phase extraction and preconcentration prepared by photoinitiated in situ polymerization within a microfluidic device. Anal Chem 2001, 73, (21), 5088-5096.
11. Quirino, J. P.; Dulay, M. T.; Zare, R. N., On-line preconcentration in capillary electrochromatography using a porous monolith together with solvent gradient and sample stacking. Anal Chem 2001, 73, (22), 5557-5563.
12. Peterson, D. S.; Rohr, T.; Svec, F.; Frechet, J. M., Enzymatic microreactor-on-a-chip: protein mapping using trypsin immobilized on porous polymer monoliths molded in channels of microfluidic devices. Anal Chem 2002, 74, (16), 4081-4088.
13. Wilm, M.; Mann, M., Analytical properties of the nanoelectrospray ion source. Anal Chem 1996, 68, (1), 1-8.
14. Neubauer, G.; Mann, M., Mapping of phosphorylation sites of gel-isolated proteins by nanoelectrospray tandem mass spectrometry: potentials and limitations. Anal Chem 1999, 71, (1), 235-242.
15. Erdjument-Bromage, H.; Lui, M.; Lacomis, L.; Grewal, A.; Annan, R. S.; McNulty, D. E.; Carr, S. A.; Tempst, P., Examination of micro-tip reversed-phase liquid chromatographic extraction of peptide pools for mass spectrometric analysis. J Chromatogr A 1998, 826, (2), 167-181.
16. Larsen, M. R.; Cordwell, S. J.; Roepstorff, P., Graphite powder as an alternative or supplement to reversed-phase material for desalting and concentration of peptide mixtures prior to matrix-assisted laser desorption/ionization-mass spectrometry. Proteomics 2002, 2, (9), 1277-1287.
17. Rappsilber, J.; Ishihama, Y.; Mann, M., Stop and go extraction tips for matrix-assisted laser desorption/ionization, nanoelectrospray, and LC/MS sample pretreatment in proteomics. Anal Chem 2003, 75, (3), 663-670.
18. Hsu, J. L.; Chou, M. K.; Liang, S. S.; Huang, S. Y.; Wu, C. J.; Shi, F. K.; Chen, S. H., Photopolymerized microtips for sample preparation in proteomic analysis. Electrophoresis 2004, 25, (21-22), 3840-3847.
19. Hsieh, H. C.; Sheu, C.; Shi, F. K.; Li, D. T., Development of a titanium dioxide nanoparticle pipette-tip for the selective enrichment of phosphorylated peptides. J Chromatogr A 2007, 1165, (1-2), 128-135.
20. Li, S.; Dass, C., Iron(III)-immobilized metal ion affinity chromatography and mass spectrometry for the purification and characterization of synthetic phosphopeptides. Anal Biochem 1999, 270, (1), 9-14.
21. Posewitz, M. C.; Tempst, P., Immobilized gallium(III) affinity chromatography of phosphopeptides. Anal Chem 1999, 71, (14), 2883-2892.
22. Stensballe, A.; Andersen, S.; Jensen, O. N., Characterization of phosphoproteins from electrophoretic gels by nanoscale Fe(III) affinity chromatography with off-line mass spectrometry analysis. Proteomics 2001, 1, (2), 207-222.
23. Ficarro, S. B.; McCleland, M. L.; Stukenberg, P. T.; Burke, D. J.; Ross, M. M.; Shabanowitz, J.; Hunt, D. F.; White, F. M., Phosphoproteome analysis by mass spectrometry and its application to Saccharomyces cerevisiae. Nat Biotechnol 2002, 20, (3), 301-305.
24. Kinoshita, E.; Yamada, A.; Takeda, H.; Kinoshita-Kikuta, E.; Koike, T., Novel immobilized zinc(II) affinity chromatography for phosphopeptides and phosphorylated proteins. J Sep Sci 2005, 28, (2), 155-162.
25. Kokubu, M.; Ishihama, Y.; Sato, T.; Nagasu, T.; Oda, Y., Specificity of immobilized metal affinity-based IMAC/C18 tip enrichment of phosphopeptides for protein phosphorylation analysis. Anal Chem 2005, 77, (16), 5144-5154.
