| 研究生: |
章鈞 Chang, Chun |
|---|---|
| 論文名稱: |
應用壓阻式橋狀懸臂結構之表面應力機制於CMOS製程生化感測器 A PIEZORESISTIVE BRIDGE-MICROCANTILEVER BIOSENSOR BY CMOS PROCESS FOR SURFACE STRESS MEASUREMENT |
| 指導教授: |
楊世銘
Yang, Shih-Ming |
| 學位類別: |
博士 Doctor |
| 系所名稱: |
工學院 - 航空太空工程學系 Department of Aeronautics & Astronautics |
| 論文出版年: | 2010 |
| 畢業學年度: | 98 |
| 語文別: | 英文 |
| 論文頁數: | 92 |
| 中文關鍵詞: | 壓阻式微懸臂結構 、CMOS 、生化感測器 |
| 外文關鍵詞: | piezoresistive microcantilever, CMOS, biosensor |
| 相關次數: | 點閱:80 下載:5 |
| 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 |
由於微尺度懸臂結構具有高自然振頻,高表面能與低熱容量等機械物理特性,已被應用於新型生化感測器之設計與製作。當待測之生化檢體附著於微懸臂結構表面時,由其生化反應而引起分子與微結構間產生之表面應力變化將引發微結構形變,而形變可直接由包埋之壓阻層讀取。然而由於生化反應產生之表面應力為一雙軸向應力負載,加上壓阻層產生之熱效應,因此改良式的微懸臂結構設計以達到更佳之感測表現為重要關鍵。
分析結果顯示表面應力之雙軸效應對此壓阻式微懸臂結構之性能影響極大,且壓阻層之熱效應將嚴重影響生化檢體於修飾層表面之吸附狀態與表面能量。因此,本文提出一種橋狀微懸臂結構之新型設計以有效提升表面應力感測器之量測靈敏度。此設計的組成為一感應微懸臂結構與一修飾微懸臂結構由一傳遞結構連結,表面應力之雙軸效應可藉由傳遞結構之傳導,近似於分子力顯微鏡之原理,由修飾微懸臂結構傳導至感應微懸臂結構成為單軸之應變,同時將熱效應隔絕於感應微懸臂結構。本文也提出整合於此感測器晶片之橋式電路,用以消除電路所產生雜訊。
本文首次提出一利用半導體標準CMOS 製程之生化感測器晶片設計與製作,同時為整合此壓阻式橋狀微懸臂結構與微流體系統於單一感測晶片。感測器晶片之微結構釋放、修飾層沉積與微流道封裝可利用簡易之後製程來達成。經分析與設計,此一生化感測器之靈敏度可藉由適當的改變感應微懸臂結構與修飾微懸臂結構之長度比與傳遞結構之剛性來得到提升。本文提出之壓阻式橋狀微懸臂結構與整合感測器晶片於標準CMOS 製程之分析、設計與製造將可提供此生化感測器一個嶄新、可靠且經濟之研究方向。
Many new biosensors design based on microcantilever have been proposed by using the fast and sensitive response of micromechanical detection. Microsensors based on piezoresistive microcantilevers have been proposed to measure the surface stress change by molecule adsorption from biochemical reaction on an immobilized surface. However, the sensor performance is adversely influenced by the biaxial effect of the surface stress and the thermal effect of the piezoresistor during operation. Improved microcantilever design for better performance is desirable.
Analyses show that the biaxial effect of surface stress is crucial to surface stress measurement and the thermal effect from the piezoresistor is lethal to the biochemical agent adsorbed on the immobilized layer and change the surface energy of the adsorption layer. An innovative bridge-microcantilever design is developed to improve the measurement sensitivity. The design is an immobilized cantilever connected to the sensing cantilever by a transmitter such that biaxial surface stress can be converted into uniaxial strain similar to AFM operation and the thermal effect can be isolated. An integrated bridge circuit design in biosensor chip is also proposed to provide signal conditioning for improving sensor performance. A biosensor chip with integrated piezoresistive bridge-microcantilever and microchannel is fabricated by standard complementary metal-oxide-semiconductor (CMOS) process. The immobilized layer on microcantilever and seal of microchannel can be accomplished by lift-off technique and polydimethylsiloxane (PDMS) channel cover in post-processing. Analyses show that the sensitivity of the biosensor can be increased by the design parameters of the length ratio of the two cantilevers and the transmitter rigidity.
