跳到主要內容

臺灣博碩士論文加值系統

(44.200.194.255) 您好!臺灣時間:2024/07/23 03:32
字體大小: 字級放大   字級縮小   預設字形  
回查詢結果 :::

詳目顯示

我願授權國圖
: 
twitterline
研究生:林瑋瑩
研究生(外文):Wei-Yin Lin
論文名稱:恆溫無酵素放大技術於SARS-CoV-2的應用
論文名稱(外文):Isothermal Enzyme-free Amplification Targeting on SARS-CoV-2
指導教授:林啟萬林啟萬引用關係
指導教授(外文):Chii-Wann Lin
口試委員:彭盛裕施博仁
口試委員(外文):Sheng-Yu PengPo-Jen Shih
口試日期:2021-07-24
學位類別:碩士
校院名稱:國立臺灣大學
系所名稱:醫學工程學研究所
學門:工程學門
學類:綜合工程學類
論文種類:學術論文
論文出版年:2021
畢業學年度:109
語文別:中文
論文頁數:63
中文關鍵詞:新型冠狀病毒恆溫無酵素放大技術表面電漿子共振
外文關鍵詞:Severe Acute Respiratory Syndrome Coronavirus 2Isothermal Enzyme-free AmplificationSurface Plasmon Resonance
DOI:10.6342/NTU202102641
相關次數:
  • 被引用被引用:0
  • 點閱點閱:25
  • 評分評分:
  • 下載下載:0
  • 收藏至我的研究室書目清單書目收藏:0
誌謝 I
中文摘要 II
Abstract III
圖目錄 VIII
表目錄 X
第 一 章 緒論 1
1.1研究背景與重要性 1
1.2研究動機與目的 5
1.3章節架構 6
第 二 章 基本原理與文獻回顧 7
2.1新型冠狀病毒 7
2.1.1新型冠狀病毒介紹 7
2.1.2新型冠狀病毒的數據共享 10
2.1.3現行的標準核酸篩檢方式 11
2.2恆溫無酵素的放大技術 14
2.2.1雜交連鎖反應 14
2.2.2催化髮夾組裝 15
2.2.3恆溫無酵素技術的序列設計 18
2.2.4檢測上的應用 19
2.3表面電漿子共振感測技術 20
2.3.1表面電漿子共振原理 21
2.3.2表面電漿子共振生物感測器 22
2.3.3表面化學修飾方式 23
2.4雜交反應的障礙與排除 25
第 三 章 研究材料與方法 28
3.1反應序列設計及驗證方法 28
3.1.1設計SARS-CoV-2病毒檢測序列 28
3.1.2電泳驗證 28
3.1.3探針序列設計 29
3.2表面電漿子共振系統 29
3.2.1感測晶片的構造 30
3.2.2強度式表面電漿子共振感測器系統架構 30
3.2.3操作介面 32
3.2.3訊號量測與分析 34
3.2.4感測晶片再生方式 35
第 四 章 結果與討論 36
4.1序列資訊 36
4.2電泳印證 38
4.2.1 HCR 38
4.2.2 CHA 40
4.3 優化恆溫無酵素放大反應之SPR量化分析 42
4.3.1探針修飾量與放大反應的量化分析 42
4.3.2 PEG濃度對於訊號的影響 45
4.3.3 stem長度對於訊號的影響 47
4.3.4鹽度對於SPR訊號的影響 48
4.4 探針與目標序列之特異性測試 50
4.5 臨床測試的可行性 50
第 五 章 結論與未來展望 52
第 六 章 參考文獻 54
[1]U.S. Centers For Disease Control and Prevention. (2020). How COVID-19 Spreads. U.S. Department of Health & Human Services. Retrived from https://www.cdc.gov/coronavirus/2019-ncov/prevent-getting-sick/how-covid-spreads.html?CDC_AA_refVal=https%3A%2F%2Fwww.cdc.gov%2Fcoronavirus%2F2019-ncov%2Fprepare%2Ftransmission.html
[2]Jayaweera, M., Perera, H., Gunawardana, B., & Manatunge, J. (2020). Transmission of COVID-19 virus by droplets and aerosols: A critical review on the unresolved dichotomy. Environmental research, 109819. doi: 10.1016/j.envres.2020.109819
[3]Wang, J., & Du, G. (2020). COVID-19 may transmit through aerosol. Irish Journal of Medical Science (1971-), 1-2. doi: 10.1007/s11845-020-02218-2
[4]Wurtz, N., Penant, G., Jardot, P., Duclos, N., & La Scola, B. (2021). Culture of SARS-CoV-2 in a panel of laboratory cell lines, permissivity, and differences in growth profile. European Journal of Clinical Microbiology & Infectious Diseases, 40(3), 477-484. doi: Culture of SARS-CoV-2 in a panel of laboratory cell lines, permissivity, and differences in growth profile
[5]McAuley, J., Fraser, C., Paraskeva, E., Trajcevska, E., Sait, M., Wang, N., . . . Strugnell, R. (2021). Optimal preparation of SARS-CoV-2 viral transport medium for culture. Virology Journal, 18(1), 1-6. doi: 10.1186/s12985-021-01525-z
