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，分子與微結構間所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。然而由於壓阻層之熱效應，且生化反應產生之表面應力為一雙軸向應力負載；因此微懸臂結構之力學行為對壓阻層之訊號量測是生化感測器之重要關鍵。

　　本文提出一個二維力學模型以分析微懸臂結構於表面應力與熱效應負載之下之力學行為。分析結果顯示表面應力之雙軸效應對此壓阻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表面應力之量測。因此，本文提出一種條狀式分子吸附層之設計以及一種微型雙懸臂結構之新型設計以解決此熱效應並有效提升感測器之表面應力量測靈敏度。本文也提出整合於此感測器晶片之橋式電路分析輔以訊號處理，用以消除電路偏壓讀值以及溫度漂移所產生之雜訊。

　　同時為整合此壓阻微懸臂結構與微流體系統於單一感測晶片，本文首次提出一相容於半導體標準CMOS 製程之生化感測器晶片設計與製作。感測器晶片之微結構釋放與微流道封裝可利用簡易之後製程來達成。經由晶片實際的量測，證實微懸臂結構顯著之熱效應與條狀式分子吸附層設計之效能。以硫醇 (thiol) 修飾之單股DNA (ssDNA) 為例實際應用此生化感測器晶片之線上量測，結果顯示單股DNA 引發之等效表面應力變化為0.15 N/m,晶片之表面應力量測靈敏度為3.5 10-5 m/N，優於現存文獻之研究成果。本文提出之壓組式微懸臂結構與整合感測器晶片之分析、設計與製造將可提供此生化感測器一個嶄新的研究方向。

　　Many new biosensors design based on microcantilever have been proposed by using the fast and sensitive response of micromechanical detection. Microcantilever with embedded piezoresistor has been proposed recently to measure the surface stress change induced by bioanalytes. However, such biosensors are vulnerable to the thermal effect from piezoresistor and the biaxial effect of surface stress from biochemical reaction. Improved microcantilever design for better performance is desirable.

　　This study proposes a two-dimensional mechanics model to analyze the piezoresistive effect of the four-layer microcantilever under surface stress and thermal loading. Analyses show that the biaxial effect of surface stress is crucial and the thermal effect from the piezoresistor is lethal to surface stress measurement. A stripe pattern design on the immobilized layer is proposed to improve the surface stress sensitivity while minimizing the thermal effect. In addition, an innovative double-microcantilever design is also developed to isolate the thermal effect. In sensor operation, however, different layer composition of active and reference microcantilever leads to an offset voltage and the associated temperature drift. 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 microcantilever and microchannel is fabricated by complementary metal-oxide-semiconductor (CMOS) compatible 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. An on-chip biosening of thiol-modified ssDNA is conducted to validate the sensor performance. Measurement result shows the induced surface stress from the immobilized ssDNA is approximately 0.15 N/m, and the surface stress sensitivity of the biosensor is calculated as m/N. Design, analysis and experimental verification demonstrate that the microcantilever with embedded piezoresistor and signal conditioning circuit is preferable to biosensor applications.

