帳號:guest(216.73.216.88)          離開系統
字體大小: 字級放大   字級縮小   預設字形  

詳目顯示

以作者查詢圖書館館藏以作者查詢臺灣博碩士論文系統以作者查詢全國書目
作者(中文):羅學章
作者(外文):Lo, Xue-Chang
論文名稱(中文):剪切式表面聲波生物感測器偵測轉鐵蛋白受體與模擬分析
論文名稱(外文):Simulation of Transferrin Receptor CD71 Detection based on a Shear Horizontal Surface Acoustic Wave Type of Biosensor
指導教授(中文):饒達仁
指導教授(外文):Yao, Da-Jeng
口試委員(中文):陳柏安
李明蒼
口試委員(外文):Chen, Bo-An
Lee, Ming-Tsang
學位類別:碩士
校院名稱:國立清華大學
系所名稱:工程與系統科學系
學號:107011531
出版年(民國):109
畢業學年度:108
語文別:中文
論文頁數:84
中文關鍵詞:剪切式表面聲波轉鐵蛋白受體模擬
外文關鍵詞:Shear Horizontal Surface Acoustic WaveTransferrin ReceptorSimulation
相關次數:
  • 推薦推薦:0
  • 點閱點閱:457
  • 評分評分:*****
  • 下載下載:0
  • 收藏收藏:0
本文提出生物感測器系統和有限元素數值模型,利用剪切式表面聲波(Shear Horizontal Mode Surface Acoustic Wave, SH-SAW)原理研究高靈敏的感測器。將模擬結果與實驗結果進行比較,討論感測器靈敏度並建立半經驗模型來預測生物分子轉鐵蛋白受體(transferrin receptor, CD71)的濃度對感測器響應。
利用有限元素分析法模擬感測器特性。得知在頻域研究分析中,透過模擬和量測發現中心頻率分別為122.6 MHz和122.3 MHz;時間相依中,在耦和共振分析下,靈敏度較高的配置具有高平均剪應力於表面,分析剪應力可以預測感測器配置靈敏度大小;特徵頻率下分析出質量靈敏度並建立了一個半經驗模型,透過實驗驗證其係數,可將生物分子的濃度與SH SAW感測器的頻移做關聯性,有效而準確地分析頻 移對目標物分子濃度的分布性,降低了感測薄膜中質傳分析的複雜性。
實驗利用36°YX Black LiTaO3當作壓電材料進行黃光微影製程技術完成感測晶片且用陣列化電路進行訊號量測。實驗目的以偵測低濃度生物分子為目標,在感測區表面進行修飾上鏈黴親和素(Streptavidin),在以生物素化的抗體(Biotinylated antibody)與表面鍵結,以檢測癌症相關的生物標誌物轉鐵蛋白受體抗原為目標。首先對生化處理的表面接上帶有螢光的生物素與表面鍵結以確認表面修飾的活性。對於多次量測做濃度-頻率關係圖,可得在不同高度波導層下量測觀察到1.4 µm的靈敏度會大於0.5 µm,最低是0.8 µm;轉鐵蛋白受體抗原量測時低於1.66 μg/mL 的抗原濃度時,靈敏度水平為947 Hz/μg/mL SH SAW 感測器的濃度與頻移之間顯示出指數關係,測量結果表明此免疫感測器對抗體抗原的質量附載有明確的反應。
表面聲波作為微質量感測器具有結構簡單、成本低、靈敏度高、且可以即時偵測到各種生物分子的訊息,定量測定薄膜上微量的吸附變化已被廣泛應用於各種領域中。
In this work, surface acoustic wave (SH SAW) biosensor, which is label free and performs highly sensitive horizontal shear, have been proposed experimentally and numerically. With the proposed model, estimate the concentration of a cancer related biomarker antigen transferrin receptor CD71 in the sample.
