Title

新型兩性雙離子性4-乙烯基吡啶羧基甜菜鹼刷狀高分子於生物惰性晶片之設計

Translated Titles

Novel design of bio-inert sensor chips grafted with zwitterionic 4-vinylpyridine carboxybetaine polymer brushes

Authors

劉子豪

Key Words

雙離子高分子 ; 抗沾黏 ; 氣相穩定性 ; 雙親性 ; 表面電漿共振 ; zwitterionic polymer ; antifouling ; air-stability ; amphiphilicity ; surface plasmon resonance

PublicationName

清華大學材料科學工程學系學位論文

Volume or Term/Year and Month of Publication

2016年

Academic Degree Category

碩士

Advisor

嚴大任;張雍

Content Language

英文

Chinese Abstract

抗沾粘技術廣泛使用在生物及工程上的應用已經超過二十年,從隱形眼鏡到船舶塗料都能見到其蹤跡。近年來,藉由模仿細胞膜組成的結構,由正電及負電集團所形成的雙離子材料可以透過靜電作用力與水分子產生強烈的鍵結並形成水合層,因此能夠擁有高度的抗蛋白吸付並同時具有良好的血液相容性,這些特性使得雙離子材料在眾多抗沾粘材料中展現極大的潛力。然而,利用雙離子材料改質過後的材料表面變得非常親水,而該親水表面在空氣中會擁有較高的表面能,這將使材料表面容易吸附髒污。因此,在抗沾粘領域中,科學家致力於發展一個具有能在氣相中穩定並同時能達到超低蛋白質吸附特性的雙離子材料。 在此研究中,我們成功合成具有雙離子特性的4-乙烯基吡啶羧基甜菜鹼,且利用表面起始自由基轉移聚合法將其成功接枝在材料表面上。除此之外,我們藉由表面電漿共振量測定量描述所合成分子的抗吸付能力,並藉由調控像是單體濃度及溶劑的離子強度等合成參數,使得該分子可達最佳7.5 ng/cm2超低蛋白質吸附的程度。更進一步,在血液貼附測試中,我們亦得到材料表面同樣具有抵抗血小板及血球的貼附的特性,確認該分子的生物惰性。最後,具有雙離子特性的4-乙烯基吡啶羧基甜菜鹼表面在水相環境中的油相接觸角約130度,與一般熟知的雙離子性甜菜鹼表面相仿,此結果也解釋了兩者表面在水相環境中抗蛋白質吸付的特性。另一方面,此雙離子表面在氣相環境中的水接觸角約為80度,明顯高出一般熟知的雙離子性甜菜鹼表面(約6度),顯示出其有較低的表面自由能,而能在氣相中有較穩定的特性。 總結以上,我們成功設計並合成出此新穎的雙離子性4-乙烯基吡啶羧基甜菜鹼,且成功將此材料接枝於材料表面,與一般熟知的雙離子材料甜菜鹼表面相比,此晶片表面不僅擁有良好的生物惰性,也擁有較高的氣相穩定性,可被使用在更多應用上。

English Abstract

Antifouling technique has been developed for over two decades and used in many biomedical and engineering applications ranging from contact lenses to marine coating. Among so many different antifouling materials, zwitterionic antifouling materials attract growing attentions around the world because their prefect protein-resistance and hemocompatibility. The structure of zwitterionic materials, bio-inspired from cell membranes, is similar to phosphatidylcholine, which contains positive and negative charges and thus can strongly bind with water molecules and form a hydration layer by electrostatically induced interaction, resulting in highly resistant to protein adsorption. Yet, a zwitterionic-polymer modified surface will become too hydrophilic and promote dirt adhesion or surface contamination much easier in air; herein, there appears a great demand on developing an air-stable zwitterionic material. On the other hand, to develop such zwitterionic material should achieve super-low fouling level as well. To approach these two requirements, in this work, we successfully synthesize and characterize a new zwitterionic material, zwitterionic 4-vinylpyridine carboxybetaine (z4VP) and then grafted zwitterionic poly(4-vinylpyridine carboxybetaine) (zP4VP) brushes from a gold surface via surface-initiated atom transfer radical polymerization (SI-ATRP) to reduce nonspecific protein adsorption and blood cell attachment. Besides, by changing different parameters of SI-ATRP such as a monomer concentration and ionic strength of a solvent, we obtained the optimized conditions for antifouling performance of the zP4VP system. In addition, to measure protein adsorption, we employ surface plasmon resonance (SPR) and the results suggest that the zP4VP surface can indeed reduce protein adsorption down to 7.5 ng/cm2, a super-low fouling level. The consistent results of platelets and blood cell attachment on the zP4VP surface observed by a confocal laser scanning microscopy (CLSM) are also provided to further confirm the antifouling performance of the zP4VP surface. Further, an oil contact angle of both the zP4VP surface and well-known poly(sulfobetaine methacrylate) (PSBMA) surface in the water is around 130 degrees which reveals a low interfacial energy in the water and explains their high hydrophilicity to resist protein adsorption. On the other hand, the zP4VP surface with a water contact angle (CA) around 80 degrees indicates the surface energy of the zP4VP surface is lower than the PSBMA surface (~6 degree) in the air. As a result, we claim that the zP4VP surface indeed exhibits the air-stable property. With the abovementioned properties of the z4VP, we summarize that the zP4VP surface not only exhibits a similar antifouling capability compared to the PSBMA surface in the water but also possesses relatively higher air-stable characterization than the PSBMA surface evidenced by both SPR and CA measurement.

