簡易檢索 / 詳目顯示

研究生: 呂紹瑋
Shao-Wei Lu
論文名稱: 開發3D列印微流道系統結合液相層析質譜分析法用於人類肝臟微粒體代謝反應實驗 /開發具結構開-闔轉換之核酸適體感測系統-以卡西酮濫用藥物為例
Development of 3D-printing microfluidic system coupling to LC-MS for human liver microsomal reaction system / Development of a Aptasensor System with Structural openings and conversions - Take the example of cathinone drug abuse
指導教授: 陳品銓
Pin-Chuan Chen
口試委員: 陳珮珊
Pai-Shan Chen
劉沂欣
Yi-Hsin Liu
曾修暘
Hsiu-Yang Tseng
陳品銓
Pin-Chuan Chen
學位類別: 碩士
Master
系所名稱: 工程學院 - 機械工程系
Department of Mechanical Engineering
論文出版年: 2023
畢業學年度: 112
語文別: 中文
論文頁數: 97
中文關鍵詞: 核酸適體濫用藥物層析微流晶片感測器毒品檢測
外文關鍵詞: DNA aptamer, conformational change, on-off strategy, rapid screening
相關次數: 點閱:82下載:1
分享至:
查詢本校圖書館目錄 查詢臺灣博碩士論文知識加值系統 勘誤回報

酵素液與藥物的代謝反應一直都是一項重要的研究,代謝反應會使身
體對外在環境做出適當的反應,反過來說,人們可以藉由代謝反應的結果來
推算人體內的 酵素液與外來藥物產生的反 應結果或是對人體可能產生的副
作用,提早進行預防或是找尋解決方法。 然而,有鑑於酵素液與藥物的代謝
反應實驗需要經過十分繁瑣的流程,因而非常耗時。因此本研究旨在利用光
固化 3D列印技術開發一晶片,在模擬人體內環境溫度的情況下,將 加藥、
酵素液與藥物代謝反應、過濾、引導檢測等步驟於晶片本體上執行,省去了
傳統實驗上的液體移動、人為安裝拆卸管材等流程 ,使的實驗耗時大幅縮短
及增加 方便性 。 本研究利用 光固化 3D列印技術製作晶片 ,使晶片本身擁有
極高強度 ,搭配液相層析質譜儀進行檢測,藉由將在晶片內部進行反應的 代
謝後藥物導入質譜儀檢測, 紀錄其產生的質譜訊號 並 多次 與標準品做比對
並藉由同種藥物多次上機進行晶片穩定性測試 ,證明於晶片內產生的代謝
反應與標準品的反應為相同結果, 在檢化 實驗流程的同時獲得相同的代謝
反應結果。
基於 DNA核酸適體 的 傳感器是檢測特定分子的有力工具。然而,合成
卡西酮作為 一種新型精神活性物質 ,近 年 來 大受歡迎。由於卡西酮的核心 结
構易於合成,濫用者可以通過合成核心結構 來逃避法律制裁。因此,極需開
發一種具有核心結構靶向性和可變 換構象 特性的 DNA核酸適體傳感器,以
供現場使用。在此,我們 針對 合 成卡西酮家族設計了一種 新型的 基於 DNA核酸適體的傳感器。在金基板 上 連接了一個短的互補 DNA 以下簡稱
cDNA)序列,然後設計了帶有尾部和螢光基團 的 核酸適體與 cDNA進行雜
交。當核酸適體 與 cDNA雜交時,設計的尾部螢光基團垂至金基板上,導
致能量轉移。將合成卡西酮導入系統後 核酸適體與 cDNA雜交,將會捕
捉合成卡西酮,從而釋放出螢光訊號 。 因此,在 目標 分析物存在的情况下,
核酸適體的構象變化會引發螢光訊號的改變 。 該系統 在 5 nM 至 20 μM 的
濃度範圍内顯示出線性校正曲線 R2 = 0.993)),檢測極限為 60 pM。值得
注意的是,該檢測系統 可在 2 小時内快速改變訊號,從而實現高效的現場
檢測 。


The metabolic reaction of enzymes and drugs has always been an important study. The metabolic response enables the body to respond appropriately to the external environment, and in turn, the results of the metabolic response can be used to predict the outcome of the reaction between the enzymes and drugs in the body, or the possible side effects on the body, so that early prevention or solutions can be found. However, the metabolic reactions of enzymes and drugs are time-consuming because of the tedious process involved. Therefore, this study aims to develop a chip using light-curing 3D printing technology to perform the steps of drug dosing, metabolic reaction of enzyme solution and drug, filtration, and conductive detection on the chip itself under the simulation of human body's ambient temperature, which eliminates the traditional experimental processes such as liquid movement, human installation and removal of tubing, and greatly reduces the time-consumption of the experiments and increases the convenience.
