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完整後設資料紀錄
DC 欄位 | 值 | 語言 |
---|---|---|
dc.contributor.advisor | 林?輝 | |
dc.contributor.author | Jung-Chih Chen | en |
dc.contributor.author | 陳榮治 | zh_TW |
dc.date.accessioned | 2021-06-13T04:13:17Z | - |
dc.date.available | 2013-08-03 | |
dc.date.copyright | 2011-08-03 | |
dc.date.issued | 2011 | |
dc.date.submitted | 2011-07-28 | |
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dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/32674 | - |
dc.description.abstract | 石英微天平(Quartz qurstal microbalance;QCM)之理論與技術皆已十分成熟,藉以開發成一免疫感測器(Immunosensor)。石英晶體微天平法常見於極微量生化物質感測技術上,尤其在微生物檢測部分甚是;然而,QCM法用途雖不少,但卻少有臨床檢體實例。
本團隊具備微量生化物質分析經驗與癌症臨床檢體感測技術,在結合石英晶體微天平法後,更是集效率、靈敏、省時、經濟於一身。 本研究試圖在石英晶體表面修飾上生物標記物(Biomarkers),也就是固定生物標記物之抗體在石英晶體表面,利用抗體-抗原彼此間會產生專一性吸附(Specific binding)之原理,藉此能夠進行包含癌症腫瘤標記等生物標記物之感測功能。 在第一部份實驗中,選用非小細胞肺癌(西方國家最常見致死的癌症,它包含了鱗狀細胞癌、腺癌、大細胞癌以及支氣管肺泡肺癌等)腫瘤因子的標記物:EGFr Ag-Ab當作研究對象;並利用特殊界面改質材料--Thiosalicylic acid (TSA)來修飾石英晶體表面,且導入Protein G來避免非專一性吸附。 經實驗證實,有使用Protein G進行抗體Site specific orientation步驟的結果,比一般化學吸附(Chemical cross-linking)固定抗體之方法效果來得好。另外,由實驗結果發現,經特定部位(Site-specific)固定抗體後之電極可經由0.1 M的氫氧化鈉進行再生,且重複使用次數可達6次。 以該技術將anti-EGFr antibody接枝在修飾後石英晶體表面,用於癌症早期診斷的偵測範圍由10 ng/ml∼10 μg/mL、實際檢測極限可低於1 ng/ml,這檢測極限足以與現有ELISA檢測技術分庭抗禮,甚至遠遠超越,因此可用於癌症的早期診斷上。 再者,因QCM實驗架構可採Flow-injection reaction設計,除了避免實驗過程造成訊號干擾外,更能達到篩選、富集樣本及即時觀察作用機制...等一貫化優勢。 第二部份我們選用與新生兒腦膜炎(Neonatal meningitis)發生息息相關的一種蛋白--OmpA,由於至今尚無任何快速檢測OmpA的技術,所以本研究創新於此。且由實驗結果發現,以此技術可以測得濃度20 ng/ml∼1.20 μg/ml的OmpA抗原;在OmpA抗原偵測極限探討上,由檢量曲線推估可達2 ng/mL。OmpA雖非癌症標記物,但一樣深具臨床檢測價值與意義。 | zh_TW |
dc.description.abstract | The quartz crystal microbalance (QCM) technology has reached a mature and commonly used in biomedical sensing technology. Due to this system can detect extremely low concentrations, so it can develop into an immune sensor (Immunosensor), the most commonly used for microbial detection. However, the QCM method been widely used, but few clinical examples. As our team has the experience and analysis of trace substances in biological samples of cancer clinical sensing technology, once combined with quartz crystal microbalance method, the set of efficient, sensitive, time-saving and economic ... in one.
This study attempts to modify the quartz crystal surface with biological markers (biomarkers), which is a fixed biological marker of antibody in quartz crystal surface, and using the phenomenon of antibody and antigen specific adsorption, to detect cancer tumor markers. In the first part of the experiment, we proposes the construction of a molecular recognition layer composed of thiol molecules and further activation with EDC-NHS complexes on the surface of a quartz crystal microbalance (QCM). The use of tumor markers factor: EGFr Ag-Ab as the object of study. EGFr is usually highly expression in non-small cell lung cancer patients (the most common cancer in Western countries, which includes squamous cell carcinoma, adenocarcinoma, large cell carcinoma and bronchioloalveolar lung cancer, etc.). We use special materials: thiosalicylic acid (TSA) to modify the surface of quartz crystal, and Protein G to avoid the import of non-specific adsorption. Two different antibody immobilization patterns such as chemical cross-linking and site-specific via protein G were attempted. Accordingly, protein G mediated antibody immobilization controls the quantity and orientation of the antibody molecules on the electrode surface for its high affinity to antigens. Thus, a similar immobilization strategy was utilized for the flow-cell analysis of real-time binding of EGFr. A linear relationship was observed between the frequency shift and different EGFr concentrations (0.01–10 μg/mL), and the detection limition lower than 1 ng/mL. The stepwise assembly of the immunosensor was characterized by quartz crystal microbalance. It was also demonstrated that, the prepared sensor surface was stable enough to withstand the repeated surface regeneration with 0.1 M NaOH. In the second part, the ability to produce indigenous diagnostic tests for neonatal meningitis, that are novel, specific yet cost-effective would now provide a huge impact on public health management in developing