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完整後設資料紀錄
DC 欄位 | 值 | 語言 |
---|---|---|
dc.contributor.advisor | 黃榮山(Long-Sun Huang) | |
dc.contributor.author | Chung-Hsien Li | en |
dc.contributor.author | 李忠憲 | zh_TW |
dc.date.accessioned | 2021-06-16T06:33:32Z | - |
dc.date.available | 2017-08-08 | |
dc.date.copyright | 2014-08-08 | |
dc.date.issued | 2014 | |
dc.date.submitted | 2014-08-04 | |
dc.identifier.citation | [1] Kassner, M. E., Nemat-Nasser, S., Suo, Z., Bao, G., Barbour, J. C., Brinson, L. C., ... & van Swol, F. (2005). New directions in mechanics. Mechanics of Materials, 37(2), 231-259.
[2] Moulton, S. E., Barisci, J. N., Bath, A., Stella, R., Wallace, G. G. (2003). Investigation of protein adsorption and electrochemical behavior at a gold electrode. Journal of colloid and interface science, 261(2), 312-319. [3] Cleveland, J. P., Manne, S., Bocek, D., Hansma, P. K. (1993). A nondestructive method for determining the spring constant of cantilevers for scanning force microscopy. Review of Scientific Instruments, 64(2), 403-405. [4] Gimzewski, J. K., Gerber, C., Meyer, E., Schlittler, R. R. (1994). Observation of a chemical reaction using a micromechanical sensor. Chemical Physics Letters, 217(5), 589-594. [5] Thundat, T., Warmack, R. J., Chen, G. Y., Allison, D. P. (1994). Thermal and ambient‐induced deflections of scanning force microscope cantilevers. Applied Physics Letters, 64(21), 2894-2896. [6] Berger, R., Delamarche, E., Lang, H. P., Gerber, C., Gimzewski, J. K., Meyer, E., Guntherodt, H. J. (1997). Surface stress in the self-assembly of alkanethiols on gold. Science, 276(5321), 2021-2024. [7] Fritz, J., Baller, M. K., Lang, H. P., Rothuizen, H., Vettiger, P., Meyer, E., ... & Gimzewski, J. K. (2000). Translating biomolecular recognition into nanomechanics. Science, 288(5464), 316-318. [8] Wu, G., Datar, R. H., Hansen, K. M., Thundat, T., Cote, R. J., Majumdar, A. (2001). Bioassay of prostate-specific antigen (PSA) using microcantilevers.Nature biotechnology, 19(9), 856-860. [9] Wee, K. W., Kang, G. Y., Park, J., Kang, J. Y., Yoon, D. S., Park, J. H., Kim, T. S. (2005). Novel electrical detection of label-free disease marker proteins using piezoresistive self-sensing micro-cantilevers. Biosensors and Bioelectronics, 20(10), 1932-1938. [10] Ndieyira, J. W., Watari, M., Barrera, A. D., Zhou, D., Vogtli, M., Batchelor, M., Cooper, M. A., Strunz, T., Horton, M. A., Abell, C., Rayment, T., Aeppli, G., McKendry, R. A. (2008). Nanomechanical detection of antibiotic–mucopeptide binding in a model for superbug drug resistance. Nature Nanotechnology, 3(11), 691-696. [11] Loui, A., Ratto, T. V., Wilson, T. S., McCall, S. K., Mukerjee, E. V., Love, A. H., Hart, B. R. (2008). Chemical vapor discrimination using a compact and low-power array of piezoresistive microcantilevers. Analyst, 133(5), 608-615. [12] Alvarez, M., Calle, A., Tamayo, J., Lechuga, L. M., Abad, A., Montoya, A. (2003). Development of nanomechanical biosensors for detection of the pesticide DDT. Biosensors and Bioelectronics, 18(5), 649-653. [13] Cherian, S., Gupta, R. K., Mullin, B. C., Thundat, T. (2003). Detection of heavy metal ions using protein-functionalized microcantilever sensors.Biosensors and Bioelectronics, 19(5), 411-416. [14] Vidic, A., Then, D., Ziegler, C. (2003). A new cantilever system for gas and liquid sensing. Ultramicroscopy, 97(1), 407-416. [15] Fagan, B. C., Tipple, C. A., Xue, Z., Sepaniak, M. J., Datskos, P. G. (2000). Modification of micro-cantilever sensors with sol-gels to enhance performance