[6]Calderaro, A., Arcangeletti, M. C., De Conto, F., Buttrini, M., Montagna, P., Montecchini, S., . . . Chezzi, C. (2020). SARS-CoV-2 infection diagnosed only by cell culture isolation before the local outbreak in an Italian seven-week-old suckling baby. International Journal of Infectious Diseases, 96, 387-389. doi: 10.1016/j.ijid.2020.05.035
[7]Perera, R. A., Tso, E., Tsang, O. T., Tsang, D. N., Fung, K., Leung, Y. W., . . . Poon, L. L. (2020). SARS-CoV-2 virus culture from the upper respiratory tract: Correlation with viral load, subgenomic viral RNA and duration of illness. medRxiv. doi: 10.1101/2020.07.08.20148783
[8]Park, W. B., Kwon, N.-J., Choi, S.-J., Kang, C. K., Choe, P. G., Kim, J. Y., . . . Kim, N. J. (2020). Virus isolation from the first patient with SARS-CoV-2 in Korea. Journal of Korean Medical Science, 35(7). doi: 10.3346/jkms.2020.35.e84
[9]Li, Z., Yi, Y., Luo, X., Xiong, N., Liu, Y., Li, S., . . . Chen, W. (2020). Development and clinical application of a rapid IgM‐IgG combined antibody test for SARS‐CoV‐2 infection diagnosis. Journal of medical virology, 92(9), 1518-1524. doi: 10.1002/jmv.25727
[10]Sethuraman, N., Jeremiah, S. S., & Ryo, A. (2020). Interpreting diagnostic tests for SARS-CoV-2. Jama, 323(22), 2249-2251. doi: 10.1001/jama.2020.8259
[11]Lassaunière, R., Frische, A., Harboe, Z. B., Nielsen, A. C., Fomsgaard, A., Krogfelt, K. A., & Jørgensen, C. S. (2020). Evaluation of nine commercial SARS-CoV-2 immunoassays. medRxiv. doi: 10.1101/2020.04.09.20056325
[12]Mak, G. C., Lau, S. S., Wong, K. K., Chow, N. L., Lau, C., Lam, E. T., . . . Tsang, D. N. (2020). Analytical sensitivity and clinical sensitivity of the three rapid antigen detection kits for detection of SARS-CoV-2 virus. Journal of Clinical Virology, 133, 104684. doi: 10.1016/j.jcv.2020.104684
[13]Krueger, L. J., Gaeddert, M., Koeppel, L., Bruemmer, L., Gottschalk, C., Miranda, I. B., . . . Nikolai, O. (2020). Evaluation of the accuracy, ease of use and limit of detection of novel, rapid, antigen-detecting point-of-care diagnostics for SARS-CoV-2. medRxiv. doi: 10.1101/2020.10.01.20203836
[14]Oh, S.-M., Jeong, H., Chang, E., Choe, P. G., Kang, C. K., Park, W. B., . . . Kim, N. J. (2021). Clinical Application of the Standard Q COVID-19 Ag Test for the Detection of SARS-CoV-2 Infection. Journal of Korean Medical Science, 36(14). doi: 10.3346/jkms.2021.36.e101
[15]Mak, G. C., Cheng, P. K., Lau, S. S., Wong, K. K., Lau, C., Lam, E. T., . . . Tsang, D. N. (2020). Evaluation of rapid antigen test for detection of SARS-CoV-2 virus. Journal of Clinical Virology, 129, 104500. doi: 10.1016/j.jcv.2020.104500
