請用此 Handle URI 來引用此文件：
http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/90743完整後設資料紀錄
| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 林啟萬 | zh_TW |
| dc.contributor.advisor | Chii-Wann Lin | en |
| dc.contributor.author | 江佳陵 | zh_TW |
| dc.contributor.author | Chia-Ling Chiang | en |
| dc.date.accessioned | 2023-10-03T17:25:33Z | - |
| dc.date.available | 2023-11-30 | - |
| dc.date.copyright | 2023-10-03 | - |
| dc.date.issued | 2023 | - |
| dc.date.submitted | 2023-07-27 | - |
| dc.identifier.citation | [1] I. Ahmed, A. Majeed, and R. Powell, "Heparin induced thrombocytopenia: diagnosis and management update," Postgraduate medical journal, vol. 83, no. 983, pp. 575-582, 2007.
[2] A. Cuker, "Heparin-induced thrombocytopenia: present and future," Journal of thrombosis and thrombolysis, vol. 31, pp. 353-366, 2011. [3] E. Shantsila, G. Y. Lip, and B. H. Chong, "Heparin-induced thrombocytopenia: a contemporary clinical approach to diagnosis and management," Chest, vol. 135, no. 6, pp. 1651-1664, 2009. [4] T. E. Warkentin et al., "Heparin-induced thrombocytopenia in patients treated with low-molecular-weight heparin or unfractionated heparin," New England Journal of Medicine, vol. 332, no. 20, pp. 1330-1336, 1995. [5] R. Strauss, M. Wehler, K. Mehler, D. Kreutzer, C. Koebnick, and E. G. Hahn, "Thrombocytopenia in patients in the medical intensive care unit: bleeding prevalence, transfusion requirements, and outcome," Critical care medicine, vol. 30, no. 8, pp. 1765-1771, 2002. [6] T. Gallo et al., "A computerized scoring system to improve assessment of heparin‐induced thrombocytopenia risk," Journal of Thrombosis and Haemostasis, vol. 17, no. 2, pp. 383-388, 2019. [7] M. Nagler and A. Cuker, "Profile of Instrumentation Laboratory’s HemosIL® AcuStar HIT-Ab (PF4-H) assay for diagnosis of heparin-induced thrombocytopenia," Expert review of molecular diagnostics, vol. 17, no. 5, pp. 419-426, 2017. [8] J. B. Giles, E. C. Miller, H. E. Steiner, and J. H. Karnes, "Elucidation of Cellular Contributions to Heparin-Induced Thrombocytopenia Using Omic Approaches," Frontiers in Pharmacology, vol. 12, p. 4162, 2022. [9] S. Hosseini et al., "Advantages, disadvantages and modifications of conventional ELISA," Enzyme-linked Immunosorbent Assay (ELISA) From A to Z, pp. 67-115, 2018. [10] X. Liu et al., "Sensitivity-enhancement of wavelength-modulation surface plasmon resonance biosensor for human complement factor 4," Analytical biochemistry, vol. 333, no. 1, pp. 99-104, 2004. [11] J.-Y. Kim, Z.-C. Zeng, L. Xiao, and Z. D. Schultz, "Elucidating protein/ligand recognition with combined surface plasmon resonance and surface enhanced Raman spectroscopy," Analytical chemistry, vol. 89, no. 24, pp. 13074-13081, 2017. [12] J.