Topic Category 工學院 > 材料科學工程學系
工程學 > 工程學總論
Reference
  1. [1] Ratner, B.D. and S.J. Bryant, Biomaterials: Where We Have Been and Where We Are Going. Annual Review of Biomedical Engineering, 2004. 6(1): p. 41-75.
    連結:
  2. [2] Zhang, L., Z. Cao, T. Bai, L. Carr, J.-R. Ella-Menye, C. Irvin, B.D. Ratner and S. Jiang, Zwitterionic hydrogels implanted in mice resist the foreign-body reaction. Nat Biotech, 2013. 31(6): p. 553-556.
    連結:
  3. [3] Bryers, J.D., Medical Biofilms. Biotechnology and bioengineering, 2008. 100(1): p. 1-18.
    連結:
  4. [4] Li, M., K.G. Neoh, L.Q. Xu, R. Wang, E.-T. Kang, T. Lau, D.P. Olszyna and E. Chiong, Surface modification of silicone for biomedical applications requiring long-term antibacterial, antifouling, and hemocompatible properties. Langmuir, 2012. 28(47): p. 16408-16422.
    連結:
  5. [5] Jiang, S. and Z. Cao, Ultralow‐fouling, functionalizable, and hydrolyzable zwitterionic materials and their derivatives for biological applications. Advanced Materials, 2010. 22(9): p. 920-932.
    連結:
  6. [6] Vaisocherová, H., W. Yang, Z. Zhang, Z. Cao, G. Cheng, M. Piliarik, J. Homola and S. Jiang, Ultralow Fouling and Functionalizable Surface Chemistry Based on a Zwitterionic Polymer Enabling Sensitive and Specific Protein Detection in Undiluted Blood Plasma. Analytical Chemistry, 2008. 80(20): p. 7894-7901.
    連結:
  7. [7] Zhang, Z., J.A. Finlay, L. Wang, Y. Gao, J.A. Callow, M.E. Callow and S. Jiang, Polysulfobetaine-Grafted Surfaces as Environmentally Benign Ultralow Fouling Marine Coatings. Langmuir, 2009. 25(23): p. 13516-13521.
    連結:
  8. [8] Chatzinikolaidou, M., M. Laub, H. Rumpf and H.P. Jennissen, Biocoating of Electropolished and Ultra-Hydrophilic Titanium and Cobalt Chromium Molybdenum Alloy Surfaces with Proteins. Materialwissenschaft und Werkstofftechnik, 2002. 33(12): p. 720-727.
    連結:
  9. [9] Hoffman, A.S., Letter to the Editor: A general classification scheme for “hydrophilic” and “hydrophobic” biomaterial surfaces. Journal of Biomedical Materials Research, 1986. 20(9): p. ix-xi.
    連結:
  10. [10] Chang, Y., S.-C. Liao, A. Higuchi, R.-C. Ruaan, C.-W. Chu and W.-Y. Chen, A Highly Stable Nonbiofouling Surface with Well-Packed Grafted Zwitterionic Polysulfobetaine for Plasma Protein Repulsion. Langmuir, 2008. 24(10): p. 5453-5458.
    連結:
  11. [11] Chen, S., L. Li, C. Zhao and J. Zheng, Surface hydration: Principles and applications toward low-fouling/nonfouling biomaterials. Polymer, 2010. 51(23): p. 5283-5293.
    連結:
  12. [12] Roth, C.M. and A.M. Lenhoff, Electrostatic and van der Waals contributions to protein adsorption: computation of equilibrium constants. Langmuir, 1993. 9(4): p. 962-972.
    連結:
  13. [13] Johnson, C.A., P. Wu and A.M. Lenhoff, Electrostatic and van der Waals Contributions to Protein Adsorption: 2. Modeling of Ordered Arrays. Langmuir, 1994. 10(10): p. 3705-3713.
    連結:
  14. [14] Sin, M.-C., S.-H. Chen and Y. Chang, Hemocompatibility of zwitterionic interfaces and membranes. Polym J, 2014. 46(8): p. 436-443.
    連結:
  15. [15] Liu, L., W. Li and Q. Liu, Recent development of antifouling polymers: structure, evaluation, and biomedical applications in nano/micro-structures. Wiley Interdisciplinary Reviews: Nanomedicine and Nanobiotechnology, 2014. 6(6): p. 599-614.
