本研究成功提升快速檢測試劑中全血分離效率，於快速檢測試劑上方增加一層改質之高分子纖維薄膜，利用毛細現象將血球(Blood cells)與血漿(Plasma)分離，提升其全血分離效果。研究策略是利用高分子纖維濾膜特定孔徑结構可產生天然物理屏障，具有截留顆粒能力與高透過性的高分子微孔濾膜，使血球滯留在膜表面或其纖維所形成之孔徑中，且在薄膜透過表面改質方法，降低血液過濾時所造成溶血(Hemolysis)與血栓(Thrombus)現象，預防血液在纖維薄膜時凝固無法送達檢測區，達到提升快速檢測試劑中全血分離效果，提高試劑的鑑別度。本研究將對不同材質薄膜(聚硫醚維膜、混合纖維膜、醋酸纖維膜)、不同薄膜孔徑(0.22 µm、0.8 µm、1.2 µm、2 µm、5 µm)、不同改質方式(熱分解接枝法、過氧化氫氧化法)、不同改質溫度(60°C、70°C、80°C、90°C)、不同肝素濃度(1 IU/mL、10 IU/mL、100 IU/mL) 下對脂肪酸結合蛋白(Fatty acid binding protein, FABP)試劑的過濾效果進行探討。由實驗結果發現，採用經熱分解接枝法改質的醋酸纖維膜孔徑2 μm、反應溫度80°C、肝素濃度100 IU/mL，可使反應試劑背景灰階值從190提升至230，效果提升幅度為21%，且試劑的控制線灰階值仍維持於140、測試線灰階值維持於180 。因此，由實驗可得到，利用改質高分子先微薄膜能降低試劑觀測區之背景值，可提高試劑測試線(Result line)、控制線(Control line)的鑑別度。

This study successfully used the modified fiber membrane to improve the filtration efficiency for blood separation in the rapid test strip.The fiber membrane had the specific pore size which can generate the physical barriers to remain the blood cells and used the chemical modification method to decrease the hemolysis and thrombus conditions in the rapid test strip. Modified fiber membrane can improve the filtration efficiency to decrease the interference of the background value in the rapid test strips. This study was discussed the filtration efficiency in FABP strip under different material of the fiber membrane(Polyether sulfone, Mixed cellulose ester and Acetate cellulose), different membrane pore sizes(0.22 µm, 0.8 µm, 1.2 µm, 2 µm and 5 µm), different chemical modification method(thermal decomposition method and the hydrogen peroxide oxidation method), different chemical modification temperature(60°C, 70°C, 80°C and 90°C), different Heparin concentration(1 IU/mL, 10 IU/mL and 100 IU/mL). When the fiber membrane is Acetate cellulose and pore size is 2 µm which is used the thermal decomposition method to modify the fiber membrane under modification temperature is 80°C and Heparin concentration is 100 IU/mL, the grayscale of the test strip background increased from 190 to 230, and filtration efficiency was increased to 21%, but the grayscale of result line and control line is still 180 and 140. Therefore, this modified fiber membrane can improve the filtration efficiency and the discrimination by decreasing the interference of the background value in the rapid test strips.

[1] P. Hernandez, L. Cortina, H. Artaza, N. Pol, R. M. Lam, E. Dorticos, C. Macias, C. Hernandez, L. D. Vall, A. Blanco, A. Martinez and F. Diaz, “Autologous bone-marrow mononuclear cell implantation in patients with severe lower limb ischaemia: a comparison of using blood cell separator and Ficoll density gradient centrifugation,” Atherosclerosis, vol. 194, pp. 52-56, 2007.
[2] R. K. Ockner, J. A. Manning and R. B. Poppenhausen, “Binding protein for fatty acids in cytosol of intestinal mucosa, liver, myocardium and other tissues, ” Science, vol. 177, pp.56-58, 1972.
[3] V. D. Vusse and J. Glatz, “Cellular fatty acid binding proteins: current concepts and future directions,” Molecular and Cellular Biochemistry, vol. 98, pp. 237-251, 1990.
[4] A. W. Zimmerman and J. H. Veerkamp, “New insights into the structure and function of fatty acid-binding proteins,” Molecular and Cellular Biochemistry, vol. 59, pp. 1096-1116, 2002.
[5] T. Nakata, A. Hashimoto, M. Hase, K. Tsuchihashi and K. Shimamoto, “Human heart-type fatty acid-binding protein as an early diagnostic and prognostic marker in acute coronary syndrome,” Cardiology, vol. 99, pp. 96-104, 2003.
[6] T. Watanabe, Y. Ohkubo, H. Matsuoka, H. Kimura, Y. Sakai, Y. Ohkaru, T. Tanaka and Y. Kitaura, “Development of a simple whole blood panel test for detection of human heart-type fatty acid-binding protein,” Clinical Biochemistry, vol. 34, pp. 257-263, 2001.
[7] R. W. McNaught and J. T. France, “Studies of the biochemical basis of steroid sulphatase deficiency: Preliminary evidence suggesting a defect in membrane-enzyme structure,” Journal of Steroid Biochemistry, vol. 13, pp. 363-373, 1980.
[8] 聯華脂肪酸接合蛋白全血試劑說明書，聯華生技股份有限公司，2010.