In frequency domain simulation, it sets up computational model as SH SAW center frequency. The center frequency was found to be 122.6 MHz and 122.3 MHz from simulation and measurement, respectively. In time dependent study, the results show that the configuration with higher sensitivity has a high average shear stress on the surface. The analysis of the shear stress can predict the sensitivity of the sensor configuration. By Eigen-mode analysis, different slope in the plots represent that the mass sensitivity varies with different thickness of the guiding layer.
The SH-SAW devices were fabricated by MEMS techniques, and interdigital transducers (IDTs) were deposited on the piezoelectric substrate (36°YX-Black LiTaO3). The self-assembled film was functionalized on the silicon dioxide layer to capture target. With the concentration of the targeted biomarker varied from 0.66~4.16 μg/mL, a typical exponential relation was found between the concentration and the frequency shift of the SH-SAW sensor, and the sensitivity level is found to be 974 Hz/(μg/mL) as the biomarker concentration is less than 1.66 μg/mL. Experimental results showed a clear response of this immunosensor to the mass-loading effects of the antibody-antigen.
Finally, an empirical model was proposed to calculate the frequency shift which corresponding to the concentration of specific biomolecules. The developed method is useful for quickly estimating the frequency shift with respect to the concentration of the target molecules in the simulation for SH-SAW sensors.
目錄
摘要
第1章----------1
第2章----------5
第3章----------17
第4章----------29
第5章----------42
第6章----------58
第7章----------75
第8章----------77
參考文獻----------80

[1] D. Ivnitski, I. Abdel-Hamid, P. Atanasov, and E. Wilkins, "Biosensors for detection of pathogenic bacteria," Biosensors and Bioelectronics, vol. 14, no. 7, pp. 599-624, 1999.
[2] P. Leonard et al., "Advances in biosensors for detection of pathogens in food and water," Enzyme and Microbial Technology, vol. 32, no. 1, pp. 3-13, 2003.
[3] A. L. Campaña et al., "Enzyme-based electrochemical biosensors for microfluidic platforms to detect pharmaceutical residues in wastewater," Biosensors, vol. 9, no. 1, p. 41, 2019.
[4] M.-I. Rocha-Gaso, C. March-Iborra, Á. Montoya-Baides, and A. Arnau-Vives, "Surface generated acoustic wave biosensors for the detection of pathogens: A review," Sensors, vol. 9, no. 7, pp. 5740-5769, 2009.
[5] I. J. Woolley, E. M. Wood, R. M. Sramkoski, P. A. Zimmerman, J. P. Miller, and J. W. Kazura, "Expression of Duffy antigen receptor for chemokines during reticulocyte maturation: using a CD71 flow cytometric technique to identify reticulocytes," Immunohematology, vol. 21, no. 1, pp. 15-20, 2005.
[6] S. D. Dertinger et al., "Enumeration of micronucleated CD71-positive human reticulocytes with a single-laser flow cytometer," Mutation Research/Genetic Toxicology and Environmental Mutagenesis, vol. 515, no. 1-2, pp. 3-14, 2002.
[7] P. Aisen, "Transferrin receptor 1," The international journal of biochemistry & cell biology, vol. 36, no. 11, pp. 2137-2143, 2004.
[8] B. H. Davis et al., "2006 Bethesda International Consensus recommendations on the flow cytometric immunophenotypic analysis of hematolymphoid neoplasia: medical indications," Cytometry Part B: Clinical Cytometry: The Journal of the International Society for Analytical Cytology, vol. 72, no. S1, pp. S5-S13, 2007.
[9] D. K. Marsee, G. S. Pinkus, and H. Yu, "CD71 (transferrin receptor) an effective marker for erythroid precursors in bone marrow biopsy specimens," American journal of clinical pathology, vol. 134, no. 3, pp. 429-435, 2010.
[10] H. O. Habashy et al., "Transferrin receptor (CD71) is a marker of poor prognosis in breast cancer and can predict response to tamoxifen," Breast cancer research and treatment, vol. 119, no. 2, p. 283, 2010.
