臺灣博碩士論文加值系統

本研究以奈米矽（nanostructured silicon, nSi）作為質譜晶片之分析基材，吾稱此方法為nSi-MS。nSi-MS無需基質輔助以及高靈敏度的特點，特別適合小分子分析物的分析；並且，其簡易前處理以及樣本量需求少的優勢能使分析流程僅在15分鐘內即可快速完成。
於研究中，我們針對nSi-MS質譜檢測平台，首先進行樣本前處理以及樣本分離的實驗測試，其中包括了尿液檢體雜質的前處理、混合生肽樣本的分離以及等電位電泳轉置技術的整合，評估nSi質譜晶片進行簡易前處理的表現及效能。
並且，我們進一步利用nSi質譜晶片的高靈敏度特點，針對目前濫用問題嚴重的多種小分子濫用管制藥品進行實驗，實驗樣本同時包括了藥用標準品及毒癮者的真實尿液檢體，共有安非他命、甲基安非他命、可待因、嗎啡、愷他命及MDEA等六種小分子藥物，並對其檢測線性(Linearity)、檢測靈敏度(Limit of detection)、檢測重複性(Repeatibility)及定量分析(Quantification)等表現進行討論，全面了解 nSi-MS 質譜檢測平台對小分子分析物的檢測能力以及其質譜檢測平台於生物醫學領域的未來發展方向和潛力。

In this study, the nanostructured silicon (nSi) material was used as the mass spectrometry (MS) analysis substrate (nSi-MS). nSi-MS method especially suits for the detection of low m/z value analytes because of its’ matrix-free and high sensitivity characteristics; its’ simple pre-treatment and less sample consumption can also make analysis rapidly accomplished under 15 minute.
Urine specimen pre-treatment, peptides mixture separation and isoelectric focusing 2-D electrophoresis direct transfer had been proceeded to evaluate the specific pre-treatment performance of nSi-MS.
And we also applied nSi-MS to those small molecular abused drugs to realize the performance in low m/z value range. Standard drug samples and addict urine specimens were both investigated in this research, including amphetamine, methamphetamine, codeine, morphine, ketamine and MDEA; limit of detection, linearity, repeatability and quantitative analysis have been assayed and discussed in this document in order to fully understand the nSi-MS technique capability in small molecule detection and its’ future development potential in biomedical field.

摘要 IV
ABSTRACT V
目錄 VII
圖目錄 IX
表目錄 XII
第一章 緒論 1
1-1 研究背景 1
1-2 研究目標 2
1-3 論文架構 3
第二章 文獻回顧 5
2-1 表面輔助雷射脫附游離法 5
2-2 薄層層析 7
2-3 極薄薄層層析 8
2-4 屑片狀多孔聚合物 9
2-5 多孔矽結構分離技術應用 11
2-6 等電位電泳轉置基質輔助雷射質譜分析 13
2-7 氣相層析質譜法 14
2-8 液相層析質譜法 16
2-9 安非他命、甲基安非他命之特性、代謝途徑及藥理 18
2-9-1 安非他命類藥物之歷史回顧 18
2-9-2 安非他命與甲基安非他命 19
2-9-3 安非他命類之藥物藥理特性與代謝 20
2-10 鴉片類藥物及其代謝物之特性與藥理 22
2-10-1 鴉片類藥物之歷史回顧 22
2-10-2 嗎啡之藥理特性與代謝 22
2-10-3 可待因之藥理特性 23
2-11 愷他命之特性、代謝途徑及藥理 25
2-11-1 愷他命類藥物之歷史回顧 25
2-11-2 愷他命之藥理特性與代謝 26
第三章 材料與方法 28
3-1 實驗設備與材料 28
3-1-1 實驗設備 28
3-1-2 實驗材料與藥品 29
3-2 藥品配製 30
3-3 實驗方法 33
3-3-1 製備質譜分析奈米矽(nSi)結構 33
3-3-2 製備質譜分析奈米矽(nSi)分離晶片 34
3-3-3 管制藥品標準品nSi-MS分析 35
3-3-4 尿液檢體nSi-MS分析 36
3-3-5 尿液檢體nSi-MS專一性抗體分析 36
3-3-6 尿液檢體nSi-MS定量 37
3-3-7 nSi分離晶片尿液純化分析 38
3-3-8 nSi分離晶片胜肽樣本分離分析 38
3-3-9 等電位電泳二維轉置nSi-MS分析 39
第四章 結果與討論 41
4-1 nSi分離晶片尿液檢體前處理分析 41
4-2 nSi分離晶片胜肽樣本分離分析 44
4-3 等電位電泳二維轉置nSi-MS分析 48
4-4 管制藥品標準品nSi-MS分析 50
4-4-1 nSi-MS 之可行性與檢測靈敏度 50
4-4-2 nSi-MS 之檢測線性與準確再現性 57
4-5 尿液檢體nSi-MS分析 59
4-6 尿液檢體專一性抗體nSi-MS分析 61
4-7 尿液檢體nSi-MS定量分析 66
第五章 結論與未來展望 69
參考文獻 71

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