-F. Masson, "Surface plasmon resonance clinical biosensors for medical diagnostics," ACS sensors, vol. 2, no. 1, pp. 16-30, 2017. [13] C. Fasolato, Surface enhanced Raman spectroscopy for biophysical applications: using plasmonic nanoparticle assemblies. Springer, 2018. [14] M. Krstić and S. Ražić, "Analytical approaches to the characterization of solid drug delivery systems with porous adsorbent carriers," Current Medicinal Chemistry, vol. 25, no. 33, pp. 3956-3972, 2018. [15] P. Rostron, S. Gaber, and D. Gaber, "Raman spectroscopy, review," laser, vol. 21, p. 24, 2016. [16] J. McLean, "The thromboplastic action of cephalin," American Journal of Physiology-Legacy Content, vol. 41, no. 2, pp. 250-257, 1916. [17] W. H. Howell and E. Holt, "Two new factors in blood coagulation—heparin and pro-antithrombin," American Journal of Physiology-Legacy Content, vol. 47, no. 3, pp. 328-341, 1918. [18] T. Barrowcliffe, "History of heparin," Heparin-A Century of progress, pp. 3-22, 2012. [19] A. Charles and D. Scott, "Studies on heparin: II. Heparin in various tissues," Journal of Biological Chemistry, vol. 102, no. 2, pp. 431-435, 1933. [20] C. H. Best, "Preparation of heparin and its use in the first clinical cases," Circulation, vol. 19, no. 1, pp. 79-86, 1959. [21] E. Johnson et al., "Four heparin preparations: anti-Xa potentiating effect of heparin after subcutaneous injection," Thrombosis and haemostasis, vol. 35, no. 03, pp. 586-591, 1976. [22] V. Kakkar, B. Djazaeri, J. Fok, M. Fletcher, M. Scully, and J. Westwick, "Low-molecular-weight heparin and prevention of postoperative deep vein thrombosis," Br Med J (Clin Res Ed), vol. 284, no. 6313, pp. 375-379, 1982. [23] U. Schmitz-Huebner et al., "Clinical efficacy of low molecular weight heparin in postoperative thrombosis prophylaxis," Klinische Wochenschrift, vol. 62, no. 8, pp. 349-353, 1984. [24] M. Koller, U. Schoch, P. Buchmann, F. Largiadèr, A. von Felten, and P. G. Frick, "Low Molecular Weight Heparin (KABI2165) as Thromboprophylaxis in Elective Visceral Surgery," Thrombosis and haemostasis, vol. 56, no. 06, pp. 243-246, 1986. [25] R. D. Hull et al., "Low-molecular-weight heparin vs heparin in the treatment of patients with pulmonary embolism," Archives of internal medicine, vol. 160, no. 2, pp. 229-236, 2000. [26] W. Ageno and A. G. Turpie, "Therapy of unstable angina with the low molecular weight heparins," Vascular Medicine, vol. 5, no. 4, pp. 217-223, 2000. [27] B. W. Cook, "Anticoagulation management," in Seminars in interventional radiology, 2010, vol. 27, no. 04: © Thieme Medical Publishers, pp. 360-367. [28] R. J. Malloy, J. Rimsans, M. Rhoten, K. Sylvester, and J. Fanikos, "Unfractionated heparin and low-molecular-weight heparin," Anticoagulation Therapy, pp. 31-57, 2018. [29] B. Chong, "Heparin-induced thrombocytopenia," Journal of thrombosis and haemostasis, vol. 1, no. 7, pp. 1471-1478, 2003. [30] S. Ataei et al., "High-yield production of recombinant platelet factor 4 by harnessing and honing the gram-negative bacterial secretory apparatus," Plos one, vol. 15, no. 5, p. e0232661, 2020. [31] M. M. Prechel and J. M. Walenga, "Emphasis on the role of PF4 in the incidence, pathophysiology and treatment of heparin induced thrombocytopenia," Thrombosis journal, vol. 11, no. 1, pp. 1-9, 2013. [32] M. K. Horne III and B. R. Alkins, "Platelet binding of IgG from patients with heparininduced thrombocytopenia," Journal of Laboratory and Clinical Medicine, vol. 127, no. 5, pp. 435-442, 1996. [33] J. I. Shen and W. C. Winkelmayer, "Use and safety of unfractionated heparin for anticoagulation during maintenance hemodialysis," American journal of kidney diseases, vol. 60, no. 