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完整後設資料紀錄
DC 欄位 | 值 | 語言 |
---|---|---|
dc.contributor.advisor | 蔡孟勳 | |
dc.contributor.author | Yi-Chen Yang | en |
dc.contributor.author | 楊依珍 | zh_TW |
dc.date.accessioned | 2021-06-16T05:17:28Z | - |
dc.date.available | 2019-08-21 | |
dc.date.copyright | 2014-08-21 | |
dc.date.issued | 2014 | |
dc.date.submitted | 2014-08-17 | |
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dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/56164 | - |
dc.description.abstract | 許多傳統的生物製劑效價試驗與臨床診斷分析方法,如用於減毒活菌疫苗效價試驗之培養後計算菌落數的方法,或是用於病毒基因分型的直接定序法,均相當耗時費力,甚至部份方法需要以肉眼判讀,因此結果易因操作人員不同而有差異。鑒於快速或多重檢測目標物之新興生物技術平台逐漸普遍,我們因此嘗試應用新興生物技術來改善傳統生物製劑效價試驗及病毒分型檢測平台。
卡介苗是由減毒的牛結核分枝桿菌(Mycobacterium bovis) 製備而成的活菌疫苗,傳統的效價分析方法是將疫苗復溶培養後以肉眼判讀菌落數,然而牛結核分枝桿菌生長極為緩慢,約需培養4週才能評估其效價,且判讀結果可能有人為差異存在。因此我們建立了快速準確且可信賴之卡介苗效價評估方法,結果顯示利用該方法於4小時內所得之效價結果與傳統方法所得結果相當一致。 此外,目前C型肝炎病毒 (hepatitis C virus, HCV) 有6種基因型,由於病毒基因型最近被納入C型肝炎治療指引中,顯示其在C型肝炎治療中扮演重要角色,然而目前現行的病毒基因分型方法多無法自同一混合基因型檢體中同時檢測出兩種基因型。為能在同一檢體中檢測不同基因型,我們利用懸浮微珠系統來同步檢測,所建立的HCV基因分型方法能在同一檢體中正確檢測出兩種HCV基因型,且能自HCV/HIV 混合檢體中正確檢測出HCV基因型,極具潛力成為快速準確且可信賴之HCV基因分型方法。 這些研究成果顯示我們應用新興生物技術改善傳統生物製劑效價及病毒分型檢測平台之之策略相當成功,未來仍將能持續應用新興生物技術來改善傳統生物製劑效價及病毒分型檢測平台。 | zh_TW |
dc.description.abstract | Most of the traditional assay used for biologics evaluation & clinical diagnosis, such as direct culturing and counting Colony-Forming Unit (CFU) for potency assay of live attenuated vaccine or direct sequencing for virus genotyping are labor-intensive or time-consuming, and depend upon visual read-out of the image, which may cause different results due to different operators. Since the novel techniques for rapid or multiplexing detection are getting more popular, we therefore tried to improve the potency assay for biologics evaluation and the virus genotyping detection assay using the novel biotechniques.
The Bacille Calmette-Guerin (BCG) vaccine is a live attenuated vaccine prepared from a strain of Mycobacterium bovis. The conventional method to determine the potency of the BCG vaccine is to count the number of colony forming units (CFU). However, M. bovis is a slow growing organism and it takes at least four weeks incubation for the potency assay. The results of the potency assay could also vary due to manual counting. Therefore, we developed a rapid and reliable method to determine the potency of M. bovis BCG. The total handing time of the assay is only 4 hours and the results showed a very good agreement with the results from conventional CFU method. In addition, there are more than six different genotypes of hepatitis C virus (HCV) around the world and they play an important role in the treatment of Hepatitis C patients. However, most of the current genotyping methods are unable to detect mixed genotypes from two or more HCV infections. In order to detect different HCV genotypes in a sample, we applied suspension bead array technology to identify HCV genotypes simultaneously. The assay is capable to detect two different HCV genotypes within a sample and identify HCV in HCV/HIV mixed samples. The features of rapid and reliable make this assay became a potential genotyping method for HCV genotyping in the future. Our studies demonstrate that the novel biotechniques can improve the potency assay for biologics evaluation and the virus genotyping assay. Therefore, improvement strategies utilizing novel biotechniques for virus genotyping and biologics’ potency measurement could be constantly applied in the future. | en |