26. Pinkse, M. W.; Uitto, P. M.; Hilhorst, M. J.; Ooms, B.; Heck, A. J., Selective isolation at the femtomole level of phosphopeptides from proteolytic digests using 2D-NanoLC-ESI-MS/MS and titanium oxide precolumns. Anal Chem 2004, 76, (14), 3935-3943.
27. Larsen, M. R.; Thingholm, T. E.; Jensen, O. N.; Roepstorff, P.; Jorgensen, T. J., Highly selective enrichment of phosphorylated peptides from peptide mixtures using titanium dioxide microcolumns. Mol Cell Proteomics 2005, 4, (7), 873-886.
28. Wolschin, F.; Wienkoop, S.; Weckwerth, W., Enrichment of phosphorylated proteins and peptides from complex mixtures using metal oxide/hydroxide affinity chromatography (MOAC). Proteomics 2005, 5, (17), 4389-4397.
29. Kweon, H. K.; Hakansson, K., Selective zirconium dioxide-based enrichment of phosphorylated peptides for mass spectrometric analysis. Anal Chem 2006, 78, (6), 1743-1749.
30. Goshe, M. B.; Conrads, T. P.; Panisko, E. A.; Angell, N. H.; Veenstra, T. D.; Smith, R. D., Phosphoprotein isotope-coded affinity tag approach for isolating and quantitating phosphopeptides in proteome-wide analyses. Anal Chem 2001, 73, (11), 2578-2586.
31. Oda, Y.; Nagasu, T.; Chait, B. T., Enrichment analysis of phosphorylated proteins as a tool for probing the phosphoproteome. Nat Biotechnol 2001, 19, (4), 379-382.
32. Zhou, H.; Watts, J. D.; Aebersold, R., A systematic approach to the analysis of protein phosphorylation. Nat Biotechnol 2001, 19, (4), 375-378.
33. Knight, Z. A.; Schilling, B.; Row, R. H.; Kenski, D. M.; Gibson, B. W.; Shokat, K. M., Phosphospecific proteolysis for mapping sites of protein phosphorylation. Nat Biotechnol 2003, 21, (9), 1047-54.
34. Thompson, A. J.; Hart, S. R.; Franz, C.; Barnouin, K.; Ridley, A.; Cramer, R., Characterization of protein phosphorylation by mass spectrometry using immobilized metal ion affinity chromatography with on-resin beta-elimination and Michael addition. Anal Chem 2003, 75, (13), 3232-43.
35. Ballif, B. A.; Villen, J.; Beausoleil, S. A.; Schwartz, D.; Gygi, S. P., Phosphoproteomic analysis of the developing mouse brain. Mol Cell Proteomics 2004, 3, (11), 1093-101.
36. Nuhse, T. S.; Stensballe, A.; Jensen, O. N.; Peck, S. C., Large-scale analysis of in vivo phosphorylated membrane proteins by immobilized metal ion affinity chromatography and mass spectrometry. Mol Cell Proteomics 2003, 2, (11), 1234-43.
37. Motoyama, A.; Xu, T.; Ruse, C. I.; Wohlschlegel, J. A.; Yates, J. R., 3rd, Anion and cation mixed-bed ion exchange for enhanced multidimensional separations of peptides and phosphopeptides. Anal Chem 2007, 79, (10), 3623-34.
38. Rush, J.; Moritz, A.; Lee, K. A.; Guo, A.; Goss, V. L.; Spek, E. J.; Zhang, H.; Zha, X. M.; Polakiewicz, R. D.; Comb, M. J., Immunoaffinity profiling of tyrosine phosphorylation in cancer cells. Nat Biotechnol 2005, 23, (1), 94-101.
39. Thelemann, A.; Petti, F.; Griffin, G.; Iwata, K.; Hunt, T.; Settinari, T.; Fenyo, D.; Gibson, N.; Haley, J. D., Phosphotyrosine signaling networks in epidermal growth factor receptor overexpressing squamous carcinoma cells. Mol Cell Proteomics 2005, 4, (4), 356-76.
