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研究生:徐承暘
研究生(外文):Cheng-Yang Hsu
論文名稱:自動化拉曼量測系統開發及磁性奈米材料合成並應用在尿液結晶微結石偵測
論文名稱(外文):Development of Auto Raman Detective System and Synthesis Magnetic Nano Particles applied in Urinary crystal and Urinary Stone
指導教授:江惠華江惠華引用關係
指導教授(外文):HuiHua Kenny Chiang
學位類別:碩士
校院名稱:國立陽明大學
系所名稱:生醫光電研究所
學門:工程學門
學類:生醫工程學類
論文種類:學術論文
論文出版年:2014
畢業學年度:102
語文別:中文
論文頁數:83
中文關鍵詞:尿液結晶尿結石拉曼光譜磁奈米顆粒Labview
外文關鍵詞:Urinary crystalsUrinary StoneRaman SpectroscopyNonoparticlesLabview
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  • 被引用被引用:0
  • 點閱點閱:220
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  • 下載下載:24
  • 收藏至我的研究室書目清單書目收藏:0
尿路結石是泌尿科中為一種常見的疾病,當患者發病到至治療完畢後,仍有很大的機率再度復發。然而患者的結石形成,又和後天飲食或先天體質有很大的關聯,所以在獲得患者結石成分組成是非常重要的。當得知的結石種類後,可以提供臨床醫師做適當的藥物治療,及提供病人正確的飲食方式,避免再度手術的風險,因此可減少醫療費用的浪費。
本研究利用光學檢測技術-拉曼光譜,作為臨床生物分析的工具。其優點為拉曼訊號不會到水份的干擾,並且其光譜的頻帶較窄,因此具有高的鑑別度,且檢測快速,對不同物質擁有專一的峰值。因此,從頻譜中的峰值位置即可得知物質成分,適合用在材料或生物分子的檢測分析。而本研究,使用拉曼光譜的鑑測技術應用於尿路結石與尿液結晶的成分組成分析,應用此技術可以輔助臨床醫生客觀的檢測方式。
目前擬開發出一套自動化檢測系統,其中結合了拉曼光譜儀、磁性奈米顆粒與螢光系統。此偵測裝置可專一性針對尿液中的鈣類結晶,做集合回收的動作並且利用材料上的螢光標定尿結晶的位置,將分析後的螢光位置訊號送給移動平台,最後在收集拉曼訊號做頻譜分析,利用此裝置可縮短找尋尿路結晶與微結石的時間,並且還可以得知尿路結晶/微結石之種類。對結石患者可以提供更多資訊,免於再度手術造成醫療資源浪費。對於正常人,可以做定量化的檢測方便日後當作健檢的依據。

Urinary Stone is a common disease in Urological system,when people suffering from this disease , doctors will give them treatments . And the recurrent rate of urinary stone is high. However urinary stone formation have large relevance between patient's diet and genetic, so it’s important to know the composition of the stone. If knowing the composition of urinary stone , the doctor would give medicine treatment or diet suggestion that can avoid the risk of operation and reducing the waste of medical expense.
In this research , we use Raman Spectroscopy as a tool to detect urinary stone and crystals . Raman technology have some advantages which would not interfere with the water signal, and its spectral band is narrow, and therefore has a high discrimination , rapid detection of different substances with specific peaks. Therefore, from the peak position in the spectra that can be suitable for use in detection and analysis . If we apply this technology in the hospital , it can offer some objective information to the doctor , .
For now, we have developed an automatic detection system, which combines raman spectroscopy and fluorescent systems. This detection device with magnetic nanoparticles can specific bonded for calcium-based stone or crystals , and label the location of crystals. This technology can reduce the searching time of urine sample . and will help us to know the type of crystal or stone quickly.

目錄
致謝 i
中文摘要 ii
英文摘要 iii
目錄 iv
圖表目錄 vii
第一章 序論 1
1.1研究背景 1
1.2尿路結石簡介 4
2.高鈣含量食物 11
1.3文獻回顧 13
1.4研究動機與研究目的 14
第二章 理論基礎 16
2.1 拉曼簡介 16
2.1.1 拉曼散射簡史 16
2.1.2 拉曼散射原理 17
2.2磁性奈米粒子 24
2.2.1 磁性理論 25
2.2.2 奈米氧化鐵的合成方式 29
2.3 LabVIEW簡介 30
第三章 實驗材料與系統架設 33
3.1 實驗流程 33
3.1.1 尿液樣本處理流程 33
3.1.2 氧化鐵奈米粒子的合成與表面修飾 35
3.1.3尿路結石標準成分配製 38
3.2儀器簡介 40
3.2.1自組785 nm近紅外光拉曼光譜儀 40
3.2.2自動化系統偵測流程 41
3.2.3系統儀器介紹 42
3.3 材料分析儀器 45
3.3.1穿透式顯微鏡(Transmission Electron Microscope,TEM) 46
3.3.2掃描式電子顯微鏡(Scanning Electron Microscope,SEM) 47
3.3.3感應耦合電漿質譜分析儀(Inductively Coupled Plasma-mass Spectrometer,ICP-MS) 48
3.3.4超導量子干涉磁量儀 (Superconducting Quantum Interference Device, SQUID) 49
3.3.5化學分析電子儀(Electron Spectroscopy for Chemical Analysis ,ESCA) 50
第四章 研究結果 51
4.1 磁性奈米氧化鐵粒子特性分析 52
4.1.1磁性奈米氧化鐵粒子結構鑑定 52
4.1.2 XPS磁性奈米氧化鐵表面修飾分析 53
4.1.3 ICP磁性奈米氧化鐵修飾分析 58
4.1.4 SQUID磁場特性分析. 60
4.2磁性奈米粒子的表面分布 621
4.2.1奈米材料表面分布SEM圖 62
4.2.2 SEM圖晶體影像處裡 66
4.2.3 元素分析儀計算與晶體模型模擬 67
4.2.4 晶體模型磁力計算 69
4.3拉曼光譜儀量測之實際臨床樣本 70
4.4自動化系統開發 71
4.4.1 Labview螢光影像處理 72
4.4.2移動平台-馬達控制 74
4.4.3 自動化量測系統-拉曼光譜儀訊號量測 75
第五章 討論 76
第六章 未來展望 78
參考文獻 79