Akbar, M. and Shanblatt, M. A., “Temperature composition of piezoresistive pressure sensors,” Sens. Actuators A., vol. 33, pp. 155-162, 1992.
Angus, H., “Surface films on precious metal contacts,” Brit J. Appl. Phys., vol. 13, pp. 58-63, 1962.
Binning, G., Quate, C. F., and Gerber, C. H., “Atomic force microscope,” Phys. Rev. Lett., vol. 56, pp. 930-933, 1986.
Barnes, J. R., Stephenson, R. J., Welland, M. E., Gerber, C. H., and Gimzewski, J. K., “Photothermal spectroscopy with femtojoule sensitivity based on micromechanics, ” Nature, vol. 372, pp. 372-379, 1994.
Bustillo, J. M., Howe, R. T., and Muller, R. S., “Surface micromachining for microelectromechanical systems,” Proc. of the IEEE , vol. 86, no. 8, 1998.
Buhler, J., Funk, J., Korvink, J. G., Steiner, F. P., Sarro, P. M., and Baltes, H., ” Electrostatic aluminum micromirrors using double-pass metallization,” Journal of Microelectromechanical Systems, vol. 6, no. 2, pp. 126-35, 1997.
Buhler, J., “Deformable micromirror arrays by CMOS technology,” Ph.D. thesis, ETH Zurich, Zurich, Switzerland, 1997.
Baller, M. K., Lang, H. P., Battiston, F. M., Fritz, J., Berger, R., Ramseyer, J. -P., Fornaro, P., Meyer, E., GuKntherodt, H. -J., Brugger, J., Drechsler, U., Rothuizen, H., Despont, M., Vettiger, P., Gerber, C. H., and Gimzewski, J. K., “A cantilever array-based artificial nose,” Ultramicroscopy, vol. 82, pp. 1-9, 2000.
Berger, R., Lang, H. P., Gerber, C. H., Gimzewski, J. K., Fabian, J. H., Scandella, L., Meyer, E., and Cuntherodt, H.-J., “Micromechanical thermogravimetry,” Chem. Phys. Lett., vol. 294, pp. 363-369, 1998.
Berger, R., Delamarche, E., Lang, H. P., Gerber, C. H., Gimzewski, J. K., Meyer, E., and Guntherodt, 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 Guntherodt, H. –J., “Thermal analysis using a micromechanical calorimeter, ” Appl. Phys. Lett. vol. 69, pp. 40-42, 1996.
Bashir, R., Gupta, A., Neudeck, G. W., McElfresh, M., and Gomez, R., “On the design of piezoresistive silicon cantilevers with stress concentration regions for scanning probe microscopy applications,” J. Micromech. Microeng., vol. 10, pp. 483-491, 2000.
Coughlin, R. F, and Driscoll, F. F., Operational amplifiers and linear integrated circuits. Prentice-Hall, 6th, 2001.
Cunningham, A. J., Introduction to bioanalytical sensors. New York: John Wiley, 1998.
Chaplin, M. and Bucke, C., Enzyme technology. New York: Cambridge Univ. Press, 1990.
Cosfold, R. J. O. and Kuhr, W., “Capillary biosensor for glutamate,” Anal. Chem., vol. 68, pp. 2164-2169, 1996.
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.
Florin, E. L., Moy, V. T., and Gaub, H. E., “Adhesion force between individual ligand-receptor pairs,” Science, vol. 294, pp. 415-417, 1994.
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.
Fritz, J., Baller, M. K., Lang, H. P., Rothuizen, H., Vettiger, P., Meyer, E., Guntherodt, H.-J., Gerber, C. H., and Gimzewski, J. K., “Translating biomolecular recognition into nanomechanics,” Science, vol.288, pp. 316-318, 2000.
Gibbs, J. W., “The scientific papers of J. Willard Gibbs,” vol.1 (Longmans-Green, London), pp. 5, 1906.
Gakkestad, J., Ohlckers, P., and Halbo, L., “Compensation of sensitivity shift in piezoresistive pressure sensors using linear voltage excitation,” Sens. and Actuators, vol. 49, pp. 11-15, 1995.
Griffith L. G., and Naughton, G., “Tissue engineering-current challenges and expanding opportunities,” Science, vol. 295, pp. 1009-1014, 2002.
Healy, B. G. and Walt, D. R., “Fast temporal response fiber-optic chemical sensors based on the photodeposition of micrometer-scale polymer arrays,” Anal. Chem., vol. 69, pp. 1078-1080, 1995.
Hierold, C., Hildebrandt, A., Naher, 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.
Harley, J. A., “Advances in piezoresistive probes for atomic force microscopy,” Ph. D Thesis, Stanford University, 2000.
Hansen, O., and Boisen, A., “Noise in piezoresistive atomic force microscopy,” Nano- technology, vol. 10, pp. 51-60, 1999.
Herne, T. M. and Tarlov, M. J., “Characterization of DNA probes immobilized on gold surface,” J. Am. Chem. Soc., vol. 119, pp. 8916-8920, 1997.
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.
Ishihara, T., Suzuki, K., Suwazono, S., Hirata, M., and Tanjgawa, H., “CMOS integrated silicon pressure sensor,” IEEE J. Solid-State Circuits, vol. Sc-22, no. 2, 1987.
Josse, F., ”Acoustic wave liquid-phase-based microsensors,” Sens. Actuators B, vol. 44, pp. 199-208, 1994.
Koch, R. and Albermann, R. Thin Solid films, vol. 129, pp. 63, 1985.
