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研究生:沈庭瑤
研究生(外文):Ting-Yao SHEN
論文名稱:可攜式表面電漿共振儀器於即時檢測古柯鹼代謝物濃度之應用
論文名稱(外文):Real-Time Detection of Benzoylecgonine by Using the Portable Surface Plasmon Resonance System
指導教授:李光申李光申引用關係
指導教授(外文):Oscar K. Lee
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:2016
畢業學年度:104
語文別:英文
論文頁數:47
中文關鍵詞:表面電漿共振儀器古柯鹼代謝物可攜式儀器即時檢測
外文關鍵詞:Surface plasmon resonanceBenzoylecgoninePortable systemReal-time detection
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生物傳感器可在生物醫學領域中提供生物樣品的快速檢測。生物傳感器不只能監測幹細胞的分化過程、偵測蛋白質和定量蛋白質的濃度、檢測病原體還能製成生物晶片檢測毒品濫用。其中,表面電漿共振儀為廣泛使用之一種工具,因為表面電漿共振儀的靈敏度高,並且可以透過訊號改變即時檢測樣品狀態。
古柯鹼,又譯為可卡因,是一種具有強烈刺激性以及成癮性的藥物,吸食者通常利用此藥物來製造快感,此藥物易產生耐受性,因此成癮者必需一直增加使用劑量才能帶來相同效果。古柯鹼會阻礙腦部神經傳傳導物質多巴胺的傳遞,並影響正腎上腺素、血清素正常攝取,它也能輕易的越過血腦屏障,導致腦部的損傷。目前,不論在美國或是台灣,古柯鹼都是被嚴重濫用的藥物之一。因此,如何建立一個快速以及簡單測量古柯鹼及其代謝物的儀器已經成為一個重要課題。
根據文獻顯示,目前偵測古柯鹼代謝物的方法有氣相層析質譜儀、液相層析質譜儀以及酵素連結免疫吸附法…等等,但這些方法皆需要繁複的樣品製備流程。因此在本研究中,我們設計了一個新穎且可攜帶式的表面電漿共振儀,操作簡單,且無須標定檢測物的即時觀測系統,來檢測古柯鹼的主要代謝物。研究結果顯示,此台儀器的解析度可以高達10-5單位折射率;我們也利用這台儀器,成功的建立古柯鹼代謝物的標準曲線。綜觀上述結果,我們成功的設計一台可攜帶式的表面電漿共振儀器,並且利用它建立古柯鹼代謝物的標準曲線,奠定了一個快速藥物檢測的基石。我們期望這項研究不只能檢測古柯鹼,更能檢測其他毒品之代謝物,讓藥物檢測省去繁複的樣品製備過程,快速得到檢測結果。

Nowadays, biosensors are ideal for the rapid detection in the biological field such as for monitoring the differentiation of stem cells, detection of proteins and their quantification, detection of pathogens, drugs abuse test etc. Among the biosensors, surface plasmon resonance (SPR) biosensors have been considered as a powerful and widely used because of its high sensitivity and real-time detection.
Cocaine, also called as benzoylmethylecgonine or coke. It is a strong stimulant, addictive drug and commonly used for recreation. It inhibits the reuptake of serotonin, norepinephrine, and dopamine, and can easily cross the blood–brain barrier, may lead to the breakdown of the barrier. No matter in U.S.A. or Taiwan, cocaine is one of the most abusive drugs. Is it necessary to build up a system which can rapidly and easily test cocaine or its metabolism, benzoylecgonine (BZE).
According to the literatures, there are many ways can be use in benzoylecgonine detection, including gas chromatography mass spectrometry (GC-MS), liquid chromatography mass spectrometry (LC-MS), and enzyme-linked immunosorbent assay (ELISA). However, we need to go through many processes to prepare the samples for these detection ways.
In our study, we proposed a novel portable surface plasmon resonance system which can easily use, label free and real-time detect the main metabolism of cocaine, benzoylecgonine. The results showed that the resolution of this portable surface plasmon resonance system can reach to 10-5 RIU. We also successfully established a standard curve of benzoylecgonine by using this portable system.
In summary, this potable surface plasmon resonance system provides a real-time detection way for the detection of benzoylecgonine. We expect that this study can not only detect benzoylecgonine but also the metabolisms of other drugs.

Content i
Table content iii
Figure content iv
中文摘要 v
Abstract vii
Abbreviations ix
1 Introduction 1
1.1 Drugs Abuse and Addiction 1
1.2 Cocaine 1
1.2.1 Effects of Cocaine in Human Body 2
1.2.2 Metabolic Pathway in Human Body 3
1.2.3 Traditional Examination Methods of Benzoylecgonine 3
1.3 Biosensor 4
1.4 Surface Plasmon Resonance 5
1.4.1 Principal of Evanescent Wave 6
1.4.2 Surface Plasmon Wave 7
1.4.3 Coupling Methods of Surface Plasmon Resonance 8
1.5 Motivation 10
2 Materials and Methods 11
2.1 Prism Cleaning 11
2.2 Gold Film Coating 11
2.3 Surface Modification on Gold 12
2.4 Microfluidic Device 13
2.5 Sample Preparation 14
2.6 Portable Surface Plasmon Resonance 14
2.6.1 Set Up 14
2.6.2 LabVIEW Program 15
2.6.3 Parameter Setting and Detection Procedures 16
2.7 Data Processing and Data Analysis 17
3 Results 18
3.1 SPR System Setup and Laser Calibration 18
3.2 SPR System Resolution Test 19
3.3 Surface Modification and Antibody Coating Condition Test 20
3.4 Specificity Control and Antibody Control of Coated Prism 20
3.5 Establish a Standard Curve of Benzoylecgonine 22
4 Discussion 23
5 Conclusion 25
6 Reference 26
7 Tables 29
8 Figures 31


Table content
Table 1. Brief comparison between various schemes in SPR sensing 29
Table 2. Resolution calculation of portable SPR system. 30


Figure content
Figure 1. Major Metabolites of Cocaine[8]. 31
Figure 2. Schematic diagram briefly describes the components of biosensor. 32
Figure 3. Surface plasmons. 33
Figure 4. Schematic diagram of grating structure. 34
Figure 5. (a) Otto configuration. (b) Kretschmann configuration. 34
Figure 6. Using Optical fiber to generate surface plasmon resonance. 35
Figure 7. (a) The schematic diagram of our special design prism. (b) The picture of our special design prism. 36
Figure 8. (a) Showing the components of microfluidic device. (b) Microfluidic device after combination. (c) The combination of microfluidic device and prism. 37
Figure 9. (a) Schematic setup diagram of novel portable SPR system. 38
Figure 10. Figure of the working panels of LabVIEW system. 39
Figure 11. Different SPR curves from four different prims. 40
Figure 12. Resolution test of portable SPR system. 41
Figure 13. Surface modification and antibody immobilization test. 42
Figure 14. Specificity control. 43
Figure 15. (a) Specificity control group: intensity comparison between BZE and BSA solutions. (b) The average value and standard deviation. 44
Figure 16. Antibody control. 45
Figure 17. (a) Antibody control group: intensity comparison between immobilized anti-BZE and anti-IgG (b) The average value and standard deviation from (a). 46
Figure 18. BZE standard curve. 47



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