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系統識別號 U0026-0812200912024867
論文名稱(中文) 應用電化學原理偵測嗎啡,尼古丁分子 以及生物離子濃度並整合微流體技術之研究
論文名稱(英文) Multiple Electrochemical Systems Using Microfluidic Technology for Detecting Morphine, Nicotine and Bio-indicators
校院名稱 成功大學
系所名稱(中) 工程科學系碩博士班
系所名稱(英) Department of Engineering Science
學年度 94
學期 2
出版年 95
研究生(中文) 翁振勛
研究生(英文) Chen-Hsun Weng
電子信箱 b88501113@ntu.edu.tw
學號 n9693426
學位類別 碩士
語文別 英文
論文頁數 100頁
口試委員 指導教授-李國賓
口試委員-楊瑞珍
口試委員-曾繁根
中文關鍵字 電化學  嗎啡  微機電系統  微閥門  分子模板  銨離子  鈣離子  鉀離子  電流式感測  微幫浦  微流體  離子選擇性電極  電位式感測  氫離子  尼古丁 
英文關鍵字 Ammonium ion  Calcium ion  Potassium ion  Hydrogen ion  Electrochemical  Amperometric  Ion Selective Electrodes.  Potentiometric  Molecularly Imprinted Polymer  Microfluidics  Micropumps  MEMS  Microvalves  Morphine  Nicotine 
學科別分類
中文摘要 本研究成功地結合微流體技術,分子模版技術,離子選擇性薄膜以及電化學感測方法來偵測嗎啡,尼古丁和生物離子濃度在一微流體操控系統中。首先我們將3,4-Ethylenedioxythiopfene (EDOT)作為單體,以電聚合方式包覆沉澱聚合後之分子模板於感測電極上。MIP-PEDOTmo修飾電極以定電位方式感測電極,利用蠕動式幫浦自動地將嗎啡樣品傳送到感測電極上。在流速控制為92μl/min下其線性感測範圍為0.01~0.2mM,感測靈敏度為1.649 mA/cm2-mM。
第二部份,利用尼古丁分子模板修飾感測電極在微流體系統中。整合了微流體控制模組以及電化學感測模組於系統中。當操作電位在0.86V下來量測尼古丁氧化反應電流,其線性感測範圍為0~5mM,感測靈敏度為41.89 mA/cm2-mM,感測下限為1.8μM。再者並研究可待因和葡萄糖對尼古丁感測的影響,實驗結果顯示此微流體系統可以成功的偵測尼古丁濃度。
第三部份,製作一電位式固態選擇性薄膜電極感測四種不同離子濃度,分別為氫離子,鉀離子,鈣離子和銨離子。利用電化學方法分別將白金電極電鍍上一層氧化銥薄膜作為感測氫離子電極。並在其他白金感測電極上塗佈上一層離子選擇性薄膜,添加適當的鉀/鈣/銨離子親和物分別為valinomycin,3,6-dioxaoctanediamide and nonactin。利用陣列式的微流體晶片以能斯特(Nerstian)響應在環境溫度25 oC ± 5 oC下,分別偵測出電位/酸鹼值之比為62.62 mV ± 2.5 mV/pH,電位/鉀離子濃度之比為53.76 mV ± 3 mV/-log[K+],電位/鈣離子濃度之比為25.77 mV ± 2mV/-log[Ca2+]和電位/銨離子濃度之比為52.69 mV± 2mV/-log[NH4+]。且其線性感測範圍在酸鹼值偵測方面為pH 2~10,而鉀、鈣和銨離子線性感測範圍為0.1~10-6 M。
將微流體技術,分子模版技術以及電化學感測方法結合而成一新型的感測晶片其具有高靈敏度,高選擇性以及只須少量的樣品即可量測的優點。利用微機電製程技術,設計並製作出一個利用分子模板作為感測元件和利用聚二甲基矽氧烷(Polydimethylsiloxane, PDMS)製作成微流道,微幫浦和微閥門並整合而成微流體多功能感測晶片。
最後本研究成功的提出一個簡便的方法來感測嗎啡,尼古丁和生物離子濃度如酸鹼值,鉀,鈣和銨離子濃度。對未來的生化分析提供了一種可攜帶式、便利且穩定的研究工具。我們期待分子模版與微流體元件的整合將帶給生物醫學領域更多應用及重大貢獻。



英文摘要 This study reports a microfluidic system for detecting morphine (MO), nicotine (NIC) and bio-indicators (a pH indicator, potassium, calcium and ammonium ions) using a combination of a molecularly imprinted polymer (MIP), ion selective membranes and electrochemical sensing techniques. First, a monomer called 3, 4-Ethylenedioxythiophene (EDOT), was used to mix with morphine molecules through an electropolymerization process on a sensing electrode. The modified MIP-PEDOTmo (poly-ethylenedioxythiophene for morphine) electrode was then used for detecting the morphine via the amperometric method. The morphine samples were automatically transported to the MIP-PEDOTmo sensing electrode using a peristaltic micropump. Experimental data show that the sensitivity of the MIP-morphine sensor is 1.649 mA/cm2-mM in detecting morphine concentration ranging from 0.01 to 0.2 mM at a flow rate of 92 μl/min.