40. Zhang, Y.; Wolf-Yadlin, A.; Ross, P. L.; Pappin, D. J.; Rush, J.; Lauffenburger, D. A.; White, F. M., Time-resolved mass spectrometry of tyrosine phosphorylation sites in the epidermal growth factor receptor signaling network reveals dynamic modules. Mol Cell Proteomics 2005, 4, (9), 1240-50.
41. Liang, S. S.; Makamba, H.; Huang, S. Y.; Chen, S. H., Nano-titanium dioxide composites for the enrichment of phosphopeptides. J Chromatogr A 2006, 1116, (1-2), 38-45.
42. Zhang, Y.; Wang, X.; Shan, W.; Wu, B.; Fan, H.; Yu, X.; Tang, Y.; Yang, P., Enrichment of low-abundance peptides and proteins on zeolite nanocrystals for direct MALDI-TOF MS analysis. Angew Chem Int Ed Engl 2005, 44, (4), 615-7.
43. Chen, C. T.; Chen, W. Y.; Tsai, P. J.; Chien, K. Y.; Yu, J. S.; Chen, Y. C., Rapid enrichment of phosphopeptides and phosphoproteins from complex samples using magnetic particles coated with alumina as the concentrating probes for MALDI MS analysis. J Proteome Res 2007, 6, (1), 316-25.
44. Chen, C. T.; Chen, Y. C., Fe3O4/TiO2 core/shell nanoparticles as affinity probes for the analysis of phosphopeptides using TiO2 surface-assisted laser desorption/ionization mass spectrometry. Anal Chem 2005, 77, (18), 5912-9.
45. Zhang, X.; Ye, J.; Jensen, O. N.; Roepstorff, P., Highly Efficient Phosphopeptide Enrichment by Calcium Phosphate Precipitation Combined with Subsequent IMAC Enrichment. Mol Cell Proteomics 2007, 6, (11), 2032-42.
46. Koch, C. A.; Anderson, D.; Moran, M. F.; Ellis, C.; Pawson, T., SH2 and SH3 domains: elements that control interactions of cytoplasmic signaling proteins. Science 1991, 252, (5006), 668-74.
47. Hunter, T., 1001 protein kinases redux--towards 2000. Semin Cell Biol 1994, 5, (6), 367-76.
48. Pandey, A.; Podtelejnikov, A. V.; Blagoev, B.; Bustelo, X. R.; Mann, M.; Lodish, H. F., Analysis of receptor signaling pathways by mass spectrometry: identification of vav-2 as a substrate of the epidermal and platelet-derived growth factor receptors. Proc Natl Acad Sci U S A 2000, 97, (1), 179-84.
49. He, X. D.; Ge, X. W.; Liu, H. R.; Wang, M. Z.; Zhang, Z. C., Synthesis of cagelike polymer microspheres with hollow core/porous shell structures by self-assembly of latex particles at the emulsion droplet interface. Chemistry of Materials 2005, 17, (24), 5891-5892.
50. Mamedov, A. A.; Kotov, N. A.; Prato, M.; Guldi, D. M.; Wicksted, J. P.; Hirsch, A., Molecular design of strong single-wall carbon nanotube/polyelectrolyte multilayer composites. Nat Mater 2002, 1, (3), 190-4.
51. Ericson, L. M.; Fan, H.; Peng, H.; Davis, V. A.; Zhou, W.; Sulpizio, J.; Wang, Y.; Booker, R.; Vavro, J.; Guthy, C.; Parra-Vasquez, A. N.; Kim, M. J.; Ramesh, S.; Saini, R. K.; Kittrell, C.; Lavin, G.; Schmidt, H.; Adams, W. W.; Billups, W. E.; Pasquali, M.; Hwang, W. F.; Hauge, R. H.; Fischer, J. E.; Smalley, R. E., Macroscopic, neat, single-walled carbon nanotube fibers. Science 2004, 305, (5689), 1447-50.