and immobilize chemically selective phases. Talanta, 53(3), 599-608. [16] Vancura, C., Ruegg, M., Li, Y., Hagleitner, C., Hierlemann, A. (2005). Magnetically actuated complementary metal oxide semiconductor resonant cantilever gas sensor systems. Analytical chemistry, 77(9), 2690-2699. [17] Zimmermann, M., Volden, T., Kirstein, K. U., Hafizovic, S., Lichtenberg, J., Brand, O., Hierlemann, A. (2008). A CMOS-based integrated-system architecture for a static cantilever array. Sensors and Actuators B: Chemical,131(1), 254-264. [18] Huang, C. W., Hsueh, H. T., Huang, Y. J., Liao, H. H., Tsai, H. H., Juang, Y. Z., Lin, T. H., Lu, S. S., Lin, C. T. (2013). A fully integrated wireless CMOS microcantilever lab chip for detection of DNA from Hepatitis B virus (HBV). Sensors & Actuators: B. Chemical, 181 , 867-873. [19] Cheng, L. H., Chang, Y. C., Hu, W. C., Liao, H. H., Tsai, H. H., Juang, Y. Z., Lu, Y. W. Using a CMOS-BioMEMS cantilever sensor for orchid virus detection. [20] Thaysen, J., Boisen, A., Hansen, O., Bouwstra, S. (2000). Atomic force microscopy probe with piezoresistive read-out and a highly symmetrical Wheatstone bridge arrangement. Sensors and actuators A: Physical, 83(1), 47-53. [21] Johansson, A., Hansen, O., Hales, J., Boisen, A. (2006). Temperature effects in Au piezoresistors integrated in SU-8 cantilever chips. Journal of Micromechanics and Microengineering, 16(12), 2564. [22] Davies, J. E. (2007). The pharmacological basis of therapeutics. [23] Facts, D.I., Facts and Comparisons. Inc., St. Louis. MO, 1997. 19. [24] Tortonese, M., Barrett, R. C., Quate, C. F. (1993). Atomic resolution with an atomic force microscope using piezoresistive detection. Applied physics letters,62(8), 834-836. [25] Lavrik, N.V., Sepaniak, M. J., Datskos, P. G. (2004). Cantilever transducers as a platform for chemical and biological sensors. Review of scientific instruments, 75(7): p. 2229-2253. [26] Tudor, M. J., Andres, M. V., Foulds, K. W. H., Naden, J. M. (1988, September). Silicon resonator sensors: interrogation techniques and characteristics. IEE Proceedings D (Control Theory and Applications). Vol. 135. No. 5. [27] Lang, H.P., Hegner, M., Gerber, C. (2005).Cantilever array sensors. Materials Today, 8(4): p. 30-36. [28] Sarid, D., Coratger, R., Ajustron, F., Beauvillain, J. (1991). Scanning Force Microscopy-with applications to electric, magnetic and atomic forces.Microscopy Microanalysis Microstructures, 2(6), 649-649. [29] Thaysen, J. (2001). Cantilever for bio-chemical sensing integrated in a microliquid handling system. Diss. Technical University of DenmarkDanmarks Tekniske Universitet, Department of Micro-and NanotechnologyInstitut for Mikro-og Nanoteknologi. [30] Smith, C. S. (1954). Piezoresistance effect in germanium and silicon. Physical review, 94(1), 42. [31] Goericke, F. T. (2007). Simulation, fabrication and characterization of piezoresistive bio-/chemical sensing microcantilevers. [32] Harkey, J. A., Kenny, T. W. (2000). 1/f noise considerations for the design and process optimization of piezoresistive cantilevers. Microelectromechanical Systems, Journal of, 9(2), 226-235. [33] Lu, N. C., Gerzberg, L., Lu, C. Y., Meindl, J. D. (1981). Modeling and optimization of monolithic polycrystalline silicon resistors. Electron Devices, IEEE Transactions on, 28(7), 818-830. [34] Townsend, P. H., Barnett, D. M., Brunner, T. A. (1987). Elastic relationships in layered composite media with approximation for the case of thin films on a thick substrate. Journal of Applied Physics, 62(11), 