Second, the developed sensing system can sense the concentration of NIC by fabricating NIC-imprinted TiO2 sites on a microelectrode in an automatic format. The modular design of the sensing systems allows us to integrate a microfluidic control module and an electrochemical sensing module for a sensitive and selective detection of NIC. A steady-state oxidation current response of NIC at 0.86 V at each concentration level varying from 0 to 5 mM was shown. A linear detection ranging from 0 to 5 mM, with a sensitivity of 41.89 μA/mM•cm2 and a detection limit of 1.8 μM, respectively, was obtained. To investigate the selectivity of the developed method, cotinine (COT) and glucose (Glu) were chosen as the interferents. The corresponding current responses of NIC and its interferents were shown. Experimental data show that the developed system can successfully detect NIC concentration with a high sensitivity and selectivity.
Third, a microfluidic device with an all-solid-state potentiometric sensor array was developed by using microfabrication technology. The sensor array included a pH indicator, potassium (K+), calcium (Ca2+) and ammonium (NH4+) ion-selective microelectrodes. The pH indicator was an iridium oxide modified platinum microelectrode fabricated by using thin-film technology. The iridium oxide was deposited by using the electrochemical method. The ion-selective microelectrodes for other three bio-indicators were platinum coated with silicon rubber based ion-selective membranes mixed with potassium (valinomycin), calcium (3,6-dioxaoctanediamide) and ammonium (nonactin) ionophores, respectively. The arrayed microfluidic sensing device showed near Nerstian responses with slopes of 62.04 mV ± 2.5 mV/pH, 53.98 mV ± 3 mV/-log[K+], 25.06 mV± 2mV/-log[Ca2+] and 52.69 mV± 2mV/-log[NH4+] at 25oC ± 5oC, and a linear response within the pH range of 2-10, with potassium, calcium and ammonium concentrations between 0.1 M and 10-6 M.
Key components including MIP films, a PDMS (Polydimethylsiloxane)-based microchannel, a peristaltic micropump, microvalves and sensing microelectrodes were integrated by utilizing Micro-electro-mechanical-systems (MEMS) technologies. In this study, the device provided a convenient way to measure the concentration of morphine, nicotine, hydrogen, potassium, calcium and ammonium ions which are important physiology parameters.



論文目次 Abstract…………………………………………………………….I
中文摘要………………………………………………………… IV
致謝……………………………………………………………… VI
Table of Contents………………………………………………VIII
List of Tables……………………………………………………XII
List of Figures…………………………………………………XIII
Nomenclature………………………………………………….XIX

Chapter 1: Introduction 1
1. 1 MEMS and Lab-on-a-chip technology 1
1. 2 MIP technology 3
1. 3 Electrochemical technology 5
1. 4 Literature Survey 7
1.4. 1 The method for detection of morphine 7
1.4. 2 The method for detection of nicotine 11
1.4. 3 The method for detection of bio-indicators 13
1. 5 Motivation and Objectives 14
Chapter 2: Design and Theory 20
2. 1 The Microfluidic Control System 20
2.1. 1 The principle of micropumps and microvalves 20
2.1. 2 The design of microchannels 21
2. 2 The Electrochemical Method 23
2.2. 1 The principle of amperometric detection 24
2.2. 2 The principle of potentiometric detection 27
Chapter 3 : Fabrication 32
3. 1 Overview of Fabrication 32
3. 2 On-chip Sensing Electrode Systems 33
3.2. 1 Glass substrate cleaning 33
3.2. 2 Patterning 34
3.2. 3 Metal deposition 35
3.2. 4 Lift-off fabrication 36
3. 3 Microfluidic Control Module 37
3.3. 1 Substrate cleaning 37
3.3. 2 SU-8 mold fabrication 38
3.3. 3 PDMS casting 39
3. 4 The Fabrication of Modified Electrodes 40
3.4. 1 The MIP modified electrodes for morphine detection 40
3.4. 2 The MIP modified electrodes for nicotine detection 42
3.4. 3 The fabrication of all solid-state membrane ion-selective electrode 44
3.5 Experimental setup 45
Chapter 4 : Results and Discussion 51
4. 1 The Chip for Detecting Morphine 51
4.1. 1 Performance of the microfluidic system 52
4.1. 2 Performance of morphine detection 55
4. 2 The Chip for Detecting Nicotine 58
4.2. 1 Performance of the microfluidic modular system 59
4.2. 2 Performance of nicotine detecting 60
4. 3 The Chip for Detecting Four Bio-indicators 62
4.3. 1 Performance of the microfluidic system for bio-indicator sensing 63
4.3. 2 Performance of bio-indicator detection 63
Chapter 5: Conclusions and Future Work 80
References 83
Biography 98
Publication 99

參考文獻 [1] T. R. Hsu, “MEMS & Microsystems Design and Manufacture,” New York: McGraw-Hill, 2002.