Baller, M. K., Lang, H. P., Fritz, J., Gerber, C. H., Gimzewski, J. K., Drechsler, U., Rothuizen, H., Despont, M., Vettiger, P., Battiston, F. M., Berger, R., Ramseyer, J. P., Fornaro, P., Meyer, E., Güntherodt, H. -J., “A cantilever array-based artificial nose,” Ultramicroscopy, vol. 82, pp. 1-9, 2000.
Barnes, J. R., Stephenson, R. J., Welland, M. E., Gerber, C. H., Gimzewski, J. K., “Photothermal spectroscopy with femtojoule sensitivity based on micromechanics, ” Nature, vol. 372, pp. 372-379, 1994.
Berger, R., Delamarche, E., Lang, H. P., Gerber, C. H., Gimzewski, J. K., Meyer, E., and Güntherodt, H.-J., “Surface stress in the self-assembly of alkanethiols on gold probed by a force microscopy technique,” Appl. Phys. A, vol.66, pp. 55-59, 1998.
Berger, R., Gerber, C. H., Gimzewski, J. K., Meyer, E., and Güntherodt, H. -J., “Thermal analysis using a micromechanical calorimeter, ” Appl. Phys. Lett. vol. 69, pp. 40-42, 1996.
Berger, R., Lang, H. P., Gerber, C. H., Gimzewski, J. K., Fabian, J. H., Scandella, L., Meyer, E., and Güntherodt, H.-J., “Micromechanical thermogravimetry,” Chem. Phys. Lett., vol. 294, pp. 363-369, 1998.
Binning, G., Quate, C. F., and Gerber, C. H., “Atomic force microscope,” Phys. Rev. Lett., vol. 56, pp. 930-933, 1986.
Britton, J. C. L., Jones, R. L., Oden, P. I., Hu, Z., Warmack, R. J., Smith, S. F., Bryan, W. L., Rochelle, J. M., “Multiple-input microcantilever sensors,” Ultramicroscopy, vol. 82, pp. 17-21, 2000.
Buhler, J., “Deformable micromirror arrays by CMOS technology,” Ph.D. thesis, ETH Zurich, Zurich, Switzerland, 1997.
Buhler, J., Funk, J., Korvink, J. G., Steiner, F. P., Sarro, P. M., and Baltes, H., “Electrostatic aluminum micromirrors using double-pass metallization,” J. Microelectromech. Syst., vol. 6, no. 2, pp. 126-35, 1997.
Bustillo, J. M., Howe, R. T., and Muller, R. S., “Surface micromachining for microelectromechanical systems,” Proc. of the IEEE , vol. 86, no. 8, 1998.
Chaplin, M. and Bucke, C., Enzyme technology. New York: Cambridge Univ. Press, 1990.
Cunningham, A. J., Introduction to bioanalytical sensors. New York: John Wiley, 1998.
Dahmen, K., Lehwald, S., and Ibach, H., “Bending of crystalline plates under the influence of surface stress-a finite element analysis,” Surf. Sci., vol. 446, pp. 161-173, 2000.
Fedder, G. K., Santhanam, S., Reed, M. L., Eagle, S. C., Guillou, D. F., Lu, M. S. C., and Carley, L. R., “Laminated high-aspect-ratio microstructures in a conventional CMOS process,” Proceedings. IEEE, The Ninth Annual International Workshop on Micro Electro Mechanical Systems. IEEE: New York, NY, USA. pp. 13-18, 1996.
Florin, E. L., Moy, V. T., and Gaub, H. E., “Adhesion force between individual ligand-receptor pairs,” Science, vol. 294, pp. 415-417, 1994.
Fritz, J., Baller, M. K., Lang, H. P., Rothuizen, H., Vettiger, P., Meyer, E., Güntherodt, H.-J., Gerber, C. H., and Gimzewski, J. K., “Translating biomolecular recognition into nanomechanics,” Science, vol.288, pp. 316-318, 2000.
Griffith L. G., and Naughton, G., “Tissue engineering-current challenges and expanding opportunities,” Science, vol. 295, pp. 1009-1014, 2002.
Hierold, C., Hildebrandt, A., Näher, U., Scheiter, T., Mensching, B., Steger, M., and Tielert, R., “A pure CMOS surface-micromachined integrated accelerometer,” Sens. Actuators A , vol. A57, no. 2, pp. 111-16, 1996.