    連結:
  16. [16] Leduc, E.H. and S.J. Holt, HYDROXYPROPYL METHACRYLATE, A NEW WATER-MISCIBLE EMBEDDING MEDIUM FOR ELECTRON MICROSCOPY. The Journal of Cell Biology, 1965. 26(1): p. 137-155.
    連結:
  17. [17] Chen, Q., D. Zhang, G. Somorjai and C.R. Bertozzi, Probing the surface structural rearrangement of hydrogels by sum-frequency generation spectroscopy. Journal of the American Chemical Society, 1999. 121(2): p. 446-447.
    連結:
  18. [18] Mrabet, B., M.N. Nguyen, A. Majbri, S. Mahouche, M. Turmine, A. Bakhrouf and M.M. Chehimi, Anti-fouling poly(2-hydoxyethyl methacrylate) surface coatings with specific bacteria recognition capabilities. Surface Science, 2009. 603(16): p. 2422-2429.
    連結:
  19. [19] Yoshikawa, C., A. Goto, Y. Tsujii, T. Fukuda, T. Kimura, K. Yamamoto and A. Kishida, Protein Repellency of Well-Defined, Concentrated Poly(2-hydroxyethyl methacrylate) Brushes by the Size-Exclusion Effect. Macromolecules, 2006. 39(6): p. 2284-2290.
    連結:
  20. [20] Harris, J.M., Poly (ethylene glycol) chemistry: biotechnical and biomedical applications. Journal, 2013. p.
    連結:
  21. [22] Lahiri, J., L. Isaacs, J. Tien and G.M. Whitesides, A Strategy for the Generation of Surfaces Presenting Ligands for Studies of Binding Based on an Active Ester as a Common Reactive Intermediate: A Surface Plasmon Resonance Study. Analytical Chemistry, 1999. 71(4): p. 777-790.
    連結:
  22. [23] Zheng, J., L. Li, S. Chen and S. Jiang, Molecular Simulation Study of Water Interactions with Oligo (Ethylene Glycol)-Terminated Alkanethiol Self-Assembled Monolayers. Langmuir, 2004. 20(20): p. 8931-8938.
    連結:
  23. [24] Zheng, J., L. Li, H.-K. Tsao, Y.-J. Sheng, S. Chen and S. Jiang, Strong Repulsive Forces between Protein and Oligo (Ethylene Glycol) Self-Assembled Monolayers: A Molecular Simulation Study. Biophysical Journal, 2005. 89(1): p. 158-166.
    連結:
  24. [25] Li, L., S. Chen, J. Zheng, B.D. Ratner and S. Jiang, Protein Adsorption on Oligo(ethylene glycol)-Terminated Alkanethiolate Self-Assembled Monolayers:  The Molecular Basis for Nonfouling Behavior. The Journal of Physical Chemistry B, 2005. 109(7): p. 2934-2941.
    連結:
  25. [26] Lee, J.H., H.B. Lee and J.D. Andrade, Blood compatibility of polyethylene oxide surfaces. Progress in Polymer Science, 1995. 20(6): p. 1043-1079.
    連結:
  26. [27] He, Y., Y. Chang, J.C. Hower, J. Zheng, S. Chen and S. Jiang, Origin of repulsive force and structure/dynamics of interfacial water in OEG-protein interactions: a molecular simulation study. Physical Chemistry Chemical Physics, 2008. 10(36): p. 5539-5544.
    連結:
  27. [28] Luk, Y.-Y., M. Kato and M. Mrksich, Self-Assembled Monolayers of Alkanethiolates Presenting Mannitol Groups Are Inert to Protein Adsorption and Cell Attachment. Langmuir, 2000. 16(24): p. 9604-9608.
    連結:
  28. [29] Ostuni, E., R.G. Chapman, R.E. Holmlin, S. Takayama and G.M. Whitesides, A Survey of Structure−Property Relationships of Surfaces that Resist the Adsorption of Protein. Langmuir, 2001. 17(18): p. 5605-5620.
    連結:
  29. [30] Shen, M., L. Martinson, M.S. Wagner, D.G. Castner, B.D. Ratner and T.A. Horbett, PEO-like plasma polymerized tetraglyme surface interactions with leukocytes and proteins: in vitro and in vivo studies. Journal of Biomaterials Science, Polymer Edition, 2002. 13(4): p. 367-390.
    連結:
  30. [31] Singer, S.J. and G.L. Nicolson, The Fluid Mosaic Model of the Structure of Cell Membranes. Science, 1972. 175(4023): p. 720-731.
    連結:
  31. [34] Ishihara, K., H. Oshida, Y. Endo, T. Ueda, A. Watanabe and N. Nakabayashi, Hemocompatibility of human whole blood on polymers with a phospholipid polar group and its mechanism. Journal of Biomedical Materials Research, 1992. 26(12): p. 1543-1552.
    連結:
  32. [35] Iwasaki, Y. and K. Ishihara, Phosphorylcholine-containing polymers for biomedical applications. Analytical and Bioanalytical Chemistry, 2005. 381(3): p. 534-546.
    連結:
  33. [36] Ishihara, K., T. Ueda and N. Nakabayashi, Preparation of phospholipid polymers and their properties as polymer hydrogel membranes. Polym J, 1990. 22(5): p. 355-360.
    連結:
  34. [37] Holmlin, R.E., X. Chen, R.G. Chapman, S. Takayama and G.M. Whitesides, Zwitterionic SAMs that Resist Nonspecific Adsorption of Protein from Aqueous Buffer. Langmuir, 2001. 17(9): p. 2841-2850.
    連結:
  35. [38] Kane, R.S., P. Deschatelets and G.M. Whitesides, Kosmotropes Form the Basis of Protein-Resistant Surfaces. Langmuir, 2003. 19(6): p. 2388-2391.
    連結:
  36. [39] Tsai, W.B., Q. Shi, J.M. Grunkemeier, C. Mcfarland and T.A. Horbett, Platelet adhesion to radiofrequency glow-discharge-deposited fluorocarbon polymers preadsorbed with selectively depleted plasmas show the primary role of fibrinogen. Journal of Biomaterials Science, Polymer Edition, 2004. 15(7): p. 817-840.
    連結:
  37. [40] Ladd, J., Z. Zhang, S. Chen, J.C. Hower and S. Jiang, Zwitterionic Polymers Exhibiting High Resistance to Nonspecific Protein Adsorption from Human Serum and Plasma. Biomacromolecules, 2008. 9(5): p. 1357-1361.
    連結:
  38. [41] Chang, Y., W.-J. Chang, Y.-J. Shih, T.-C. Wei and G.-H. Hsiue, Zwitterionic Sulfobetaine-Grafted Poly(vinylidene fluoride) Membrane with Highly Effective Blood Compatibility via Atmospheric Plasma-Induced Surface Copolymerization. ACS Applied Materials & Interfaces, 2011. 3(4): p. 1228-1237.
    連結:
  39. [42] Zhang, Z., T. Chao, L. Liu, G. Cheng, B.D. Ratner and S. Jiang, Zwitterionic Hydrogels: an in Vivo Implantation Study. Journal of Biomaterials Science, Polymer Edition, 2009. 20(13): p. 1845-1859.
    連結:
  40. [43] Zhang, Z., T. Chao, S. Chen and S. Jiang, Superlow Fouling Sulfobetaine and Carboxybetaine Polymers on Glass Slides. Langmuir, 2006. 22(24): p. 10072-10077.
    連結:
  41. [44] Zhang, Z., S. Chen and S. Jiang, Dual-Functional Biomimetic Materials:  Nonfouling Poly(carboxybetaine) with Active Functional Groups for Protein Immobilization. Biomacromolecules, 2006. 7(12): p. 3311-3315.
    連結:
  42. [45] Yang, W., H. Xue, W. Li, J. Zhang and S. Jiang, Pursuing “Zero” Protein Adsorption of Poly(carboxybetaine) from Undiluted Blood Serum and Plasma. Langmuir, 2009. 25(19): p. 11911-11916.
    連結:
  43. [46] Zhang, Z., M. Zhang, S. Chen, T.A. Horbett, B.D. Ratner and S. Jiang, Blood compatibility of surfaces with superlow protein adsorption. Biomaterials, 2008. 29(32): p. 4285-4291.