[11] G. Magro et al., "Aberrant expression of TfR1/CD71 in thyroid carcinomas identifies a novel potential diagnostic marker and therapeutic target," Thyroid, vol. 21, no. 3, pp. 267-277, 2011.
[12] M. Ohkuma et al., "Absence of CD71 transferrin receptor characterizes human gastric adenosquamous carcinoma stem cells," Annals of surgical oncology, vol. 19, no. 4, pp. 1357-1364, 2012.
[13] C. Kendall, I. Ionescu-Matiu, and G. R. Dreesman, "Utilization of the biotin/avidin system to amplify the sensitivity of the enzyme-linked immunosorbent assay (ELISA)," Journal of immunological methods, vol. 56, no. 3, pp. 329-339, 1983.
[14] J.-L. Guesdon, T. Ternynck, and S. Avrameas, "The use of avidin-biotin interaction in immunoenzymatic techniques," Journal of Histochemistry & Cytochemistry, vol. 27, no. 8, pp. 1131-1139, 1979.
[15] 孙圣和, "现代传感器发展方向," 2009.
[16] L. C. Clark Jr and C. Lyons, "Electrode systems for continuous monitoring in cardiovascular surgery," Annals of the New York Academy of sciences, vol. 102, no. 1, pp. 29-45, 1962.
[17] G. Cui et al., "Electrochemical biosensor," ed: Google Patents, 2007.
[18] T. Matsuo and K. D. Wise, "An integrated field-effect electrode for biopotential recording," IEEE Transactions on Biomedical Engineering, no. 6, pp. 485-487, 1974.
[19] P. Bergveld and N. de Rooij, "From conventional membrane electrodes to ion-sensitive field-effect transistors," Medical and Biological Engineering and Computing, vol. 17, no. 5, pp. 647-654, 1979.
[20] C.-S. Lee, S. Kim, and M. Kim, "Ion-sensitive field-effect transistor for biological sensing," Sensors, vol. 9, no. 9, pp. 7111-7131, 2009.
[21] A. J. Haes and R. P. Van Duyne, "A nanoscale optical biosensor: sensitivity and selectivity of an approach based on the localized surface plasmon resonance spectroscopy of triangular silver nanoparticles," Journal of the American Chemical Society, vol. 124, no. 35, pp. 10596-10604, 2002.
[22] X. Fan, I. M. White, S. I. Shopova, H. Zhu, J. D. Suter, and Y. Sun, "Sensitive optical biosensors for unlabeled targets: A review," analytica chimica acta, vol. 620, no. 1-2, pp. 8-26, 2008.
[23] M. A. Cooper, "Optical biosensors in drug discovery," Nature reviews Drug discovery, vol. 1, no. 7, p. 515, 2002.
[24] M. Yakovleva, S. Bhand, and B. Danielsson, "The enzyme thermistor—A realistic biosensor concept. A critical review," Analytica chimica acta, vol. 766, pp. 1-12, 2013.
[25] I. Mannelli, M. Minunni, S. Tombelli, and M. Mascini, "Quartz crystal microbalance (QCM) affinity biosensor for genetically modified organisms (GMOs) detection," Biosensors and bioelectronics, vol. 18, no. 2-3, pp. 129-140, 2003.
[26] Z. Shen, M. Huang, C. Xiao, Y. Zhang, X. Zeng, and P. G. Wang, "Nonlabeled quartz crystal microbalance biosensor for bacterial detection using carbohydrate and lectin recognitions," Analytical chemistry, vol. 79, no. 6, pp. 2312-2319, 2007.
[27] E. Howe and G. Harding, "A comparison of protocols for the optimisation of detection of bacteria using a surface acoustic wave (SAW) biosensor," Biosensors and Bioelectronics, vol. 15, no. 11-12, pp. 641-649, 2000.
[28] Y. Hur, J. Han, J. Seon, Y. E. Pak, and Y. Roh, "Development of an SH-SAW sensor for the detection of DNA hybridization," Sensors and Actuators A: Physical, vol. 120, no. 2, pp. 462-467, 2005.
