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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 許聿翔 | zh_TW |
| dc.contributor.advisor | Yu-Hsiang Hsu | en |
| dc.contributor.author | 林鈺洲 | zh_TW |
| dc.contributor.author | Yu-Zhou Lin | en |
| dc.date.accessioned | 2023-10-24T16:29:56Z | - |
| dc.date.available | 2025-08-07 | - |
| dc.date.copyright | 2023-10-24 | - |
| dc.date.issued | 2023 | - |
| dc.date.submitted | 2023-08-11 | - |
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| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/90959 | - |
| dc.description.abstract | 本研究為一種可使用人源腫瘤組織開發腫瘤晶片模型的微流道裝置。藉由微流體設計及操控技術在培養腔室中產生血管新生及腫瘤培養所需之培養環境，成功於體外建立具人血管的體腫瘤組織模型，將可做為藥物發展及篩選的研發平台。本研究所開發的腫瘤晶片可培養出平均血管直徑為15.6 μm的血管組織，並於培養第4天即可形成血管網絡，並於第9天即可與流道完成吻合連接。並於實驗驗證所發展出的血管組織會向腫瘤組織生長，在腫瘤尺寸範圍200-220 μm3的血管平均直徑為48.08 μm為相較於腫瘤尺寸範圍10-100 μm3的血管平均直徑30.43 μm增加1.58倍。本研究並以化療藥物進行實驗驗證，其結果顯示10倍藥物濃度的腫瘤組織壞死程度是1倍藥物濃度的1.77倍，且相較於控制組為4.6倍。最後，本研究並驗證此腫瘤模型的微環境，確認此腫瘤模型含有原人體腫瘤組織的免疫B細胞，藉此驗證腫瘤微環境的細胞多樣性，同時此腫瘤模型可將組織液取樣，以監測在培養過程中的pH值。
本研究所開發的腫瘤晶片模型提供更近似體內腫瘤環境的模型系統，將可提供具血管化的腫瘤體外模型，用以進行腫瘤藥物篩選研究，並加速藥物篩選時程及整體可靠度。 | zh_TW |
| dc.description.abstract | This study reports a microfluidic device that can develop tumor-on-a-chip models using human tumor tissue. Microfluidic technology is applied to create the physiological environment required for angiogenesis and tumor in the culture chamber. This microfluidic device successfully develops a human tumor model with human blood vessels. It can serve as an in vitro model system for drug development and screening. The vascular network has an average diameter of 15.6 μm, and a vascular network can be formed within 4 days. The developed vessels can form anastomosis in 9 days. It is also verified experimentally that the developed vascular tissue can grow toward the tumor tissue. The average diameter of blood vessels in the tumor size range of 200-220 μm3 is 48.08 μm, which is 1.58 times greater than the average diameter of blood vessels in the tumor size range of 10-100 μm3, which is 30.43 μm3. The capability to use this device for drug screening also is verified using a standard chemotherapy drug. The results show that the level of treated tumor tissue damage at 10X dosage is 1.77 times larger than that of 1X dosage and was 4.6 times larger than that of the control group. Finally, the microenvironment of the tumor model also is verified. It is found that the immune B cells of the original human tumor tissue can be retained in the mode, and tumor fluid can be sampled to monitor pH value during cultivation.
In summary, the developed tumor-on-a-chip device provides a new model system with a more tumor-mimetic environment. It provides a reliable vascularized tumor model for speeding up tumor drug screening studies. | en |
| dc.description.provenance | Submitted by admin ntu (admin@lib.ntu.edu.tw) on 2023-10-24T16:29:56Z No. of bitstreams: 0 | en |
| dc.description.provenance | Made available in DSpace on 2023-10-24T16:29:56Z (GMT). No. of bitstreams: 0 | en |
| dc.description.tableofcontents | 目錄