    連結:
  44. [47] Zhang, Z., H. Vaisocherová, G. Cheng, W. Yang, H. Xue and S. Jiang, Nonfouling Behavior of Polycarboxybetaine-Grafted Surfaces: Structural and Environmental Effects. Biomacromolecules, 2008. 9(10): p. 2686-2692.
    連結:
  45. [48] Shao, Q. and S. Jiang, Effect of Carbon Spacer Length on Zwitterionic Carboxybetaines. The Journal of Physical Chemistry B, 2013. 117(5): p. 1357-1366.
    連結:
  46. [49] Li, D., Q. Zheng, Y. Wang and H. Chen, Combining surface topography with polymer chemistry: exploring new interfacial biological phenomena. Polymer Chemistry, 2014. 5(1): p. 14-24.
    連結:
  47. [50] Chang, Y., S. Chen, Z. Zhang and S. Jiang, Highly Protein-Resistant Coatings from Well-Defined Diblock Copolymers Containing Sulfobetaines. Langmuir, 2006. 22(5): p. 2222-2226.
    連結:
  48. [51] De Vos, W.M., G. Meijer, A. De Keizer, M.A. Cohen Stuart and J.M. Kleijn, Charge-driven and reversible assembly of ultra-dense polymer brushes: formation and antifouling properties of a zipper brush. Soft Matter, 2010. 6(11): p. 2499-2507.
    連結:
  49. [52] Kuo, W.-H., M.-J. Wang, H.-W. Chien, T.-C. Wei, C. Lee and W.-B. Tsai, Surface Modification with Poly(sulfobetaine methacrylate-co-acrylic acid) To Reduce Fibrinogen Adsorption, Platelet Adhesion, and Plasma Coagulation. Biomacromolecules, 2011. 12(12): p. 4348-4356.
    連結:
  50. [53] Chang, Y., Y.J. Shih, C.J. Lai, H.H. Kung and S. Jiang, Blood‐Inert Surfaces via Ion‐Pair Anchoring of Zwitterionic Copolymer Brushes in Human Whole Blood. Advanced Functional Materials, 2013. 23(9): p. 1100-1110.
    連結:
  51. [54] Chang, Y., Y. Chang, A. Higuchi, Y.-J. Shih, P.-T. Li, W.-Y. Chen, E.-M. Tsai and G.-H. Hsiue, Bioadhesive Control of Plasma Proteins and Blood Cells from Umbilical Cord Blood onto the Interface Grafted with Zwitterionic Polymer Brushes. Langmuir, 2012. 28(9): p. 4309-4317.
    連結:
  52. [55] Feng, W., J.L. Brash and S. Zhu, Non-biofouling materials prepared by atom transfer radical polymerization grafting of 2-methacryloloxyethyl phosphorylcholine: Separate effects of graft density and chain length on protein repulsion. Biomaterials, 2006. 27(6): p. 847-855.
    連結:
  53. [56] Nguyen, A.T., J. Baggerman, J.M.J. Paulusse, C.J.M. Van Rijn and H. Zuilhof, Stable Protein-Repellent Zwitterionic Polymer Brushes Grafted from Silicon Nitride. Langmuir, 2011. 27(6): p. 2587-2594.
    連結:
  54. [57] Wang, J.-S. and K. Matyjaszewski, Controlled/"living" radical polymerization. atom transfer radical polymerization in the presence of transition-metal complexes. Journal of the American Chemical Society, 1995. 117(20): p. 5614-5615.
    連結:
  55. [58] Pyun, J., T. Kowalewski and K. Matyjaszewski, Synthesis of Polymer Brushes Using Atom Transfer Radical Polymerization. Macromolecular Rapid Communications, 2003. 24(18): p. 1043-1059.
    連結:
  56. [59] Hawker, C.J., A.W. Bosman and E. Harth, New Polymer Synthesis by Nitroxide Mediated Living Radical Polymerizations. Chemical Reviews, 2001. 101(12): p. 3661-3688.
    連結:
  57. [60] Blomberg, S., S. Ostberg, E. Harth, A.W. Bosman, B. Van Horn and C.J. Hawker, Production of crosslinked, hollow nanoparticles by surface‐initiated living free‐radical polymerization. Journal of Polymer Science Part A: Polymer Chemistry, 2002. 40(9): p. 1309-1320.