[29] F. Di Pietrantonio et al., "Detection of odorant molecules via surface acoustic wave biosensor array based on odorant-binding proteins," Biosensors and Bioelectronics, vol. 41, pp. 328-334, 2013.
[30] K. Chang et al., "Label-free and high-sensitive detection of human breast cancer cells by aptamer-based leaky surface acoustic wave biosensor array," Biosensors and Bioelectronics, vol. 60, pp. 318-324, 2014.
[31] N. Moll et al., "Multipurpose Love acoustic wave immunosensor for bacteria, virus or proteins detection," Irbm, vol. 29, no. 2-3, pp. 155-161, 2008.
[32] 楊啟榮, 李清鋒, and 施建富, "表面聲波生化感測器原理與應用技術," 2004.
[33] G. N. Ferreira, A.-C. Da-Silva, and B. Tomé, "Acoustic wave biosensors: physical models and biological applications of quartz crystal microbalance," Trends in biotechnology, vol. 27, no. 12, pp. 689-697, 2009.
[34] R. M. Lequin, "Enzyme immunoassay (EIA)/enzyme-linked immunosorbent assay (ELISA)," Clinical chemistry, vol. 51, no. 12, pp. 2415-2418, 2005.
[35] M. Puiu, A.-M. Gurban, L. Rotariu, S. Brajnicov, C. Viespe, and C. Bala, "Enhanced sensitive Love wave surface acoustic wave sensor designed for immunoassay formats," Sensors, vol. 15, no. 5, pp. 10511-10525, 2015.
[36] S. J. Ippolito, K. Kalantar-Zadeh, D. A. Powell, and W. Wlodarski, "A 3-dimensional finite element approach for simulating acoustic wave propagation in layered SAW devices," in IEEE Symposium on Ultrasonics, 2003, 2003, vol. 1, pp. 303-306: IEEE.
[37] A. Abdollahi, Z. Jiang, and S. A. Arabshahi, "Evaluation on mass sensitivity of SAW sensors for different piezoelectric materials using finite-element analysis," IEEE transactions on ultrasonics, ferroelectrics, and frequency control, vol. 54, no. 12, pp. 2446-2455, 2007.
[38] M. Gaso, Y. Jiménez, L. Francis, and A. Arnau, "Love wave biosensors: a review," State of the art in biosensors-general aspects, InTech., pp. 277-310, 2013.
[39] S. Trivedi and H. B. Nemade, "Finite element simulation of a highly sensitive SH-SAW delay line sensor with SiO $$ _ {} $$ micro-ridges," Microsystem Technologies, vol. 24, no. 8, pp. 3537-3547, 2018.
[40] J. Brookes, R. Bufacchi, J. Kondoh, D. M. Duffy, and R. A. McKendry, "Determining biosensing modes in SH-SAW device using 3D finite element analysis," Sensors and Actuators B: Chemical, vol. 234, pp. 412-419, 2016.
[41] P. M. Moubarak, P. Ben-Tzvi, and M. E. Zaghloul, "A self-calibrating mathematical model for the direct piezoelectric effect of a new MEMS tilt sensor," IEEE Sensors Journal, vol. 12, no. 5, pp. 1033-1042, 2011.
[42] T. Yan et al., "Formation mechanism of black LiTaO3 single crystals through chemical reduction," Journal of Applied Crystallography, vol. 44, no. 1, pp. 158-162, 2011.
[43] T.-T. Wu, Z.-C. Hsu, and Z.-G. Huang, "Band gaps and the electromechanical coupling coefficient of a surface acoustic wave in a two-dimensional piezoelectric phononic crystal," Physical Review B, vol. 71, no. 6, p. 064303, 02/28/ 2005.
[44] C. Campbell, Surface Acoustic Wave Devices for Mobile and Wireless Communications, Four-Volume Set. Academic press, 1998.