[2] J. W. Gardner, V. K. Varadan, and O. O., “Awadelkarim, Microsensors, MEMS, and Smart Devices,” New York: John Wiley & Sons, 2001.
[3] S. E. Lyshevski, “MEMS and NEMS: Systems, Devices, and Structures,” New York: CRC Press, 2002.
[4] D. R. Reyes, D. Lossifidis, P. A. Auroux and A. Manz, “Micro total analysis system. 1. Introduction, theory and technology,” Analytical Chemistry, 74, 2623-2636,2002.
[5] P. A. Auroux, D. Lossifidis, D. R. Reyes and A. Manz, “Micro total analysis system. 2. Analytical standard operations and applications,” Analytical Chemistry, 74, 2637-2652, 2002.
[6] T. Vilkner, D. Janasek and A. Manz, “Micro total analysis systems. Recent developments,” Analytical Chemistry, 76, 3373-3386, 2004.
[7] R. Raiteri, M. Grattarola, and R. Berger, “Micromechanics senses biomolecules,” Materials Today, 5, 22-29, 2002.
[8] K. K. Jaln, “Biotechnological applications of lab-chips and microarrays,” Trends in Biotechnology, 18, 278-280, 2000.
[9] N. H. Chiem and D. J Harrison, “Microchip systems for immunoassay: an integrated immunoreactor with electrophoretic separation for serum theophylline determination,” Clinical Chemistry, 44, 591-598, 1998.
[10] D. Kriz, K. Mosbach, “Competitive amperometric morphine sensor based on an agarose immobilized molecularly imprinted polymer,” Analytica Chimica Acta, 300, 71–75, 1995.
[11] E. Reid, H. M. Hill, I. D. Wilson, “Drug development assay approaches including molecular imprinting and biomarkers,” The Royal Society of Chemistry, Cambridge, UK, 28-36, 1998.
[12] K. C. Ho, W. M. Yeh, T. S. Tung, J. Y. Liao, “Amperometric detection of morphine based on poly(3,4-ethylenedioxythiophene) immobilized molecularly imprinted polymer particles prepared by precipitation polymerization,” Analytica Chimica Acta, 542, 90-96, 2005.
[13] F. S. Ligler, C.A.R. Taitt, “Optical biosensors: present and future, Amsterdam, Netherlands,” Elsevier Science, 2002.
[14] A. G. Mayes, K. Mosbach, “Molecularly imprinted polymers: useful materials for analytical chemistry,” Trends in Analytical Chemistry, 16, 321-332, 1997.
[15] O. Ramstrm, K. Mosbach, “Synthesis and catalysis by molecularly imprinted materials,” Current Opinion in Chemical Biology, 3, 759-764, 1999.
[16] K. Haupt, K. Mosbach, “Molecularly imprinted polymers and their use in biomimetic sensors,” Chemical Reviews, 100, 2495-2504, 2000.
[17] S.A. Piletsky, S. Alcock, A. P. F. Turner, “Molecular imprinting: at the edge of the third millennium,” Trends Biotechnology, 19, 9-12, 2001.