3, pp. 473-486, 2012. [34] R. W. Wood, "XLII. On a remarkable case of uneven distribution of light in a diffraction grating spectrum," The London, Edinburgh, and Dublin Philosophical Magazine and Journal of Science, vol. 4, no. 21, pp. 396-402, 1902. [35] L. Rayleigh, "On the dynamical theory of gratings," Proceedings of the Royal Society of London. Series A, Containing Papers of a Mathematical and Physical Character, vol. 79, no. 532, pp. 399-416, 1907. [36] U. Fano, "The theory of anomalous diffraction gratings and of quasi-stationary waves on metallic surfaces (Sommerfeld’s waves)," JOSA, vol. 31, no. 3, pp. 213-222, 1941. [37] R. H. Ritchie, "Plasma losses by fast electrons in thin films," Physical review, vol. 106, no. 5, p. 874, 1957. [38] A. Otto, "Excitation of nonradiative surface plasma waves in silver by the method of frustrated total reflection," Zeitschrift für Physik A Hadrons and nuclei, vol. 216, no. 4, pp. 398-410, 1968. [39] E. Kretschmann, "Die bestimmung optischer konstanten von metallen durch anregung von oberflächenplasmaschwingungen," Zeitschrift fur physik, vol. 241, no. 4, pp. 313-324, 1971. [40] B. Liedberg, C. Nylander, and I. Lunström, "Surface plasmon resonance for gas detection and biosensing," Sensors and actuators, vol. 4, pp. 299-304, 1983. [41] R. B. Schasfoort, Handbook of surface plasmon resonance. Royal Society of Chemistry, 2017. [42] A. K. Sharma, R. Jha, and B. Gupta, "Fiber-optic sensors based on surface plasmon resonance: a comprehensive review," IEEE Sensors journal, vol. 7, no. 8, pp. 1118-1129, 2007. [43] Y. Saad, M. Selmi, M. H. Gazzah, A. Bajahzar, and H. Belmabrouk, "Performance enhancement of a copper-based optical fiber SPR sensor by the addition of an oxide layer," Optik, vol. 190, pp. 1-9, 2019. [44] A. H. Almawgani, M. G. Daher, S. A. Taya, M. M. Olaimat, A. R. Alhawari, and I. Colak, "Detection of blood plasma concentration theoretically using SPR-based biosensor employing black phosphor layers and different metals," Plasmonics, vol. 17, no. 4, pp. 1751-1764, 2022. [45] Abcam. "KD value: a quantitative measurement of antibody affinity." Abcam. https://www.abcam.com/primary-antibodies/kd-value-a-quantitive-measurement-of-antibody-affinity (accessed. [46] A. Smekal, "Zur quantentheorie der dispersion," Naturwissenschaften, vol. 11, no. 43, pp. 873-875, 1923. [47] C. V. Raman and K. S. Krishnan, "A new type of secondary radiation," Nature, vol. 121, no. 3048, pp. 501-502, 1928. [48] P. Graves and D. Gardiner, "Practical raman spectroscopy," Springer, vol. 10, pp. 978-3, 1989. [49] E. Smith and G. Dent, Modern Raman spectroscopy: a practical approach. John Wiley & Sons, 2019. [50] A. S. Hughes, "Biosensing on the End of an Optical Fiber," The George Washington University, 2015. [51] F. Frederix et al., "Reduced nonspecific adsorption on covalently immobilized protein surfaces using poly (ethylene oxide) containing blocking agents," Journal of biochemical and biophysical methods, vol. 58, no. 1, pp. 67-74, 2004. [52] C. Lausted, Z. Hu, and L. Hood, "Quantitative serum proteomics from surface plasmon resonance imaging," Molecular & Cellular Proteomics, vol. 7, no. 12, pp. 2464-2474, 2008. [53] Y.