人體呼出氣體的檢測，是日趨重要的非侵入性健康狀態檢測的方式。慢性肺阻塞(COPD)與支氣管性氣喘(BA)，在許多方面十分相像，但治療方式大有不同，導致在臨床上很難快速診斷，並進行治療。本研究利用熱脫附儀氣相層析質譜儀(TD-GC-MS)聯用系統，針對COPD病患、BA病患、與未患病的常人呼出氣體樣品進行分析，證明透過TD-GC-MS系統可以成功分析樣品中化合物, 並且以此區別COPD病患、BA病患以及非病患的差異。
在本研究中，先利用每次檢驗都會出現、因吸附材料裂解而產生的六甲基環三矽氧烷 (Cyclotrisiloxane, hexamethyl-)作為內標，計算各檢驗到的化合物，相對於六甲基環三矽氧烷的相對濃度。接者，先簡單的比較化合物出現機率，確定可以用檢測到的化合物對研究對象分群。再用決策樹法細分，透過特定的化合物鑑定順序判定待測者的狀態，為常人、COPD 病患或是BA 病患。最後，以交叉比對的方式，證實此研究方式並非只適用於特定群體。
在本研究中，以耗時極短的分析方式，僅以總共50個呼氣樣品即可達到常人、COPD 病患與BA 病患分別為高達100%、94%與70%的平均分辨正確率。

Human exhaled breath measurement is one of important non-invasive health monitoring methods. The symptoms of bronchial asthma (BA) and chronic obstructive pulmonary disease (COPD) are similar, but different treatments for these two diseases. In this research, thermal desorption (TD) tendon with gas chromatography–mass spectrometry (GC-MS) system has been used to develop a screen method for the COPD patients, BA patients, and normal people.
In this research, “Cyclotrisiloxane, hexamethyl-“has been used as an internal standard for the evaluation of the relative concentration for all the detected volatile organic compounds (VOCs). First, we compare the relative concentration of VOCs from empty airbags and from the samples that were exhaled from COPD, BA patients, and normal people. Then, decision tree with deliberately ordered VOCs is used to identify the situation of every object. Cross validation is used to verify the data between the certain groups of samples. The breath from these three kinds of people could be simply distinguished and the average classification accuracy of normal people, COPD patients and BA patients are 100%, 94% and 70% respectively.

目錄
第一章 緒論 1
第二章 文獻回顧 4
2.1 氣體分析法 4
2.1.1 PTR-MS 4
2.1.2 FTIR 5
2.1.3 TDLAS 6
2.1.4 FID 7
2.1.5 GC-MS 8
2.2 COPD與BA病人呼出氣體相關研究 9
2.3 樣品預濃縮 10
2.3.1 固相微萃取 (SPME) 10
2.3.2 熱脫附 (TD) 11
2.4 數據分析方法 13
2.4.1 主要成分分析 (Principal components analysis, PCA) 14
2.4.2 符號檢定 (Sign test) 15
2.4.3 決策樹 (Decision Tree) 16
2.4.4 交叉驗證 (Cross Validation) 17
第三章 實驗裝置與實驗設計 19
3.1 採樣管介紹與校正 (Conditioning) 20
3.2 實驗參數設計 21
3.2.1 熱脫附儀 (TD) 21
3.2.2 氣相層析儀/質譜儀 (GC/MS) 22
3.3 樣品採樣 23
3.3.1 臨床資訊與人體呼出氣體取得 23
3.3.2 採樣至採樣管與病人呼出氣體進樣 25
3.4 數據分析 26
3.4.1 滯留時間(Retention time, Rt) 26
3.4.2 訊號峰高度(Peak Height) 27
3.4.3 訊號峰面積(Peak Area) 27
第四章 結果與討論 29
4.1 背景雜訊檢測 29
4.1.1 採樣管與儀器系統背景雜訊 29
4.1.2 氣體採樣袋背景雜訊 31
4.2 病患呼出氣體檢測 34
4.3 數據處理 39
4.3.1 標準化 39
4.3.2 比較法與分類 42
4.3.3 決策樹分析與交叉分析 56
第五章 未來工作 82
第六章 參考文獻 85

 
表目錄
表4.1二十次採樣管背景雜訊中VOC出現次數…………………………………31
表4.2 COPD病人呼出氣體中揮發性有機化合物出現次數……………………...34
表4.3 BA病人呼出氣體中揮發性有機化合物出現次數…………………………36
表4.4常人呼出氣體中揮發性有機化合物出現次數……………………………...38
表4.5一個病人檢測結果其峰面積值與標準化後的結果………………………...41
表4.6五個空的氣體採樣袋檢測結果標準化後平均的結果……………………...42
表4.7一個病患檢測結果的數據分析……………………………………………...46
表4.8出現機率結果比較…………………………………………………………...49
表4.9 COPD、BA和常人呼出氣體分析結果比較(一)…………………………...53
表4.10 COPD、BA和常人呼出氣體分析結果比較(二)………………………….54
表4.11不同化合物的個狀態人群呼氣樣品中的數值分布最大值與最小值…….64
表4.12其中一位COPD患者呼氣樣品檢測數值標準化與判定結果……………71
表4.13交叉驗證結果正確率比較………………………………………………….79

 
圖目錄
圖2.1質子轉移反應質譜儀設計示意圖………………………………………….....4
圖2.2傅立葉轉換紅外光譜儀設計概念圖……………………………………….....5
圖2.3可調式二極體雷射吸收光譜術基本原理概念圖………………………….....6
圖2.4火焰離子化偵檢器設計示意圖…………………………………………….....7
圖2.5 氣象層析儀串聯質譜儀工作原理示意圖……………………………………9
圖2.6固相微萃取裝置結構示意圖………………………………………………...11
圖2.7主成分分析法分析方式示意圖……………………………………………...15
圖2.8決策樹分析方式示意圖……………………………………………………...17
圖3.1實驗儀器(TD-GC-MS)配置圖……………………………………………….19
圖3.2兩階段脫附流程圖…………………………………………………………...22
圖3.3氣體採樣袋…………………………………………………………………...24
圖3.4實驗氣體採樣裝置…………………………………………………………...26
圖3.5滯留時間定義………………………………………………………………...27
圖3.6訊號峰的重要樞點…………………………………………………………...28
圖3.7基線點到基線點波峰訊號面積……………………………………………...28
圖4.1採樣管進行第一次分析程序與第二次分析程序的結果比較……………...30
圖4.2十個空的氣體採樣袋檢測結果總離子層析(TIC)圖………………………..33
圖4.3一個典型的COPD總離子層析結果圖全圖(a)與局部(b)………………….39
圖4.4 COPD及BA各十位病患檢測分析結果……………………………………43
圖4.5 COPD、BA及常人呼出氣體比較(1)……………………………………….51
圖4.6 COPD、BA及常人呼出氣體比較(2)……………………………………….52
圖4.7初始研究方法流程圖………………………………………………………...53
圖4.8第二種研究方法流程圖……………………………………………………...57
圖4.9呼氣檢測結果數值分布的可能情況………………………………………...58
圖4.10呼氣檢測結果數值分布可能情況與戴測樣品檢測數值可能分布……….61
圖4.11進行決策樹分析可能出現的三種情況…………………………………….77
圖4.12 進行決策樹分析的做法程序示意圖………………………………………78

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