52. Gao, J.; Itkis, M. E.; Yu, A.; Bekyarova, E.; Zhao, B.; Haddon, R. C., Continuous spinning of a single-walled carbon nanotube-nylon composite fiber. J Am Chem Soc 2005, 127, (11), 3847-54.
53. Shi Kam, N. W.; Jessop, T. C.; Wender, P. A.; Dai, H., Nanotube molecular transporters: internalization of carbon nanotube-protein conjugates into Mammalian cells. J Am Chem Soc 2004, 126, (22), 6850-1.
54. Kam, N. W.; Dai, H., Carbon nanotubes as intracellular protein transporters: generality and biological functionality. J Am Chem Soc 2005, 127, (16), 6021-6.
55. Zhang, Y.; Yu, X.; Wang, X.; Shan, W.; Yang, P.; Tang, Y., Zeolite nanoparticles with immobilized metal ions: isolation and MALDI-TOF-MS/MS identification of phosphopeptides. Chem Commun (Camb) 2004, (24), 2882-3.
56. Kawahara, M.; Nakamura, H.; Nakajima, T., Group Separation of Ribonucleosides and Deoxyribonucleosides on a New Ceramic Titania Column. Analytical Sciences 1989, 5, (6), 763-764.
57. Matsuda, H.; Nakamura, H.; Nakajima, T., New Ceramic Titania - Selective Adsorbent for Organic-Phosphates. Analytical Sciences 1990, 6, (6), 911-912.
58. Ikeguchi, Y.; Nakamura, H., Determination of organic phosphates by column-switching high performance anion-exchange chromatography using on-line preconcentration on titania. Analytical Sciences 1997, 13, (3), 479-483.
59. Ikeguchi, Y.; Nakamura, H., Selective enrichment of phospholipids by titania. Analytical Sciences 2000, 16, (5), 541-543.
60. Xue, Y.; Wei, J.; Han, H.; Zhao, L.; Cao, D.; Wang, J.; Yang, X.; Zhang, Y.; Qian, X., Application of open tubular capillary columns coated with zirconium phosphonate for enrichment of phosphopeptides. J Chromatogr B Analyt Technol Biomed Life Sci 2009, 877, (8-9), 757-764.
61. Sturm, M.; Leitner, A.; Smatt, J. H.; Mechtler, K.; Lindner, W., Tin Dioxide Microspheres as a Promising Material for Phosphopeptide Enrichment Prior to Liquid Chromatography-(Tandem) Mass Spectrometry Analysis. Adv Funct Mater 2008, 18, 2381-2389.
62. Leitner, A.; Sturm, M.; Smatt, J. H.; Jarn, M.; Linden, M.; Mechtler, K.; Lindner, W., Optimizing the performance of tin dioxide microspheres for phosphopeptide enrichment. Anal Chim Acta 2009, 638, (1), 51-7.
63. Zhou, H.; Tian, R.; Ye, M.; Xu, S.; Feng, S.; Pan, C.; Jiang, X.; Li, X.; Zou, H., Highly specific enrichment of phosphopeptides by zirconium dioxide nanoparticles for phosphoproteome analysis. Electrophoresis 2007, 28, (13), 2201-15.
64. Sugiyama, N.; Masuda, T.; Shinoda, K.; Nakamura, A.; Tomita, M.; Ishihama, Y., Phosphopeptide enrichment by aliphatic hydroxy acid-modified metal oxide chromatography for nano-LC-MS/MS in proteomics applications. Mol Cell Proteomics 2007, 6, (6), 1103-9.
65. Reynolds, E. C.; Riley, P. F.; Adamson, N. J., A selective precipitation purification procedure for multiple phosphoseryl-containing peptides and methods for their identification. Anal Biochem 1994, 217, (2), 277-84.
66. Ruse, C. I.; McClatchy, D. B.; Lu, B.; Cociorva, D.; Motoyama, A.; Park, S. K.; Yates, J. R., 3rd, Motif-specific sampling of phosphoproteomes. J Proteome Res 2008, 7, (5), 2140-50.
67. Wu, J.; Shakey, Q.; Liu, W.; Schuller, A.; Follettie, M. T., Global profiling of phosphopeptides by titania affinity enrichment. J Proteome Res 2007, 6, (12), 4684-9.
