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研究生： 夏聖傑
Sheng-Chieh Hsia
論文名稱： 利用線上樣品分段與三維列印技術開發監測活體動物腦中金屬元素動態變化趨勢的連線分析系統介面
Advancing Hyphenation of In-vivo Microdialysis Sampling to an ICP-MS Using Online Segmentation and 3-Dimensional Printing Technique for Monitoring of Dynamic Variations of Living Rat Brain Metal Ions
指導教授： 孫毓璋
口試委員: 蔡東湖
楊末雄
楊重熙
孫毓璋
學位類別： 碩士
Master
系所名稱： 原子科學院 - 生醫工程與環境科學系
Department of Biomedical Engineering and Environmental Sciences
論文出版年： 2014
畢業學年度： 102
語文別： 中文
論文頁數： 132
中文關鍵詞： 微量金屬 、大腦 、感應耦合電漿質譜儀 、線上分段技術 、3D列印技術
外文關鍵詞： Trace metals, Brain, ICP-MS, Segmentation technique, 3D printing technique
相關次數： 點閱：3  下載：0 
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    • 　腦中微量金屬元素的恆定，扮演著調節正常生理功能與神經傳導的關鍵角色，而在監測活體動物腦中微量金屬元素動態變化趨勢的研究發展過程中，雖然藉由串聯微透析取樣裝置與感應耦合電漿質譜儀，可以提供直接且非常重要的微量金屬元素動態變化資訊，但受限於現今繁複的樣品前處理程序與無法客製化的連線分析系統介面，導致分析系統出現時間解析能力過長與連線元件的多樣性不足等問題。為了克服上述難題，本研究分別開發了以多向選擇閥輔助的線上樣品分段與平行多樣品前處理介面，建立一套具有高時間解析能力與高樣品處理通量的連線分析系統（MD-Parallel in-Tube SPE-ICP-MS）；另外，為了增進連線分析系統介面的多樣性，本研究亦首次利用三維列印技術自行製作內建樣品環（Sample loop）的二向轉動閥組件，作為串聯微透析取樣與感應耦合電漿質譜儀之間的流動注入分析裝置，並完成另一套MD-3DP Valve-ICP-MS連線分析系統的建立。
    在完成上述連線分析系統的最佳化探討與分析性能確效後，本研究亦實際應用所建立的連線分析系統進行監測活體大鼠腦中，因急性去極化效應（灌流高濃度鉀離子）及興奮性刺激（灌流NMDA）時，腦細胞間液內微量金屬元素的即時動態變化趨勢。由實驗結果中可發現，當受到急性去極化與興奮性刺激之後，腦細胞間液內鈣及鋅等微量金屬元素的濃度，會發生顯著的降低與升高的情形，據此說明本研究所建立的二套連線分析系統，確實具有監測活體動物腦中微量金屬元素動態變化趨勢監測的能力。預期本研究所開發之連線分析系統，能為日後微小微量分析（Micro-trace analysis）的研究，提供一個嶄新的思維方式。

    中文摘要 I 英文摘要 III 第一章　前言 1 1.1　微量金屬元素對於人體與大腦的重要性 1 1.1.1　人體中的微量金屬元素 1 1.1.2　腦中的微量金屬元素 2 I.　微量金屬元素對於腦部慢性疾病的影響 2 II.　微量金屬元素在神經傳導機制中的角色 4 1.2　活體動物大腦內微量金屬元素研究的發展回顧 7 1.2.1　非活體內模式的大腦中微量金屬研究 8 1.2.2　活體內的大腦內微量金屬研究 11 1.3　活體動物大腦內微量金屬元素研究的困難 13 1.4　樣品分段（Segmentation）與三維列印（Three-dimensional printing）技術的應用 15 1.4.1　Lab-on-Valve與樣品分段技術 15 1.4.2　三維列印技術的應用 24 1.5 研究目的 27 第二章　實驗儀器、裝置與其原理 29 2.1　微透析探針取樣裝置 29 2.2　感應耦合電漿質譜法 