dc.description.provenance | Made available in DSpace on 2021-06-16T05:17:28Z (GMT). No. of bitstreams: 1 ntu-103-D96642007-1.pdf: 5084269 bytes, checksum: abb691d1c43ee9ea61f5028773005bc7 (MD5) Previous issue date: 2014 | en |
dc.description.tableofcontents | 口試委員會審訂書 I
ABSTRACT II 中文摘要 IV CONTENTS V LIST OF TABLES VIII LIST OF FIGURES IX ABBREVIATIONS XI CHAPTER 1: LITERATURE REVIEW 1 1. NOVEL BIOTECHNIQUES 2 1.1. FLOW CYTOMETRY 2 1.2. LIQUID MICROARRAY 4 SIGNIFICANE 8 CHAPTER 2: DETERMINE THE POTENCY ASSAY OF BCG VACCINES BY FLOW CYTOMETER 14 1. INTRODUCTION 15 1.1. A BRIEF INTRODUCTION OF BCG VACCINE 15 1.2. THE ASSAYS USED FOR POTENCY EVALUATION OF BCG VACCINE 15 1.3. PROPOSED CONCEPT 16 1.4. FLOW CHART OF THE STUDY 17 2. RESULTS AND DISCUSSION 18 2.1. DETERMINE THE VIABILITY OF BCG BY FLOW CYTOMETRY 18 2.2. EVALUATE THE BCG RECOVERING TIME 19 2.3. EVALUATE THE SUITABILITY OF THE VIABLE COUNT METHODS 19 2.4. A COMPARATIVE STUDY OF POTENCY ASSAY FOR BCG VACCINE 20 3. CONCLUSION 21 4. MATERIALS AND METHODS 22 4.1. BCG VACCINE 22 4.2. DETERMINE THE VIABILITY OF BCG BY FLOW CYTOMETRY 22 4.3. GROWTH OF M. BOVIS BCG 23 4.4. DETERMINE THE VIABLE COUNTS OF BCG 23 4.5. STATISTICAL ANALYSIS 24 CHAPTER 3: DEVELOPMENT OF A RELIABLE MULTIPLEX GENOTYPING ASSAY FOR HCV USING A SUSPENSION BEAD ARRAY 34 1. INTRODUCTION 35 1.1. A BRIEF INTRODUCTION OF HCV 35 1.2. HCV GENOTYPE AND DISEASE SEVERITY 36 1.3. HCV GENOTYPE AND ANTI-VIRAL THERAPY 36 1.4. THE TRADITIONAL ASSAYS USED FOR HCV GENOTYPING 38 1.5. PROPOSED CONCEPT 41 1.6. FLOW CHART OF THE STUDY 42 2. RESULTS 42 2.1. THE GENOTYPE-SPECIFIC TSPS DESIGNED FOR THE HCV GENOTYPING ARRAY 42 2.2. SENSITIVITY AND SPECIFICITY OF THE HCV GENOTYPING ARRAY 44 2.3. CLINICAL EVALUATION OF THE HCV GENOTYPING ARRAY 45 3. DISCUSSION 46 4. MATERIALS AND METHODS 53 4.1. PRIMERS AND TARGET-SPECIFIC PRIMERS (TSPS) DESIGN 53 4.2. HCV GENOTYPING ARRAY PROTOCOL 53 4.3. TESTING THE GENOTYPE-SPECIFIC TSPS USING SYNTHESIZED HCV GENOTYPE PLASMIDS 55 4.4. SENSITIVITY AND SPECIFICITY EVALUATION 56 4.5. CLINICAL EVALUATION 56 CHAPTER 4: REFERENCES 75 APPENDIX: CURRICULUM VITAE 84 APPENDIX: PUBLICATIONS 88 | |
dc.language.iso | en | |
dc.title | 應用新興生物技術改善BCG疫苗效價試驗及HCV基因分型檢測平台 | zh_TW |
dc.title | Improve the potency assay for BCG vaccine and HCV genotyping assay by novel biotechniques | en |
dc.type | Thesis | |
dc.date.schoolyear | 102-2 | |
dc.description.degree | 博士 | |
dc.contributor.oralexamcommittee | 李宣書,楊志元,賴亮全,李宜靜 | |
dc.subject.keyword | 流式細胞儀,卡介苗,效價試驗,懸浮微珠偵測系統,C型肝炎病毒,基因分型方法, | zh_TW |
dc.subject.keyword | Flow cytometer,BCG,Potency assay,suspension bead array,Hepatitis C virus (HCV),genotyping assay, | en |
dc.relation.page | 109 | |
dc.rights.note | 有償授權 | |
dc.date.accepted | 2014-08-17 | |
dc.contributor.author-college | 生物資源暨農學院 | zh_TW |
dc.contributor.author-dept | 生物科技研究所 | zh_TW |
顯示於系所單位: | 生物科技研究所 |
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