Please use this identifier to cite or link to this item: http://hdl.handle.net/11455/35775
標題: 可同時量測細胞呼吸活性與酸化率之細胞晶片的研發
A cell-based chip for the simultaneous measurement of cellular respiratory activity and acidification rate
作者: 林孝安
Lin, Shiau-An
關鍵字: 氧化銥
Iridium oxide
細胞呼吸活性
酸化率
微通道鹽橋
細胞晶片
cellular respiration
acidification rate
salt bridge microchannel
cell-based chip
出版社: 生物產業機電工程學系所
引用: 詹珮甄,陳英忠,2001,以鈦酸鉛鎂薄膜作為場效型氫離子感測元件之研究. 林瑋宸,吳靖宙,2008,結合pH微感測器之微流體晶片於細胞代謝活性的評估 袁佳吟,吳靖宙,2009,結合圖樣化細胞培養之溶氧電極陣列晶片於細胞呼吸活性的評估. Alberts B., Bray D. and Lewis J., 1994, Molecular Biology of the Cell, Garland Publing, Inc. Alderman J., Hynes J., Floyd S. M., Kruger J., O’Connor R. and Papkovsky D. B., 2004, A low-volume platform for cell-respirometric screening based on quenched-luminescence oxygen sensing, Biosensors and Bioelectronics 19 1529-1535. Amano Y., Okumura C., Yoshida M., Katayama H., Unten S., Arai J., Tagawa T., Hoshina S., and Ishikawa H., 1999. Measuring respiration of cultured cell with oxygen electrode as a metabolic indicator for drug screening. Human Cell, 12, 3. Andreescu S., Sadik O. A., and McGee D. W., 2004. Autonomous Multielectrode System for Monitoring the Interactions of Isoflavonoids with Lung Cancer Cells, Anal Chem. 76, 2321-2330. Bard A. J., and Faulkner L. R.. 2001. In electrochemical methods: fundamental and applications: 2nded.,John Wiley & Sons, Inc.,Hoboken. Bergveld P., 1970, Development of an ion-sensitive solid-state device for neurophysiological measurements, IEEE T. Bio-Mrd. Eng. 17 70-71. Bezbaruah A. N. and Zhang T. C., 2002, Fabrication of anodically electrodeposited iridium oxide film pH microelectrodes for microenvironmental studies, Anal. Chem. 74 5726-5733. Bousse L., 1996, Whole cell biosensors, Sens. Actuator, B 34 270-275. Carroll S. and Baldwin R. P., 2010, Self-calibrating microfabricated iridium oxide pH electrode array for remote monitoring, Anal. Chem. 82 878-885. Chen Y., Taylor P. L. and Scherson D., 2009. Electrochemical and In Situ Optical Studies of Supported Iridium Oxide Films in Aqueous Solutions. J. Electrochem.Soc., 156 (1), F14-F21. Cogan S. F., Plante T. D. and Ehrlich J., 2004, Sputtered iridium oxide films (SIROFs) for low-impedance neural stimulation and recording electrodes, Proc. 26th Annu. Int. Conf. IEEE Eng. Med. Biol. Soc.2 4153-4156. Errachid A., Zine N., Samitier J., Bausells J., 2004, FET-based chemical sensor systemsfabricated with standard technologies. Electroanalysis, 16:1843–51. Gao F. G., Jeevarajan A. S. and Anderson M. M., 2004, Long-term continuous monitoring of dissolved oxygen in cell culture medium for perfused bioreactors using optical oxygen sensors, Biotechnology and Bioengineering 86 425-433. Ges I. A., Ivanov B. L., Schaffer D. K., Lima E. A., Werdich A. A. and Baudenbacher F. J., 2005. Thin-film IrOx pH microelecrode for microfluidic-based Microsystems, Biosens. Bioelectron. 21 248-256. Ges I. A., Ivanov B. L., Werdich A. A. and Baudenbacher F. J., 2007, Differential pH measurements of metabolic cellular activity in nl culture volumes using microfabricated iridium oxide electrodes, Biosens. Bioelectron. 22 1303-1310. Hafeman D. G., Parce J. W. and McConnell H. M. , 1988, Light-addressable potentiometric sensor for biochemical systems. Science, 240, 1182-1185. Hafner F., 2000. Cytosensor microphysiometer: technology and recent applications. Biosens Bioelectron, 15:149–58. Karasinski J., Andreescu S., and Sadik O. A., 2005. Multiarray Sensors with Pattern Recognition for the Detection, Classification, and Differentiation of Bacteria at Subspecies and Strain Levels, Anal Chem. 77, 7941-7949. Kitahara T., Koyama N., Matsuda J., Hirakata Y., Kamihira S., Kohno S., Nakashima M., Sasaki H., 2003, Evaluation of Newly Developed Oxygen Meters with Multi-Channels and Disposable Oxygen Electrode Sensors for Antimicrobial Susceptibility Testing, Biol Pharm Bulletin , 26, 1229-1234. Koudelka M., 1986. Performance characteristics of a planar Clark-type oxygen sensor. Sensors and Actuators 9: 249-258 Lehmann M., Baumann W., Brischwein M., Gahle H. J., Freund I., Ehret R., 2001. Investigation of cell–sensor hybrid structures by focused ion beam (FIB) technology. Biosens Bioelectron. 