| 研究生: |
胡維禮 Hu, Wei-Li |
|---|---|
| 論文名稱: |
利用阻抗量測於環型指叉電極陣列進行糖化血色素所佔血色素比例之研究 Ratio of Hba1c to Hemoglobin on Ring-shaped Interdigital Electrode Arrays Based on Impedance Measurement |
| 指導教授: |
張凌昇
Jang, Ling-Sheng |
| 學位類別: |
碩士 Master |
| 系所名稱: |
電機資訊學院 - 電機工程學系 Department of Electrical Engineering |
| 論文出版年: | 2013 |
| 畢業學年度: | 101 |
| 語文別: | 英文 |
| 論文頁數: | 53 |
| 中文關鍵詞: | 環形指叉式電極 、糖化血色素 、血色素 、微流道 、阻抗量測 、生醫感測器 、糖化血色素比例量測 |
| 外文關鍵詞: | Ring-shape Interdigital Electrode, Glycated Hemoglobin (HbA1c), Hemoglobin (Hb), Microfluidic Channel, Impedance Measurement, Capacitor Biosensor, Ratio of HbA1c to Hb |
| 相關次數: | 點閱:161 下載:2 |
| 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 |
於步調快速的當今,人們往往追求效率而忽略了自身的健康,導致糖尿病患者的數量節節上升,因此糖尿病的偵測和預防遂成為一項不可避免的議題,根據研究指出,糖化血色素能有效偵測或防治糖尿病併發症的產生,與一般血糖不同的是,糖化血色素短時間內不易受到運動、飲食的影響有大幅的變化,所以用糖化血色素作為糖尿病的偵測依據較為精準可靠。當今量測糖化血色素的技術仍受到成本昂貴,操作複雜,不易攜帶等限制,因此本篇的研究便著重在研發出一種成本較低,可攜式的生物感測晶片。
本篇研究採用了環形指叉電極來偵測糖化血色素所佔的比例,重點不單純著重在量測出糖化血色素的濃度,更是要量出糖化血色素所占整體血色素的比例,正常人的糖化血色素所占比例約在5%左右,一般來講,如果大於7%就可視為糖尿病患者,首先為了在電極上面固定住蛋白質,得先將自主性單分子層附著於金電極上面,蛋白質與單分子層間的交互作用會使得蛋白質鍵結上去,蛋白質附著的多寡會影響到交流電阻抗的變化,以其不同的阻抗變化情形便可推測出蛋白質的濃度,而為了得到糖化血色素所占的比例,本篇利用將包含所有血色素的濃度和僅有糖化血色素的濃度做比較,此種情況需要兩個電極陣列來做阻抗量測,以及在量測的玻片前端加入了分離糖化血色素的流道,最後藉由附著前和附著後的阻抗變化,成功檢測出了7%的糖化血色素,本研究已相當接近實際病理學上的應用。
It’s essential to monitor the long-term glucose concentration in the blood of the diabetic patients, and glycated hemoglobin (HbA1c) has became one of the most important mark to diagnose. This study presents an on-chip biosensor for detecting the glycated hemoglobin as a ratio to total hemoglobin (Hb) based on impedance measurement. In the measurement process, no any other reagent is required. It’s label-free, and low sample volume needed.
The ring-shaped interdigital electrodes were coated with the self-assembled monolayer (SAM) to immobilize the proteins and measured the before-after impedance deviations via the impedance analyzer. The roughness of glass substrates was further improved by buffer oxide etchant (BOE), and distribution uniformity of the proteins were also improved which was examined by fluorescent images.
Various concentrations of Hb and HbA1c were measured via before-after impedance deviations. After HbA1c separation process, the ratio of HbA1c to total Hb was measured by the differential capacitance ΔC of the proteins calculated from the equivalent circuit model. ΔC would rise with the percentage of HbA1c, and was good linearity after 7% in 200 ng/µL Hb and HbA1c. The proposed detection method is much close to actual point-of-care diagnostics to diabetic patients with the advantage of low-cost and easy fabrication.
