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完整後設資料紀錄
DC 欄位 | 值 | 語言 |
---|---|---|
dc.contributor.advisor | 沈弘俊(Horn-Jiunn Sheen) | |
dc.contributor.author | Wen-Fei Yang | en |
dc.contributor.author | 楊文斐 | zh_TW |
dc.date.accessioned | 2021-07-11T14:38:04Z | - |
dc.date.available | 2022-08-07 | |
dc.date.copyright | 2017-08-07 | |
dc.date.issued | 2017 | |
dc.date.submitted | 2017-07-31 | |
dc.identifier.citation | [1] A. Hoos and C. Cordon-Cardo, Tissue microarray profiling of cancer specimens and cell lines: opportunities and limitations. Laboratory investigation, 2001. 81(10): p. 1331-1338.
[2] J.C. Mills, K.A. Roth, R.L. Cagan, and J.I. Gordon, DNA microarrays and beyond: completing the journey from tissue to cell. Nature Cell Biology, 2001. 3(8): p. E175-E178. [3] A. Sassolas, B.D. Leca-Bouvier, and L.J. Blum, DNA biosensors and microarrays. Chemical reviews, 2008. 108(1): p. 109-139. [4] K.-I. Chen, B.-R. Li, and Y.-T. Chen, Silicon nanowire field-effect transistor-based biosensors for biomedical diagnosis and cellular recording investigation. Nano Today, 2011. 6(2): p. 131-154. [5] M.L. Kovarik, D.M. Ornoff, A.T. Melvin, N.C. Dobes, Y. Wang, A.J. Dickinson, P.C. Gach, P.K. Shah, and N.L. Allbritton, Micro total analysis systems: fundamental advances and applications in the laboratory, clinic, and field. Analytical chemistry, 2012. 85(2): p. 451-472. [6] A. Manz, N. Graber, and H.á. Widmer, Miniaturized total chemical analysis systems: a novel concept for chemical sensing. Sensors and actuators B: Chemical, 1990. 1(1): p. 244-248. [7] A.R. Grayson, R.S. Shawgo, A.M. Johnson, N.T. Flynn, Y. Li, M.J. Cima, and R. Langer, A BioMEMS review: MEMS technology for physiologically integrated devices. Proceedings of the IEEE, 2004. 92(1): p. 6-21. [8] S. Trietsch, T. Hankemeier, and H. Van der Linden, Lab-on-a-chip technologies for massive parallel data generation in the life sciences: A review. Chemometrics and Intelligent Laboratory Systems, 2011. 108(1): p. 64-75. [9] K.N. Han, C.A. Li, and G.H. Seong, Microfluidic chips for immunoassays. Annual review of analytical chemistry, 2013. 6: p. 119-141. [10] D. Dey and T. Goswami, Optical biosensors: a revolution towards quantum nanoscale electronics device fabrication. BioMed Research International, 2011. 2011. [11] D. Grieshaber, R. MacKenzie, J. Voeroes, and E. Reimhult, Electrochemical biosensors-sensor principles and architectures. Sensors, 2008. 8(3): p. 1400-1458. [12] G. Marrazza, Piezoelectric biosensors for organophosphate and carbamate pesticides: a review. Biosensors, 2014. 4(3): p. 301-317. [13] J. Homola, S.S. Yee, and G. Gauglitz, Surface plasmon resonance sensors: review. Sensors and Actuators B: Chemical, 1999. 54(1): p. 3-15. [14] W. Tan, Y. Huang, T. Nan, C. Xue, Z. Li, Q. Zhang, and B. Wang, Development of protein A functionalized microcantilever immunosensors for the analyses of small molecules at parts per trillion levels. Analytical chemistry, 2009. 82(2): p. 615-620. [15] R. Vaughan, C. O’sullivan, and G. Guilbault, Development of a quartz crystal microbalance (QCM) immunosensor for the detection of Listeria monocytogenes. Enzyme and Microbial Technology, 2001. 