Ibach, H., “The role of surface stress in reconstruction, epitaxial growth and stabilization of mesoscopic structures,” Surf. Sci. Rep., vol. 29, pp. 193-263, 1997.
Ibbotson, R. H., Dunn, R. J., Djakov, V., Ko Ferrigno, P., Huq, S. E., “Polyimide microcantilever surface stress sensor using low-cost, rapidly-interchangeable, spring-loaded microprobe connections,” Microelectron. Eng., vol. 85, pp. 1314-1317, 2008.
Kale, N. S., Nag, S., Pinto, R., Rao, V. R., “Fabrication and characterization of a polymeric microcantilever with an encapsulated hotwire CVD polysilicon piezoresistor,” J. Microelectromech. Syst., vol. 18, pp. 79-87, 2009.
Kane, B. J. and Kovacs, G. T. A., “A CMOS compatible traction stress sensing element for use in highresolution tactile imaging, “ 8th International Conference on Solid-State Sensors and Actuators and Eurosensors IX. Digest of Technical Paper. Stockholm, Sweden. pp. 648-51, 1995.
Khaled, A.-R. A., Vafai, K., Yang, M., Zhang, X., and Ozkan, C. S., “Analysis, control and augmentation of microcantilever deflections in bio-sensing systems,” Sens. Actuators B, vol. 94, pp. 103-115, 2003.
Kim, B. H., Kern, D. P., Raible, S., Weimar, U., “Fabrication of micromechanical mass-sensitive resonators with increased mass resolution using SOI substrate,” Microelectron. Eng., vol. 61-62, pp. 947-953, 2002.
Kloeck, B. and De Rooij, N. F., “Mechanical sensors,” in Semiconductor Sensors, S. M. Sze, Ed. New York: Wiley, 1994.
Kruglick, E. J. J., Warneke, B. A., and Pister, K. S. J., “CMOS 3-axis accelerometers with integrated amplifier,” Proceedings MEMS 98. IEEE. Eleventh Annual International Workshop on Micro Electro Mechanical Systems. 1998, IEEE: New York, NY, USA. pp. 631-6.
Kukta, R. V., Kouris, D., and Sieradzki, K., “Adatoms and their relation to surface stress,” J. Mech. Phys. Solids, vol. 51, pp. 1243-1266, 2003.
Lechuga, L. M., Tamayo, J., Álvarez, M., Carrascosa, L. G., Yufera, A., Doldán, R., Peralías, E., Rueda, A., Plaza, J. A., Zinoviev, K., Domínguez, C., Zaballos, A., Moreno, M., Martínez-A, C., Wenn, D., Harris, N., Bringer, C., Bardinal, V., Camps, T., Vergnenègre, C., Fontaine, C., Díaz, V., Bernad, A., “A highly sensitive microsystem based on nanomechanical biosensors for genomics applications,” Sens. Actuators B, vol. 118, pp. 2-10, 2006.
Lee, G. U., kidwell, D. A., and Colton, R. J., “Sensing discrete streptavidin-biotin interactions with atomic force microscopy,” Langmuir, vol.10, pp. 345-357, 1994.
Lin, L. and Yun, W., “Design, optimization and fabrication of surface micromachined pressure sensors,” Mechatronics, vol. 8, pp. 505-519, 1998.
Linnemann, R., Gotszalk, T., Hadjiiski, L., and Rangelow, I. W., “Characterization of a cantilever with an integrated deflection sensor,” Thin solid films, vol. 264, pp. 159-164, 1995.
Mardou, M., Fundamental of microfabrication. New York: CRC Press, 2nd ed., 2001.
Mertens, J., Rogero, C., Calleja, M., Ramos, D., Martin-Gago, J. A., Briones, C., Tamayo, J., “Label-free detection of DNA hybridization based on hydration-induced tension in nucleic acid films,” Nature Nanotechnology, vol. 3, pp. 301-307, 2008.
Milburn, C., Zhou, J., Bravo, O., Kumar, C., Soboyejo, W.O., “Sensing Interactions Between Vimentin Antibodies and Antigens for Early Cancer Detection,” J. Biomed. Nanotechnol., vol. 1 pp. 30-38, 2005.
Moulin, A. M., O’Shea, S. J., and Welland, M. E., “Microcantilever-based biosensors,” Ultramicroscopy, vol. 82, pp. 23-31, 2000.