[16]Corman, V. M., Landt, O., Kaiser, M., Molenkamp, R., Meijer, A., Chu, D. K., . . . Schmidt, M. L. (2020). Detection of 2019 novel coronavirus (2019-nCoV) by real-time RT-PCR. Eurosurveillance, 25(3), 2000045. doi: 10.2807/1560-7917.ES.2020.25.3.2000045
[17]U.S. Centers For Disease Control and Prevention. (2020). Research Use Only 2019-Novel Coronavirus (2019-nCoV) Real-time RT-PCR Primers and Probes. U.S. Department of Health & Human Services. Retrived from https://www.cdc.gov/coronavirus/2019-ncov/lab/rt-pcr-panel-primer-probes.html
[18]Esbin, M. N., Whitney, O. N., Chong, S., Maurer, A., Darzacq, X., & Tjian, R. (2020). Overcoming the bottleneck to widespread testing: a rapid review of nucleic acid testing approaches for COVID-19 detection. Rna, 26(7), 771-783. doi: 10.1261/rna.076232.120
[19]Racine, R., & Winslow, G. M. (2009). IgM in microbial infections: taken for granted? Immunology letters, 125(2), 79-85. doi: 10.1016/j.imlet.2009.06.003
[20]Rosen, M. (2020). Fighting the COVID-19 Pandemic Through Testing. Howard Hughes Medical Institute. Retrived from https://www.hhmi.org/news/fighting-the-covid-19-pandemic-through-testing
[21]Dirks, R. M., & Pierce, N. A. (2004). Triggered amplification by hybridization chain reaction. Proceedings of the National Academy of Sciences, 101(43), 15275-15278. doi: 10.1073/pnas.0407024101
[22]Yin, P., Choi, H. M., Calvert, C. R., & Pierce, N. A. (2008). Programming biomolecular self-assembly pathways. nature, 451(7176), 318-322. doi: 10.1038/nature06451
[23]Woo, P. C., Lau, S. K., Huang, Y., & Yuen, K.-Y. (2009). Coronavirus diversity, phylogeny and interspecies jumping. Experimental Biology and Medicine, 234(10), 1117-1127. doi: 10.3181/0903-MR-94
[24]Zhou, P., Yang, X.-L., Wang, X.-G., Hu, B., Zhang, L., Zhang, W., . . . Huang, C.-L. (2020). A pneumonia outbreak associated with a new coronavirus of probable bat origin. nature, 579(7798), 270-273. doi: 10.1038/s41586-020-2012-7
[25]Hu, B., Guo, H., Zhou, P., & Shi, Z.-L. (2020). Characteristics of SARS-CoV-2 and COVID-19. Nature Reviews Microbiology, 1-14. doi: 10.1038/s41579-020-00459-7
[26]Naqvi, A. A. T., Fatima, K., Mohammad, T., Fatima, U., Singh, I. K., Singh, A., . . . Hassan, M. I. (2020). Insights into SARS-CoV-2 genome, structure, evolution, pathogenesis and therapies: Structural genomics approach. Biochimica et Biophysica Acta (BBA)-Molecular Basis of Disease, 165878. doi: 10.1016/j.bbadis.2020.165878
[27]Hannah A Bullock, A. T. (2020). Details on COVID-19. Public Health Image Library, U.S. Centers For Disease Control and Prevention. Retrived from https://phil.cdc.gov/Details.aspx?pid=23354
