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研究生: 陳庭軒
Ting-Hsuan Chen
論文名稱: 複合式微生物組織陣列自動化設備之研製
Multi-function Automatic Tissue Microarrayer for Pathological Analysis and Staining Reagent Concentration Tests
指導教授: 修芳仲
Fang-Jung Shiou
口試委員: 鄧昭瑞
Geo-Ry Tang
鍾國亮
Kuo-Liang Chung
邱奕契
Yih-Chih Chiou
王世仁
Shyh-Jen Wang
學位類別: 博士
Doctor
系所名稱: 工程學院 - 機械工程系
Department of Mechanical Engineering
論文出版年: 2011
畢業學年度: 99
語文別: 中文
論文頁數: 99
中文關鍵詞: 微生物組織陣列病理切片生物組織染劑濃度測試影像疊合基因演算法力平衡放置田口式品質工程實驗方法
外文關鍵詞: Tissue Microarray, Pathological Analysis, Staining Reagent Concentration Tests, Image Alignment, Genetic Algorithm, Force-Directed Placement Algorithm, Taguchi Method
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  • 本研究旨在開發具有病理切片與染劑濃度測試雙項功能的複合式微生物組織陣列自動化設備。並且針對生物檢體的鑽取準確性、鑽取位置數量規劃以及蠟塊封裝品質進行探討。研究的進行可分為設備規劃、影像疊合、鑽取位置與數量之指定以及最佳參數搜尋等四階段。首先是評估複合式機台的功能需求,進而構思設備之組成架構。此階段同時探討複合式功能之自動化流程概念,藉以釐清達成自動化的必要條件。其次是生物組織影像疊合方法的實踐。研究中利用基因演算法的尋優特性得到影像疊合的最佳平移與旋轉參數,藉以提升組織的鑽取準確性。第三階段論述鑽取數量與位置規劃方法。本研究嘗試以力平衡為基礎的元件放置方法,藉由持續調整元件間之彈簧常數而得到適當的鑽取數量與位置。最後的階段則是為了提升組織陣列蠟塊的封裝品質,因而利用田口式品質工程實驗方法取得較佳的封裝製程參數。由實作開發的機台進行實驗後發現,使用者可以完整地規劃生物檢體的鑽取數量與位置,而系統也可以準確的自動鑽取並得到品質良好的生物檢體。至於使用穩健化設計得到的製程參數,能夠有效的提升微生物組織陣列蠟塊的封裝品質。


    This study aims to develop a multi-function automatic tissue microarrayer that incorporates functions accommodating both the pathological analysis and the staining reagent concentration tests. Furthermore, tissue alignment accuracy, tissue punching position and quantity planning, and tissue microarray block (TMA) package quality are also discussed. This study contains four stages. First, through evaluating functional requirements including both pathological analysis and staining concentration tests, the possible structure to design the apparatus is considered based on these concepts. In addition, a concept of automatic flow is also discussed in order to find out the necessary condition for achieving multi-function automation. A genetic algorithm (GA) is then performed to obtain the optimal translation and rotation parameters for image alignment to improve alignment accuracy. Next, a punching position and quantity planning is discussed using force-directed placement algorithm to continually modify the spring constant between components and establish the appropriate punching position and quantity. Finally, to improve the TMA block package quality, Taguchi method is employed for TMA process to obtain the optimal assembly process parameter. Experimental results revealed that self-developed tissue microarrayer can not only efficiently enhance tissue alignment accuracy but also completely plan tissue punching position and quantity. As for TMA process, the robust parameters can obviously improve the package quality of TMA block.

    摘要 I Abstract II 致謝 III 目錄 IV 圖索引 VII 表索引 IX 符號說明 X 第一章 緒論 1 1.1研究動機與目的 2 1.3文獻探討 3 1.4研究方法 6 1.5本文架構 7 第二章 微生物組織陣列 8 2.1技術要點 8 2.2手動製作程序 9 2.3市售儀器 11 2.4應用分類 13 第三章 實驗設備 16 3.1實驗系統建置 16 3.2自動化流程規劃 21 第四章 生物組織影像疊合方法 26 4.1 數位影像處理 26 4.1.1數位影像基礎 26 4.1.2二值處理與邏輯運算 27 4.1.3圓形偵測 28 4.2影像相似度量測 29 4.3搜尋最佳影像相似度 30 4.3.1基因演算法簡介 31 4.3.2最佳相似度之搜尋流程 32 4.4影像疊合實驗結果 36 4.4.1基於影像特徵之影像疊合 36 4.4.2基於灰階強度之影像疊合 38 4.4.4自動與人工製作的比較實驗 41 第五章 鑽取數量與位置規劃方法 43 5.1邊緣檢測 43 5.2初始放置 46 5.3力平衡放置 47 5.4演算流程 50 5.5實驗結果 53 第六章 最適化封裝方法 55 6.1田口式品質工程實驗方法 56 6.2品質特性與量測系統 57 6.3製程參數的選擇 60 6.4直交表實驗 61 6.5訊號雜訊比分析 65 6.6因子主效果分析 66 6.7變異數分析 68 6.8最佳參數組合驗證實驗 70 第七章 結論與未來展望 73 參考文獻 76 附錄A TMA相關名詞介紹 82 附錄B 手動製作TMA蠟塊示意圖 84 附錄C 組織切片設備 87 附錄D 市售儀器規格說明 88 附錄E 組織加熱與冷卻設備 93 附錄F 正規化相關係數原理與應用 94 附錄G 基於影像特徵之影像疊合實驗結果 95 附錄H 基於灰階強度之影像疊合實驗結果 97 附錄I 實驗設備實體圖 98 作者簡介 99

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