圖目錄
圖 1. 1 尿路結石於各國的盛行率 1
圖 1. 2 尿路結石復發率與時間關係 2
圖 1. 3 北市立聯合醫院尿液沉渣分析儀 3
圖 1. 4 尿路結石主要產生位置示意圖 5

圖2. 1 (i)螢光機制 (ii)紅外光吸收 (iii)拉曼光散射;h為蒲朗克常數,為光頻率 18
圖2. 2 史托克及反史托克拉曼能階變化示意圖 19
圖2. 3 雷利、史托克、反史托克之能量變化及數目比較 20
圖2. 4 入射光的電磁場產生之誘導偶極 20
圖2. 5 磁距產生示意圖(a.)電子繞原子核軌道運動(b.)磁距方向(c.)電子自旋 26
圖2. 6 磁滯現象,其中MR為殘留磁化量Ms為飽和磁化量;Hc為矯頑磁力 27
圖2. 7 典型的Langevin equation 27
圖2. 8 LabVIEW前置面板(front panel) 30
圖2. 9 LabVIEW後端程式(block diagram) 30
圖 3. 1 實驗流程圖 33
圖 3. 2 由左至右為EDC、NHS、氧化鐵、雙磷酸根 35
圖 3. 3 EDC、NHS、磷酸根混合後示意圖 36
圖 3. 4 超音波破碎機實驗圖 36
圖 3. 5 由左至右分別為超音波清洗機、離心機、離心管 37
圖 3. 6 離心清洗後濃縮的產物 37
圖 3. 7 自組拉曼光譜儀及光路圖 40
圖 3. 8 自動化量測系統流程圖 41
圖 3. 9 自動化量測系統架設圖 44
圖 4. 1 (a)磁石攪拌製程TEM圖(b)超音波破碎機製程之TEM圖 51
圖 4. 2 (a)、(b)分別為磁石攪拌製程及超音波破碎機製程 53
圖 4. 3超音波破碎機反應時間(a)1 hr、(b)2 hr 54
圖 4. 4 氧化鐵製程參數不同之數據(a)0 mg Gelatin(b)4 mg Gelatin 55
圖 4. 5 雙磷酸根修飾兩次之數據 56
圖 4. 6合成氧化鐵之磁化率分析 59
圖 4. 7 室溫中保存的氧化鐵磁化率分析 60
圖 4. 8 冰箱中保存的氧化鐵磁化率分析 60
圖 4. 9 (a)、(b)、(c)皆為單水草酸鈣與磁性奈米材料結合之SEM圖 62
圖 4. 10 (a)、(b)、(c)雙水草酸鈣與磁性奈米材料結合之SEM圖 63
圖 4. 11 (a)、(b)、(c)氫氧基磷灰石與磁性奈米材料結合之SEM圖 64
圖 4. 12 (a)SEM原始影像(b)銳化後SEM影像與 (c)ROI圈選區域 65
圖 4. 13 元素分析儀之鈣與鐵比例關係 66
圖 4. 14 (a)ROI分解之三角形區域面積(b)ROI分解之長方形區域面積 67
圖 4. 15 高倍率奈米顆粒與尿結晶結合之SEM圖 68
圖 4. 16 相機拍攝之螢光影像圖 71
圖 4. 17 (a)原始影像(b)灰階影像(c)取樣影像(d)樣本點分析 72
圖 4. 18 785 nm拉曼光譜儀量測之雙水草酸鈣光譜 74
圖 4. 19 785 nm拉曼光譜儀量測之單水草酸鈣光譜 74

表目錄
表1. 1 各類結石患者應注意的食物攝取 11
表1. 2 不同藥物可溶解的結石 12
表 3. 1 表面修飾時各藥品所需的參數劑量 35
表 3. 2 本團隊開發之自動化量測系統儀器及零件規格清單 42
表 4. 1 XPS數據所計算出Fe、O、P比例關係 53
表 4. 2 (a)1 hr、(b)2 hr反應時間 Fe、O與P比例關係 54
表 4. 3 不同參數0與4 mg Gelatin之Fe、O與P之比例關係 55
表 4. 4 雙磷酸根修飾實驗比較之Fe、O與P比例關係 57
表 4. 5 利用超音波破碎機測得之ICP重量百分濃度 57
表 4. 6 單磷酸根與雙磷酸根之比較濃度表 58
表 4. 7 實際尿液樣本量測表 69
表 4. 8 統計後實驗數據 70



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