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完整後設資料紀錄
DC 欄位 | 值 | 語言 |
---|---|---|
dc.contributor.advisor | 陳珮珊 | zh_TW |
dc.contributor.advisor | Pai-shan Chen | en |
dc.contributor.author | 吳弈欣 | zh_TW |
dc.contributor.author | Yi-Hsin Wu | en |
dc.date.accessioned | 2023-09-08T16:06:27Z | - |
dc.date.available | 2023-11-09 | - |
dc.date.copyright | 2023-09-08 | - |
dc.date.issued | 2023 | - |
dc.date.submitted | 2023-08-01 | - |
dc.identifier.citation | [1] S. Kailasam, LC-MS – What Is LC-MS, LC-MS Analysis and LC-MS/MS, 2022. https://www.technologynetworks.com/analysis/articles/lc-ms-what-is-lc-ms-lc-ms-analysis-and-lc-msms-348238.
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dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/89511 | - |
dc.description.abstract | 本研究旨在開發將3D列印微流道裝置結合至液相層析質譜分析法之新穎系統,以改進現有的體外肝臟微小體代謝反應以及紙噴灑游離法等分析方法,並且嘗試並優化使用紙噴灑游離法檢測微小RNA。本研究所開發之:(1) 3D列印微流道肝臟微小體代謝裝置-液相層析質譜分析系統整合了傳統使用人類肝臟微小體進行藥物代謝物體外合成以及液相層析質譜的分析流程。此一微流道裝置可以成功進行肝臟微小體之藥物代謝反應且其反應效率與傳統方法相仿,該裝置亦搭載超過濾濾膜以將試樣中的肝臟微小體濾除,並可搭配六向閥直接進行液相層析質譜分析。此一系統具良好的精準性及再現性,其在連續分析中的訊號遲滯時間以及訊號積分面積之相對標準誤差僅有0.91%及2.53%。(2) 3D列印紙基微管柱-液相層析質譜分析系統解決了傳統紙基材料的諸多劣勢,包含有限的分析時間、嚴重的樣品擴散、再現性不佳以及缺乏可靠的層析分離能力等等。此製程可於一分鐘內在一片紙張當中建構出精確的3D微流道結構。此一設計可以減少樣品於紙基上的任意擴散,並且大幅增強紙基的強度。紙基微管柱可在沒有額外支撐器材之存在下,提供長達 50 分鐘以上的分析時間。紙基微管柱可以重複清洗利用,清洗並不會造成訊號減弱且五次清洗-使用間的訊號強度之相對標準誤差僅有9.5%。紙基微管柱可以搭配液相層析儀進行梯度沖堤,在一片紙材上完成3種具有不同極性的精神活性物質及代謝物methamphetamine, 7-aminonitrazepam, 以及morphine-3-glucuronide之層析分離,三種物質於紙基微管柱上之層析解析度達0.50 至1.21。紙基微管柱搭配液相層析質譜法在血漿樣品的中偵測極限達0.5至1 ng mL-1,並且有優秀的線性範圍(5 至 500 ng mL-1 , R2 介於0.9925及0.9999之間)及良好的準確性(bias介於 -13% ~ 9.1%),且僅需使用1 μL之樣品。本研究所開發之紙基微管柱裝置展現了良好的分析性能且可以適用廣泛的分析對象,為具有相當潛力之生醫檢測分析技術。本研究亦嘗試以PSI-MS分析微小RNA分子。實驗發現,常規使用的親水性濾紙基材並不適合用以作為PSI-MS分析微小RNA的材料,而疏水性材料如經silicone或樹脂處理過後的濾紙皆能成功檢測到微小RNA。 | zh_TW |
dc.description.abstract | In this study, systems combining 3D printing microfluidic technology and liquid chromatography-mass spectrometry (LC-MS) were carried out, regarding the in vitro human liver microsomal(HLM) metabolic reaction, the paper spray ionization-mass spectrometry(PSI-MS), and the microRNA detection using PSI-MS. (1)A 3D print-microfluidic HLM reaction device-LC-MS system integrating the HLM reaction for drug metabolism and LC-MS was developed. The system successfully allowed HLM reaction to occur with a similar efficiency compared to the traditional method. The device also came with an ultrafiltration unit to exclude the microsomes into the LC-MS system, which allowed a direct analysis through the incorporation of a 6-port vale. The proposed system showed a good precision and reproducibility where the RSD of the chromatographic retention time and the peak area of a series of acquisition was only 0.91% and 2.53%. (2) A novel approach termed µPC-LC-MS, which combines stereolithography 3D printing with microfluidic paper-based columns and liquid chromatography-mass spectrometry was proposed. This method addresses the limitations of traditional PSI-MS, such as short lifespan, inability to reuse, analyte diffusion, and the lack of proper chromatography. By fabricating well-defined microchannels in a piece of filter paper within seconds, we significantly improved the substrate's lifespan, allowing 50 minutes per analysis using continuous solvent supply for LC pumps. Reuse of up to 5 cycles without compromising the signal, overloading, or carry-over was achieved in a single μPC, with a reproducibility of 9.5%. We successfully separated three psychoactive substances/metabolites with the chromatographic resolution ranging from 0.50 to 1.21, achieving great sensitivity (0.5 - 1 ng mL-1 LOD) and good accuracy (87.0% to 109.1%). The method demonstrated linearity across 3 magnitudes in plasma and water, with a R2 ranging from 0.9925 to 0.9999, using only 1 µL of plasma. These results showcase the robustness and sensitivity of the µPC-LC-MS, suggesting µPC-LC-MS to be a promising bioanalysis platform using μPADs technology. (3) Additionally, the detection of miRNA using PSI-MS was also investigated, in which the traditional hydrophilic paper substrate was proved to be not suitable for miRNA detection in PSI-MS. In contrast, the hydrophobic substates provided an improved performance for miRNA detection. According to the results, we assume that this effect may stem from the fact that the hydrophilic paper substrate might provide a retention that was too strong towards the hydrophilic, multiple-charged miRNA molecules, hence hampering the detection. | en |