In this study, we utilized light-curing 3D printing technology to produce chips with extremely high strength, and used liquid chromatography mass spectrometry (LC-MS/MS) to detect the metabolites reacting inside the chips, recorded their mass spectral signals and compared them with the standards several times, and tested the stability of the chips with the same drug several times on board the machine, which proved that the metabolic reactions inside the chips were the same as those of the standards, and that we could obtain the same results of metabolism reactions in the same way as the experimental process.
DNA aptamer-based sensors serve as a robust tool for detecting specific molecules. However, synthetic cathinone, a new psychoactive substance, has boomed significantly recently. Given the ease-synthesis core structure of the cathinone, the abuser can synthesize the core structure to avoid the administration of the law. Thus, a DNA aptamer with core structure targeting and switchable conformation properties aptasensor was urgent to develop for on-site use. Here, a novel DNA aptamer-based sensor is designed for the family of synthetic cathinones. A short complementary DNA (cDNA) sequence was attached to the gold substrate, and subsequently, the aptamer, designed with a tail and a fluorescent group, underwent hybridization with the cDNA. As the aptamer hybridized with the cDNA, the designed tail's conformation prolapsed onto the substrate, resulting in an energy transfer and the absence of a signal. Upon the introduction of synthetic cathinone into the system, the aptamer de-hybrid from the cDNA and target to the synthetic cathinone, leading to the release of the fluorescence signal. Therefore, a conformational change in the DNA aptamer triggers a fluorescence signal alteration in the presence of the target analyte. The system demonstrates a linear calibration curve within the concentration range of 5 nM to 20 μM (R2 = 0.993) and achieves a limit of detection of 60 pM. Notably, the platform facilitates rapid signal change within 2 hours, thereby enabling efficient on-site detection.

摘要 IV Abstract VI 誌謝 10 目錄 11 圖目錄 15 Part 1. 