16, 195–204. Manz A., Becker H. and Widmer H. M., 1990, Miniaturized total chemical analaysis systems: A novel concept for chemical sensing, Sens, Actuator B: Chem 1 244-248 Marzouk S. A., Ufer S., Buck R. P., Johnson T. A., Dunlap L. A., Cascio W. E., 1998. Electrodeposited iridium oxide pH electrode for measurement of extracellular myocardial acidosis during acute ischemia. Anal. Chem. 70, 5054-5061. Mizutani F., Sato Y., Hirata Y. and Iijima S., 2001. Interference-free amperometric measurement of urea in biological samples using an electrode coated withtri-enzyme/polydimethylsiloxane-bilayer membrane. Analytica Chimica Acta 441: 175-181. Niedrach L. W., 1980, New Membrane-type pH sensor for use in high temperature- high pressure water, J. Electrochem. Soc. 127 2122-2130. Nishizawa M., Takoh K. and Matsue T., 2002, Micropatterning of HeLa Cells on Glass Substrates and Evaluation of Respiratory Activity Using Microelectrodes, American Chemical Society 18 3645-3649. O’Riordan T. C., Fitzgergerald K., Ponomarev G. V., Mackrill J., Hynes J., Taylor C. and Papkovsky D. B., 2007, Sensing intracellular oxygen using near-infrared phosphorescent probes and live-cell fluorescence imaging, American Journal of Physiology-Regulatory, Integrative and Comparative Physiology, 292 1613-1620. Owicki J. W., Bousse L. J., Hafeman D. G., Kirk G. L., Olson J. D., Wada H. G., 1994. The lightaddressable potentiometric sensor: principles and biological applications. Ann Rev Biophys Biomol Struct, 23:87–113. Poghossian A. and Schoning M. J., 2006. Silicon-based chemical and biologically field-effect sensors. In: Grimes CA. Dickey EC, Pishko MV, editors. Encyclopedia of sensors, 9. Stevenson Ranch: American Scientific Publishers, 463-534. Richardson N. J., Gardner S. and Rawson D. M., 1991, A chemically mediated amperometric biosensor for monitoring eubacterial respiration, Journal of Applied Bacteriology 70 422-426. Schoning M. J., Wagner T., Wang C., Otto R., Yoshinobu T., 2005. Development of a handheld 16 channel pen-type LAPS for electrochemical sensing. Sens Actuators B 108:808–14. Starr C., 1994, BIOLOGY: Concepts and Applications: 2nd Edition, California: Wadsworth. Stein B., George M., Gaub H. E., Behrends J. C., Parak W. J., 2003. Spatially resolved monitoring of cellular metabolic activity with a semiconductor-based biosensor. Biosens Bioelectron, 18:31–41. Suzuki H., Hirakawa T., Sasaki S. and Karube I., 1999, An integrated three-electrode system with a micromachined liquid-junction Ag/AgCl reference electrode, Anal. Chim. Acta 387 103-112. Suzuki H., Hirakawa T., Sasaki S. and Karube I., 2000, An integrated module for sensing pO(2), pCO(2), and pH, Anal. Chim. Acta 405 57-65 Suzuki H., Kojima N., Sugama A. and Takei F., 1990, Development of a miniature clark-type oxygen electrode using semiconductor technology and its improvement for practical applications, Sens. Actuators, B 2 185-191. Suzuki H., Kojima N., Sugama A., Takei F. and Ikegami K., 1990, Disposable oxygen electrodes fabricated by semiconductor techniques and their application to biosensors, Sens. Actuators, B 1 528-532. Suzuki H., Shiroishi H., Sasaki S. and Karube I., 1999, Microfabricated liquid junction Ag/AgCl reference electrode and its application to a one-chip potentiometric sensor, Anal. Chem. 71 5069-5075. Suzuki H., Sugama A. and Kojima N., 1990, Miniature clark-type oxygen electrode with a