dc.description.provenance | Submitted by admin ntu (admin@lib.ntu.edu.tw) on 2023-09-08T16:06:27Z No. of bitstreams: 0 | en |
dc.description.provenance | Made available in DSpace on 2023-09-08T16:06:27Z (GMT). No. of bitstreams: 0 | en |
dc.description.tableofcontents | 誌謝 i
中文摘要 ii Abstract iii Contents v Figures viii Tables xii Terminology xiii Chapter 1. Introduction 1 1.1. LC-MS/MS 1 1.2. Ambient ionization MS techniques 6 1.3. Paper spray ionization (PSI) 8 1.3.1. PSI-MS 8 1.3.2. Enhancing PSI-MS 9 1.3.3. Paper chromatography 15 1.4. Microfluidic device 16 1.5. Paper-based microfluidics devices (μPADs) 17 1.5.1. μPADs & PSI-MS 21 1.6. in vitro human liver microsomal metabolic system 23 1.6.1. Drug metabolism in the human body 23 1.6.2. Human liver microsome 24 1.7. Drug abuse 26 1.8. MicroRNA 28 1.8.1. miRNA as biomarker and diagnostic 30 1.8.2. miRNA detection using PSI-MS 31 1.8.3. miR-181 family 33 1.9. Objectives and Aims 35 Chapter 2. Material and Methods 36 2.1. HLM-reaction chip 36 2.1.1. Materials and reagents 36 2.1.2. Design and Manufacturing 36 2.1.3. Temperature monitoring 37 2.1.4. in vitro human liver microsomal metabolic reaction 38 2.1.5. Time course study of HLM reaction 39 2.1.6. LC-MS/MS 39 2.2. Micro-paper column (μPC) 40 2.2.1. Materials and chemicals 40 2.2.2. Instrumentation of Paper spray ionization – MS 41 2.2.3. Fabrication of the μPC 42 2.2.4. Optimization of the μPC design 43 2.2.5. Evaluate the spray performance of μPC 46 2.2.6. Paper column chromatography (μPC-LC-MS) 47 2.2.7. Calibration curves and LOD 47 2.2.8. Method validation 48 2.2.9. Statistical analysis 48 Chapter 3. Results and Discussion 49 3.1. Development of in vitro microfluidic HLM reaction-LC-MS system 49 3.1.1. Design of the microfluidic HLM reaction device 49 3.1.2. Assessment of the ultrafiltration membrane pressure 50 3.1.3. Validation of the microfluidic device-LC-MS system 52 3.1.4. Temperature monitoring inside the reaction chamber 53 3.1.5. HLM reaction compare to the traditional method 54 3.2. Development of 3D printing micro-paper column (3DP μPC) 55 3.2.1. MS signal optimization of selected compounds 55 3.2.2. Characterization of the μPC 63 3.2.3. MS setup optimization 65 3.2.4. Characterization of the paper column 67 3.2.5. Spray performance of the paper chip 70 3.3. Determination of abused substances using μPC-LC-MS 72 3.3.1. Paper column chromatography 72 3.3.2. Analytical performance 77 3.4. Development of submarine-μPC 82 3.4.1. Characterization of submarine-μPC-MS 82 3.5. Detection of miRNA using PSI-MS 86 3.5.1. Characterization and optimization of miRNA using ESI-MS 86 3.5.2. Challenges in miRNA detection using regular PSI-MS 88 3.5.3. Hydrophobic materials aid in miRNA detection 90 Chapter 4. Conclusion 94 Reference 97 Appendix 104 | - |
dc.language.iso | en | - |
dc.title | 開發3D列印微流道系統結合液相層析質譜分析法:紙基微管柱及肝臟細胞微小體反應裝置 | zh_TW |
dc.title | Development of 3D-printing microfluidic system coupling to LC-MS: Micro-paper column and human liver microsomal reaction system | en |
dc.type | Thesis | - |
dc.date.schoolyear | 111-2 | - |
dc.description.degree | 碩士 | - |
dc.contributor.oralexamcommittee | 陳品銓;龔秀妮 | zh_TW |
dc.contributor.oralexamcommittee | Pin-Chuan Chen;Hsiu-Ni Kung | en |
dc.subject.keyword | 液相層析質譜法,3D列印,紙基微流道晶片,藥物代謝,人類肝臟微小體,紙噴灑游離法,微小RNA, | zh_TW |
dc.subject.keyword | Liquid chromatography-mass spectrometry,3D printing stereolithography,drug metabolism,human liver microsome,microfluidics,paper-based microfluidics,paper spray ionization,microRNA, | en |
dc.relation.page | 105 | - |
dc.identifier.doi | 10.6342/NTU202302331 | - |
dc.rights.note | 同意授權(限校園內公開) | - |
dc.date.accepted | 2023-08-01 | - |
dc.contributor.author-college | 醫學院 | - |
dc.contributor.author-dept | 毒理學研究所 | - |
顯示於系所單位: | 毒理學研究所 |
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