[1] Sicree R, Shaw J, Zimmet P (2012) The global burden. Diabetes and impaired glucose tolerance. IDF diabetes atlas 5th Edition. www.idf.org/diabetesatlas/. Accessed 10 April 2013 1997.
[2] Herman, William H. "The economic costs of diabetes: is it time for a new treatment paradigm?." Diabetes care 36.4 (2013): 775-776.
[3] Chandalia, H. B., and P. R. Krishnaswamy. "Glycated hemoglobin." Current science-bangalore- 83.12 (2002): 1522-1532. 2.
[4] Kilpatrick, Eric S. "Glycated haemoglobin in the year 2000." Journal of clinical pathology 53.5 (2000): 335-339.
[5] The Diabetes Control and Complications Trial Research Group. “The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus.” N. Eng. J. Med (1993): 329, 977-986.
[6] Bunn, H. Franklin, et al. "Further identification of the nature and linkage of the carbohydrate in hemoglobin A1c." Biochemical and biophysical research communications 67.1 (1975): 103-109.
[7] Lionel Menard, M. E. Dempsey, L. A. Biankstein, H. Aleyasslne, M. Wacks, and J. S. Soeidner, “Quantitative Determinationof GlycosylatedHemoglobinA1 by Agar Gel Electrophoresis”, Clinical Chemistry 26 (1980): 1598-1602.
[8] Weitzhandler, Michael, et al. "Protein variant separations by cation-exchange chromatography on tentacle-type polymeric stationary phases." Journal of Chromatography A 828.1 (1998): 365-372.
[9] Peterson, Karen P., et al. "What is hemoglobin A1c? An analysis of glycated hemoglobins by electrospray ionization mass spectrometry." Clinical chemistry 44.9 (1998): 1951-1958.
[10] Barman, Ishan, et al. "Raman spectroscopy-based sensitive and specific detection of glycated hemoglobin." Analytical chemistry 84.5 (2012): 2474-2482.
[11] Chuang, Ya-Chun, et al. "Detection of glycated hemoglobin (HbA1c) based on impedance measurement with parallel electrodes integrated into a microfluidic device." Sensors and Actuators B: Chemical 171-172 (2012): 1222-1230.
[12] Song, Seung Yeon, and Hyun C. Yoon. "Boronic acid-modified thin film interface for specific binding of glycated hemoglobin (HbA1c) and electrochemical biosensing." Sensors and Actuators B: Chemical 140.1 (2009): 233-239.
[13] Qu, Lan, et al. "A micro-potentiometric hemoglobin immunosensor based on electropolymerized polypyrrole–gold nanoparticles composite." Biosensors and Bioelectronics 24.12 (2009): 3419-3424.
[14] Fang, Lei, et al. "A single-use, disposable iridium-modified electrochemical biosensor for fructosyl valine for the glycoslated hemoglobin detection." Sensors and Actuators B: Chemical 137.1 (2009): 235-238.
[15] Siva Rama Krishna, V., et al. "Detection of glycated hemoglobin using 3-Aminophenylboronic acid modified graphene oxide." Life Science Systems and Applications Workshop (LiSSA), (2011) IEEE/NIH. IEEE, 1-4.
[16] Vlandas, Alexis, et al. "Enzyme-free sugar sensing in microfluidic channels with an affinity-based single-wall carbon nanotube sensor." Analytical chemistry 82.14 (2010): 6090-6097.
[17] Xue, Qiannan, et al. "CMOS and MEMS based micro hemoglobin-A1c biosensors fabricated by various antibody immobilization methods." Sensors and Actuators A: Physical 169.2 (2011): 282-287.
[18] Hsieh, K. M., Lan, K. C., Hu, W. L., Chen, M. K., Jang, L. S., Wang, M. H., “Glycated Hemoglobin Affinity Biosensors with Ring-Shaped Interdigital Electrodes on Impedance Measurement,” Biosensors and Bioelectronics, 49 (2013): 450–456.