three-electrode configuration, Sens. Actuators, B 2 297-303. Suzuki H., Sugama A. and Kojima N., 1993, Micromachined clark oxygen electrode, Sens. Actuators, B 10 91-98. Suzuki H., Tamiya E. and Karube I., 1988, Development of micro-oxygen electrode and its application to micro-glucose sensor. Proc. MRS Int. Meeting on Advanced Materials 14 115-120. Suzuki H., Tamiya E. and Karube I., 1988, Fabrication of an oxygen electrode using semiconductor technology. Anal. Chem. 60 1078-1080. Thedinga E., Kob A., Holst H., Keuer A., Drechsler S., Niendorf R., Baumann W., Freund I., Lehmann M. and Ehret R., 2007, Online monitoring of cell metabolism for studying pharmacodynamic effects, Toxicol. Appl. Pharmacol. 220 33-44. Thedinga E., Kob A., Holst H., Keuer A., Drechsler S., Niendorf R., 2007. Online monitoring of cell metabolism for studing pharmacodynamic effects. Toxicol Appl Pharmacol, 220, 33–44. Wagner T., Schoning M. J., 2007. Light-addressable potentiometric sensors (LAPS):recent trends and applications. In: Alegret S,MerkociA, editors. Electrochemical sensor analysis, 49. Amsterdam: Elsevier 87–128. Wagner T., Yoshinobu T., Rao C., Otto R., Schoning M. J., 2006. All-in-one solid-state device based on a light-addressable potentiometric sensor platform. Sens Actuators B. 117:472–9. Wang P., Xu G. and Qin L., 2005, Cell-based biosensors and its application in biomedicine, Sens. Actuator, B 108 576-584. Wang P., Xu G., Qin L., Xu Y., Li Y., Li R., 2005. Cell-based biosensors and its application in biomedicine. Sens Actuators B. 108:576–84. Wang Y. C., Choi M. H., and Han J., 2004, Two-dimensional protein separation with advanced sample and buffer isolation using microfluidic valves, Anal. Chem. 76 4426-31. Wiest J., Brischwein M., Ressler J., Otto A. M., Grothe H. and Wolf B., 2005, Cellular assays with multiparametric bioelectronic sensor chip, CHIMIA 59 243-246. Wiest J., Schmidhuber M., Ressler J., Scholz A., Brischwein M. and Wolf B., 2005, Cell based assays for diagnostic and therapy on multiparametric biosensor chips with an intelligent mobile lab, IFMBE Proc 10 132-135. Wu C. C., Lin W. C. and Fu S. Y., 2011, The open container-used microfluidic chip using IrOx ultramicroelectrodes for the in situ measurement of extracellular acidification, Biosens. Bioelectron. 26 4191-4197. Wu C. C., Luk H. N., Lin Y. T. T. and Yuan C. Y., 2010, A clark-type oxygen chip for in situ estimation of the respiratory activity of adhering cells, Talanta 81 228-234. Wu C. C., Yasukawa T., Shiku H. and Matsue T., 2005, Fabrication of miniature clark oxygen sensor integrated with microstructure, Sens. Actuators, B 110 342-349. Xia Y. and Whitesides G. M., 1998, Softlithography, Annual Review Material Science 28 153-184. Yamanaka K., 1989, Anodically Electrodeposited Iridium Oxide Films (AEIROF) from Alkaline Solutions for Electrochromic Display Devices, Jpn. J. Appl. Phys. 28 632-637. Yang H., Kang S. K., Choi C. A., Kim H., Shin D. H., Kim Y. S. and Kim Y. T., 2003, An iridium oxide reference electrode for use in microfabricated biosensors and biochips, Lab Chip 4 42-46. Yasukawa T., Maekawa E. and Mizutani F., 2009. Immobilization of glucose oxidase on a poly(dimethylsiloxane) layer by using poly(L-Lysine) as a polymer backbone, Analytical Sciences 25: 1159-1162. Yotter R. A. and Wilson D. M., 2004, Sensor technologies for monitoring metabolic activity in single cells – Part Ⅰ: optical methods, IEEE Sensors Journal 4 395-411. Yotter R. A. and Wilson D. M., 2004, Sensor technologies for monitoring metabolic activity in single cells – Part Ⅱ: optical methods, IEEE Sensors Journal 4 412-429. Zottmann M., Wiest J., Flurschutz T., Schmidhuber M. and Wolf B., 2009, Sensor chips for multiparametric real time monitoring of cell metabolism and drug response, IFMBE Proceedings 25 45-48.