[9] M. R. Goyal, Biofluid dynamics of the human body system, Apple academic press, 2013.
[10] W. J. Webe and E. J. LeBoeuf, “Processes for advanced treatment of water,” Water Science and Technology, vol. 40, pp. 11-19, 1999.
[11] 盧文章、楊子岳，薄膜程序回收石化產業放流水之應用，環保月刊，七月號(第一期廢水專輯)，第195-205頁，2001。
[12] R. N. T. Freeman, “Wettable phosphorylcholine-containing polymers useful in blood fltration,” Materials in Medicine, vol. 14, pp. 39-45, 2003.
[13] S. Thorslund, O. Klett, F. Nikolajeff, K. Markides and J. Bergquist, “A hybrid poly(dimethylsiloxane) microsystem for on-chip wholeblood filtration optimized for steroid screening,” Biomedical Microdevices, vol. 8, pp. 73-79, 2006.
[14] A. Cenci, S. Koren, B. Filipi and C. Stropnik, “Porcine blood cell separation by porous cellulose acetate membranes,” Cytotechnology, vol. 26, pp. 165-171, 1998.
[15] T. G. Grasel and S. L. Cooper, “Properties and biological interactions of polyurethane anionomers: effect of sulfonate incorporation,” Journal of Biomedical Materials Research, vol. 23, pp. 311-338, 1989.
[16] M. H. Moon, S. G. Yang, J. Y. Lee and S. Lee, “Combination of gravitational splitt fractionation and field-flow fractionation for size-sorting and characterization of sea sediment,” Analytical and Bioanalytical Chemistry, vol. 381, pp. 1299-1304, 2005.
[17] J. Mueller and R. Davis, “Protein fouling of surface-modified polymeric microfiltration membranes,” Journal of Membrane Science, vol.116, pp. 47-60, 1996.
[18] Y. C. Tyan, J. D. Liao, K. Y. Hsu and Y. D. Wu, “Comparative study of immobilized collagen onto varied porous fabric surfaces activated by O2 microwave plasma,” BME’99 Conference, pp. 203-204, 1999.
[19] O. Demuth, “Surface treatment of textile polymers by microwave plasma,” European Polymer Federation, vol. 8 pp. 14-18, 1987.
[20] I. Gancarz, G. Po niak, M. Bryjak and A. Frankiewicz, “Modification of polysulfone membranes Plasma grafting and plasma polymerization of acrylic acid,” Acta Polymerica, vol. 50, pp. 317-326, 1999.
[21] Y. Ikada and Y. Uyama, “Lubricating Polymer Surfaces,” Technomic Pub, pp. 73-90, 1993.
[22] M. Raif, “Molecular interface characterization on human bone matrix,” Biomaterials, vol. 14, pp. 978-982, 1993
[23] S. Sano, K. Kato and Y. Ikada, “Introduction of functional groups onto the surface of polyethylene for protein immobilization,” Biomaterials, vol. 14, pp. 817-822, 1993.
[24] K. Ishihara, R. Aragaki, T. Ueda, A. Watenabe and N. Nakabayashi, “Reduced thrombogenicity of polymers having phospholipid polar groups,” Journal of Biomedical Materials Research, vol. 24, pp. 1069-1077, 1990.
[25] Y. J. Li, R. Bahulekar, T. M. Chen, Y. F. Wang, M. Kodama and T. Nakaya, “The effect of alkyl chain length of amphiphilic phospholipid polyurethanes on haemocompatibilities,” Macromolecular Chemistry and Physics, vol. 197, pp. 2827-2832, 1996.
[26] J. H. Lee, G. Khang, J. W. Lee, H. B. Lee, “Platelet Adhesion on to Chargeable Functional Group Gradient Surface,” Journal of Biomedical Materials Research, vol. 40, pp. 180-186, 1998.
[27] T. M. Ko, J. C. Lin and S. L. Cooper, “Surface characterization and platelet adhesion studies of plasma-sulphonated polyethylene,” Biomaterials, vol. 14, pp. 657-664, 1993.
[28] P. S. Damus, M. Hicks and R. D. Rosenberg, “Anticoagulant action of heparin,” Nature, vol. 246, pp.355-357, 1973.
[29] J. M. Courtney, N. M. K. Lamba, S. Sundaram and C. D. Forbes, “Biomaterials for blood-contacting applications,” Biomaterials, vol. 15, pp. 737-742, 1994.
[30] 蔡靖彥，常見藥品手冊，合記出版社，第431-433頁，2002。
[31] F. C. Kung, W. L. Chou and M. C. Yang1, “In vitro evaluation of cellulose acetate hemodialyzer immobilized with heparin,” Polymers for Advanced Technologies, vol. 17, pp. 453-462, 2006.
[32] 李端、殷明，藥理學，人民衛生出版社，第275-277頁，2005。
[33] B. D. Ranter, A. B. Johnston and T. J. Lenk, “Biomaterial surfaces,” Journal of Biomedical Materials Research, vol. 21, pp. 59-89, 1987.
[34] J. Chen, Y. C. Nho and J. S. Park, “Grafting polymerization of acrylic acid onto preirradiated polypropylene fabric,” Radiation Physics and Chemistry, vol. 52, pp. 201-206, 1998.