-L. Yeh, "Real-time measurement of glucose concentration and average refractive index using a laser interferometer," Optics and Lasers in Engineering, vol. 46, no. 9, pp. 666-670, 2008. [54] C. Pappas, M. Basalekou, E. Konstantinou, N. Proxenia, S. Kallithraka, and Y. Kotseridis, "Evaluation of a Raman spectroscopic method for the determination of alcohol content in Greek spirit Tsipouro," Current Research in Nutrition and Food Science Journal, vol. 4, no. Special Issue Nutrition in Conference October 2016, pp. 01-09, 2016. [55] J. Giergiel, C. Reed, J. Hemminger, and S. Ushioda, "Surface plasmon polariton enhancement of Raman scattering in a Kretschmann geometry," The Journal of Physical Chemistry, vol. 92, no. 19, pp. 5357-5365, 1988. [56] I. Skurlov et al., "Charge Transfer from Lead Sulfide Quantum Dots to MoS 2 Nanoplatelets," Optics and Spectroscopy, vol. 128, pp. 1236-1240, 2020. [57] M. Holgado, F. J. Sanza, A. López, Á. Lavín, R. Casquel, and M. F. Laguna, "Description of an advantageous optical label-free biosensing interferometric read-out method to measure biological species," Sensors, vol. 14, no. 2, pp. 3675-3689, 2014. [58] Y. Jeong and S. M. Kang, "Formation of Zirconium (IV)–Heparin Complex Multilayers on Solid Surfaces for Long‐Lasting Antiplatelet Application," Macromolecular Bioscience, vol. 19, no. 9, p. 1900154, 2019. [59] C. Chesterman, J. R. McGready, D. Doyle, and F. Morgan, "Plasma levels of platelet factor 4 measured by radioimmunoassay," British journal of haematology, vol. 40, no. 3, pp. 489-500, 1978. [60] S. Caponi et al., "Raman micro-spectroscopy study of living SH-SY5Y cells adhering on different substrates," Biophysical chemistry, vol. 208, pp. 48-53, 2016. [61] B. Fazio et al., "SERS detection of Biomolecules at Physiological pH via aggregation of Gold Nanorods mediated by Optical Forces and Plasmonic Heating," Scientific reports, vol. 6, no. 1, pp. 1-13, 2016. [62] R. Wojnarowska, J. Polit, D. Broda, M. Gonchar, and E. Sheregii, "Surface enhanced Raman scattering as a probe of the cholesterol oxidase enzyme," Applied Physics Letters, vol. 106, no. 10, p. 103701, 2015. [63] N. Kuhar, S. Sil, and S. Umapathy, "Potential of Raman spectroscopic techniques to study proteins," Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy, vol. 258, p. 119712, 2021. [64] J. R. Reimers, M. J. Ford, A. Halder, J. Ulstrup, and N. S. Hush, "Gold surfaces and nanoparticles are protected by Au (0)–thiyl species and are destroyed when Au (I)–thiolates form," Proceedings of the National Academy of Sciences, vol. 113, no. 11, pp. E1424-E1433, 2016. [65] M. D. P. Rodríguez-Torres, L. Diaz-Torres, M. Olmos-López, P. Salas, and C. Gutiérrez, "UVA mediated synthesis of gold nanoparticles in pharmaceutical-grade heparin sodium solutions," in Plasmonics: Metallic Nanostructures and Their Optical Properties XI, 2013, vol. 8809: SPIE, pp. 244-251. [66] M. d. P. Rodriguez-Torres, L. A. Díaz-Torres, B. E. Millán-Chiu, R. García-Contreras, G. Hernández-Padrón, and L. S. Acosta-Torres, "Antifungal and cytotoxic evaluation of photochemically synthesized heparin-coated gold and silver nanoparticles," Molecules, vol. 25, no. 12, p. 2849, 2020. | - |
| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/90743 | - |