摘要: 近幾年來結合微製程製作的細胞感測器,已廣泛受到重視,藉由量測細胞外溶氧濃度與pH值的變化,可得知細胞呼吸活性與酸化率的狀態。研究中藉由微製程技術與電沈積技術製作非Clark-type溶氧電極與IrOx-pH電極,分別被用以量測細胞呼吸活性與酸化率。在0.6~1.0 mA/cm2範圍內電流密度(current density, CD)所沈積的IrOx電極其靈敏度與厚度並無顯著差異。比較以0.8 mA/cm2沈積五分鐘(5M/0.8CD-),十分鐘(10M/0.8CD-)與15分鐘沈積(15M/0.8CD-deposited) IrOx-pH電極的90 % (t90)反應時間,分別為2.2 ± 0.9 s、 7.1 ± 0.7 s與12.8 ± 1.6 s,顯示膜愈薄反應時間愈短,在長期穩定度上以15M/0.8CD-deposited電極的電位漂移量最小,僅為0.33 ± 0.12 mV/hr。藉由整合晶片上的IrOx參考電極與微通道鹽橋的連結,晶片式溶氧與pH電極可同時量測,並無互相cross talk的現象,使量測上呈現良好再現性。在晶片操作模式下,在250秒後得到穩定擴散限制電流,且在低於20 μL/min流速下,不干擾整體量測。此電極晶片化的整合所發展之細胞晶片感測器,未來可用於評估不同藥物對細胞影響的程度,可增加藥物在動物或臨床試驗的速度與減少成本的花費。
Recently, the cell-based biosensors fabricated by microfabrication techniques have attracted a wide interest. The cellular respiration and acidification rate can be estimated by the change in the dissolved oxygen concentration and the pH. In this study, the microfabricated non-Clark type oxygen sensors and the electrodeposited IrOx-pH electrodes were used for the measurement of cellular respiratory and acidification, respectively. The sensitivity and thickness of IrOx electrodes electrodeposited in the range of 0.6~1.0 mA/cm2 current density (CD) doesn’t present significant difference. To Compare the effect of different electrodepositing time of 5 min (5M/0.8CD-), 10 min (10M/0.8CD-) and 15 min (15M/0.8CD-) IrOx electrodes electrodeposited at 0.8 mA/cm2 on the response time, the 90% response time were 2.2 ± 0.9 s, 7.1 ± 0.7 s and 12.8 ± 1.6 s, respectively. The result reveals that the thinner the film is, the shorter the response time becomes. However, in long-term stability test the 15M/0.8CD-depostied IrOx-pH exhibited the smallest potential drifting of 0.33 ± 0.12 mV/hr. With the utilization of on-chip IrOx reference electrode and the salt bridge microchannel, the chip-type oxygen and pH electrodes could measure simultaneously without cross talk and have great reproducibility. The diffusion-limited current could reach stable after applying reducing potential for 250 s. Moreover, the O2 and pH measurement was not affected by the convection when the flow rate was less than 20 μL/min. The chip-type cell-based biosensor can be used to estimate the effect of drugs on the cellular physiological behavior in the future, resulting in promoting the progress of drug tests on the experiments of animal and clinic diagnosis and reducing the cost.
URI: http://hdl.handle.net/11455/35775
其他識別: U0005-1608201214370400
文章連結: http://www.airitilibrary.com/Publication/alDetailedMesh1?DocID=U0005-1608201214370400
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