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.
Kloeck, B. and De Rooij, N. F., “Mechanical sensors,” in Semiconductor Sensors, S. M. Sze, Ed. New York: Wiley, 1994.
Kan, 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.
Kassegne, S., Madou, M., Whitten, R., Zoval, J., Mather, E., Sarkar, K., Hodko, D., and Maity, S., “Design issues in SOI-based high-sensitivity piezoresistive cantilever devices,” Proceeding of the SPIE Conference on Smart Structures and Materials, San Diego, CA, pp. 1-6, 2002.
Kerr, D. R. and Milnes, A. G., “Piezoresistive properties of silicon diffused layers,” J. Appl. Phys., vol. 34, no. 4, pp. 727-731, 1963.
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.
Kopp, M. U., de Mello, A. J., and Manz, A., “Chemcial amplification: continuous-flow PCR on a chip,” Science, vol. 280, pp. 1046-1048, 1998.
Kanda, Y., “Piezoresistance effect silicon,” Sen. Actuator A, vol. 28, pp. 83-91, 1991.
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.
Lavrik, N. V., Sepaniak, M. J., and Datskos, P. G., “Cantilever transducers as a platform for chemical and biological sensors,” Rev. Sci. Instrum., vol. 75, pp. 1-25, 2004.
Lopez-Martin, A. J., Osa, J. I., Zuza, M., and Carlosena, A., “Analysis of a negative impedance converter as a temperature compensator for bridge sensors,” IEEE Trans. Instrumentation and Measurement, vol. 52, no. 4, pp. 1068-1072, 2003.
Liu, C. W., “Fabrication development for micro channel system by MEMS technology with measurements of the inside thermal transport process,” Ph. D Thesis, National Cheng Kung University, Taiwan, 2004.
Lee, G. U., kidwell, D. A., and Colton, R. J., “Sensing discrete streptvidin-biotin interactions with atomic force microscopy,” Langmuir, vol.10, pp. 345-357, 1994.
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.
Lin, L. and Yun, W., “Design, optimization and fabrication of surface micromachined pressure sensors,” Mechatronics, vol. 8, pp. 505-519, 1998.
Martinez, R. E., Augustyniak, W. M., and Golovchenko, J. A., Phys. Rev. Lett. vol. 64, pp. 1035, 1990.
Moulin, A. M., O’Shea, S. J., and Welland, M. E., “Microcantilever-based biosensors,” Ultramicroscopy, vol. 82, pp. 23-31, 2000.
Mardou, M., Fundamental of microfabrication. New York: CRC Press, 2nd ed., 2001.
Mason, W. P., Forst, J. J., and Tornillo, L. M., “Recent developments in semiconductor strain transducers,” Semiconductor and Conventional Strain Gages, pp. 110-12-, New York, 1962.
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.
Nam, J. -M., Thaxton, C. S., and Mirkin, C. A., “Nanoparticle-based bio-bar codes for the ultra sensitive detection of proteins,” Science, vol. 301, pp. 1884-1886, 2003.
Obermeier, E. and Kopystynski, P., “Polysilicon as a material for microsensor applications,” Sens. Actuator A, vol. 30, pp. 149-155, 1992.
Okahata, Y., Kawase, M., Niikura, K., Ohtake, F., Furusawa, H., and Ebara, Y., “Kinetic measurement of DNA hybridization on an oligonucleotide-immobilized 27MHz quartz crystal microbalance,” Anal. Chem., vol. 70, pp. 1288-1296, 1998.
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.
Rasmunssen P. A., Thaysen, J., Hansen, O., Eriksen, S. C., and Boisen, A., “Optimized cantilever biosensor with piezoresistive read-out,” Ultramicroscopy, vol. 97, pp. 371-376, 2003.
Raiteri, R., Grattarola, M., Butt, H. J., and Skladal, P., “Micromechanical cantilever-based biosensors,” Sens. Actuators. B, vol. 79, pp. 115-126, 2001.
Sprotte, A., Buckhorst, R., Brockherde, W., Hostika, B., and Bosch, D., “CMOS magnetic-field sensor system,” IEEE J. Solid-State Circuits, vol. 32, no. 8, pp. 1002-1005, 1994.
Stoney, G. G., “The tension of metallic films deposited by electrolysis,” Proc. Roy. Soc. London A Mater., vol. 82, pp. 172-175, 1909.
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.
Senturia, S. D., “A piezoresistive pressure sensor,” in Microsystem Design, Kluwer Academic Publishers, 2001.
Timoshenko, S. P., J. Opt. Soc. Am., vol. 11, pp. 233, 1925.
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.
Tufte, O. N. and Stelzer, E. L., “Piezoresistive properties of silicon diffused layers,” J. Appl. Phys., vol. 34, no.2, pp. 313-318, 1963.
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.
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.
Wu, G., Ji, H., Hansen, K., Thundat A., Datar, R., Cote, R., Hagan, M. F., Chakraborty, A. K., and Majumdar, “Origin of nanomechancial cantilever motion generated from biomolecular interactions,” Proceedings of the National Academy of Science, vol. 98, no. 4, pp. 1560-1564, 2001.