    連結:
  58. [61] Madruga, E.L., From classical to living/controlled statistical free-radical copolymerization. Progress in Polymer Science, 2002. 27(9): p. 1879-1924.
    連結:
  59. [62] Barner‐Kowollik, C., T.P. Davis, J. Heuts, M.H. Stenzel, P. Vana and M. Whittaker, RAFTing down under: Tales of missing radicals, fancy architectures, and mysterious holes. Journal of Polymer Science Part A: Polymer Chemistry, 2003. 41(3): p. 365-375.
    連結:
  60. [63] Husseman, M., E.E. Malmström, M. Mcnamara, M. Mate, D. Mecerreyes, D.G. Benoit, J.L. Hedrick, P. Mansky, E. Huang, T.P. Russell and C.J. Hawker, Controlled Synthesis of Polymer Brushes by “Living” Free Radical Polymerization Techniques. Macromolecules, 1999. 32(5): p. 1424-1431.
    連結:
  61. [64] Matyjaszewski, K. and J. Xia, Atom Transfer Radical Polymerization. Chemical Reviews, 2001. 101(9): p. 2921-2990.
    連結:
  62. [65] Ran, J., L. Wu, Z. Zhang and T. Xu, Atom transfer radical polymerization (ATRP): A versatile and forceful tool for functional membranes. Progress in Polymer Science, 2014. 39(1): p. 124-144.
    連結:
  63. [66] Jones, D.M., A.A. Brown and W.T.S. Huck, Surface-Initiated Polymerizations in Aqueous Media:  Effect of Initiator Density. Langmuir, 2002. 18(4): p. 1265-1269.
    連結:
  64. [67] Zhang, Z., S. Chen, Y. Chang and S. Jiang, Surface Grafted Sulfobetaine Polymers via Atom Transfer Radical Polymerization as Superlow Fouling Coatings. The Journal of Physical Chemistry B, 2006. 110(22): p. 10799-10804.
    連結:
  65. [68] Edmondson, S., V.L. Osborne and W.T. Huck, Polymer brushes via surface-initiated polymerizations. Chemical society reviews, 2004. 33(1): p. 14-22.
    連結:
  66. [69] Kooyman, R.P., Physics of surface plasmon resonance. Handbook of Surface Plasmon Resonance, 2008. 1(p.
    連結:
  67. [70] Homola, J., S.S. Yee and G. Gauglitz, Surface plasmon resonance sensors: review. Sensors and Actuators B: Chemical, 1999. 54(1–2): p. 3-15.
    連結:
  68. [71] Kretschmann, E. and H. Raether, Notizen: radiative decay of non radiative surface plasmons excited by light. Zeitschrift für Naturforschung A, 1968. 23(12): p. 2135-2136.
    連結:
  69. [72] Otto, A., Excitation of nonradiative surface plasma waves in silver by the method of frustrated total reflection. Zeitschrift für Physik, 216(4): p. 398-410.
    連結:
  70. [73] Lukosz, W. and K. Tiefenthaler, Embossing technique for fabricating integrated optical components in hard inorganic waveguiding materials. Opt. Lett., 1983. 8(10): p. 537-539.
    連結:
  71. [74] Lin, K., Y. Lu, J. Chen, R. Zheng, P. Wang and H. Ming, Surface plasmon resonance hydrogen sensor based on metallic grating with high sensitivity. Opt. Express, 2008. 16(23): p. 18599-18604.
    連結:
  72. [75] Cai, D., Y. Lu, K. Lin, P. Wang and H. Ming, Improving the sensitivity of SPR sensors based on gratings by double-dips method (DDM). Opt. Express, 2008. 16(19): p. 14597-14602.
    連結:
  73. [76] Liedberg, B., C. Nylander and I. Lunström, Surface plasmon resonance for gas detection and biosensing. Sensors and Actuators, 1983. 4(p. 299-304.
    連結:
  74. [77] Rodriguez-Emmenegger, C., E. Brynda, T. Riedel, M. Houska, V. Šubr, A.B. Alles, E. Hasan, J.E. Gautrot and W.T.S. Huck, Polymer Brushes Showing Non-Fouling in Blood Plasma Challenge the Currently Accepted Design of Protein Resistant Surfaces. Macromolecular Rapid Communications, 2011. 32(13): p. 952-957.
    連結:
  75. [78] Kooyman, R.P.H., H. Kolkman, J. Van Gent and J. Greve, Surface plasmon resonance immunosensors: sensitivity considerations. Analytica Chimica Acta, 1988. 213(p. 35-45.
    連結:
  76. [79] Tong, L., H. Wei, S. Zhang and H. Xu, Recent Advances in Plasmonic Sensors. Sensors (Basel, Switzerland), 2014. 14(5): p. 7959-7973.
    連結:
  77. [80] El-Hamshary, H., M. El-Garawany, F.N. Assubaie and M. Al-Eed, Synthesis of poly(acrylamide-co-4-vinylpyridine) hydrogels and their application in heavy metal removal. Journal of Applied Polymer Science, 2003. 89(9): p. 2522-2526.
    連結:
  78. [81] Rivas, B.L., B. Quilodrán and E. Quiroz, Trace metal ion retention properties of crosslinked poly(4-vinylpyridine) and poly(acrylic acid). Journal of Applied Polymer Science, 2004. 92(5): p. 2908-2916.
    連結:
  79. [82] Caruso, U., A. De Maria, B. Panunzi and A. Roviello, Poly (4‐vinylpyridine) as the host ligand of metal‐containing chromophores for second‐order nonlinear optical active materials. Journal of Polymer Science Part A: Polymer Chemistry, 2002. 40(17): p. 2987-2993.
    連結:
  80. [83] Caruso, U., R. Centore, B. Panunzi, A. Roviello and A. Tuzi, Grafting Poly(4-vinylpyridine) with a Second-Order Nonlinear Optically Active Nickel(II) Chromophore. European Journal of Inorganic Chemistry, 2005. 2005(13): p. 2747-2753.
    連結:
  81. [84] Harnish, B., J.T. Robinson, Z. Pei, O. Ramström and M. Yan, UV-Cross-Linked Poly(vinylpyridine) Thin Films as Reversibly Responsive Surfaces. Chemistry of Materials, 2005. 17(16): p. 4092-4096.
    連結:
  82. [85] Li, D., Q. He, Y. Yang, H. Möhwald and J. Li, Two-Stage pH Response of Poly(4-vinylpyridine) Grafted Gold Nanoparticles. Macromolecules, 2008. 41(19): p. 7254-7256.
    連結:
  83. [86] Li, D., Y.J. Jang, J. Lee, J.-E. Lee, S.T. Kochuveedu and D.H. Kim, Grafting poly(4-vinylpyridine) onto gold nanorods toward functional plasmonic core-shell nanostructures. Journal of Materials Chemistry, 2011. 21(41): p. 16453-16460.
    連結:
  84. [87] Li, D., Q. He, Y. Cui and J. Li, Fabrication of pH-Responsive Nanocomposites of Gold Nanoparticles/Poly(4-vinylpyridine). Chemistry of Materials, 2007. 19(3): p. 412-417.
    連結:
  85. [88] Lee, J.-E., K. Chung, Y.H. Jang, Y.J. Jang, S.T. Kochuveedu, D. Li and D.H. Kim, Bimetallic Multifunctional Core@Shell Plasmonic Nanoparticles for Localized Surface Plasmon Resonance Based Sensing and Electrocatalysis. Analytical Chemistry, 2012. 84(15): p. 6494-6500.
    連結:
  86. [89] Li, Y., M.J. Yang and Y. She, Humidity sensitive properties of crosslinked and quaternized poly(4-vinylpyridine-co-butyl methacrylate). Sensors and Actuators B: Chemical, 2005. 107(1): p. 252-257.
    連結:
  87. [90] Tiller, J.C., S.B. Lee, K. Lewis and A.M. Klibanov, Polymer surfaces derivatized with poly(vinyl-N-hexylpyridinium) kill airborne and waterborne bacteria. Biotechnology and Bioengineering, 2002. 79(4): p. 465-471.
    連結:
  88. [91] Laschewsky, A., Structures and synthesis of zwitterionic polymers. Polymers, 2014. 6(5): p. 1544-1601.
    連結:
  89. [92] Wendler, U., J. Bohrisch, W. Jaeger, G. Rother and H. Dautzenberg, Amphiphilic cationic block copolymers via controlled free radical polymerization. Macromolecular Rapid Communications, 1998. 19(4): p. 185-190.
    連結:
  90. [93] Jaeger, W., U. Wendler, A. Lieske and J. Bohrisch, Novel Modified Polymers with Permanent Cationic Groups. Langmuir, 1999. 15(12): p. 4026-4032.
    連結:
  91. [94] Wang, J., Y. Zong, R. Fu, Y. Niu, G. Yue, Z. Quan, X. Wang and Y. Pan, Poly(4-vinylpyridine) supported acidic ionic liquid: A novel solid catalyst for the efficient synthesis of 2,3-dihydroquinazolin-4(1H)-ones under ultrasonic irradiation. Ultrasonics Sonochemistry, 2014. 21(1): p. 29-34.
    連結:
  92. [95] Gui, Z., J. Qian, Q. An, H. Xu and Q. Zhao, Synthesis, characterization and flocculation performance of zwitterionic copolymer of acrylamide and 4-vinylpyridine propylsulfobetaine. European Polymer Journal, 2009. 45(5): p. 1403-1411.
    連結:
  93. [96] Shafi, H.Z., Z. Khan, R. Yang and K.K. Gleason, Surface modification of reverse osmosis membranes with zwitterionic coating for improved resistance to fouling. Desalination, 2015. 362(p. 93-103.
    連結:
  94. [97] Venault, A., K.M. Trinh and Y. Chang, A zwitterionic zP(4VP-r-ODA) copolymer for providing polypropylene membranes with improved hemocompatibility. Journal of Membrane Science, 2016. 501(p. 68-78.
    連結:
  95. [98] Chen, S., J. Zheng, L. Li and S. Jiang, Strong Resistance of Phosphorylcholine Self-Assembled Monolayers to Protein Adsorption:  Insights into Nonfouling Properties of Zwitterionic Materials. Journal of the American Chemical Society, 2005. 127(41): p. 14473-14478.
    連結:
  96. [99] Jung, L.S., C.T. Campbell, T.M. Chinowsky, M.N. Mar and S.S. Yee, Quantitative Interpretation of the Response of Surface Plasmon Resonance Sensors to Adsorbed Films. Langmuir, 1998. 14(19): p. 5636-5648.
    連結:
  97. [101] Mondal, P., S. Saha and P. Chowdhury, Simultaneous polymerization and quaternization of 4‐vinyl pyridine. Journal of Applied Polymer Science, 2013. 127(6): p. 5045-5050.
    連結:
  98. [103] Owens, D.K. and R. Wendt, Estimation of the surface free energy of polymers. Journal of applied polymer science, 1969. 13(8): p. 1741-1747.
    連結:
  99. [21] Abuchowski, A., T. Van Es, N. Palczuk and F. Davis, Alteration of immunological properties of bovine serum albumin by covalent attachment of polyethylene glycol. Journal of Biological Chemistry, 1977. 252(11): p. 3578-3581.
  100. [32] Zwaal, R.F.A. and A.J. Schroit, Pathophysiologic Implications of Membrane Phospholipid Asymmetry in Blood Cells. Blood, 1997. 89(4): p. 1121-1132.
  101. [33] 門磨, 義., 宣. 中林, 英. 増原 and 淳. 山内, ホスホリルコリン基を有するポリマーの合成と溶血性. 高分子論文集, 1978. 35(7): p. 423-427.
  102. [100] Sahiner, N., A facile method for the preparation of poly (4-vinylpyridine) nanoparticles and their characterization. Turkish Journal of Chemistry, 2009. 33(1): p. 23-31.
  103. [102] Rabel, W., Einige Aspekte der Benetzungstheorie und ihre Anwendung auf die Untersuchung und Veränderung der Oberflächeneigenschaften von Polymeren. Farbe und Lack, 1971. 77(10): p. 997-1006.