29(10): p. 635-638. [16] D.R. Shankaran, K.V. Gobi, and N. Miura, Recent advancements in surface plasmon resonance immunosensors for detection of small molecules of biomedical, food and environmental interest. Sensors and Actuators B: Chemical, 2007. 121(1): p. 158-177. [17] P.-S. Chung, Y.-J. Fan, H.-J. Sheen, and W.-C. Tian, Real-time dual-loop electric current measurement for label-free nanofluidic preconcentration chip. Lab on a Chip, 2015. 15(1): p. 319-330. [18] Y.-C. Wang, A.L. Stevens, and J. Han, Million-fold preconcentration of proteins and peptides by nanofluidic filter. Analytical chemistry, 2005. 77(14): p. 4293-4299. [19] Q. Pu, J. Yun, H. Temkin, and S. Liu, Ion-enrichment and ion-depletion effect of nanochannel structures. Nano letters, 2004. 4(6): p. 1099-1103. [20] J.H. Lee, Y.-A. Song, and J. Han, Multiplexed proteomic sample preconcentration device using surface-patterned ion-selective membrane. Lab on a Chip, 2008. 8(4): p. 596-601. [21] P.S. Dittrich, K. Tachikawa, and A. Manz, Micro total analysis systems. Latest advancements and trends. Analytical chemistry, 2006. 78(12): p. 3887-3908. [22] R. Wood, XLII. On a remarkable case of uneven distribution of light in a diffraction grating spectrum. The London, Edinburgh, and Dublin Philosophical Magazine and Journal of Science, 1902. 4(21): p. 396-402. [23] U. Fano, The theory of anomalous diffraction gratings and of quasi-stationary waves on metallic surfaces (Sommerfeld’s waves). JOSA, 1941. 31(3): p. 213-222. [24] A. Hessel and A. Oliner, A new theory of Wood’s anomalies on optical gratings. Applied Optics, 1965. 4(10): p. 1275-1297. [25] R. Ritchie, Plasma losses by fast electrons in thin films. Physical Review, 1957. 106(5): p. 874. [26] E. Kretschmann and H. Raether, Notizen: radiative decay of non radiative surface plasmons excited by light. Zeitschrift für Naturforschung A, 1968. 23(12): p. 2135-2136. [27] A. Otto, Excitation of nonradiative surface plasma waves in silver by the method of frustrated total reflection. Zeitschrift für Physik, 1968. 216(4): p. 398-410. [28] K.L. Lee and P.K. Wei, Enhancing surface plasmon detection using ultrasmall nanoslits and a multispectral integration method. Small, 2010. 6(17): p. 1900-1907. [29] C.L. Wong and M. Olivo, Surface plasmon resonance imaging sensors: a review. Plasmonics, 2014. 9(4): p. 809-824. [30] B. Liedberg, C. Nylander, and I. Lunström, Surface plasmon resonance for gas detection and biosensing. Sensors and actuators, 1983. 4: p. 299-304. [31] J. Homola, Present and future of surface plasmon resonance biosensors. Analytical and bioanalytical chemistry, 2003. 377(3): p. 528-539. [32] T.W. Ebbesen, H.J. Lezec, H. Ghaemi, T. Thio, and P. Wolff, Extraordinary optical transmission through sub-wavelength hole arrays. Nature, 1998. 391(6668): p. 667-669. [33] W.L. Barnes, A. Dereux, and T.W. Ebbesen, Surface plasmon subwavelength optics. Nature, 2003. 424(6950): p. 824-830. [34] A.G. Brolo, R. Gordon, B. Leathem, and K.L. Kavanagh, Surface plasmon sensor based on the enhanced light transmission through arrays of nanoholes in gold films. Langmuir, 2004. 