[45] Y. Shimizu, "Current status of piezoelectric substrate and propagation characteristics for SAW devices," Japanese journal of applied physics, vol. 32, no. 5S, p. 2183, 1993.
[46] M. Y. Dvoesherstov, S. Petrov, V. Cherednik, and A. Chirimanov, "The temperature coefficients of delay of surface acoustic waves in LGS and LGN crystals in a wide temperature range," Technical Physics, vol. 46, no. 3, pp. 346-347, 2001.
[47] M. Gonzalez, "Impact of Li non-stoichiometry on the performance of acoustic devices on LiTaO3 and LiNbO3 single crystals," 2016.
[48] R. White and F. Voltmer, "Direct piezoelectric coupling to surface elastic waves," Applied physics letters, vol. 7, no. 12, pp. 314-316, 1965.
[49] J. Kirschner, "Surface Acoustic Wave Sensors (SAWS)."
[50] J. W. Grate and R. A. McGill, "Dewetting effects on polymer-coated surface acoustic wave vapor sensors," Analytical Chemistry, vol. 67, no. 21, pp. 4015-4019, 1995.
[51] G. Zhang, "Nanostructure-enhanced surface acoustic waves biosensor and its computational modeling," journal of Sensors, vol. 2009, 2009.
[52] J. Kushibiki, H. Ishiji, T. Kobayashi, N. Chubachi, I. Sahashi, and T. Sasamata, "Characterization of 36/spl deg/YX-LiTaO/sub 3/wafers by line-focus-beam acoustic microscopy," IEEE transactions on ultrasonics, ferroelectrics, and frequency control, vol. 42, no. 1, pp. 83-90, 1995.
[53] M. I. Cheema and A. G. Kirk, "Implementation of the perfectly matched layer to determine the quality factor of axisymmetric resonators in COMSOL," in COMSOL conference, 2010.
[54] G. Kovacs, M. Anhorn, H. Engan, G. Visintini, and C. Ruppel, "Improved material constants for LiNbO/sub 3/and LiTaO/sub 3," in IEEE symposium on ultrasonics, 1990, pp. 435-438: IEEE.
[55] R. Manenti, "Surface Acoustic Wave Resonators for Quantum Information," Citeseer, 2013.
[56] P. Russer, Electromagnetics, microwave circuit and antenna design for communications engineering. Artech House, 2003.
[57] S. Maiti and P. Paira, "Biotin conjugated organic molecules and proteins for cancer therapy: A review," European journal of medicinal chemistry, vol. 145, pp. 206-223, 2018.
[58] N. Ramakrishnan, H. B. Nemade, and R. P. Palathinkal, "Mass loading in coupled resonators consisting of SU-8 micropillars fabricated over SAW devices," IEEE Sensors Journal, vol. 11, no. 2, pp. 430-431, 2010.
[59] Z. Li, Y. Jones, J. Hossenlopp, R. Cernosek, and F. Josse, "Design considerations for high sensitivity guided SH-SAW chemical sensor for detection in aqueous environments," in Proceedings of the 2004 IEEE International Frequency Control Symposium and Exposition, 2004., 2004, pp. 185-192: IEEE.
[60] F. Josse, F. Bender, R. Cernosek, and K. Zinszer, "Guided SH-SAW sensors for liquid-phase detection," in Proceedings of the 2001 IEEE International Frequncy Control Symposium and PDA Exhibition (Cat. No. 01CH37218), 2001, pp. 454-461: IEEE.
[61] A. A. Kortt, E. Nice, and L. C. Gruen, "Analysis of the binding of the Fab fragment of monoclonal antibody NC10 to influenza virus N9 neuraminidase from tern and whale using the BIAcore biosensor: effect of immobilization level and flow rate on kinetic analysis," Analytical biochemistry, vol. 273, no. 1, pp. 133-141, 1999.
[62] 簡俊謙 and 高曜煌, "表面聲波元件之設計及其在寬頻振盪器之應用," 1999.

 
 
 
 
第一頁 上一頁 下一頁 最後一頁 top
* *