[18] D. Kriz, O. Ramstrom, K. Mosbach, “Molecular imprinting-new possibilities for sensor technology,” Analytical Chemistry, 69, A345-A34, 1997.
[19] H. Suzuki, T. Hirakawa, S. Sasaki, I. Karube, “An integrated module for sensing pO2, pCO2, and pH,” Analytica Chimica Acta, 405, 57-65, 2000.
[20] H. Suzuki, A. Sugama, N. Kojima, “Miniature clark-type oxygen electrode with a three-electrode configuration,” Sensors and Actuators, B, 2, 297-303, 1990.
[21] J. Joseph, H. Gomathi, G. P. Rao, “Comparative study of the transport characteristics of metal cations in metal hexacyanoferrate matrices,” Bulletin of Electrochemistry, 18, 231-236, 2002.
[22] A. J. Bard, “Electrochemical Method: Fundamentals and Applications 2nd ed.,” John Wiley & Sons, New York, 465, 2001.
[23] M. LAMBRECHTS and W. SANSEN, “Biosensor: Micro-electrochemical Device,” Institute of Physics Publishing Bristol, Philadelphia and New York, 132-135, 1992.
[24] E. M. Tess, and J. A. Aox, “Chemical and biochemical sensors basedon advances in materials chemistry,” Journal of Pharmaceutical and Biomedical Analysis, 19, 55-68, 1999.
[25] K. J. Vetter, “Electrochemical kinetics-theoretical and experimental aspects,” Academic Press Inc, 40-45, 73-79, 483-487, 1961.
[26] Robin F. B. Turner, D. Jed Harrison, and Henry P. Baltes, “A CMOS potentiostat for amperometric chemical sensors,” IEEE Journal of Solid-State Circuits, 22, 3, 473-478, 1987.
[27] Haiyan Wang ,Shaolin Mu. “Bioelectrochemical Characteristics of cholesterol oxidase immobilized in a polyaniline film,” Sensor and Actuator B, 56, 22-30, 1999.
[28] W. M. Yeh, K. C. Ho, “Amperometric morphine sensing using a molecularly imprinted polymer-modified electrode,” Analytica Chimica Acta, 542, 76-82, 2005.
[29] K. Yunus, A. C. Fisher, “Voltammetry under microfluidic control, a flow cell proach,” Electroanalysis, 22, 1782-1786, 2003.
[30] A. M. Gilson, D. E. Joranson, M. A. Maurer, K. M. Ryan, J. P. Garthwaite, “Progress to achieve balanced state policy relevant to pain management and palliative care: 2000-2003,” Journal of Pain & Palliative Care Pharmacotherapy, 19, 7-20, 2005.
[31] S. E. Abram, M. Marsala, T. L. Yaksh, “Analgesic and neurotoxic effects of intrathecal corticosteroids in rats,” Anesthesiology, 81, 198-205, 1994.
[32] S. H. Jenkins, H. B. Halsall, W. J. Heineman, in: A. P. F. Turner (Ed.), “Advances in Biosensors,” 1, JAI Press, London, 171-228, 1991.
[33] H. M. Lee, C. W. Lee, “Determination of morphine and codeine in blood and bile by gas chromatography with a derivation procedure,” Journal of Analytical Toxicology, 15, 182-187, 1991.
[34] G. Chari, A. Gulati, R. Bhat, I. R. Tebbett, “High-performance liquid chromatographic determination of morphine, morphine-3-glucuronide, morphine-6-glucuronide and codeine in biological samples using multi-wavelength forward optical detection,” Journal of chromatography, B, 571, 263-270, 1991.
[35] F. Tagliaro, D. Franchi, R. Dorizzi, M. Marigo, “High-performance liquid chromatographic determination of morphine in biological samples: an overview of separation methods and detection techniques,” Journal of chromatography, B, 488, 215–228, 1989.
[36] M. E. Soares, V. Seabra, M. L. Bastos, “Comparative-study of different extractive procedures to quantify morphine in urine by HPLC-UV,” Journal of Liquid Chromatography, 15, 1533–1541, 1992.
[37] J. G. Guillot, M. Lefebvre, J. P. Weber, “Determination of heroin, 6-acetylmorphine, and morphine in biological fluids using their propionyl derivatives with ion trap GC-MS,” Journal of Analytical Toxicology, 21, 127–133, 1997.