20(12): p. 4813-4815. [35] H. Becker and U. Heim, Hot embossing as a method for the fabrication of polymer high aspect ratio structures. Sensors and Actuators A: Physical, 2000. 83(1): p. 130-135. [36] 張哲豪, 流體微熱壓製程開發研究. 臺灣大學機械工程學研究所學位論文, 2004: p. 1-113. [37] S.Y. Chou, P.R. Krauss, and P.J. Renstrom, Nanoimprint lithography. Journal of Vacuum Science & Technology B, 1996. 14(6): p. 4129-4133. [38] H. Tan, A. Gilbertson, and S.Y. Chou, Roller nanoimprint lithography. Journal of Vacuum Science & Technology B, 1998. 16(6): p. 3926-3928. [39] Epstein, M.A, Achong, B.G, and Barr, Y.M, Virus particles in cultured lymphoblasts from Burkitt's lymphoma. The Lancet, 1964. 1: p. 702–703. [40] Chi Young Ok, T.G. Papathomas, L.J. Medeiros, and K.H. Young, EBV-positive diffuse large B-cell lymphoma of the elderly. Blood, 2013. 122: p. 328-340. [41] Henle W, Henle G, Epidemiologic aspects of Epstein–Barr virus (EBV)-associated diseases. Annals of the New York Academy of Sciences, 1980. 354: p. 326–331. [42] N. Mishchuk and P. Takhistov, Electroosmosis of the second kind. Colloids and Surfaces A: Physicochemical and Engineering Aspects, 1995. 95(2): p. 119-131. [43] E. Gongadze, U. Rienen, and A. Iglič, Generalized stern models of the electric double layer considering the spatial variation of permittvity and finite size of ions in saturation regime. Cellular and Molecular Biology Letters, 2011. 16(4): p. 576-594. [44] A. Plecis, R.B. Schoch, and P. Renaud, Ionic transport phenomena in nanofluidics: experimental and theoretical study of the exclusion-enrichment effect on a chip. Nano letters, 2005. 5(6): p. 1147-1155. [45] F.C. Leinweber and U. Tallarek, Nonequilibrium electrokinetic effects in beds of ion-permselective particles. Langmuir, 2004. 20(26): p. 11637-11648. [46] S.S. Dukhin, Electrokinetic phenomena of the second kind and their applications. Advances in colloid and interface science, 1991. 35: p. 173-196. [47] F.-C. Chien, C.-Y. Lin, J.-N. Yih, K.-L. Lee, C.-W. Chang, P.-K. Wei, C.-C. Sun, and S.-J. Chen, Coupled waveguide–surface plasmon resonance biosensor with subwavelength grating. Biosensors and Bioelectronics, 2007. 22(11): p. 2737-2742. [48] J. Homola and M. Piliarik, Surface plasmon resonance (SPR) sensors, in Surface plasmon resonance based sensors. 2006, Springer. p. 45-67. [49] G. Tristram, D. Stites, A. Terr, and J. Imboden, Medical immunology. Appleton &, 2001: p. 148-167. [50] V.M. Mirsky, M. Riepl, and O.S. Wolfbeis, Capacitive monitoring of protein immobilization and antigen–antibody reactions on monomolecular alkylthiol films on gold electrodes. Biosensors and Bioelectronics, 1997. 12(9–10): p. 977-989. [51] K.-L. Lee, J.-B. Huang, J.-W. Chang, S.-H. Wu, and P.-K. Wei, Ultrasensitive biosensors using enhanced Fano resonances in capped gold nanoslit arrays. Scientific reports, 2015. 5. [52] M.-Y. Pan, K.-L. Lee, W.-S. Tsai, L. Wang, and P.-K. Wei, Determination of the effective index and thickness of biomolecular layer by Fano resonances in gold nanogrid array. Optics express, 2015. 23(17): p. 21596-21606. [53] K.-L. Lee, S.-H. Wu, C.-W. Lee, and P.