4438-4444. [35] Hong, S., Weihs, T. P., Kwon, O. K., Bravman, J. C. (1989, September). Cantilever beam micro-contacts in a multi-chip interconnection system. InElectronic Manufacturing Technology Symposium, 1989, Proceedings. Seventh IEEE/CHMT International (pp. 239-245). IEEE. [36] Tada, H., Kumpel, A. E., Lathrop, R. E., Slanina, J. B., Nieva, P., Zavracky, P., Miaoulis, I. N., Wong, P. Y. (2000). Thermal expansion coefficient of polycrystalline silicon and silicon dioxide thin films at high temperatures. Journal of applied physics, 87(9), 4189-4193. [37] Sandberg, R., Molhave, K., Boisen, A., Svendsen, W. (2005). Effect of gold coating on the Q-factor of a resonant cantilever. Journal of micromechanics and microengineering, 15(12), 2249. [38] 陳獻宗, 當代神經學, 橘井文化事業有限公司, 2003. [39] Raiteri, R., Grattarola, M., Butt, H. J., Skladal, P. (2001). Micromechanical cantilever-based biosensors. Sensors and Actuators B: Chemical, 79(2), 115-126. [40] Aarnoutse, R. E., Schapiro, J. M., Boucher, C. A., Hekster, Y. A., Burger, D. M. (2003). Therapeutic drug monitoring. Drugs, 63(8), 741-753. [41] 賴沛均, 姚淑惠, 賴振榕, 謝右文, Valproic acid 與Carbapenem 類藥品交互作用顯著影響藥物血中濃度案例報告,Formosa Journal of Clinical Pharmacy, vol. 18. No. 3. pp. 67-77, 2010. [42] Ivan, R., Jonathan, B., David, M. 原著,陳豪勇鑑修,王聖予、陳建和編譯,免疫學,第五版,藝軒圖書出版社, 2002。 [43] http://en.wikipedia.org/wiki/Antibody. [44] 洪維廷, 應用壓阻式微懸臂梁生物感測器偵測巴斯德桿菌之研究.國立台灣大學工學院應用力學研究所碩士論文, 2009. [45] 莊榮輝,分子間之主要交互作用力, http://juang.bst.ntu.edu.tw/BC2008/index.html [46] 林世明, 應用生化學課堂講義: Protein-protein interaction kinetics on the sensing chip, 2008. [47] Yen, Y. K. (2009). A Study on an Integrated Miniature Piezoresistive Microcantilever Biosensor and its Applications, Graduate Institute of Applied Mechanics College of Engineering National Taiwan University Doctoral Dissertation. [48] 林世明, 應用生化學課堂講義: 晶片蛋白質薄膜製造技術, 2008. [49] 辜煜夫, 壓阻式微懸臂梁生化感測系統溫度效應之量測、消除與應用, 國立台灣大學工學院應用力學研究所碩士論文, 2009. [50] 林隆翊, 壓阻式微懸臂梁生物感測元件於抗癲癇藥物之研究, 國立台灣大學工學院應用力學研究所碩士論文, 2011. [51] 張凱峯, 利用電場操控蛋白質佈植於壓阻式生物感測器之藥物治療監測應用. 臺灣大學應用力學研究所學位論文, 2012: p. 1-112. [52] http://ebs.cic.org.tw/ebs/equiIntroduction/equiIntroductionAction_doQuery.action [53] http://www.fz-juelich.de/inb/inb-1/protein-protein_interaction | |
dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/57042 | - |
dc.description.abstract | 近年來由於國內人口趨於高齡化,在預防勝於治療的觀點下,生醫檢測晶片應用於居家照護自我檢測的需求也就與日俱增。然而,鑒於目前普及的免螢光標定SPR生物感測器不適用於小分子生物量測,且醫院的傳統檢測設備成本昂貴,因此,本研究建立於商業化標準製程TSMC 0.35μm 2P4M CMOS之技術平台下,搭配BioMEMS後製程及MEMS後製程發展一可應用於小分子藥物量測的低成本、可攜式、微型化、高靈敏度、免螢光標記及能快速即時檢測的微懸臂樑感測晶片,並期未來能透過相容性高的標準CMOS製程整合後端電路,於感測晶片上實現多項功能,成為一跨領域的整合系統,以取代傳統高成本的大型檢測設備。
此外,壓阻式微懸臂樑易受溫度效應影響,僅1°C變化便能屏蔽量測到的生物訊號,因此,本論文針對標準CMOS製程製作之微懸臂樑感測晶片的熱效應予以研究,以建立一具熱效應自補償系統的微懸臂樑感測元件,而能應用於生醫檢測,以符合檢驗上之精確量測需求,並提高診斷與治療的便利性。然而,實驗結果顯示,微懸臂樑於室溫下及交變的溫度環境中量測時,可透過熱補償系統將溫度效應自我扣除。 最後,具有熱補償系統的標準CMOS製程之壓阻式微懸臂樑感測器,應用於小分子的抗癲癇藥物丙戊酸之濃度監測中,可成功定量分析出50μg/ml、75μg/ml及100μg/ml的訊號反應,此外,將相同樣本以醫院現行檢測的方式作驗證,得到良好的一致性,說明此晶片於未來取代傳統檢測儀器的前瞻性。 | zh_TW |
dc.description.abstract | With the growing interest and fast development in bio-nanotechnology, biosensing tools have been moving towards miniaturization, high sensitivity, portability and wireless networking. In this study, piezoresistive microcantilever biosensor is made with the foundry process by TSMC. The sensor manufacturing technology utilizes 0.35 um 2P4M CMOS process with post MEMS processes of silicon dry etching, and with post BioMEMS process of gold metallization. Meanwhile, this biosensing mechanism is based on protein-drug recognition, which results in conformational change and thus induced cantilever deflection.