[38] R. Dams, T. Benijts, W. E. Lambert, A. P. De Leenheer, “Simultaneous determination of in total 17 opium alkaloids and opioids in blood and urine by fast liquid hromatography-diode-array detection-fluorescence detection, after solid-phase extraction,” Journal of chromatography, B, 773, 53–61, 2002.
[39] S. W. Lewis, P. S. Francis, K. F. Lim, G. E. Jenkins, X. D. Wang, “Pulsed flow chemistry: a new approach to solution handling for flow analysis coupled with chemiluminescence detection,” Analyst, 125, 1869–1874, 2000.
[40] G. Sakai, K. Ogata, T. Uda, N. Miura, N. Yamazoe, “A surface plasma resonance-based immunosensor for highly sensitive detection of morphine,” Sensors and Actuators, B, Chem, 495–12, 1998.
[41] F. Xu, M. Gao, L. Wang, T.Zhou, L. Jin, J. Jin, “Amperometric determination of morphine on cobalt hexacyanoferrate modified electrode in rat brain microdialysates,” Talanta, 58, 427–432, 2002.
[42] A. I. Bouquillon, D. Freeman, D. E. Moulin, “Simultaneous solid-phase extraction and chromatographic analysis of morphine and hydromorhpine in plasma by high-performance liquid chromatography with electrochemical detection,” Journal of chromatography, B, 577, 354-357, 1992.
[43] M. E. Eldefrawi, N. L. Azer, N. Nath, N. A. Anis, M. S. Bangalore, K. P. O’Connell, R. P. Schwartz, J. Wright, “A sensitive solid-phase fluoroimmunoassay for detection of opiates in Urine,” Applied Biochemistry and Biotechnology, 87, 25-35, 2000.
[44] L. Ye, K. Mosbach, “Molecularly imprinted microspheres as antibody binding mimics,” Reactive and Functional Polymers, 48, 149-157, 2001.
[45] T. C. Chou, K. M. Ng, S. H. Wang, “Gold-solid polymer electrolyte sensor for detecting dissolved oxygen in water,” Sensors and Actuators, B, 66, 184-186, 2000.
[46] F. Tagliaro, D. Franchi. R. Dorizzi. M. Marigo, “High performance liquid chromatographic determination of morphine in biological samples: an overview of separation methods and detection techniques,” Journal of chromatography, B, 488, 215-228, 1989.
[47] W. J. Liaw, S. T. Ho, J. J. Wang, O. Y. P. Hu, J. H. Li, “Determination of morphine by high-performance liquid chromatography with electrochemical detection: application to human and rabbit pharmacokinetic studies,” Journal of chromatography, B, 714, 237-245, 1998.
[48] A. J. Cunningham, “Introduction to Bioanalytical Sensors,” Wiley, New York, 267, 1998.
[49] B. A. Rashid, G. W. Aherne, M. F. Katmeh, P. Kwasowski, D. Stevenson, “Determination of morphine in urine by solid-phase immunoextraction and high-performance liquid chromatography with electrochemical detection,” Journal of chromatography, A, 797, 245-250, 1998.
[50] A. W. E. Wright, J. Watt, M. Kennedy, T. Cramond, M. T. Smith, “Quantification of morphine, morphine-3-glucuronide, and morphine-6-glucuronide in plasma and cerebrospinal-fluid using solid-phase extraction and high-performance liquid-chromatography with electrochemical detection,” Therapeutic Drug Monitoring, 16, 200-208, 1994.
[51] R. J. Ansell, D. Kriz, K. Mosbach, “Molecularly imprinted polymers for bioanalysis: chromatography, binding assays and biomimetic sensors,” Current Opinion in Chemical Biology, 7, 89–94, 1996.
[52] H. C. Hsu, L. C. Chen, K.C. Ho, “Colorimetric detection of morphine in a molecularly imprinted polymer using an aqueous mixture of Fe3+ and [Fe(CN)6]3-,” Analytica Chimica Acta, 504, 141-147, 2004.
[53] E. Reid, H. M. Hill, I. D. Wilson, “Drug development assay approaches including molecular imprinting and biomarkers,” The Royal Society of Chemistry, Cambridge, UK, 28-36, 1998.
[54] L. Campanella, G. Favero, M. Tomassetti, “Direct determination of nicotine in antismoking pharmaceutixal products and in tobacco using an inhibition biosensor,” Analytical Letters, 34, 855-866, 2001.