-K. Wei, Sensitive biosensors using Fano resonance in single gold nanoslit with periodic grooves. Optics express, 2011. 19(24): p. 24530-24539. [54] 李瑋航, 開發奈米預濃縮與週期性奈米金屬閘表面電漿共振感測器結合於免標定光學免疫分析平台. 臺灣大學生醫電子與資訊學研究所學位論文, 2016: p. 1-81. [55] ZEON. ZEP520A Data Sheet. 2010; Available from: https://www.zeonchemicals.com/pdfs/ZEP520A.pdf. [56] MicroChem. S1800 Series Data Sheet. Available from: http://microchem.com/products/images/uploads/S1800_Photoresist.pdf. [57] 李國翰, 利用奈米壓印技術整合奈米預濃縮機制與週期性奈米金屬狹縫表面電漿共振感測器於免標定免疫分析平台. 臺灣大學應用力學研究所學位論文, 2016: p. 1-73. [58] MicroChem. SU-8 Data Sheet. Available from: http://microchem.com/pdf/SU-82000DataSheet2025thru2075Ver4.pdf. [59] V. Sunkara, D.-K. Park, H. Hwang, R. Chantiwas, S.A. Soper, and Y.-K. Cho, Simple room temperature bonding of thermoplastics and poly (dimethylsiloxane). Lab on a Chip, 2011. 11(5): p. 962-965. [60] K.S. Lee and R.J. Ram, Plastic–PDMS bonding for high pressure hydrolytically stable active microfluidics. Lab on a Chip, 2009. 9(11): p. 1618-1624. | |
dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/77948 | - |
dc.description.abstract | 本研究目的為開發新型免疫分析檢測裝置,藉由奈米壓印將奈米流體預濃縮(Nanofluidic Preconcentration)微流道與週期性奈米金屬狹縫表面電漿共振(Surface Plasmon Resonance, SPR)感測器整合於同一片塑膠基板上。首先將待測活性分子進行預濃縮,再藉由調整電位差來控制濃縮區塊,使其準確移動於表面電漿共振晶片上方,最後量測其光譜訊號紅移(Redshift)以進行後續免疫分析。
矽晶圓母模製程,首先係利用電子束微影(E-beam Lithography)和反應離子蝕刻(Reactive Ion Etching, RIE)在矽晶圓基材上定義週期性奈米狹縫結構。接著使用正光阻作為作為乾蝕刻阻擋層,在奈米結構上方定義出微米流道遮罩,並使用感應耦合電漿離子蝕刻(Inductively Coupled Plasma Reactive Ion Etching, ICP-RIE)技術完成微米流道與奈米狹縫於同一片矽晶圓母模上。之後以環烯烴類聚合物(Cyclic Olefin Polymer, COP)作為晶片材料,與矽晶圓母模進行奈米熱壓印將結構轉印至此高分子聚合物上,經由遮罩濺鍍完成局部鍍金,再使用奈米多孔性材料Nafion®作為奈米流道鋪設於兩表面電漿共振晶片間,確立奈米預濃縮結構。最後使用聚二甲基矽氧烷(Polydimethylsiloxane, PDMS)作為覆蓋材料,經由化學表面修飾及氧電漿表面改質接合COP與PDMS,即完成本免標定免疫分析晶片。 本研究檢測之樣本為人類皰疹病毒第四型(Epstein-Barr virus, EBV)抗體,通入30 ng/mL的重組蛋白抗原(Latent Membrane Protein 1, LMP1)於濃縮流道內,藉由操控電壓使濃縮區塊限定於奈米狹縫晶片上,接著比對實驗組與對照組的穿透特性光譜,經由紅移量的差異和LMP1抗原濃度參考曲線,我們發現濃縮將30 ng/mL抗原濃度提升至約300 µg/mL,倍率達10,000倍,並藉此再將3 pg/mL濃度抗原進行濃縮,驗證得出其最小檢測濃度為3 pg/mL。 總結言之,此以奈米壓印技術成功達到量產與低成本的快速製程,且奈米流體預濃縮降低了檢測下限,加上表面電漿共振具有高靈敏度、即時性、和免標定的優勢,我們藉由簡便的量測系統完成了一個免標定且微量的超低濃度檢測平台。 | zh_TW |
dc.description.abstract | In this study, an immunoassay platform that integrating nanofluidic preconcentrator with periodic metallic surface plasmon resonance sensor by nanoimprinting has been developed. The concentrated protein was trap in the sensing area of SPR in a microfluidic channel by electrical potential difference. Then, measuring the spectral signal red-shift of antibody-antigen interaction on periodic metallic slits for subsequent immunoassay.
The periodic nano-grating structure were clarified and fabricated on a silicon wafer by E-beam lithography and reactive ion etching, then the microchannel mold were fabricated by inductively coupled plasma reactive ion etching. These structure was transferred onto a cyclic olefin polymer by nanoimprint lithography. The gold was deposited on the grating structure of COP by sputter. A porous material, Nafion, was used as the ion-selective channel, was aligned to the grating structure on COP. Overlay were made by PDMS. After the chemically modified surface treatment, the COP can be bond with PDMS by oxygen