[19] Liepold, P., et al. "DNA-arrays with electrical detection: A label-free low cost technology for routine use in life sciences and diagnostics." Bioelectrochemistry 67.2 (2005): 143-150.
[20] Stöllner, Daniela, et al. "Membrane-immobilized haptoglobin as affinity matrix for a hemoglobin-A1c immunosensor." Analytica Chimica Acta 470.2 (2002): 111-119.
[21] Qu, Lan, et al. "A micro-potentiometric hemoglobin immunosensor based on electropolymerized polypyrrole–gold nanoparticles composite." Biosensors and Bioelectronics 24.12 (2009): 3419-3424.
[22] Son, Seo Young, et al. "Electrochemical Assay for Glycated Hemoglobin based on the Magnetic Particle-supported Concentration Coupled to Boronate-diol Interactions." Bull. Korean. Chem. Soc. 31.7 (2010): 2103.
[23] Přibyl, Jan, and Petr Skládal. "Quartz crystal biosensor for detection of sugars and glycated hemoglobin." Analytica chimica acta 530.1 (2005): 75-84.
[24] Přibyl, Jan, and Petr Skládal. "Development of a combined setup for simultaneous detection of total and glycated haemoglobin content in blood samples." Biosensors and Bioelectronics 21.10 (2006): 1952-1959.
[25] Chang, Byoung-Yong, et al. "Two-channel microelectrochemical bipolar electrode sensor array." Analyst 137.12 (2012): 2827-2833.
[26] Yuan, Ruo, et al. "Direct electrochemistry and enzymatic activity of hemoglobin in positively charged colloid Au nanoparticles and hemoglobin layer-by-layer self-assembly films." Science in China Series B: Chemistry 50.5 (2007): 620-628.
[27] Manz, Andréas, N. Graber, and H. M. Widmer. "Miniaturized total chemical analysis systems: a novel concept for chemical sensing." Sensors and actuators B: Chemical 1.1 (1990): 244-248.
[28] J. W. Gardner, V. Varadan, and O. Awadelkarim, Microsensors, MEMS and Smart Devices. New York: Wiley, (2001).
[29] Harms, Peter, Yordan Kostov, and Govind Rao. "Bioprocess monitoring." Current opinion in biotechnology 13.2 (2002): 124-127.
[30] Liepold, P., et al. "DNA-arrays with electrical detection: A label-free low cost technology for routine use in life sciences and diagnostics." Bioelectrochemistry 67.2 (2005): 143-150.
[31] Melin, Jessica, and Stephen R. Quake. "Microfluidic large-scale integration: the evolution of design rules for biological automation." Annu. Rev. Biophys. Biomol. Struct. 36 (2007): 213-231.
[32] Blow, Nathan. "Microfluidics: the great divide." Nature Methods 6.9 (2009): 683-686.
[33] Jeon, Noo Li, et al. "Microfluidics section: design and fabrication of integrated passive valves and pumps for flexible polymer 3-dimensional microfluidic systems." Biomedical Microdevices 4.2 (2002): 117-121.
[34] Guan, Yan-Xia, et al. "The use of a micropump based on capillary and evaporation effects in a microfluidic flow injection chemiluminescence system." Talanta 68.4 (2006): 1384-1389.
[35] Harris, N. R., et al. "A silicon microfluidic ultrasonic separator." Sensors and Actuators B: Chemical 95.1 (2003): 425-434.
[36] Becker, Holger, and Laurie E. Locascio. "Polymer microfluidic devices." Talanta 56.2 (2002): 267-287.
[37] Stjernström, Mårten, and Johan Roeraade. "Method for fabrication of microfluidic systems in glass." Journal of Micromechanics and Microengineering 8.1 (1998): 33.
[38] Wang, Xiao-Song, et al. "Shell cross-linked cylinders of polyisoprene-b-ferrocenyldimethylsilane: formation of magnetic ceramic replicas and microfluidic channel alignment and patterning." Journal of the American Chemical Society 125.42 (2003): 12686-12687.
