| 研究生: |
盧彥池 Lu, Yan-chih |
|---|---|
| 論文名稱: |
利用面型微加工製作單細胞生物晶片平台 Using Surface Micromachining Implement Single Cell Biochip Platform |
| 指導教授: |
羅錦興
Liao, Chia-Sheng 黃榮俊 Huang, Jung-Chun |
| 學位類別: |
碩士 Master |
| 系所名稱: |
工學院 - 奈米科技暨微系統工程研究所 Institute of Nanotechnology and Microsystems Engineering |
| 論文出版年: | 2007 |
| 畢業學年度: | 95 |
| 語文別: | 中文 |
| 論文頁數: | 142 |
| 中文關鍵詞: | 離子通道 、膜片鉗制 、電生理 、微機電 |
| 外文關鍵詞: | Ion Channel, Patch Clamp, Electrophysiology, MEMS |
| 相關次數: | 點閱:155 下載:2 |
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膜片箝制(Patch Clamp)技術,是電生理學中研究離子通道機制最成熟完備的一項工具,傳統膜片箝制方式是使用玻璃吸管(pipette)移動到要紀錄的細胞上。此方式可得到正確且精準的資訊,但卻需要純熟的操作技術,且相當耗費時間導致只能得到少量的紀錄資訊。電壓箝制(voltage clamp)則是一種量測離子通道性質的方式,給予一定程度的電壓來記錄細胞膜間的離子電流進出以及反應,藉此可觀測細胞的動作電位(action potential)變化的情形,從而估算通道電容或電阻的參數。
此研究延續了本實驗室長久以來的成果,除了將用以取代傳統玻璃電極的新式膜片鉗晶片製造出來,並對其效能加以改善,提升製程良率以及減低製造成本,本研究中利用改變晶片的結構材料以及製造程序,再加上利用BOE潤飾微孔洞之製程,把此膜片鉗晶片之微孔洞能縮小到1μm以下的程度,將能有效提高量測離子電流的準確性,而整體的結構層厚度能相當一致地縮減到7μm以下,理論上,局部串聯電阻將可降低,其值也較穩定。另外,製造上取消了需要昂貴專利的BOSCH ICP製程,並且以仿製面型微加工的方式取代了精準度較差的體型微加工,在大量提高量率後製造成本也隨之降低,使此晶片將來在學術以及市場上更具競爭潛力。
Patch clamp is a well-developed electrophysiological recording technique used to study ion channel function and regulation. The conventional method of performing patch clamp technique employs a glass micropipette onto the cell by manual manipulation. Despite this technique is extremely sensitive and information-rich, but requires a highly-skilled operator and is limited in throughput. Voltage clamp that determine the behavior of the ion channel conductance responsible for the generation of the action potential is the another method to record the flow of ionic current across the cell membrane. The method is held a constant membrane potential while the ionic current flowing through the membrane is measured.
This research continue the achievement of our laboratory. We not only replace traditional patch clamp of glass electrode by patch clamp chip, but also improve its efficacy, field and cost down. In this research we reduce the patch hole below 1μm using the method of changing structure material, process flow, and an additional process of BOE dipping. Then the accurate rate could be arised. By this we also reduce the whole structure thickness of the chip identically which can make local series resistance lower and stablely. Besides in the process we cancel the BOSCH ICP that has expensive patent cost, and replace bulk micromachining process by surface micromachining like process to raise filed, hence this chip would have much more competition potential.
[1] 甘惠君, 王文生, 黃文奎, 陳方中,” 利用自組裝微小透鏡陣列增加有機發光二極體的光耦合效率”, 交通大學顯示科技研究所,2006
[2] 楊錫杭, 黃俊瑋,”微齒輪機構的技術發展”, 國立中興大學精密工程研究所,2003
[3] T. Lehnert, R. Netzer, ”Realization of hollow SiO2 micronozzles for electrical measurements on living ell” , Apply physics letters, vol.81,2002
[4] 劉侑鑫,”微流道輔助葡萄糖微感測陣列之研製”,私立南台科技大學機械工程研究所碩士論文,2006
[5] 陳明正,”新型微壓力感測器之改良及其於微流道壓力感測器之應用”,私立淡江大學機械工程學系碩士論文,2000
[6] 侯勝發,” Quasi-LIGA-like製程研製二維振動式微陀螺儀”,國立成功大學機械工程學系碩士論文,1999
[7] Answers.com 網頁2007年6月資料 http://www.answers.com/topic/accelerometer?cat=health/
[8] 吳建中,”早產兒能量消耗量測之微型感測器的研製”,國立成功大學電機工程學系博士論文,2004
[9] Sandia National Laboratories 網頁2007年6月資料
http://mems.sandia.gov/scripts/index.asp
[10] Urbanski et al., Applied Physics Letters, 2006
[11] 德國 Protron Mikrotechnik 網頁2007年6月資料
http://www.protron-mikrotechnik.de/products/products_rf_e.htm
[12] 科景電子新聞 網頁2007年6月資料
http://www.sciscape.org/news_detail.php?news_id=1286/