[28]Elbe, S., & Buckland‐Merrett, G. (2017). Data, disease and diplomacy: GISAID's innovative contribution to global health. Global Challenges, 1(1), 33-46. doi: 10.1002/gch2.1018
[29]Shu, Y., & McCauley, J. (2017). GISAID: Global initiative on sharing all influenza data–from vision to reality. Eurosurveillance, 22(13), 30494. doi: 10.2807/1560-7917.ES.2017.22.13.30494
[30]Sayers, E. W., Cavanaugh, M., Clark, K., Pruitt, K. D., Schoch, C. L., Sherry, S. T., & Karsch-Mizrachi, I. (2021). GenBank. Nucleic Acids Research, 49(D1), D92-D96. doi: 10.1093/nar/gkaa1023
[31]Sayers, E. W., Beck, J., Bolton, E. E., Bourexis, D., Brister, J. R., Canese, K., . . . Klimke, W. (2021). Database resources of the national center for biotechnology information. Nucleic Acids Research, 49(D1), D10. doi: 10.1093/nar/gkv1290
[32]Korf, I., Yandell, M., & Bedell, J. (2003). Blast: " O'Reilly Media, Inc.".
[33]Madden, T. (2013). The BLAST sequence analysis tool The NCBI Handbook [Internet]. 2nd edition: National Center for Biotechnology Information (US).
[34]Boratyn, G. M., Camacho, C., Cooper, P. S., Coulouris, G., Fong, A., Ma, N., . . . Merezhuk, Y. (2013). BLAST: a more efficient report with usability improvements. Nucleic Acids Research, 41(W1), W29-W33. doi: 10.1093/nar/gkt282
[35]Saiki, R. K., Scharf, S., Faloona, F., Mullis, K. B., Horn, G. T., Erlich, H. A., & Arnheim, N. (1985). Enzymatic amplification of beta-globin genomic sequences and restriction site analysis for diagnosis of sickle cell anemia. Science, 230(4732), 1350-1354. doi: 10.1126/science.2999980
[36]Saiki, R. K., Gelfand, D. H., Stoffel, S., Scharf, S. J., Higuchi, R., Horn, G. T., . . . Erlich, H. A. (1988). Primer-directed enzymatic amplification of DNA with a thermostable DNA polymerase. Science, 239(4839), 487-491. doi: 10.1126/science.239.4839.487
[37]Udugama, B., Kadhiresan, P., Kozlowski, H. N., Malekjahani, A., Osborne, M., Li, V. Y., . . . Chan, W. C. (2020). Diagnosing COVID-19: the disease and tools for detection. ACS nano, 14(4), 3822-3835. doi: 10.1021/acsnano.0c02624
[38]Lu, R., Wu, X., Wan, Z., Li, Y., Zuo, L., Qin, J., . . . Zhang, C. (2020). Development of a novel reverse transcription loop-mediated isothermal amplification method for rapid detection of SARS-CoV-2. Virologica Sinica, 35(3), 344-347. doi: 10.3390/ijms21082826
[39]Park, G.-S., Ku, K., Baek, S.-H., Kim, S.-J., Kim, S. I., Kim, B.-T., & Maeng, J.-S. (2020). Development of reverse transcription loop-mediated isothermal amplification assays targeting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The Journal of Molecular Diagnostics, 22(6), 729-735. doi: 10.1016/j.jmoldx.2020.03.006