However, thermal effect is the most important issue when it comes to detection of biomarker by piezoresistive microcantilever. Only 1 celcius degree change may override the real bio signal. As a result, the self-compensation system of thermal effect is developed in this study. In this thermal effect of the cantilever, the temperature coefficient of resistance (TCR) effect was about 7 times larger than the bimorph effect. Finally, thermal effect of a CMOS BioMEMS microcantilever under room temperature and fluctuated temperature environment can be eliminated by the thermal compensation system. The detection of the anti-epileptic drug valproic acid concentration of 50 μg/ml、75 μg/ml and 100 μg/ml was achieved by a thermally compensated CMOS BioMEMS microcantilever. Meanwhile, the comparison and limitation result to the conventional method PETINIA was conducted. The values give a promising result for microcantilever biosensor to be further developed on the wireless point-of-care system. | en |
dc.description.provenance | Made available in DSpace on 2021-06-16T06:33:32Z (GMT). No. of bitstreams: 1 ntu-103-R01543010-1.pdf: 5074449 bytes, checksum: 2caf59deba15a056ebdc89796a45225f (MD5) Previous issue date: 2014 | en |
dc.description.tableofcontents | 誌謝 I
摘要 II ABSTRACT III 目錄 IV 表目錄 VII 圖目錄 VIII 符號對照表 XII 第一章 緒論 1 1.1前言 1 1.2研究動機及目的 2 1.3文獻回顧 3 1.3.1 微懸臂樑感測器 3 1.3.3應用CMOS製程之微懸臂樑感測器 9 1.3.4 微懸臂樑於熱效應補償之研究 11 1.3.4 癲癇症與抗癲癇藥物 12 1-4 論文大綱 19 第二章 生物感測器 20 2.1生物的免疫反應 20 2.1.1抗體 21 2.1.2抗體-抗原辨識 22 2.2生物感測器之基本原理 25 2.3 辨識分子層的固定化技術 26 2.4表面電漿共振生物感測器(SPR) 28 2.5 粒子增強型比濁抑制免疫分析法 29 2.6 微懸臂樑生物感測器 31 第三章 壓阻式微懸臂樑之特性分析與量測 35 3.1基本微懸臂樑理論 35 3.2壓阻材料特性分析 37 3.2.1壓阻因子 38 3.2.2壓阻效應與應力分析 40 3.3微懸臂樑尺寸分析 47 3.4雜訊分析 50 3.5 CMOS壓阻式微懸臂樑的機電特性量測 51 3.6 CMOS壓阻式微懸臂樑的機械特性量測 55 第四章 CMOS BioMEMS壓阻式微懸臂樑設計製作 57 4.1 CMOS BioMEMS壓阻式微懸臂樑設計 57 4.2 CMOS BioMEMS壓阻式微懸臂樑製作 59 4.3電路板設計與製作 61 4.4微流道系統設計與製作 62 4.4.1微流道基板製作 62 4.4.2微流道上蓋製作 63 4.5 CMOS BioMEMS壓阻式微懸臂樑感測系統之封裝 64 第五章 溫度效應之量測、消除與應用 66 5.1溫度對壓阻的影響探討 66 5.1.1壓阻熱效應 66 5.1.2雙膜效應 67 5.2溫度效應之影響量測 75 5.3熱效應自補償系統 78 5.3.1實驗架構與方法 79 5.3.2實驗結果 82 5.4小分子抗癲癇藥物丙戊酸之量測 84 5.4.1實驗架構與方法 85 5.4.2實驗結果 88 第六章 結論與未來展望 92 6.1結論 92 6.2未來展望 93 參考文獻(References) 94 | |
dc.language.iso | zh-TW | |
dc.title | 具熱補償設計之標準CMOS製程微懸臂樑於抗癲癇藥物丙戊酸之量測 | zh_TW |
dc.title | Detection of Anti-epileptic Drug Valproic Acid By Thermally Self-Compensated CMOS BioMEMS Microcantilever | en |
dc.type | Thesis | |
dc.date.schoolyear | 102-2 | |
dc.description.degree | 碩士 | |
dc.contributor.oralexamcommittee | 沈弘俊(Horn-Jiunn Sheen),陳俊杉(Chuin-shan Chen) | |
dc.subject.keyword | 熱效應,壓阻式微懸臂樑,CMOS BioMEMS,丙戊酸, | zh_TW |
dc.subject.keyword | Thermal effect,Piezoresistive Microcantilever,CMOS BioMEMS,PETINIA,Valproic acid, | en |
dc.relation.page | 99 | |
dc.rights.note | 有償授權 | |
dc.date.accepted | 2014-08-05 | |
dc.contributor.author-college | 工學院 | zh_TW |
dc.contributor.author-dept | 應用力學研究所 | zh_TW |
顯示於系所單位: | 應用力學研究所 |
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