Nguyen, C. T.-C., Katehi, L. P. B., and Rebeiz, G. M., “Micromachined devices for wireless communications,” Proc. IEEE. Int. Microwave. Symp., vol. 86, no. 8, pp. 1756–68, 1998.
Pei, J., Tian, F., Thundat, T., “Glucose biosensor based on the microcantilever,” Anal. Chem., vol. 76, pp. 292-297, 2004.
Pister, K. S. J., Judy, M. W., Burgett, S. R., and Fearing, R. S., “Microfabricated hinges,” Sens. Actuators A, vol. 33, pp. 249–256, 1992.
Raiteri, R., Grattarola, M., Butt, H. J., and Skládal, P., “Micromechanical cantilever-based biosensors,” Sens. Actuators. B, vol. 79, pp. 115-126, 2001.
Sader, J. E., “Surface stress induced deflections of cantilever plates with application to atomic force microscope: rectangular plates,” J. Appl. Phys., vol. 89, no. 5, pp. 2911-2921, 2001.
Stoney, G. G., “The tension of metallic films deposited by electrolysis,” Proc. Roy. Soc. London A Mater., vol. 82, pp. 172-175, 1909.
Thaysen, J., “Cantilever for bio-chemical sensing integrated in a microliquid handing system,” Ph. D Thesis, Technology University of Denmark, 2001.
Thaysen, J., Boisen, A., Hansen, O., and Bouwstra, S., “Atomic force microscopy probe with piezoresistive read-out and highly symmetrical Wheastone bridge arrangement,” Sens. Actuators A, vol. 83, pp. 47-53, 2000.
Thaysen, J., Marie, R., and Boisen, A., “Cantilever based bio-chemical sensor integrated in a microliquid handling system,” 14 IEEE International Conference on Micro Electro Mechanical Systems, Proceeding, 401-404, 2001.
Tortonese, M., Yamada, H., Barret, R. C., and Quate, C. F., “Atomic force microscopy using a piezoresistive cantilever,” in Tech. Dig. International Conference on Solid-State Sensors and Actuators (Transducers’91), pp. 448-451, 1991.
Vettiger, P., Cross, G., Despont, M., Drechsler, U., Durig, U., Gotsmann, B., Haberle, W., Lantz, M. A., Routhuizen, H. E., Stutz, R., and Binning, G. K., “The ‘Millipede’-Nanotechnology entering data storage,” IEEE Transactions on Nanotechnology, vol. 1, no.1, pp. 39-54, 2002.
Voiculescu, I., Zaghloul, M. E., McGill, R. A., Houser, E., Fedder, G. K., “Electrostatically actuated resonant microcantilever beam in CMOS technology for the detection of chemical weapons,” IEEE Sensors J., vol. 5, pp. 641-647, 2005.
Vilms, J. and Kerps, D., “Simple stress formula for multilayered thin film on a thick substrate,” J. Appl. Phys., vol. 53, no. 3, pp. 1536-1537, 1982.
Wee, K.W., Kang, G.Y., Park, J., Kang, J.Y., Yoon, D.S., Park, J.H., Kim, T.S., “Novel electrical detection of label-free disease marker proteins using piezoresistive self-sensing micro-cantilevers,” Biosens. Bioelectron., vol. 20, pp. 1932-1938, 2005.
Wu, G., Datar, R.H., Hansen, K.M., Thundat, T., Cote, R.J., Majumdar, A., “Bioassay of prostate-specific antigen (PSA) using microcantilevers,” Nat. Biotechnol., vol. 19, pp. 856-860, 2001.
Yang, S. M., Chang, C., Yin, T. I., “On the temperature compensation of parallel piezoresistive microcantilevers in CMOS biosensor,” Sens. Actuators B, vol. 129, pp. 678–684, 2008.
Yang, S. M. and Yin, T. I., “Design and analysis of piezoresistive microcantilever for surface stress measurement in biochemical sensor,” Sens. Actuators B, vol. 120, pp. 736–744, 2007.
Yang, S. M., Yin, T. I., Chang, C., “Development of a double-microcantilever for surface stress measurement in microsensors,” Sens. Actuators B, vol. 121, pp. 545–551, 2007.
Zimmermann, M., Volden, T., Kristein, K. U., Hafizovic, S., Lichtenberg, J., Brand, O., Hierlemann, A., “A CMOS-based integrated-system architecture for a static cantilever array,” Sens. Actuators B, vol. 131, pp. 254–264, 2008.