[40]Yan, C., Cui, J., Huang, L., Du, B., Chen, L., Xue, G., . . . Sun, Y. (2020). Rapid and visual detection of 2019 novel coronavirus (SARS-CoV-2) by a reverse transcription loop-mediated isothermal amplification assay. Clinical Microbiology and Infection, 26(6), 773-779. doi: 10.1016/j.cmi.2020.04.001
[41]Li, B., Ellington, A. D., & Chen, X. (2011). Rational, modular adaptation of enzyme-free DNA circuits to multiple detection methods. Nucleic Acids Research, 39(16), e110-e110. doi: 10.1093/nar/gkr504
[42]Ang, Y. S., & Yung, L.-Y. L. (2016). Rational design of hybridization chain reaction monomers for robust signal amplification. Chemical Communications, 52(22), 4219-4222. doi: 10.1039/c5cc08907g
[43]Li, S., Li, P., Ge, M., Wang, H., Cheng, Y., Li, G., . . . Lin, D. (2020). Elucidation of leak-resistance DNA hybridization chain reaction with universality and extensibility. Nucleic Acids Research, 48(5), 2220-2231. doi: 10.1093/nar/gkaa016
[44]Wu, T.-H., Chang, C.-C., Yang, C.-H., Lin, W.-Y., Ee, T. J., & Lin, C.-W. (2020). Hybridization Chain Reactions Targeting the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). International journal of molecular sciences, 21(9), 3216. doi: 10.3390/ijms21093216
[45]Huang, J., Wu, Y., Chen, Y., Zhu, Z., Yang, X., Yang, C. J., . . . Tan, W. (2011). Pyrene‐excimer probes based on the hybridization chain reaction for the detection of nucleic acids in complex biological fluids. Angewandte Chemie International Edition, 50(2), 401-404. doi: 10.1002/anie.201005375
[46]Huang, J., Wang, H., Yang, X., Quan, K., Yang, Y., Ying, L., . . . Wang, K. (2016). Fluorescence resonance energy transfer-based hybridization chain reaction for in situ visualization of tumor-related mRNA. Chemical science, 7(6), 3829-3835. doi: 10.1039/c6sc00377j
[47]Li, X., Wang, Y., Wang, L., & Wei, Q. (2014). A surface plasmon resonance assay coupled with a hybridization chain reaction for amplified detection of DNA and small molecules. Chemical Communications, 50(39), 5049-5052. doi: 10.1039/c4cc01374c
[48]Zheng, J., Hu, Y., Bai, J., Ma, C., Li, J., Li, Y., . . . Yang, R. (2014). Universal surface-enhanced Raman scattering amplification detector for ultrasensitive detection of multiple target analytes. Analytical chemistry, 86(4), 2205-2212. doi: 10.1021/ac404004m
[49]Liedberg, B., Nylander, C., & Lunström, I. (1983). Surface plasmon resonance for gas detection and biosensing. Sensors and actuators, 4, 299-304. doi: 10.1016/0250-6874(83)85036-7
[50]Wood, R. W. (1902). 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, 4(21), 396-402. doi: 10.1080/14786440209462857
[51]Homola, J. (2006). Electromagnetic theory of surface plasmons Surface plasmon resonance based sensors (pp. 3-44): Springer.