| dc.description.abstract | 本研究旨在開發表面電漿子共振與拉曼光譜整合之檢測系統，結合兩者優勢，包括具有即時檢測、無須標記、高靈敏度及指紋分析等，並基於表面電漿極化子會增強拉曼訊號的特性，以肝素-血小板第四因子複合物為例研究其可行性。在心血管手術、骨科手術或是侵入式手術，通常會讓患者服用肝素去避免發生血栓的情形，然而可能會出現不良的藥物反應，造成血小板減少症，稱為肝素誘導血小板減少症。目前肝素誘導血小板減少症之檢測方式會先以4T量表進行風險評估後，再進行免疫測試，其中由於抗體測試的特異性較低，可能會出現假陽性或假陰性的問題，所以為了避免誤判會再以功能測試進一步檢驗並確認。而其中的免疫測試除了要對樣品進行標記外，還需大量處理樣本及非特異性吸附等缺點。而在自行架設的SPR-Raman系統中，原先僅能量測到50 ng/mL的肝素-血小板第四因子複合物，實現至更低濃度1 ng/mL的目標物檢測，加上從不同入射偏振角度的實驗結果，皆證實於共振角處會增強拉曼散射訊號，驗證該系統的可行性。另外，還額外討論在不同入射角度下與漸逝場之穿透深度的關係，除了驗證該系統量測皆在有效範圍內之外，也發現當入射角度小於臨界角時，測量的頻譜訊號可當作一般的頻譜量測結果。最終，目標是藉由這個新型的分子檢測工具用來取代目前的免疫測試，如酵素連結免疫吸附測試，期望提高檢測品質並透過頻譜辨識去降低因非特異性吸附所造成的結果誤判，最終將提高整體檢測效率，並更精準地及早診斷和進行治療。 | zh_TW |
| dc.description.abstract | In this research, the purpose is to develop a detection system integrating surface plasmon resonance and Raman spectroscopy, including the advantages of real time detection, labeling free, high sensitivity and fingerprint analysis, etc. Besides, based on the fact that surface plasmon polaritons enhance the characteristics of Raman signal, the feasibility of heparin-platelet factor 4 complex was studied as an example. In cardiovascular surgery, orthopedic surgery, or invasive surgery, patients are usually given heparin to avoid thrombosis. However, it may occur adverse drug reactions and result in thrombocytopenia, which is called heparin-induced thrombocytopenia. The detection method for heparin-induced thrombocytopenia will be based on 4Ts score for risk assessment. Next, we continuously follow by immunoassays, in which the false positives or false negatives may occur due to the low specificity. Hence, in order to avoid misjudgment, functional assay will be further test and confirmation. In addition to labeling the sample, immunological assay also requires a lot of sample processing and non-specific adsorption problems. In self-installed SPR-Raman system, it enable to detect he target substance at a lower concentration of 1 ng/mL from the heparin-platelet factor IV complex, which can only be detected at 50 ng/mL without any enhancement. In addition, the experimental results from different incident polarization angles show that the Raman scattering signal will be enhanced at the resonance angle, which verifies the feasibility of the system. Furthermore, we also discuss the relationship between different incident angles and the penetration depth of the evanescent field. Bisides, to verification that the SPR-Raman system measurements are within the valid range, it is also found that when the incident angle is smaller than the critical angle, the spectrum can be regarded as a general spectrum measurement result. The goal of this research is to utilize this novel molecular detection tool to replace the current immunoassays, such as Enzyme-Linked Immunosorbent assay. It is expected to improve the detection quality and reduce the misjudgment of results caused by non-specific adsorption through spectrum identification. Ultimately, it will improve the overall detection efficiency and more accurate early diagnosis and treatment. | en |
| dc.description.provenance | Submitted by admin ntu (admin@lib.ntu.edu.tw) on 2023-10-03T17:25:33Z No. of bitstreams: 0 | en |