[39] Ohm, Christian, Christophe Serra, and Rudolf Zentel. "A Continuous Flow Synthesis of Micrometer‐Sized Actuators from Liquid Crystalline Elastomers." Advanced Materials 21.47 (2009): 4859-4862.
[40] Leclerc, Eric, Yasuyuki Sakai, and Teruo Fujii. "Microfluidic PDMS (polydimethylsiloxane) bioreactor for large‐scale culture of hepatocytes." Biotechnology progress 20.3 (2004): 750-755.
[41] Eteshola, E., and D. Leckband. "Development and characterization of an ELISA assay in PDMS microfluidic channels." Sensors and Actuators B: Chemical 72.2 (2001): 129-133.
[42] Charati, S. G., and S. A. Stern. "Diffusion of gases in silicone polymers: molecular dynamics simulations." Macromolecules 31.16 (1998): 5529-5535.
[43] Szita, Nicolas, et al. "Monitoring of cell growth, oxygen and pH in microfermentors." Micro Total Analysis Systems (2002): 7-9.
[44] Varshney, Madhukar, et al. "A label-free, microfluidics and interdigitated array microelectrode-based impedance biosensor in combination with nanoparticles immunoseparation for detection of Escherichia coli O157: H7 in food samples." Sensors and Actuators B: Chemical 128.1 (2007): 99-107.
[45] Varshney, Madhukar, and Yanbin Li. "Interdigitated array microelectrodes based impedance biosensors for detection of bacterial cells." Biosensors and Bioelectronics 24.10 (2009): 2951-2960.
[46] Maciel, Joana, M. Cristina L. Martins, and Mário A. Barbosa. "The stability of self‐assembled monolayers with time and under biological conditions." Journal of Biomedical Materials Research Part A 94.3 (2010): 833-843.
[47] Sigal, George B., et al. "A self-assembled monolayer for the binding and study of histidine-tagged proteins by surface plasmon resonance." Analytical Chemistry 68.3 (1996): 490-497.
[48] Mai, Zhibin, et al. "Direct electrochemistry of hemoglobin adsorbed on self-assembled monolayers with different head groups or chain length." Talanta 81.1 (2010): 167-175.
[49] Dai, Zong, and Huangxian Ju. "Effect of chain length on the surface properties of ω-carboxy alkanethiol self-assembled monolayers." Phys. Chem. Chem. Phys. 3.17 (2001): 3769-3773.
[50] Park, Jin-Young, et al. "Label-free detection of DNA molecules on the dendron based self-assembled monolayer by electrochemical impedance spectroscopy." analytica chimica acta 619.1 (2008): 37-42.
[51] Terzi, Fabio, et al. "3-methylthiophene self-assembled monolayers on planar and nanoparticle Au surfaces." The Journal of Physical Chemistry B 109.41 (2005): 19397-19402.
[52] Rusmini, Federica, Zhiyuan Zhong, and Jan Feijen. "Protein immobilization strategies for protein biochips." Biomacromolecules 8.6 (2007): 1775-1789.
[53] MacBeath, Gavin, and Stuart L. Schreiber. "Printing proteins as microarrays for high-throughput function determination." Science 289.5485 (2000): 1760-1763.
[54] Zhu, Heng, et al. "Global analysis of protein activities using proteome chips." science 293.5537 (2001): 2101-2105.
[55] Wong, Shan S., and Lee-Jun C. Wong. "Chemical crosslinking and the stabilization of proteins and enzymes." Enzyme and microbial technology 14.11 (1992): 866-874.
[56] Saleemuddin, M. "Bioaffinity based immobilization of enzymes." Thermal Biosensors, Bioactivity, Bioaffinitty. Springer Berlin Heidelberg, 1999. 203-226.
[57] Huang, Chengjun, et al. "An on-chip localized surface plasmon resonance-based biosensor for label-free monitoring of antigen–antibody reaction." Microelectronic Engineering 86.12 (2009): 2437-2441.