68. Hsu, J. L.; Huang, S. Y.; Chow, N. H.; Chen, S. H., Stable-isotope dimethyl labeling for quantitative proteomics. Anal Chem 2003, 75, (24), 6843-52.
69. Huang, S. Y.; Hsu, J. L.; Morrice, N. A.; Wu, C. J.; Chen, S. H., A convenient method to extract matrix-assisted laser desorption/ionization mass spectrometry spectra from phosphate-containing peptide mixtures. Proteomics 2004, 4, (7), 1935-8.
70. Asara, J. M.; Allison, J., Enhanced detection of phosphopeptides in matrix-assisted laser desorption/ionization mass spectrometry using ammonium salts. J Am Soc Mass Spectrom 1999, 10, (1), 35-44.
71. Chirica, G. S.; Remcho, V. T., A simple procedure for the preparation of fritless columns by entrapping conventional high performance liquid chromatography sorbents. Electrophoresis 2000, 21, (15), 3093-3101.
72. Mock, K. K.; Sutton, C. W.; Cottrell, J. S., Sample immobilization protocols for matrix-assisted laser-desorption mass spectrometry. Rapid Commun Mass Spectrom 1992, 6, (4), 233-238.
73. Kalume, D. E.; Molina, H.; Pandey, A., Tackling the phosphoproteome: tools and strategies. Curr Opin Chem Biol 2003, 7, (1), 64-69.
74. Loste, E.; Fraile, J.; Fanovich, M. A.; Woerlee, G. E.; Domingo, C., Anhydrous supercritical carbon dioxide method for the controlled silanization of inorganic nanoparticles. Advanced Materials 2004, 16, (8), 739-744.
75. Yoshida, W.; Castro, R. P.; Jou, J. D.; Cohen, Y., Multilayer alkoxysilane silylation of oxide surfaces. Langmuir 2001, 17, (19), 5882-5888.
76. Rong, Y.; Chen, H. Z.; Wu, G.; Wang, M., Preparation and characterization of titanium dioxide nanoparticle/polystyrene composites via radical polymerization. Materials Chemistry and Physics 2005, 91, (2-3), 370-374.
77. Rajh, T.; Chen, L. X.; Lukas, K.; Liu, T.; Thurnauer, M. C.; Tiede, D. M., Surface restructuring of nanoparticles: An efficient route for ligand-metal oxide crosstalk. Journal of Physical Chemistry B 2002, 106, (41), 10543-10552.
78. Bezrodna, T.; Puchkovska, G.; Shimanovska, V.; Chashechnikova, I.; Khalyavka, T.; Baran, J., Pyridine-TiO2 surface interaction as a probe for surface active centers analysis. Applied Surface Science 2003, 214, (1-4), 222-231.
79. Li, G. S.; Li, L. P.; Boerio-Goates, J.; Woodfield, B. F., High purity anatase TiO2 nanocrystals: Near room-temperature synthesis, grain growth kinetics, and surface hydration chemistry. Journal of the American Chemical Society 2005, 127, (24), 8659-8666.
80. Beamson, G.; Briggs, D., High resolution XPS of organic polymers : the Scienta ESCA300 database. Wiley: Chichester, 1992; pp. 295.
81. Huang, S. Y.; Tsai, M. L.; Wu, C. J.; Hsu, J. L.; Ho, S. H.; Chen, S. H., Quantitation of protein phosphorylation in pregnant rat uteri using stable isotope dimethyl labeling coupled with IMAC. Proteomics 2006, 6, (6), 1722-34.
82. Kim, T. K.; Yoon, J. J.; Lee, D. S.; Park, T. G., Gas foamed open porous biodegradable polymeric microspheres. Biomaterials 2006, 27, (2), 152-9.
83. Koh, H. D.; Kang, N. G.; Lee, J. S., Fabrication of an open Au/nanoporous film by water-in-oil emulsion-induced block copolymer micelles. Langmuir 2007, 23, (26), 12817-20.