[52]Sellers, H., Ulman, A., Shnidman, Y., & Eilers, J. E. (1993). Structure and binding of alkanethiolates on gold and silver surfaces: implications for self-assembled monolayers. Journal of the American Chemical Society, 115(21), 9389-9401. doi: 10.1021/ja00074a004
[53]Cohen-Atiya, M., & Mandler, D. (2003). Studying thiol adsorption on Au, Ag and Hg surfaces by potentiometric measurements. Journal of Electroanalytical Chemistry, 550, 267-276. doi: 10.1016/S0022-0728(02)01145-2
[54]Ferretti, S., Paynter, S., Russell, D. A., Sapsford, K. E., & Richardson, D. J. (2000). Self-assembled monolayers: a versatile tool for the formulation of bio-surfaces. TrAC Trends in Analytical Chemistry, 19(9), 530-540. doi: 10.1016/S0165-9936(00)00032-7
[55]Herne, T. M., & Tarlov, M. J. (1997). Characterization of DNA probes immobilized on gold surfaces. Journal of the American Chemical Society, 119(38), 8916-8920. doi: 10.1021/ja9719586
[56]Peterson, A. W., Heaton, R. J., & Georgiadis, R. M. (2001). The effect of surface probe density on DNA hybridization. Nucleic Acids Research, 29(24), 5163-5168. doi: 10.1093/nar/29.24.5163
[57]Ravan, H., Kashanian, S., Sanadgol, N., Badoei-Dalfard, A., & Karami, Z. (2014). Strategies for optimizing DNA hybridization on surfaces. Analytical biochemistry, 444, 41-46. doi: 10.1016/j.ab.2013.09.032
[58]Levicky, R., Herne, T. M., Tarlov, M. J., & Satija, S. K. (1998). Using self-assembly to control the structure of DNA monolayers on gold: a neutron reflectivity study. Journal of the American Chemical Society, 120(38), 9787-9792. doi: 10.1021/ja981897r
[59]Lin, P., Ding, L., Lin, C.-W., & Gu, F. (2014). Nonfouling property of zwitterionic cysteine surface. Langmuir, 30(22), 6497-6507. doi: 10.1021/la500243s
[60]Lee, J., Park, I.-S., Kim, H., Woo, J.-S., Choi, B.-S., & Min, D.-H. (2015). BSA as additive: A simple strategy for practical applications of PNA in bioanalysis. Biosensors and Bioelectronics, 69, 167-173. doi: 10.1016/j.bios.2015.02.030
[61]Wang, R., Zhou, X., Zhu, X., Yang, C., Liu, L., & Shi, H. (2017). Isoelectric bovine serum albumin: robust blocking agent for enhanced performance in optical-fiber based DNA sensing. ACS sensors, 2(2), 257-262. doi: 10.1021/acssensors.6b00746
[62]Zhang, X., Huang, P.-J. J., Servos, M. R., & Liu, J. (2012). Effects of polyethylene glycol on DNA adsorption and hybridization on gold nanoparticles and graphene oxide. Langmuir, 28(40), 14330-14337. doi: 10.1021/la302799s
[63]Egli, M. (2002). DNA-cation interactions: quo vadis? Chemistry & biology, 9(3), 277-286. doi: 10.1016/s1074-5521(02)00116-3
[64]Špringer, T., Šípová, H., Vaisocherová, H., Štěpánek, J., & Homola, J. (2010). Shielding effect of monovalent and divalent cations on solid-phase DNA hybridization: surface plasmon resonance biosensor study. Nucleic Acids Research, 38(20), 7343-7351. doi: 10.1093/nar/gkq577
[65]Kim, S. Y., Hong, K., Kim, K., Yu, H. K., Kim, W.-K., & Lee, J.-L. (2008). Effect of N 2, Ar, and O 2 plasma treatments on surface properties of metals: American Institute of Physics.
[66]Raiber, K., Terfort, A., Benndorf, C., Krings, N., & Strehblow, H.-H. (2005). Removal of self-assembled monolayers of alkanethiolates on gold by plasma cleaning. Surface Science, 595(1-3), 56-63. doi: 10.1016/j.susc.2005.07.038
[67]Xue, Y., Li, X., Li, H., & Zhang, W. (2014). Quantifying thiol–gold interactions towards the efficient strength control. Nature communications, 5(1), 1-9. doi: 10.1038/ncomms5348
電子全文 電子全文(網際網路公開日期:20260825)
連結至畢業學校之論文網頁點我開啟連結
註: 此連結為研究生畢業學校所提供,不一定有電子全文可供下載,若連結有誤,請點選上方之〝勘誤回報〞功能,我們會盡快修正,謝謝!
QRCODE
 
 
 
 
 
                                                                                                                                                                                                                                                                                                                                                                                                               
第一頁 上一頁 下一頁 最後一頁 top