plasma. And the label-free immunoassay biochip has been done. Thereafter, Epstein-Barr Virus Antibody (EBV antibody) and Latent Membrane Protein 1 (LMP1) were used as the testing samples for future works. The result is that the concentration fold of LMP1 antigens can be raised up to approximately 10,000 folds as the 30 ng/mL of antigens was condensed to 300 µg/mL. And we successfully verify that the minimal detectable limit is about 3 pg/mL by concentrating 3 pg/mL of antigens to 30 ng/mL. In summary, by integrating preconcentrator and SPR system, we can have a label-free, preconcentration detectable platform by using simple measurement system. | en |
dc.description.provenance | Made available in DSpace on 2021-07-11T14:38:04Z (GMT). No. of bitstreams: 1 ntu-106-R04543013-1.pdf: 5667848 bytes, checksum: 3a68a09d3cbbc890c9304a12527826e4 (MD5) Previous issue date: 2017 | en |
dc.description.tableofcontents | 誌謝 I
摘要 II ABSTRACT III 目錄 IV 圖目錄 VII 表目錄 X 符號目錄 XI 第1章 導論 1 1.1 研究目的與動機 1 1.2 生物晶片簡介 1 1.2.1 微型全分析系統技術(Micro Total Analysis System, µTAS) 2 1.2.2 免疫分析原理(Immunoassay) 3 1.2.3 免疫分析方法之比較 4 1.3 預濃縮技術之發展背景 4 1.3.1 電驅動微奈米流體預濃縮晶片之發展 5 1.3.2 微奈米流體預濃縮晶片用於免疫分析 7 1.4 表面電漿共振之發展背景 8 1.4.1 表面電漿共振用於免疫分析 9 1.5 奈米壓印技術 10 1.6 人類皰疹病毒第四型簡介 13 第2章 微奈米預濃縮晶片之原理與系統架設 14 2.1 電驅動微奈米預濃縮機制之原理 14 2.1.1 電驅動微奈米流體預濃縮法 14 2.1.2 電雙層效應 15 2.1.3 生成離子空乏區與預濃縮現象 18 2.1.4 預濃縮機制 21 2.2 電驅動微奈米預濃縮之系統架設 22 2.2.1 倒立式螢光顯微鏡觀測系統 22 2.2.2 電壓控制與預濃縮檢測 23 第3章 表面電漿共振免疫晶片之原理與系統架設 25 3.1 表面電漿共振簡介 25 3.1.1 金屬表面電漿子共振 25 3.1.2 表面電漿共振激發 28 3.1.3 奈米金屬狹縫表面電漿耦合共振模態 29 3.2 週期性奈米金屬表面電漿共振用於免疫分析之原理 31 3.2.1 週期性奈米金屬表面折射率與蛋白質之關係 31 3.2.2 免疫分析之金表面處理方法 32 3.3 週期性奈米金屬表面電漿共振於免疫分析之系統架設 35 第4章 結合微奈米預濃縮與奈米金屬狹縫表面電漿共振之製程結果 36 4.1 週期性奈米結構之設計 36 4.2 微米預濃縮結構之設計 37 4.3 可預濃縮的免標定免疫分析晶片之製程結果 38 4.3.1 週期性奈米金屬結構製程 38 4.3.2 微米結構深乾蝕刻製程 41 4.3.3 同步壓印奈米狹縫與微米結構製程 43 4.3.4 週期性奈米結構之局部對位鍍金製程 45 4.3.5 Nafion®奈米流道製程 47 4.3.6 PDMS覆蓋膜製程 49 4.3.7 COP與PDMS接合製程 50 第5章 可預濃縮的免標定免疫分析晶片之量測結果與討論 52 5.1 預濃縮機制之量測結果 52 5.1.1 鈣黃綠素用於預濃縮機制之實驗方法 52 5.1.2 鈣黃綠素用於微流道中之濃縮現象 52 5.2 表面電漿共振感測器之靈敏度量測結果 53 5.3 可預濃縮的免標定免疫分析晶片之量測結果 55 5.3.1 Anti-EBV與LMP1用於免標定免疫分析晶片之實驗方法 55 5.3.2 Anti-EBV與LMP1用於免標定免疫分析晶片之量測結果 57 第6章 結論與未來展望 62 6.1 結論 62 6.2 未來展望 63 參考文獻 64 | |
dc.language.iso | zh-TW | |
dc.title | 同步壓印微米預濃縮流道與奈米狹縫表面電漿共振感測器用於免標定免疫分析 | zh_TW |
dc.title | Synchronously Imprinting Preconcentrator and Nanoslit Surface Plasmon Resonance Sensor for Immunoassay | en |
dc.type | Thesis | |
dc.date.schoolyear | 105-2 | |
dc.description.degree | 碩士 | |
dc.contributor.coadvisor | 魏培坤(Pei-Kuen Wei) | |
dc.contributor.oralexamcommittee | 盧彥文(Yen-Wen Lu),范育睿(Yu-Jui Fan) | |
dc.subject.keyword | 深反應離子蝕刻,奈米壓印技術,電驅動奈米流體預濃縮,週期性奈米金屬表面電漿共振,生物感測器,免標定免疫分析,實驗室晶片, | zh_TW |
dc.subject.keyword | Deep Reactive Ion Etching,Nanoimprint Lithography,Electrokinetic-based Nanofluidic Preconcentration,Nanoslit-based Surface Plasmon Resonance,Lab on a chip, | en |
dc.relation.page | 68 | |
dc.identifier.doi | 10.6342/NTU201702123 | |
dc.rights.note | 有償授權 | |
dc.date.accepted | 2017-07-31 | |
dc.contributor.author-college | 工學院 | zh_TW |
dc.contributor.author-dept | 應用力學研究所 | zh_TW |
顯示於系所單位: | 應用力學研究所 |
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