84. Kovacic, S.; Stefanec, D.; Krajnc, P., Highly porous open-cellular monoliths from 2-hydroxyethyl methacrylate based high internal phase emulsions (HIPEs): Preparation and void size tuning. Macromolecules 2007, 40, (22), 8056-8060.
85. Dunlap, C. J.; Carr, P. W.; McCormick, A. V., Chromatographic comparison of the pore structures of zirconia high performance liquid chromatographic materials made by the polymerization induced colloidal aggregation and the oil emulsion methods. Chromatographia 1996, 42, (5-6), 273-282.
86. Robichaud, M. J.; Sathyagal, A. N.; Carr, P. W.; Flickinger, M. C., An improved oil emulsion synthesis method for large, porous zirconia particles for packed- or fluidized-bed protein chromatography. Separation Science and Technology 1997, 32, (15), 2547-2559.
87. Yi, H.; Song, H.; Chen, X., Carbon nanotube capsules self-assembled by w/o emulsion technique. Langmuir 2007, 23, (6), 3199-204.
88. Bozkir, A.; Hayta, G., Preparation and evaluation of multiple emulsions water-in-oil-in-water (w/o/w) as delivery system for influenza virus antigens. J Drug Target 2004, 12, (3), 157-64.
89. Hwang, Y. J.; Oh, C.; Oh, S. G., Controlled release of retinol from silica particles prepared in O/W/O emulsion: the effects of surfactants and polymers. J Control Release 2005, 106, (3), 339-49.
90. Lee, M. H.; Oh, S. G.; Moon, S. K.; Bae, S. Y., Preparation of Silica Particles Encapsulating Retinol Using O/W/O Multiple Emulsions. J Colloid Interface Sci 2001, 240, (1), 83-89.
91. Lee, E. S.; Kwon, M. J.; Lee, H.; Kim, J. J., Stabilization of protein encapsulated in poly(lactide-co-glycolide) microspheres by novel viscous S/W/O/W method. Int J Pharm 2007, 331, (1), 27-37.
92. Barbier, V.; Tatoulian, M.; Li, H.; Arefi-Khonsari, F.; Ajdari, A.; Tabeling, P., Stable modification of PDMS surface properties by plasma polymerization: application to the formation of double emulsions in microfluidic systems. Langmuir 2006, 22, (12), 5230-2.
93. Dogruel, D.; Williams, P.; Nelson, R. W., Rapid tryptic mapping using enzymatically active mass spectrometer probe tips. Anal Chem 1995, 67, (23), 4343-8.
94. Zhang, G.; Lin, J.; Srinivasan, K.; Kavetskaia, O.; Duncan, J. N., Strategies for bioanalysis of an oligonucleotide class macromolecule from rat plasma using liquid chromatography-tandem mass spectrometry. Anal Chem 2007, 79, (9), 3416-24.
95. Peterson, D. S.; Rohr, T.; Svec, F.; Frechet, J. M., High-throughput peptide mass mapping using a microdevice containing trypsin immobilized on a porous polymer monolith coupled to MALDI TOF and ESI TOF mass spectrometers. J Proteome Res 2002, 1, (6), 563-8.
96. Geiser, L.; Eeltink, S.; Svec, F.; Frechet, J. M., In-line system containing porous polymer monoliths for protein digestion with immobilized pepsin, peptide preconcentration and nano-liquid chromatography separation coupled to electrospray ionization mass spectroscopy. J Chromatogr A 2008, 1188, (2), 88-96.
97. Sehgal, D.; Vijay, I. K., A method for the high efficiency of water-soluble carbodiimide-mediated amidation. Anal Biochem 1994, 218, (1), 87-91.
98. Richert, L.; Boulmedais, F.; Lavalle, P.; Mutterer, J.; Ferreux, E.; Decher, G.; Schaaf, P.; Voegel, J. C.; Picart, C., Improvement of stability and cell adhesion properties of polyelectrolyte multilayer films by chemical cross-linking. Biomacromolecules 2004, 5, (2), 284-94.
99. Sakai-Kato, K.; Kato, M.; Toyo'oka, T., On-line trypsin-encapsulated enzyme reactor by the sol-gel method integrated into capillary electrophoresis. Anal Chem 2002, 74, (13), 2943-9.