countries. Escherichia coli (K1) is the major cause of neonatal meningitis through the interaction with human brain microvascular endothelial cells (HBMEC). Outer membrane protein A (OmpA) is a major protein in the E. coli outer membrane. However, there are not any rapid detections for OmpA. Immobilization of antibodies onto the crystal will be allowed to detect OmpA antigens for nanomedicine applications. This study originally developed the aforementioned QCM method to rapidly detect OmpA antigen. The method utilizes the piezoelectric immunosensor onto whose thiol activated crystal surface the affinity-purified antibodies would be immobilized, and the main objective of this study is to optimize the surface monolayer conditions to provide efficient binding of anti-OmpA IgG antibody and to exploit sensing surface for the detection of OmpA antigen, as an alternative diagnostic test. Though, the frequency shift was lower for OmpA antibody, still it can able to detect lower than 20 ng/ml of OmpA antigen. The detection of OmpA protein by QCM method is comparatively simple and sensitive than other systems. | en |
dc.description.provenance | Made available in DSpace on 2021-06-13T04:13:17Z (GMT). No. of bitstreams: 1 ntu-100-D94548014-1.pdf: 1444313 bytes, checksum: 48a3629b7c666307cc3c556cce73e408 (MD5) Previous issue date: 2011 | en |
dc.description.tableofcontents | 口試委員會審定書…………………………………………………… I
誌謝…………………………………………………………………… II 中文摘要……………………………………………………………… III Abstract……………………………………………………………… V 目錄…………………………………………………………………… VII 圖目錄………………………………………………………………… X 實驗結果圖…………………………………………………………… XI 表目錄………………………………………………………………… XII 第一章 緒論………………………………………………………… 1 1-1 前言……………………………………………………………… 1 1-2 癌症……………………………………………………………… 2 1-2-1 癌症的病理表現……………………………………………… 3 1-2-2 癌症臨床診斷方式…………………………………………… 5 1-2-3 癌症治療方法………………………………………………… 10 1-2-4 癌症血清腫瘤標記…………………………………………… 10 1-3 固相免疫分析法………………………………………………… 13 1-3-1 抗體與抗原…………………………………………………… 15 1-3-2 酵素免疫分析法……………………………………………… 17 1-3-3 免疫聚合酶鏈反應法………………………………………… 19 1-3-4 表面電漿共振法……………………………………………… 21 1-3-5 石英晶體微天平法…………………………………………… 23 1-4 免疫生醫感測器………………………………………………… 24 1-5 研究目的………………………………………………………… 27 第二章 理論基礎…………………………………………………… 29 2-1 石英晶體微天平………………………………………………… 29 2-1-1 壓電與反壓電效應與其影響因素…………………………… 30 2-1-2 石英晶體微天平作用原理…………………………………… 33 2-1-3 壓電感測技術理論依據……………………………………… 34 2-2 石英表面的化學修飾原理……………………………………… 39 2-2-1 石英晶體表面前處理方法…………………………………… 39 2-2-2 官能基與生物分子修飾原理………………………………… 40 2-3 生醫材料固定原理與方法……………………………………… 45 2-4 專一性吸附原理………………………………………………… 46 2-5 生物分子非專一性結合的抑制………………………………… 48 第三章 實驗方法…………………………………………………… 51 3.1 實驗藥品………………………………………………………… 51 3.2 實驗設備………………………………………………………… 54 3.3 石英晶體表面修飾方法………………………………………… 56 3.4 藉由Protein G進行EGFr抗體專一性修飾步驟……………… 58 3.5 實驗裝置與分析技術…………………………………………… 59 3.6 浸泡固定方法…………………………………………………… 60 3.7 流體式(Flow-cell)反應及分析技術…………………………… 60 3.8 系統之專一性探討……………………………………………… 61 3.9 修飾電極的耐用性測試………………………………………… 62 3.10 OmpA抗體固定與其抗原偵測方式…………………………… 62 第四章 實驗結果與討論…………………………………………… 64 4.1 石英晶體表面修飾效果………………………………………… 64 4.2 以化學交聯鍵結法固定EGFr抗體之結果與討論……………… 68 4.3 以特定部位鍵結法固定EGRr抗體之結果與討論……………… 70 4.4 EGFr檢量曲線與其偵測極限探討……………………………… 72 4.5 免疫感測系統之專一性探討…………………………………… 78 4.6 EGFr感測器再生性能測試……………………………………… 80 4.7 流體式分析方式………………………………………………… 82 4.8 於修飾後的石英晶體表面進行OmpA抗體固定成效…………… 85 4.9 建立OmpA流體式分析技術與其結果探討……………………… 88 4.10 OmpA感測器之檢量曲線與其偵測極限探討………………… 90 第五章 結論…………………………………………………………… 91 參考文獻……………………………………………………………… 93 | |
dc.language.iso | zh-TW | |
dc.title | 免疫生醫感測技術應用於癌症早期診斷 | zh_TW |
dc.title | Immuno-biosensors for Carcinoma Early Detection | en |
dc.type | Thesis | |
dc.date.schoolyear | 99-2 | |
dc.description.degree | 博士 | |
dc.contributor.oralexamcommittee | 婁培人,方旭偉,鄭宗記,許淙慶 | |
dc.subject.keyword | 石英晶體微天平,免疫感測器,生物標記物,腫瘤標記,非小細胞肺癌,上皮細胞生長因子受體,新生兒腦膜炎, | zh_TW |
dc.subject.keyword | Quartz crystal microbalance (QCM),Immunosensor,Biomarkers,Tumor markers,non-small cell lung cancer,Epidermal growth factor receptor (EGFr),Flow-injection Assay (FIA),Neonatal meningitis,Outer membrane protein A (OmpA), | en |
dc.relation.page | 101 | |
dc.rights.note | 有償授權 | |
dc.date.accepted | 2011-07-28 | |
dc.contributor.author-college | 工學院 | zh_TW |
dc.contributor.author-dept | 醫學工程學研究所 | zh_TW |
顯示於系所單位: | 醫學工程學研究所 |
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