開發 3D列印微流道系統結合液相層析質譜分析法 用於人類肝臟微 粒體代謝反應實驗 第1章 Introduction 18 1.1 研究背景 18 1.2 液相層析串聯式質譜儀 19 1.2.1樣品導入系統 (Inlet system) 21 1.2.2離子源 (ion source) 21 1.2.3質量分析器 (Mass analyzer) 21 1.2.4離子偵測器 (ion detector) 22 1.2.5電腦數據處理系統 (Data 22 1.3 文獻探討 22 1.4 研究動機 .23 1.5 研究目的和目標 24 第2章 Materials and Manufacturing 25 2.1 研究設備介紹 25 2.1.1 製程設備、軟體 25 2.1.2 量 檢測設備、軟體 28 2.2 晶片設計 32 2.2.1 晶片設計 32 2.2.2 接頭設計 33 2.3 晶片製程 36 2.3.1 圖檔切層匯出 37 2.3.2 列印與後處理 38 2.3.3 濾膜黏合 39 第3章 Experiment Methods 41 3.1 藥品、實驗材料製備 41 3.2 濾膜的耐壓性測試 42 3.2.1 實驗方法與步驟 42 3.3 晶片儲存槽內溫度測試 44 3.3.1 實驗方法與步驟 44 3.4 液相層析質譜儀設定 45 3.5 體外人類肝臟 microsome的代謝反應實驗 45 3.5.1 實驗方法與步驟 46 3.6 HLM反應時間研究 47 第4章 Results and Discussion 48 4.1 濾膜的耐壓性測試 48 4.2 晶片儲存槽內溫度測試 49 4.3 體外人類肝臟 microsome的代謝反應實驗 50 4.4 HLM反應時間研究 50 第5章 Conclusion 52 Part 2. 開發具結構開 -闔轉換之核酸適體感測系統 -以卡西酮濫用藥物為例 第1章 Introduction 53 1.1 研究背景 53 1.2 核酸適體 (DNA Aptamer) 54 1.3 生物傳感器 56 1.4 適體感測器 (Aptasensor) 57 1.4.1電化學 適體感測器 (Electrochemical aptasensor) 58 1.4.2螢光 適體感測器 (Fluorescent aptasensor) 59 1.4.3比色法 適體感測器 (Colorimetric aptasensor) 60 1.4.4 Liquid crystal-based aptasensor 61 1.4.4.1 LC-solid interface aptasensor 61 1.4.4.2 LC-aqueous interface aptasensor 62 1.4.4.3 LC-droplet aptasensor 63 1.5 螢光共振能量轉移 (FRET) 64 1.6 濫用藥物 64 1.6.1新 精神活性物質 (NPS) 66 1.7 文獻探討 67 1.8 研究動機 69 1.9 研究目的和目標 70 第2章 Materials and Manufacturing 71 2.1 研究設備介紹 71 2.2 材料 /試劑 74 2.3 基板事前準備 74 2.3.1切割基板 74 2.3.2表 面清潔 75 第3章 Experiment Methods 76 3.1 配置結合緩衝液 76 3.1.1實驗方法與步驟 76 3.2 配置 核酸適體混合 cDNA溶液 77 3.3 配置 TCEP溶液 77 3.4 核酸適體與 cDNA鍵結時長測試 77 3.5 核酸適體捕捉 MDPV藥物測試 78 第4章 Results and Discussion 79 4.1 核酸適體與 cDNA鍵結時長測試 79 4.2 核酸適體捕捉 MDPV藥物測試 80 4.3 實驗參數優化 83 4.3.1核酸適體濃度、 cDNA濃度參數優化 83 4.3.2鍵結溫度參數優化 86 4.4 檢量線 86 第5章 Conclusion 89 參考文獻 90

1. National Taiwan University. 代謝(Metabolism). 2010 [cited 2023 September 21]; Available from: https://highscope.ch.ntu.edu.tw/wordpress/?p=9335.
2. Remmer, H., The role of the liver in drug metabolism. The American journal of medicine, 1970. 49(5): p. 617-629.
3. Tennant, D.A., et al., Metabolic transformation in cancer. Carcinogenesis, 2009. 30(8): p. 1269-1280.
4. Tennant, D.A., R.V. Durán, and E. Gottlieb, Targeting metabolic transformation for cancer therapy. Nature reviews cancer, 2010. 10(4): p. 267-277.
5. Pacifici, G.M., Metabolism and pharmacokinetics of morphine in neonates: A review. Clinics, 2016. 71: p. 474-480.
6. Mathijssen, R.H., et al., Clinical pharmacokinetics and metabolism of irinotecan (CPT-11). Clinical cancer research, 2001. 7(8): p. 2182-2194.
7. Yan, J., S. Li, and S. Li, The role of the liver in sepsis. International reviews of immunology, 2014. 33(6): p. 498-510.
8. Bachelor's Degree, D.o.C., National Taiwan Normal University, Yu Ziyu,. 凡第姆特方程式 (Van Deemter Equation). 2016 [cited 2023 September 20]; Available from: https://highscope.ch.ntu.edu.tw/wordpress/?p=71880.