[58] Endo, Tatsuro, et al. "Multiple label-free detection of antigen-antibody reaction using localized surface plasmon resonance-based core-shell structured nanoparticle layer nanochip." Analytical Chemistry 78.18 (2006): 6465-6475.
[59] Staerz, Uwe D., et al. "Characterization of a murine monoclonal antibody specific for an allotypic determinant on T cell antigen receptor." The Journal of Immunology 134.6 (1985): 3994-4000.
[60] Flückiger, Rudolf, Thomas Woodtli, and Willi Berger. "Quantitation of glycosylated hemoglobin by boronate affinity chromatography." Diabetes 33.1 (1984): 73-76.
[61] Zhang, Qibin, et al. "Enrichment and analysis of nonenzymatically glycated peptides: boronate affinity chromatography coupled with electron-transfer dissociation mass spectrometry." Journal of proteome research 6.6 (2007): 2323-2330.
[62] Klenk, Dennis C., et al. "Determination of glycosylated hemoglobin by affinity chromatography: comparison with colorimetric and ion-exchange methods, and effects of common interferences." Clinical chemistry 28.10 (1982): 2088-2094.
[63] Garlick, Robert L., et al. "Characterization of glycosylated hemoglobins. Relevance to monitoring of diabetic control and analysis of other proteins." Journal of Clinical Investigation 71.5 (1983): 1062.
[64] Lazcka, Olivier, F. Campo, and F. Xavier Munoz. "Pathogen detection: a perspective of traditional methods and biosensors." Biosensors and Bioelectronics 22.7 (2007): 1205-1217.
[65] Clark, Leland C., and Champ Lyons. "Electrode systems for continuous monitoring in cardiovascular surgery." Annals of the New York Academy of Sciences 102.1 (1962): 29-45.
[66] Velasco-Garcia, Maria N., and Toby Mottram. "Biosensor technology addressing agricultural problems." Biosystems Engineering 84.1 (2003): 1-12.
[67] Barbero, Giovanni, A. L. Alexe-Ionescu, and I. Lelidis. "Significance of small voltage in impedance spectroscopy measurements on electrolytic cells." Journal of applied physics 98.11 (2005): 113703-113703.
[68] Bergveld, P. "Thirty years of ISFETOLOGY: What happened in the past 30 years and what may happen in the next 30 years." Sensors and Actuators B: Chemical 88.1 (2003): 1-20.
[69] Covington, A. K. “Terminology and sonventions for microlectronic ion-selective field effect transistor devices in electrochemistry”, Pure and Appl. Chem. 66.3 (1994): 565-569.
[70] Chin, Yuan-Lung, et al. "A novel pH sensitive ISFET with on chip temperature sensing using CMOS standard process." Sensors and Actuators B: Chemical 76.1 (2001): 582-593.
[71] Northrop, John H., and M. L. Anson. "A method for the determination of diffusion constants and the calculation of the radius and weight of the hemoglobin molecule." The Journal of general physiology 12.4 (1929): 543-554.
[72] Lin, Che-Hsin, et al. "A fast prototyping process for fabrication of microfluidic systems on soda-lime glass." Journal of Micromechanics and Microengineering 11.6 (2001): 726–732.
[73] Stjernström, Mårten, and Johan Roeraade. "Method for fabrication of microfluidic systems in glass." Journal of Micromechanics and Microengineering 8.1 (1998): 33.
[74] Guo, Xi-Shan, et al. "Bispiral microelectrode and its application on protein biochip." Zhejiang Daxue Xuebao(Gongxue Ban)/Journal of Zhejiang University(Engineering Science) 39.7 (2005): 957-961.
[75] Chen, Zhenhai, and Ren C. Luo. "Design and implementation of capacitive proximity sensor using microelectromechanical systems technology." Industrial Electronics, IEEE Transactions on 45.6 (1998): 886-894.
[76] Yang, Gongjun, et al. "Development of an impedimetric immunosensor for the determination of 3-amino-2-oxazolidone residue in food samples." Analytica chimica acta 706.1 (2011): 120-127.