In this thesis, we present a new design of biosensor for fM level dopamine (DA) detection. The TSMC 0.35-um CMOS process is used for fabrication of the ion-sensitive field effect transistors (ISFET). A series of etching processes is performed after the foundry process. We use sulfuric acid to etch the stacked metal and via layers to expose the polysilicon gates, followed by the KOH etch to remove polysilicon in order to expose the gate oxide. The open-gate FET (OGFET) is thus formed for detection purpose.
The OGFET devices are integrated with sensing circuits on the same chip to form a 4×4 sensor array. The sensing circuit converts the transistor current to a digital pulse output to sense DA concentration. The linear detection range of our circuit is from 40 nA to 6 uA .
The DA molecules are immobilized on the oxide surface and result in negative charges which subsequently change the I-V characteristics of the OGFET. The device is capable to detect DA in the fM range.
We have developed in this work an ultrasensitive ISFET device by using a conventional CMOS process, with the performance comparable to those of nano-wire FET (NWFET). Most importantly, we are able to integrate the sensing device and circuit on the same chip for low cost, portable, and fM-level DA detection.

本研究目的在於開發出感測濃度達到fM(10-15 M)等級的多巴胺感測元件，此感測元件由TSMC CMOS 0.35 □m製程製作而成，我們把從製程廠製作回來的晶片，經由一連串的後製程，首先經由硫酸濕蝕刻掉金屬層，再經由KOH濕蝕刻掉多晶矽，以露出我們所需要的感測區域，而完成了感測元件OGFET(開閘極場效電晶體)。
此篇論文的特點在於將感測元件與感測電路整合在一顆晶片上，而感測電路方面則是4乘4的感測陣列，感測電路原理為將感測元件電流轉換至數位脈波輸出的感測機制，有鑑於以往傳統式ISFET感測電路為電阻式放大器，但輸出的變化量都在mv(毫伏)範圍；而我們所設計的電路正好彌補了此不足，其優點在於能夠將大範圍的電流感測出來並且以數位脈波輸出，而我們所設計的電路感測電流範圍在40 nA ~6 □A之間。
在整個晶片完成了硫酸濕蝕刻等後製程後，必須在其感測表面進行分子固定化，用意在於能夠抓取我們想要量測的生物分子(在此為多巴胺)，抓取到的多巴胺分子帶有負電，使得所量測的I-V曲線產生位移而能感測到fM(10-15 M)等級的多巴胺溶液。
我們在此篇論文中利用傳統CMOS製程開發出極靈敏的離子電晶體感測器，而能夠達到與奈米金線場效電晶體相同的感測靈敏度(NWFET)；本研究最重要的地方在於能夠將感測元件與電路整合在一個系統中，這對於低成本開發無疑是一個絕對的幫助，且因晶片面積小而能夠達到隨身攜帶的目的，對於病人的即時偵測非常的有用。

[1]P. Bergveld, “Development of an ion-sensitive solid-state device for neurophysiological measurement,” IEEE Trans. Biomed. Eng. 17, pp. 70-71, 1970.
[2]M. J. Milgrew, P. A. Hammond, D. R. S. Cumming, “The development of scalable sensor arrays using standard CMOS technology,” Sensors and Actuators B 103, pp. 37–42, 2004.
[3]J. Bausells, J. Carrabina, A. Errachid, A. Merlos, “Ion-sensitive field-effect transistors fabricated in a commercial CMOS technology,” Sensors and Actuators B 57, pp. 56–62, 1999.
[4]M. J. Milgrew, M. O. Riehle, D. R. S. Cumming, “A large transistor-based sensor array chip for direct extracellular imaging,” Sensors and Actuators B 111–112, pp. 347–353, 2005.
[5]Y.-L. Chin, J.-C. Chou, T.-P. Sun, H.-K. Liao, W.-Y. Chung, S.-K. Hsiung, “A novel SnO2/Al discrete gate ISFET PH sensor with CMOS standard process,” Sensor and Actuators B 75, pp. 36-42, 2001.
[6]D.-Sun. Kim, Y.-T. Jeong, H.-J. Park, J.-K. Shin, P. Choi, J.-H. Lee, G. Lim, “An FET-type charge sensor for highly sensitive detection of DNA sequence,” Biosensors and Bioelectronics 20, pp. 69–74, 2004.
[7]W. Y. Chunga, Y. T. Lina, D. G. Pijanowskac, C. H. Yangb, M. C. Wanga, A. Krzyskowc, W. Torbicz, “New ISFET interface circuit design with temperature compensation,” IEEE J.Microelectronics 37, PP. 1105–1114, 2006.
[8]S. V. Dzyadevych, A. P. Soldatkin, A. V. El’skaya, C. Martelet, J.–R. Nicole, “Enzyme biosensors based on ion-selective field-effect transistors,” Analytica Chimica Acta 568, pp. 248–258, 2006.
[9]P. Bergveld, “Thirty years of ISFETOLOGY What happened in the past 30 years and what may happen in the next 30 years,” Sens. Actuators B 88, pp. 1-20, 2003.
[10]P. E. Allen and D. R. Holberg, CMOS Analog Circuit Design, 2th ed., Oxford University Press, 2002.
[11]M. Schienle, C. Paulus, A. Frey, F. Hofmann, B. Holzapfl, S.-B. Petra, and R. Thewes, “A Fully Electronic DNA Sensor With 128 Positions and In-Pixel A/D Conversion,” IEEE J.Solid-State Circuits, vol. 39, no. 12, Dec. 2004.
[12]S.-R. Chang, C.-H. Chang, J.-S. Lin, M. S.-C. Lu, Y.-T. Lee, S.-R. Yeh and H. Chen, “Die-level, post-CMOS processes for fabricating open-gate, field-effect biosensor arrays with on-chip circuitry,” J. Micromech. and Microeng., vol.18, 115032, 2008.
[13]C.-H. Lin, C.-Y. Hsiao, C.-H. Hung, Y.-R. Lo, C.-C. Lee, C.-J. Su, H.-C. Lin, F.-H. Ko, T.-Y. Huang and Y.-S. Y, “Ultrasensitive detection of dopamine using a polysilicon nanowire field-effect transistor,” Chem. Commun, pp. 5749–5751, 2008.
[14]S. R. Ali, R. R. Parajuli, Y. Ma, Y. Balogun, and H. He, “Interference of Ascorbic Acid in the Sensitive Detection of Dopamine by a Nonoxidative Sensing Approach,” J. Phys. Chem. B 111, pp. 12275-12281, 2007.
[15]I.-Y. Huang, R.-S. Huang, L.-H. Lo, “Improvement of integrated Ag/AgCl thin-film electrodes by KCl-gel coating for ISFET applications,” Sensors and Actuators B 94, pp. 53–64, 2003.