9. Kinmen County Drug and Food Hygiene Section. 簡介液相層析 質譜/質譜儀 (LC MS/MS). 2023 [cited 2023 September 21]; Available from: https://phb.kinmen.gov.tw/cp.aspx?n=72C85AA55E751DE5&Create=1.
10. Shun-An Chan, T.-Y.L. The Principle and Applications of Liquid
Chromatography Tandem Mass Spectrometry. 2019 [cited 2023 September 20]; Available from: https://www.tiri.narl.org.tw/Files/Doc/Publication/InstTdy/129/01290770.pdf.
11. Kiiski, I., et al., Drug glucuronidation assays on human liver microsomes immobilized on microfluidic flow-through reactors. European Journal of Pharmaceutical Sciences, 2021. 158: p. 105677.
12. Zuo, H.-L., et al., Enzyme activity of natural products on cytochrome P450. Molecules, 2022. 27(2): p. 515.
13. National Taiwan University. 肝臟之藥物轉化機制(Drug Metabolism). 2009 [cited 2023 September 21]; Available from: https://highscope.ch.ntu.edu.tw/wordpress/?p=1013.
14. Volkow, N.D., Drugs, brains, and behavior: The science of addiction. Retrieved on March, 2010. 23(2011): p. 255-169.
15. Tuerk, C. and L. Gold, Systematic evolution of ligands by exponential enrichment: RNA ligands to bacteriophage T4 DNA polymerase. science, 1990. 249(4968): p. 505-510.
16. Chen, T., et al., Aptamer-conjugated nanomaterials for bioanalysis and biotechnology applications. Nanoscale, 2011. 3(2): p. 546-556.
17. Cho, E.J., J.-W. Lee, and A.D. Ellington, Applications of aptamers as sensors. Annual review of analytical chemistry, 2009. 2: p. 241-264.
18. Iliuk, A.B., L. Hu, and W.A. Tao, Aptamer in bioanalytical applications. Analytical chemistry, 2011. 83(12): p. 4440-4452.
19. Liu, D., Z. Wang, and X. Jiang, Gold nanoparticles for the colorimetric and fluorescent detection of ions and small organic molecules. Nanoscale, 2011. 3(4): p. 1421-1433.
20. Liu, J., Z. Cao, and Y. Lu, Functional nucleic acid sensors. Chemical reviews, 2009. 109(5): p. 1948-1998.
21. Lee, J.H., et al., Molecular diagnostic and drug delivery agents based on aptamer-nanomaterial conjugates. Advanced drug delivery reviews, 2010. 62(6): p. 592-605.
22. Mairal, T., et al., Aptamers: molecular tools for analytical applications. Analytical and bioanalytical chemistry, 2008. 390: p. 989-1007.
23. Ebrahimi, M., et al., Systematic evolution of ligands by exponential enrichment selection of specific aptamer for sensing of methamphetamine. Sensor Letters, 2013. 11(3): p. 566-570.
24. Liu, J. and Y. Lu, Fast colorimetric sensing of adenosine and cocaine based on a general sensor design involving aptamers and nanoparticles. Angewandte Chemie International Edition, 2006. 45(1): p. 90-94.
25. Yu, H., et al., In vitro isolation of small-molecule-binding aptamers with intrinsic dye-displacement functionality. Nucleic Acids Research, 2018. 46(8): p. e43-e43.
26. Stoltenburg, R., C. Reinemann, and B. Strehlitz, SELEX—A (r) evolutionary method to generate high-affinity nucleic acid ligands. Biomolecular engineering, 2007. 24(4): p. 381-403.
27. Goda, T. and Y. Miyahara, A hairpin DNA aptamer coupled with groove binders as a smart switch for a field-effect transistor biosensor. Biosensors and Bioelectronics, 2012. 32(1): p. 244-249.
28. Mao, K., et al., G-quadruplex–hemin DNAzyme molecular beacon probe for the detection of methamphetamine. RSC advances, 2016. 6(67): p. 62754-62759.