[55] W. S. Zhang and A. L. Li, “Inhibition biosensor for determination of nicotine,” Medicinal Chemistry, Higher Education Press, Beijing, 234, 1999.
[56] B. Alpar, G. Leyhausen, A. Sapotnik, H. Gunay, W. Geurtsen, “Nicotine-induced alterations in human primary periodontal ligament and gingival fibroblast cultures,” Clinical Oral Investigations, 2, 40-46, 1998.
[57] R. C. Gupta, G. D. Lundberg, “Application of gas chromatography to street drug analysis,” Journal of Toxicology-Clinical Toxicology, 11, 437, 1977.
[58] K. D. Brunnemann, M. R. Kagan, J. E. Cox, D. Hoffmann, “Analysis of 1,3-butadiene and other selected gasphase components in cigarette mainstream and sidestream smoke by gas chromatography-mass selective detection,” Carcinogenesis, 11, 1863-1868, 1990.
[59] G. Scherer, E. Richter, “Biomonitoring exposure to environmental tobacco smoke (ETS): A critical reappraisal,” Human Experimental Toxicl, 16, 449-459, 1997.
[60] M. R. Guerin, R. A. Jenkins, B. A. Tomkins, “The chemistry of environmental tobacco smoke: composition and measurement,” Lewis Publishers, 1992.
[61] J. C. Chuang, G. A. Mack, M. R. Kuhlman, N. K. Wilson, “Polycyclic aromatic hydro- carbons and their derivatives in indoor and outdoor air in an eighthome study,” Atmospheric Environment, 25, 369-380, 1991.
[62] D. Hoffmann, A. Rivenson, S. S. Hecht, “The biological significance of tobacco-specific N-nitrosamines: smoking and adenocarcinoma of the lung,” Critical Reviews in Toxicology, 26, 199-211, 1996.
[63] D. H. Phillips, “DNA adducts in human tissues: biomarkers of exposure to carcinogens in tobacco smoke,” Environmental Health Perspectives, 104, 453-458, 1996.
[64] D. Hoffmann, S. S. Hecht, “Advance in tobacco carcinogenesis. In: Chemical Carcinogenesis and Mutagenesis,” 63-102,1990.
[65] D. J. Beebe, G. A. Mensing and G. M. Walker, “Physics and Applications of Microfluidics in Biology,” Annual Review of Biomedical engineering, 4, 261-286, 2002.
[66] S. C. Jakeway, A. J. de Mello, E. L. Russell, “Miniaturized total analysis systems for biological analysis,” Fresenius Journal of Analytical Chemistry, 366, 525-539, 2000.
[67] T. Chovan, and A. Guttman, “Microfabricated devices in biotechnology and biochemical processing,” Trends in Biotechnology, 20, 116-122, 2002.
[68] W. T. Liu, L. Zhu, Q. W. Qin, Q. Zhang, H. H. Feng and S. Ang, “Microfluidic device as a new platform for immunofluorescent detection of viruses,” Lab on a Chip, 5, 1327-1330, 2005.
[69] C. F. Lin, G. B. Lee, C. H. Wang, H. H. Lee, W. Y. Liao, T. C. Chou, “Microfluidic pH-sensing chips integrated with pneumatic fluid-control devices,” Biosensors and Bioelectronics, 21, 1468-14751, 2006.
[70] A. J. Tudos, G. A. J. Besselink and R. B. M. Schasfoort, “Trends in miniaturized total analysis systems for point-of-care testing in clinical chemistry,” Lab on a Chip, 1, 83-95, 2001.
[71] E. Verpoorte, “Microfluidic chips for clinical and forensic analysis,” Electrophoresis, 23, 677-712, 2002.
[72] A. Bange, H. B. Halsall and W. R. Heineman, “Microfluidic immunosensor systems,” Biosensors and Bioelectronics, 20, 2488-2503, 2005.
[73] A. S. Rudolph, J. Reasor, “Cell and tissue based technologies for environmental detection and medical diagnostics,” Biosensors and Bioelectronics, 16, 429-431, 2001.
[74] Y. Huang, E. L. Mather, J. L. Bell and M. Madou, “MEMS-based sample preparation for molecular diagnostics,” Analytical and Bioanalytical Chemistry, 372, 49-65, 2002.
[75] D.L. Polla, A.G. Erdman, W.P. Robbins, D.T. Markus, J. Diaz-Diaz, R. Rizq, Y. Nam, H.T. Brickner, A. Wang, P. Krulevitch, “Microdevices in Medicine” Annual Review of Biomedical engineering, 2, 551-576, 2000.