| dc.description.provenance | Made available in DSpace on 2023-10-03T17:25:33Z (GMT). No. of bitstreams: 0 | en |
| dc.description.tableofcontents | 致謝 I
摘要 II Abstract III 目錄 V 圖目錄 VIII 表目錄 XII 第一章 緒論 1 1.1 研究背景 1 1.2 研究動機與目的 3 1.3 論文架構 5 第二章 文獻回顧與基本原理 6 2.1 肝素簡介 6 2.1.1 肝素的歷史發展 6 2.1.2 傳統肝素與低分子量肝素 7 2.2 肝素-血小板第四因子複合物 8 2.3 肝素誘導血小板減少症之生理機制 9 2.4 表面電漿子共振 10 2.4.1 表面電漿子共振之歷史發展 10 2.4.2 表面電漿子共振之基本原理 11 2.4.3 表面電漿子共振光譜 13 2.4.4 動力學分析 14 2.5 拉曼散射 15 2.5.1 拉曼散射之發展 15 2.5.2 拉曼散射之基本原理 16 2.6 EDC/NHS活化之機制 17 2.7 乙酸胺失活羧基之機制 18 第三章 研究材料與方法 19 3.1 材料 19 3.2 儀器 20 3.3 實驗架構 20 3.4 SPR-Raman 整合量測系統 21 3.4.1 SPR光學架構系統與LabVIEW軟體 21 3.4.2 785nm拉曼探針系統與光譜量測介面 22 3.4.3 探針流道模組載台設計 22 3.5 軟體模擬 25 3.5.1 Essential Macleod模擬各角度穿透深度 25 3.6 目標物之結合量測 26 3.6.1 生物晶片備製 26 3.6.2 抗體固定化 26 3.6.3 BI-3000 SPR系統量測 27 3.6.4 SPR-Raman系統量測 28 3.7 顯微拉曼驗證 28 3.7.1 樣品備製與量測 28 3.7.2 量測介面與方式 28 第四章 目前結果與討論 30 4.1 多功能SPR-Raman系統驗證 30 4.1.1 測量不同折射率樣品的共振角 30 4.1.2 比較在共振角與非共振角的情況下所量測的拉曼光譜 31 4.1.3 各入射角度與電場穿透深度關係 33 4.2 生物樣品檢測 34 4.2.1 Anti-PF4抗體固定化 34 4.2.2 Anti-PF4/PF4免疫檢測： 35 4.2.3 Anti-PF4/ heparin-PF4 complex免疫檢測： 37 4.2.4 不同流速與相同濃度之PF4及Heparin-PF4 complex動力學分析： 38 4.2.5 運用SPR-Raman 系統檢測Heparin-PF4 complex： 40 4.3 Micro-Raman驗證 44 第五章 結論與未來展望 49 第六章 參考文獻 51 | - |
| dc.language.iso | zh_TW | - |
| dc.subject | 非特異性吸附 | zh_TW |
| dc.subject | 非特異性吸附 | zh_TW |
| dc.subject | 肝素誘導血小板減少症 | zh_TW |
| dc.subject | 肝素 -血小板第四因子複合物 | zh_TW |
| dc.subject | 拉曼光譜 | zh_TW |
| dc.subject | 表面電漿子共振 | zh_TW |
| dc.subject | 表面電漿子共振 | zh_TW |
| dc.subject | 拉曼光譜 | zh_TW |
| dc.subject | 肝素 -血小板第四因子複合物 | zh_TW |
| dc.subject | 肝素誘導血小板減少症 | zh_TW |
| dc.subject | Heparin-PF4 complex | en |
| dc.subject | Heparin-induced thrombocytopenia | en |
| dc.subject | Non-specific adsorption | en |
| dc.subject | Heparin-induced thrombocytopenia | en |
| dc.subject | Heparin-PF4 complex | en |
| dc.subject | Raman spectroscopy | en |
| dc.subject | Surface plasmon resonance | en |
| dc.subject | Raman spectroscopy | en |
| dc.subject | Surface plasmon resonance | en |
| dc.subject | Non-specific adsorption | en |
| dc.title | 表面電漿子共振增強拉曼系統的可行性研究—以肝素-血小板第四因子複合物檢測為例 | zh_TW |
| dc.title | Feasibility Study of Surface Plasmon Resonance Enhanced Raman System - Detection of Heparin- Platelet Factor IV Complexes as an Example | en |
| dc.type | Thesis | - |
| dc.date.schoolyear | 111-2 | - |
| dc.description.degree | 碩士 | - |
| dc.contributor.coadvisor | 邱南福 | zh_TW |
| dc.contributor.coadvisor | Nan-Fu Chiu | en |
| dc.contributor.oralexamcommittee | 張憲彰;鄧志強;林宗宏 | zh_TW |
| dc.contributor.oralexamcommittee | Hsien-Chang Chang;William C. Tang;Zong-Hong Lin | en |
| dc.subject.keyword | 表面電漿子共振,拉曼光譜,肝素 -血小板第四因子複合物,肝素誘導血小板減少症,非特異性吸附, | zh_TW |
| dc.subject.keyword | Surface plasmon resonance,Raman spectroscopy,Heparin-PF4 complex,Heparin-induced thrombocytopenia,Non-specific adsorption, | en |
| dc.relation.page | 58 | - |
| dc.identifier.doi | 10.6342/NTU202302110 | - |
| dc.rights.note | 未授權 | - |
| dc.date.accepted | 2023-07-31 | - |
| dc.contributor.author-college | 工學院 | - |
| dc.contributor.author-dept | 醫學工程學系 | - |
| 顯示於系所單位： | 醫學工程學研究所 | |
文件中的檔案：
| 檔案 | 大小 | 格式 | |
|---|---|---|---|
| ntu-111-2.pdf 未授權公開取用 | 3.33 MB | Adobe PDF |
系統中的文件，除了特別指名其著作權條款之外，均受到著作權保護，並且保留所有的權利。