29. Pang, K.M., et al., Incorporation of aptamers in the terminal loop of shRNAs yields an effective and novel combinatorial targeting strategy. Nucleic acids research, 2018. 46(1): p. e6-e6.
30. Thomson, K., et al. Preliminary nanopore cheminformatics analysis of aptamer-target binding strength. in BMC bioinformatics. 2007. BioMed Central.
31. Feigon, J., T. Dieckmann, and F.W. Smith, Aptamer structures from A to ζ. Chemistry & Biology, 1996. 3(8): p. 611-617.
32. Hermann, T. and D.J. Patel, Adaptive recognition by nucleic acid aptamers. Science, 2000. 287(5454): p. 820-825.
33. Patel, D.J., et al., Structure, recognition and adaptive binding in RNA aptamer complexes. Journal of molecular biology, 1997. 272(5): p. 645-664.
34. Piganeau, N. and R. Schroeder, Aptamer structures: a preview into regulatory pathways? Chemistry & Biology, 2003. 10(2): p. 103-104.
35. Macaya, R.F., et al., Thrombin-binding DNA aptamer forms a unimolecular quadruplex structure in solution. Proceedings of the National Academy of Sciences, 1993. 90(8): p. 3745-3749.
36. Wang, K.Y., et al., A DNA aptamer which binds to and inhibits thrombin exhibits a new structural motif for DNA. Biochemistry, 1993. 32(8): p. 1899-1904.
37. Zhang, C., et al., Organophosphorus pesticides detection using broad-specific single-stranded DNA based fluorescence polarization aptamer assay. Biosensors and Bioelectronics, 2014. 55: p. 216-219.
38. Aviñó, A., et al., The effect on quadruplex stability of North-nucleoside derivatives in the loops of the thrombin-binding aptamer. Bioorganic & medicinal chemistry, 2012. 20(14): p. 4186-4193.
39. Cowan, J.A., et al., Recognition of a cognate RNA aptamer by neomycin B: quantitative evaluation of hydrogen bonding and electrostatic interactions. Nucleic acids research, 2000. 28(15): p. 2935-2942.
40. Pagano, B., et al., Stability and binding properties of a modified thrombin binding aptamer. Biophysical journal, 2008. 94(2): p. 562-569.
41. Chou, S.-H., K.-H. Chin, and A.H. Wang, DNA aptamers as potential anti-HIV agents. Trends in biochemical sciences, 2005. 30(5): p. 231-234.
42. Lin, P.-H., et al., Studies of the binding mechanism between aptamers and thrombin by circular dichroism, surface plasmon resonance and isothermal titration calorimetry. Colloids and Surfaces B: Biointerfaces, 2011. 88(2): p. 552-558.
43. Rohloff, J.C., et al., Nucleic acid ligands with protein-like side chains: modified aptamers and their use as diagnostic and therapeutic agents. Molecular Therapy-Nucleic Acids, 2014. 3.
44. Bjerregaard, N., P.A. Andreasen, and D.M. Dupont, Expected and unexpected features of protein‐binding RNA aptamers. Wiley Interdisciplinary Reviews: RNA, 2016. 7(6): p. 744-757.
45. Da Costa, J.B. and T. Dieckmann, Entropy and Mg 2+ control ligand affinity and specificity in the malachite green binding RNA aptamer. Molecular BioSystems, 2011. 7(7): p. 2156-2163.
46. Ghosh, G., D.-B. Huang, and T. Huxford, Molecular mimicry of the NF-κB DNA target site by a selected RNA aptamer. Current opinion in structural biology, 2004. 14(1): p. 21-27.
47. Horn, W.T., et al., The crystal structure of a high affinity RNA stem-loop complexed with the bacteriophage MS2 capsid: further challenges in the modeling of ligand–RNA interactions. Rna, 2004. 10(11): p. 1776-1782.