30 2.2.1 樣品導入系統 32 2.2.2 游離源 35 2.2.3 真空緩衝介面與離子聚焦透鏡 37 2.2.4 四極柱質量分析器 40 2.2.5 離子偵測器 41 2.3　三維列印技術 43 第三章　實驗材料與方法 48 3.1　儀器、配件、試劑與實驗動物 48 3.1.1　儀器裝置與配件 48 3.1.2　實驗藥品與試劑 49 3.1.3　實驗用水與容器清洗 50 3.1.4　實驗動物來源 51 3.2　分析系統的清洗與保存 51 3.2.1　微透析探針於實驗前後的清洗與保存 51 3.2.2　實驗前後，固相萃取系統的清洗與保存 52 3.3　活體大鼠腦中細胞間液內微量金屬元素動態監測連線系統（MD-Parallel in-Tube SPE-ICP-MS hyphenated system）之建立與最佳化條件探討 52 3.3.1　線上樣品分段技術的可行性探討 52 3.3.2　 MD-Parallel in-Tube SPE-ICP-MS連線分析系統之建立 54 3.3.3　系統最佳化探討 59 3.3.4　 MD-Parallel in-Tube SPE-ICP-MS連線系統分析效能評估 60 3.4　 MD-Parallel in-Tube SPE-ICP-MS連線分析系統應用於監測活體大鼠腦中細胞間液內微量金屬元素的動態變化趨勢 61 3.5　三維列印二向轉向閥與活體動物腦中細胞間液內，微量金屬元素動態監測連線分析系統（MD-3DP Valve-ICP-MS hyphenated system） 63 3.5.1　三維列印二向轉向閥的設計與分析系統的建立 63 3.5.1.1　設計與列印 63 3.5.1.2　流道表面性質與誤差探討 66 3.5.1.3　MD-3DP Valve-ICP-MS分析系統的建立 68 　　　　3.5.2　MD-3DP Valve-ICP-MS分析系統效能評估 69 3.6　MD-3DP Valve-ICP-MS分析系統應用於活體大鼠腦中細胞間液內微量金屬離子的動態監測 71 第四章　實驗結果與討論 73 4.1　活體大鼠腦中細胞間液內微量金屬元素動態監測連線系統（MD-Parallel in-Tube SPE-ICP-MS）之最佳化條件探討 73 4.1.1　線上樣品分段技術 73 4.1.1.1　進樣時間 74 4.1.1.2　線上樣品分段時間序列最佳化探討 75 4.1.2　系統最佳化探討 76 4.1.2.1　微透析取樣的回收率 76 4.1.2.2　總萃取流速（微透析取樣流速）對於萃取效率的影響 78 4.1.2.3　緩衝溶液濃度對於萃取效率的影響 79 4.1.3　MD-Parallel in-Tube SPE-ICP-MS連線分析系統效能評估 80 4.1.3.1　系統時間解析度 81 4.1.3.2　分析系統之檢量線與效能評估 83 4.1.3.3　分析系統穩定度的探討 84 4.2　應用MD-Parallel in-Tube SPE-ICP-MS連線分析系統進行活體大鼠腦中細胞間液內微量金屬離子的動態監測 85 4.2.1　活體大鼠腦中細胞間液的微量金屬離子動態監測結果 85 4.2.2　模擬腦中急性去極化後、微量金屬離子的動態監測結果 87 4.3　開發三維列印閥連線分析系統（MD-3DP Valve-ICP-MS hyphenated system）進行活體大鼠腦中細胞間液的微量金屬離子動態監測 92 4.3.1　流道的表面性質與誤差探討 92 4.3.2　內建樣品環二向閥的設計 99 4.3.3　MD-3DP Valve-ICP-MS連線分析系統效能評估 100 4.3.3.1　樣品體積對於系統分析效能的影響 102 4.3.3.2　分析系統效能評估 103 4.3.3.3　分析系統長時間穩定度的探討 105 4.4　MD-3DP Valve-ICP-MS連線分析系統應用於活體大鼠腦中細胞間液內微量金屬元素的動態監測 105 4.4.1　活體大鼠腦中細胞間液的微量金屬離子動態監測結果 106 4.4.2　模擬腦部因興奮性刺激後、微量金屬離子的動態監測結果 107 第五章　結論 115 參考文獻 117 附錄 132

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