100. Sakai-Kato, K.; Kato, M.; Toyo'oka, T., Creation of an on-chip enzyme reactor by encapsulating trypsin in sol-gel on a plastic microchip. Anal Chem 2003, 75, (3), 388-93.
101. Kato, M.; Sakai-Kato, K.; Jin, H.; Kubota, K.; Miyano, H.; Toyo'oka, T.; Dulay, M. T.; Zare, R. N., Integration of on-line protein digestion, peptide separation, and protein identification using pepsin-coated photopolymerized sol-gel columns and capillary electrophoresis/mass spectrometry. Anal Chem 2004, 76, (7), 1896-902.
102. Ma, J.; Liang, Z.; Qiao, X.; Deng, Q.; Tao, D.; Zhang, L.; Zhang, Y., Organic-inorganic hybrid silica monolith based immobilized trypsin reactor with high enzymatic activity. Anal Chem 2008, 80, (8), 2949-56.
103. Whittal, R. M.; Keller, B. O.; Li, L., Nanoliter chemistry combined with mass spectrometry for peptide mapping of proteins from single mammalian cell lysates. Anal Chem 1998, 70, (24), 5344-7.
104. Feng, S.; Ye, M.; Jiang, X.; Jin, W.; Zou, H., Coupling the immobilized trypsin microreactor of monolithic capillary with muRPLC-MS/MS for shotgun proteome analysis. J Proteome Res 2006, 5, (2), 422-8.
105. Lim, L. W.; Tomatsu, M.; Takeuchi, T., Development of an on-line immobilized-enzyme reversed-phase HPLC method for protein digestion and peptide separation. Anal Bioanal Chem 2006, 386, (3), 614-20.
106. Bartolini, M.; Andrisano, V.; Wainer, I. W., Development and characterization of an immobilized enzyme reactor based on glyceraldehyde-3-phosphate dehydrogenase for on-line enzymatic studies. J Chromatogr A 2003, 987, (1-2), 331-40.
107. Eeltink, S.; Geiser, L.; Svec, F.; Frechet, J. M., Optimization of the porous structure and polarity of polymethacrylate-based monolithic capillary columns for the LC-MS separation of enzymatic digests. J Sep Sci 2007, 30, (17), 2814-20.
108. Krenkova, J.; Foret, F., Immobilized microfluidic enzymatic reactors. Electrophoresis 2004, 25, (21-22), 3550-63.
109. Svec, F., Less common applications of monoliths: I. Microscale protein mapping with proteolytic enzymes immobilized on monolithic supports. Electrophoresis 2006, 27, (5-6), 947-61.
110. Girelli, A. M.; Mattei, E., Application of immobilized enzyme reactor in on-line high performance liquid chromatography: a review. J Chromatogr B Analyt Technol Biomed Life Sci 2005, 819, (1), 3-16.
111. Mancini, F.; Naldi, M.; Cavrini, V.; Andrisano, V., Development and characterization of beta-secretase monolithic micro-immobilized enzyme reactor for on-line high-performance liquid chromatography studies. J Chromatogr A 2007, 1175, (2), 217-26.
112. Ekstrom, S.; Onnerfjord, P.; Nilsson, J.; Bengtsson, M.; Laurell, T.; Marko-Varga, G., Integrated microanalytical technology enabling rapid and automated protein identification. Anal Chem 2000, 72, (2), 286-93.
113. Gao, J.; Xu, J.; Locascio, L. E.; Lee, C. S., Integrated microfluidic system enabling protein digestion, peptide separation, and protein identification. Anal Chem 2001, 73, (11), 2648-55.
114. Yu, L. R.; Zhu, Z.; Chan, K. C.; Issaq, H. J.; Dimitrov, D. S.; Veenstra, T. D., Improved titanium dioxide enrichment of phosphopeptides from HeLa cells and high confident phosphopeptide identification by cross-validation of MS/MS and MS/MS/MS spectra. J Proteome Res 2007, 6, (11), 4150-62.