48. Ku, T.-H., et al., Nucleic acid aptamers: an emerging tool for biotechnology and biomedical sensing. Sensors, 2015. 15(7): p. 16281-16313.
49. Zahra, Q.u.a., Q.A. Khan, and Z. Luo, Advances in optical aptasensors for early detection and diagnosis of various cancer types. Frontiers in Oncology, 2021. 11: p. 632165.
50. Chambers, J.P., et al., Biosensor recognition elements. Current issues in molecular biology, 2008. 10(1-2): p. 1-12.
51. Ellington, A.D. and J.W. Szostak, In vitro selection of RNA molecules that bind specific ligands. nature, 1990. 346(6287): p. 818-822.
52. Pfeiffer, F. and G. Mayer, Selection and biosensor application of aptamers for small molecules. Frontiers in chemistry, 2016. 4: p. 25.
53. Sudsakorn, S., et al., Determination of 1, 25-dihydroxyvitamin D2 in rat serum using liquid chromatography with tandem mass spectrometry. Journal of chromatography B, 2011. 879(2): p. 139-145.
54. He, J.-L., et al., Fluorescence aptameric sensor for strand displacement amplification detection of cocaine. Analytical chemistry, 2010. 82(4): p. 1358-1364.
55. Stojanovic, M.N., P. De Prada, and D.W. Landry, Aptamer-based folding fluorescent sensor for cocaine. Journal of the American Chemical Society, 2001. 123(21): p. 4928-4931.
56. Wang, B., et al., Aptamer induced assembly of fluorescent nitrogen-doped carbon dots on gold nanoparticles for sensitive detection of AFB1. Biosensors and Bioelectronics, 2016. 78: p. 23-30.
57. Barthelmebs, L., et al., Electrochemical DNA aptamer-based biosensor for OTA detection, using superparamagnetic nanoparticles. Sensors and Actuators B: Chemical, 2011. 156(2): p. 932-937.
58. Ferapontova, E.E., E.M. Olsen, and K.V. Gothelf, An RNA aptamer-based electrochemical biosensor for detection of theophylline in serum. Journal of the American Chemical Society, 2008. 130(13): p. 4256-4258.
59. Nguyen, B.H., et al., Label-free detection of aflatoxin M1 with electrochemical Fe3O4/polyaniline-based aptasensor. Materials Science and Engineering: C, 2013. 33(4): p. 2229-2234.
60. Pu, H., et al., Development of a highly sensitive colorimetric method for detecting 17β-estradiol based on combination of gold nanoparticles and shortening DNA aptamers. Water, Air, & Soil Pollution, 2019. 230: p. 1-9.
61. Song, K.-M., et al., Gold nanoparticle-based colorimetric detection of kanamycin using a DNA aptamer. Analytical biochemistry, 2011. 415(2): p. 175-181.
62. Yeasmin, S., et al., Colorimetric urinalysis for on-site detection of metabolic biomarkers. ACS applied materials & interfaces, 2020. 12(28): p. 31270-31281.
63. Hosseini, M., et al., Aptamer-based colorimetric and chemiluminescence detection of aflatoxin B1 in foods samples. Acta Chimica Slovenica, 2015. 62(3): p. 721-728.
64. Leung, K.-H., et al., A label-free luminescent switch-on assay for ATP using a G-quadruplex-selective iridium (III) complex. PloS one, 2013. 8(10): p. e77021.
65. Li, Y., X. Ji, and B. Liu, Chemiluminescence aptasensor for cocaine based on double-functionalized gold nanoprobes and functionalized magnetic microbeads. Analytical and bioanalytical chemistry, 2011. 401: p. 213-219.
66. Cheng, S., et al., Detection of bleomycin and its hydrolase by the cationic surfactant-doped liquid crystal-based sensing platform. Analytica Chimica Acta, 2021. 1150: p. 338247.
67. Hong, P.T.K., K. Yun, and C.-H. Jang, Liquid crystal-based droplet sensor for the detection of Hg (II) ions using an aptamer as the recognition element. BioChip Journal, 2021. 15: p. 152-161.