致謝 i 中文摘要 ii ABSTRACT iii 目錄 iv 圖目錄 viii 表目錄 xvi 第1章 緒論 1 1.1 前言 1 1.2 研究動機. 3 1.3 研究目標 3 1.4 論文架構 3 第2章 文獻回顧 5 2.1 體外腫瘤晶片組織工程方法 5 2.2 腫瘤微環境(Tumor-microenvirment) 7 2.2.1腫瘤異質性(Heterogeneity) 7 2.2.3缺氧環境(hypoxia) 8 2.2.2腫瘤內間質壓力(Interstitial Fluid Pressure) 9 2.2.4免疫環境(Ant-immune) 10 2.3 腫瘤血管新生 11 2.4 血管網絡模型開發 12 2.4.1纖維母細胞與內皮細胞血管形成作用 12 2.4.2可灌注體外血管網絡模型 13 2.4.3微流體平台血管網絡培養技術 14 2.5 顯微腫瘤組織切塊晶片 16 2.6 微流道篩藥平台 19 2.7腫瘤微流道篩藥平台 20 2.7.1腫瘤微流道免疫治療平台開發 21 2.7.2腫瘤治療藥物 22 第3章 裝置與研究規劃設計 25 3.1 腫瘤晶片裝置之設計理念 25 3.1.1人源性異種移植腫瘤組織切塊及過篩裝置設計 27 3.1.2微流體設計原理 28 3.1.3具人源性腫瘤異植體微型切塊之腫瘤晶片微流體平台設計 34 3.1.4人源性移植體切塊腫瘤晶片平台實驗系統設計 35 3.1.5人源性移植體切塊腫瘤晶片被動填充設計 43 3.2 有限元素法之微流體流場模擬建置 45 3.2.1有限元素法之建模 45 3.2.2有限元素法之統御方程式 47 3.2.3有限元素法之邊界條件 50 3.2.4有限元素法之材料屬性 51 3.2.5有限元素法之網格建立 52 第4章 平台開發與實驗方法 55 4.1 微流體平台系統之製程研發 55 4.1.1微流體晶片製程 55 4.1.2晶片光罩繪製與製作 56 4.1.3黃光微影製程 57 4.1.4微流道結構量測 68 4.1.5微流道軟微影製程與裝置組裝 69 4.2 顯微切割人源性腫瘤組織(PDX)技術開發 73 4.3 顯微切割人源性腫瘤組織(PDX)分離技術開發 74 4.4 微流體內細胞培養過程 74 4.4.1細胞培養技術 74 4.4.2微流體腔室細胞培養技術 75 4.4.3細胞腔室血管吻合術(Angiogenesis) 76 4.4.4細胞固定及螢光免疫染色 76 4.5 血管新生術與螢光圖像分析 78 4.4.1細胞濃度參數對於血管組織面積與血管直徑分析 78 4.4.2.腫瘤尺寸對於血管組織生長與血管直徑分析 79 4.4.3.藥物遞送對於腫瘤腔室之腫瘤量化分析 79 4.4.4.人源性腫瘤腔室腫瘤微環境分析 80 第5章 實驗結果與討論 81 5.1人源性移植體切塊腫瘤晶片被動填充設計 81 5.1.1被動填充理論推導結果 81 5.1.2被動填充實驗與理論驗證 84 5.2 顯微切割技術開發 85 5.2.1顯微切割技術定量 86 5.2.2人源性腫瘤組織直接進行顯微切割 87 5.2.3顯微切割人源性腫瘤組織水膠包覆技術開發 88 5.2.4顯微切割人源性腫瘤組織切割平台開發 90 5.2.5顯微切割人源性腫瘤組織分離技術開發 91 5.2.6顯微切割人源性腫瘤組織切塊技術結果 93 5.3 人源性腫瘤組織平台流場分析結果 94 5.3.1單出口腫瘤晶片三維培養平台流場 94 5.3.2三出口腫瘤晶片三維培養平台流場分析 96 5.3.3三出口腫瘤晶片三維培養平台總擴充時間分析 99 5.3.4三出口腫瘤晶片三維培養平台腫瘤因子釋放模擬分析 102 5.4 單出口人源性腫瘤組織微流道平台培養結果 105 5.4.1單出口腫瘤晶片三維培養平台-不同實驗參數下結果分析 107 5.4.2單出口腫瘤晶片三維培養平台-血管通透性驗證 113 5.4.3單出口腫瘤晶片三維培養平台-藥物效果驗證 113 5.4.4單出口腫瘤晶片三維培養平台-腫瘤尺寸與血管影響 114 5.5 三出口人源性腫瘤組織微流道平台培養結果 116 5.5.1三出口腫瘤晶片三維培養平台-不同實驗參數下結果分析 118 5.5.2三出口腫瘤晶片三維培養平台-血管新生過程 119 5.5.3三出口腫瘤晶片三維培養平台-藥物傳遞結果 122 5.6人源性腫瘤組織微環境分析 124 5.6.1人源性腫瘤組織之免疫細胞螢光染色分析 124 5.6.2三出口腫瘤晶片三維培養平台-腫瘤微環境PH驗證 125 5.6.3三出口腫瘤晶片三維培養平台-晶片內免疫細胞染色結果 127 第6章 結論與未來展望 129 6.1 結論 129 6.2 未來展望 130 Reference 131 | - |
| dc.language.iso | zh_TW | - |
| dc.subject | 血管新生 | zh_TW |
| dc.subject | 藥物篩選 | zh_TW |
| dc.subject | 腫瘤晶片 | zh_TW |
| dc.subject | 人源性腫瘤組織 | zh_TW |
| dc.subject | 微流體 | zh_TW |
| dc.subject | Drug screening | en |
| dc.subject | Microfluidics | en |
| dc.subject | Human tumor cuboid | en |
| dc.subject | Vasculature chip | en |
| dc.title | 具人源性腫瘤異植體微型切塊之人體腫瘤晶片製程開發與驗證 | zh_TW |
| dc.title | Process development and verification of a tumor-on-a-chip model with an embedded micro-dissected patient-derived tumor xenograft | en |
| dc.type | Thesis | - |
| dc.date.schoolyear | 111-2 | - |
| dc.description.degree | 碩士 | - |
| dc.contributor.oralexamcommittee | 秦咸靜;蘇裕家;董奕鍾 | zh_TW |
| dc.contributor.oralexamcommittee | Hsian-Jean Chin;Yu-Chia Su;Yi-Chung Tung | en |
| dc.subject.keyword | 微流體,人源性腫瘤組織,腫瘤晶片,血管新生,藥物篩選, | zh_TW |
| dc.subject.keyword | Microfluidics,Human tumor cuboid,Vasculature chip,Drug screening, | en |
| dc.relation.page | 137 | - |
| dc.identifier.doi | 10.6342/NTU202303174 | - |
| dc.rights.note | 未授權 | - |
| dc.date.accepted | 2023-08-12 | - |
| dc.contributor.author-college | 工學院 | - |
| dc.contributor.author-dept | 應用力學研究所 | - |
| 顯示於系所單位： | 應用力學研究所 | |
文件中的檔案：
| 檔案 | 大小 | 格式 | |
|---|---|---|---|
| ntu-111-2.pdf 未授權公開取用 | 11.51 MB | Adobe PDF |
系統中的文件，除了特別指名其著作權條款之外，均受到著作權保護，並且保留所有的權利。