[13] 吳勝男,”開啟細胞電生理的新紀元─膜片箝制術”,科學月刊,1991
[14] 輔仁大學理工學院生物技術研發中心網頁2007年6月資料
http://brc.se.fju.edu.tw/nobelist/199x/p1991.htm/
[15] Nobelprize.org 網頁2007年6月資料http://nobelprize.org/nobel_prizes/chemistry/laureates/2003/public.html/
[16] N. Fertig, Ch. Meyer, R. H. Blick, Ch. Trautmann, and
J. C. Behrends, “Microstructured glass chip for ion-channel electrophysiology,” The American Physical Society, 2001
[17] 丹麥Sophion公司 網頁2007年6月資料http://www.sophion.dk/
[18] N. Fertig, R. H. Blick, J. C. Behrends”Whole cell patch clamp recording performed on a plannar galss chip”, Biophysical Journal, Vol.82, pp. 3056-3062, 2002
[19] K. G.. Klemic, J. F. Klemic, M. A. Reed, F. J. Sigworth“Micromolded PDMS planar electrode allows patch clamp electrical recordings from cells” , Biosensors and Bioelectronics, Vol.17, pp. 597–604, 2002
[20] T. Lehnert, R. Netzer, ”Realization of hollow SiO2 micronozzles for electrical measurements on living cell” , Apply physics letters, vol. 81,2002
[21] M. Tanabe, J. Makinodan, ”Development of micro channel array with detecting electrodes for electrophysiological biomedical
sensor” , Micro Electro Mechanical Systems, pp. 407-410, 2003
[22] A. Stett, V. Bucher, C. Burkhardt. U. Weber, and
W. Nisch,“Patch-clamping of primary cardiac cells with
micro-openings in polyimide films” , Medical & Biological
Engineering & Computing, 2003
[23] 德國Cytocentrics CCS公司 網頁2007年6月資料
http://www.cytocentrics.com/
[24] B. Matthews and W. Judy, “Characterization of a Micromachined Planar Patch Clamp for Cellular Electrophysiology”, IEEE, 2003
[25] N. Picollet-D’hahan, F. Sauter, F. Ricoul, C. Pudda, F. Marcel, T. Sordel, F. Chatelain, and I. Chartier, “Multi-Patch: A chip-based ion-channel assay system for drug screening,” International Conference on MEMS, NANO and Smart Systems, 2003
[26] R. Pantoja, M. Nagarah, M. Starace, A. Melosh, R. Blunck, F. Bezanilla, and R. Heath, “Silicon chip-based patch-clamp electrodes integrated with PDMS microfluidics,” Biosensors and Bioelectronics ,Vol.20, pp.509–517, 2004
[27] J. Seo, C. Ionescu-Zanetti, J. Diamond, R. Lal, L. P. Lee,” Integrated multiple patch-clamp array chip via lateral cell trapping junctions”, Applied Physic Letters, 2004
[28] Adrian Y. Lau, Paul J. Hung, Angela R. Wu and Luke P. Lee,” Open-access microfluidic patch-clamp array with raised lateral cell trapping sites”, Lab on a Chip, Vol. 6, pp. 1510–1515,2006
[29] Brian Matthews, Jack W. Judy,” Design and Fabrication of a Micromachined Planar Patch-Clamp Substrate With Integrated Microfluidics for Single-Cell Measurements”, Journal of Microelectromechanical Systems, Vol. 15, pp. 214–222,2006
[30] Thomas Sordel, St´ephanie Garnier-Raveaud, Fabien Sauter, Catherine Pudda,” Hourglass SiO2 coating increases the performance of planar patch-clamp”, Journal of Biotechnology, Vol. 125, pp. 142–154,2006
[31] Z.L. Zhang, T. Asano, H. Uno, R. Tero, M. Suzui, S. Nakao, T. Kaito,” Fabrication of Si-based Planar Type Patch-Clamp Biosensor Using Silicon on Insulator Substrate” Thin Solid Films, 2007
[32] Sha Li, Liwei Lin,” A single cell electrophysiological analysis device with embedded electrode”, Sensors and Actuators A, Vol. 134, pp. 20–26,2007
[33] 河南工業大學網頁 http://www2.haut.edu.cn/
[34] 林紀甫,”單細胞動作電位量測晶片的研製”,國立成功大學微機電系統工程研究所碩士論文,2005
[35] 蘇永鎮,”陣列式單細胞動作電位量測平台之研製” ,國立成功大學微機電系統工程研究所碩士論文,2006
[36] 莊達人”VLSI製造技術”,高立圖書,1997
[37] 行政院國科會精密儀器發展中心”微機電系統技術與應用”,全華圖書,2003
[38] 陳軍,”膜片鉗實驗技術系列講座”,中國第四軍醫大學,1994