68. Qi, L., et al., Simultaneous detection of multiple tumor markers in blood by functional liquid crystal sensors assisted with target-induced dissociation of aptamer. Analytical chemistry, 2020. 92(5): p. 3867-3873.
69. Kiani, Z., et al., In vitro selection and characterization of deoxyribonucleic acid aptamers for digoxin. Analytica chimica acta, 2012. 748: p. 67-72.
70. Lee, K., et al., Ultrasensitive detection and risk assessment of di (2-ethylhexyl) phthalate migrated from daily-use plastic products using a nanostructured electrochemical aptasensor. Sensors and Actuators B: Chemical, 2022. 357: p. 131381.
71. Verdian, A., Z. Khoshbin, and C.-H. Chen, Development of a novel liquid crystal Apta-sensing platform using P-shape molecular switch. Biosensors and Bioelectronics, 2022. 199: p. 113882.
72. Verdian, A., Z. Rouhbakhsh, and E. Fooladi, An ultrasensitive platform for PCB77 detection: New strategy for liquid crystal-based aptasensor fabrication. Journal of Hazardous Materials, 2021. 402: p. 123531.
73. Xia, Y., et al., A visible and colorimetric aptasensor based on DNA-capped single-walled carbon nanotubes for detection of exosomes. Biosensors and Bioelectronics, 2017. 92: p. 8-15.
74. Baker, B.R., et al., An electronic, aptamer-based small-molecule sensor for the rapid, label-free detection of cocaine in adulterated samples and biological fluids. Journal of the American Chemical Society, 2006. 128(10): p. 3138-3139.
75. Rozenblum, G.T., I.G. Pollitzer, and M. Radrizzani, Challenges in electrochemical aptasensors and current sensing architectures using flat gold surfaces. Chemosensors, 2019. 7(4): p. 57.
76. Yu, Z.-g., A.L. Sutlief, and R.Y. Lai, Towards the development of a sensitive and selective electrochemical aptamer-based ampicillin sensor. Sensors and Actuators B: Chemical, 2018. 258: p. 722-729.
77. Ozaki, H., et al., Biomolecular sensor based on fluorescence-labeled aptamer. Bioorganic & Medicinal Chemistry Letters, 2006. 16(16): p. 4381-4384.
78. Rehm, D. and A. Weller, Kinetics of fluorescence quenching by electron and H‐atom transfer. Israel Journal of Chemistry, 1970. 8(2): p. 259-271.
79. Tang, Z., et al., Aptamer switch probe based on intramolecular displacement. Journal of the American Chemical Society, 2008. 130(34): p. 11268-11269.
80. Liu, J. and Y. Lu, Preparation of aptamer-linked gold nanoparticle purple aggregates for colorimetric sensing of analytes. Nature protocols, 2006. 1(1): p. 246-252.
81. Xu, Y., et al., Ultrasensitive and selective detection of SARS-CoV-2 using thermotropic liquid crystals and image-based machine learning. Cell Reports Physical Science, 2020. 1(12).
82. Deng, S., et al., Liquid crystal biosensor based on Cd 2+ inducing the bending of PS-oligo for the detection of cadmium. Health, 2015. 7(08): p. 986.
83. Chang, T.-K., et al., A liquid-crystal aptasensing platform for label-free detection of a single circulating tumor cell. Biosensors and Bioelectronics, 2022. 216: p. 114607.
84. Nguyen, D.K. and C.-H. Jang, Label-free liquid crystal-based biosensor for detection of dopamine using DNA aptamer as a recognition probe. Analytical biochemistry, 2020. 605: p. 113807.
85. Nguyen, D.K. and C.-H. Jang, A label-free liquid crystal biosensor based on specific DNA aptamer probes for sensitive detection of amoxicillin antibiotic. Micromachines, 2021. 12(4): p. 370.