[76] S. A. M. Marzouk, S. Ufer, R. P. Buck, T. A. Johnson, “Electrodeposited Iridium Oxide pH Electrode for Measurement of Extracellular Myocardial Acidosis during Acute Ischemia,” Analytical Chemistry, 70, 5054-5061, 1998.
[77] S. A. M. Marzouk, “Improved Electrodeposited Iridium Oxide pH Sensor Fabricated on Etched Titanium Substrates,” Analytical Chemistry, 75, 1258-1266, 2003.
[78] B. K. Oh, C. Y. Kim, H. J. Lee, K. L. Rho, G. S. Cha, H. Nam, “ISFET-Based Differential pCO 2 Sensors Employing a Low-Resistance Gas-Permeable Membrane ,” Analytical Chemistry, 68, 503-508, 1996.
[79] C. H. Wang, and G. B. Lee, “Automatic bio-sensing diagnostic chips integrated with micro-pumps and micro-valves for multiple disease detection,” Biosensors and Bioelectronics, 21, 419-425, 2005.
[80] L. H. He, L. H. Lim, B. S. Wu, “A continuum model for size- 405
dependent deformation of elastic films of nano-scale thickness,” International Journal of Solids and Structures, 41, 847-857, 2004.
[81] W. H. Chan, M. S. Wong, C. W. Yip, “Ion-Selective Electrode in Organic Analysis: A Salicylate Electrode,” Journal of Chemical Education, 63, 915-916, 1986.
[82] S. E. Creager; K. D. Lawrence; C. R. Tibbets, “An Easily Constructed Salicylate-Ion-Selective Electrode for Use in the Instructional Laboratory,” Journal of Chemical Education, 72, 274-276, 1995.
[83] G. H. Fricke; M. J. Kuntz “Inexpensive Solid-State Ion-Selective Electrodes for Student Use,” Journal of Chemical Education, 54, 517-520, 1977.
[84] T. K. Christopoulos; E. P. Diamandis “Use of a Sintered Glass Crucible for Easy Construction of Liquid-Membrane Ion-Selective Electrodes,” Journal of Chemical Education, 65, 648-651, 1988.
[85] B. W. Lloyd; F. L. O’Brien; W. D. Wilson, “Student Preparation and Analysis of Chloride and Calcium Ion Selective Electrodes,” Journal of Chemical Education, 53, 328-330, 1976.
[86] L. C. Clark, “Monitor and control of blood and tissue oxygen tension”, Transactions of the American Society for Artificial Internal Organs, 2, 41-49, 1956.
[87] T. M. Harris, “Potentiometric Measurement in a Freshwater Aquarium,” Journal of Chemical Education, 70, 340-341, 1993.
[88] J. L. Town; F. MacLaren; H. D. Dewald “Rotating Disk Voltammetry Experiment,” Journal of Chemical Education, 68, 352-354, 1991.
[89] A. J. Cunningham, “Introduction to Bioanalytical Sensors,” Wiley, New York, 267, 1998.
[90] M. R. Moelleer, S. Steinmeyer, T. Kraemer, “Determination of drugs abuse in blood,” Journal of Chromatography, B, 713, 91-109, 1998.
[91] P. P. Reddy, T. Kobayashi, M. Abe, N. Fujii, “Molecular imprinted Nylon-6 as a recognition material of amino acid,” European Polymer Journal, 38, 521-529, 2002.
[92] Barbe, J. Ch., F. Arendse, P. Comte, M. Jirousek, F. Lenzmann, V. Shklover, M. Gratzel, “Nanocrystalline titanium oxide electrodes for photovoltaic applications,” Journal of the American Ceramic Society, 80, 3157-3171, 1997.
[93] Nazeeruddin, K. Md., Humphry-Baker, P. Liska, M. Gratzel., “Investigation of sensitizer adsorption and the influence of protons on current and voltage of a dye-sensitized nanocrystalline TiO2 solar cell” Journal of Physical Chemistry, B 107, 8981-8987, 2003.
[94] S. A. M. Marzouk, S. Ufer, R. P. Buck, T. A. Johnson, L. A. Dunlap and W. E. Cascio, “Electrodeposited iridium oxide pH electrode for measurement of extracellular myocardial acidosis during acute ischemia,” Journal of Analytical Chemistry, 70, 5054–5061, 1998.
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