86. Ren, H., Z. An, and C.-H. Jang, Liquid crystal-based aptamer sensor for sensitive detection of bisphenol A. Microchemical Journal, 2019. 146: p. 1064-1071.
87. Rouhbakhsh, Z., A. Verdian, and G. Rajabzadeh, Design of a liquid crystal-based aptasensing platform for ultrasensitive detection of tetracycline. Talanta, 2020. 206: p. 120246.
88. Wang, Y., et al., Aptamer based bare eye detection of kanamycin by using a liquid crystal film on a glass support. Microchimica Acta, 2017. 184: p. 3765-3771.
89. Wang, Y., et al., Detection of pulmonary surfactant protein A by using an aptamer-based liquid crystal biosensor. Analytical Methods, 2018. 10(24): p. 2895-2900.
90. Noonan, P.S., R.H. Roberts, and D.K. Schwartz, Liquid crystal reorientation induced by aptamer conformational changes. Journal of the American Chemical Society, 2013. 135(13): p. 5183-5189.
91. Wang, S., et al., Sensing of cocaine using polarized optical microscopy by exploiting the conformational changes of an aptamer at the water/liquid crystal interface. Microchimica Acta, 2019. 186: p. 1-7.
92. Nguyen, D.K. and C.-H. Jang, A cationic surfactant-decorated liquid crystal-based aptasensor for label-free detection of malathion pesticides in environmental samples. Biosensors, 2021. 11(3): p. 92.
93. Verma, I., et al., Liquid crystal based detection of Pb (II) ions using spinach RNA as recognition probe. Langmuir, 2019. 35(24): p. 7816-7823.
94. Wu, W., et al., Screening of xanthine oxidase inhibitors by liquid crystal-based assay assisted with enzyme catalysis-induced aptamer release. Analytical Chemistry, 2021. 93(15): p. 6151-6157.
95. Yang, X. and Z. Yang, Simple and rapid detection of ibuprofen─ a typical pharmaceuticals and personal care products─ by a liquid crystal aptasensor. Langmuir, 2021. 38(1): p. 282-288.
96. Yang, X., et al., Simple, rapid and sensitive detection of Parkinson's disease related alpha-synuclein using a DNA aptamer assisted liquid crystal biosensor. Soft Matter, 2021. 17(18): p. 4842-4847.
97. Academia Sinica Institute, A.a.M.S. Surface plasmon coupling resonance energy transfer. 2018 [cited 2023 September 20]; Available from: https://www.nstc.gov.tw/nstc/attachments/77152d3a-9726-4836-88f8-06087d19ba1c.
98. Ministry of Health and Welfare. 111年「藥物濫用案件暨檢驗統計資料」年報. 2022 [cited 2023 September 27].
99. Britannica, T., Editors of encyclopaedia. Argon. Encyclopedia Britannica, 2020.
100. United Nations Office on Drugs and Crime. What are NPS? 2023 [cited 2023 September 21]; Available from: https://www.unodc.org/LSS/Page/NPS.
101. Madras, B.K., The growing problem of new psychoactive substances (NPS). Neuropharmacology of New Psychoactive Substances (NPS) The Science Behind the Headlines, 2017: p. 1-18.
102. Munzar, J.D., A. Ng, and D. Juncker, Comprehensive profiling of the ligand binding landscapes of duplexed aptamer families reveals widespread induced fit. Nature communications, 2018. 9(1): p. 343.
103. Chen, C.-Y., et al., Self-standing aptamers by an artificial defect-rich matrix. Nanoscale, 2018. 10(7): p. 3191-3197.
104. Liu, Y., et al., Tuning biosensor cross-reactivity using aptamer mixtures. Analytical chemistry, 2020. 92(7): p. 5041-5047.
105. Mao, K., et al., A novel colorimetric biosensor based on non-aggregated Au@ Ag core–shell nanoparticles for methamphetamine and cocaine detection. Talanta, 2017. 175: p. 338-346.

無法下載圖示
全文公開日期 2024/12/19 (校外網路)

QR CODE