本晶片為離子感測電晶體(ISFET)的延伸原件，延伸式離子感測場效電晶體(EGFET)，不同於傳統的ISFET把MOS電晶體的閘極拿掉，使用Well上層的oxide作為感測區域的方式，我們在MOS電晶體的閘極上成沉積一層金作為感測區域，藉以感測生物分子。晶片製作完成後，經過後製在閘極上沉積金，並在其上製作自我集結單分子層修飾(SAM)，因為金可以和帶有硫醇鍵(Thiol)的生物分子產生共價結合，我們可以在金上固定生物分子，此生物分子可以抓取特定不同的生物分子，而生物分子大多帶有電量，會使在金上的電量改變，電荷的改變又會對金下面閘極產生電壓的變化，進而影響MOS產生通過的電流，這其中的變化，我們使用感測電路將電流轉換成數位脈波的方式量出，量測的電流可以小到μA等級，以利量測到較微小的變化，以DNA為例，我們可以固定一股DNA在金上，當加入對應的DNA時，會產生雜交反應，兩股DNA會結合在一起，而DNA帶有負電，所以我們可以從數位脈波的變化感測出DNA在不同濃度下的變化。

EGFETs (extended gate field effect transistor) are utilized in this work for biosening applications. Unlike traditional ISFET (ion sensitive field effect transistor) in which MOSFET’s gates are removed, we deposit a thin gold film on gates to form sensing regions. After post-deposition of the gold film on gates, the self-assembled monolayer (SAM) is formed on the gold film for biomolecule detection. We immobilized the biomolecules on gold film, and the biomolecules on gold film can capture specific biomolecules. Because biomolecules have charges, it changes the charge on gold film when specific bindings occur. And the charges on gold film can impact the current in the MOSFET. Combined with CMOS circuitry, we can detect the charge change of ions in MOSFET. The current that can be detect is about μA. A self-oscillating readout circuit was used to convert the ISFET current to a digital output for measurement of multiple sensors, showing the strength of the CMOS-based approach for sensor integration.

[1] D. S. Kim, Y. T. Jeong, H. J. Park, J. K. Shin, P. Choi, J. H. Lee, and G. Lim. "An FET-type charge sensor for highly sensitive detection of DNA sequence," Biosensors and Bioelectronics 20(1), pp. 69-74, 2004
[2] M. Kamahori, Y. Ishige, and M. Shimoda, "Detection of DNA hybridization and extension reactions by an extended-gate field-effect transistor: Characterizations of immobilized DNA-probes and role of applying a superimposed high-frequency voltage onto a reference electrode," Biosensors and Bioelectronics, vol. 23, pp. 1046-1054, 2008.
[3] T. Sakata, S. Matsumoto, Y. Nakajima, and Y. Miyahara, "Potential behavior of biochemically modified gold electrode for extended-gate field-effect transistor," Japanese journal of applied physics, vol. 44, pp. 2860-2863, 2005.
[4] Y. Ishige, M. Shimoda, and M. Kamahori, "Immobilization of DNA probes onto gold surface and its application to fully electric detection of DNA hybridization using field-effect transistor sensor," JAPANESE JOURNAL OF APPLIED PHYSICS PART 1 REGULAR PAPERS SHORT NOTES AND REVIEW PAPERS, vol. 45, p. 3776, 2006.
[5] S. J. Ding, B. W. Chang, C. C. Wu, M. F. Lai, and H. C. Chang, "Electrochemical evaluation of avidin-biotin interaction on self-assembled gold electrodes," Electrochimica acta, vol. 50, pp. 3660-3666, 2005.
[6] K. Sugawara, R. Kato, T. Shirotori, H. Kuramitz, and S. Tanaka, "Voltammetric behavior of avidin-biotin interaction at a biotin/thionine modified Au electrode," Journal of Electroanalytical Chemistry, vol. 536, pp. 93-96, 2002.
[7] D. S. Kim, J. E. Park, J. K. Shin, P. K. Kim, G. Lim, and S. Shoji, "An extended gate FET-based biosensor integrated with a Si microfluidic channel for detection of protein complexes," Sensors and Actuators B: Chemical, vol. 117, pp. 488-494, 2006.
[8] P. Jaruga, H. Rodriguez, and M. Dizdaroglu, "Measurement of 8-hydroxy-2'-deoxyadenosine in DNA by liquid chromatography/mass spectrometry," Free Radical Biology and Medicine, vol. 31, pp. 336-344, 2001.
[9] O. U. Beg and R. G. Holt, "An efficient cost effective protocol for automated fluorescent DNA sequencing," Biotechnology and applied biochemistry, vol. 26, pp. 27-30, 1997.
[10] Y. Cui, Q. Wei, H. Park, and C. M. Lieber, "Nanowire nanosensors for highly sensitive and selective detection of biological and chemical species," Science, vol. 293, p. 1289, 2001.
[11] P. Bergveld, "Development of an ion-sensitive solid-state device for neurophysiological measurements," Biomedical Engineering, IEEE Transactions on, pp. 70-71, 1970.
[12] Y. L. Chin, J. C. Chou, T. P. Sun, H. K. Liao, W. Y. Chung, and S. K. Hsiung, "A novel SnO2/Al discrete gate ISFET pH sensor with CMOS standard process," Sensors and Actuators B: Chemical, vol. 75, pp. 36-42, 2001.
[13] M. N. Niu, X. F. Ding, and Q. Y. Tong, "Effect of two types of surface sites on the characteristics of Si3N4-gate pH-ISFETs," Sensors and Actuators B: Chemical, vol. 37, pp. 13-17, 1996.
[14] L. Bousse, S. Mostarshed, B. van der Schoot, and N. De Rooij, "Comparison of the hysteresis of Ta2O5 and Si3N4 pH-sensing insulators," Sensors and Actuators B: Chemical, vol. 17, pp. 157-164, 1994.
[15] J. L. Chiang, S. S. Jan, J. C. Chou, and Y. C. Chen, "Study on the temperature effect, hysteresis and drift of pH-ISFET devices based on amorphous tungsten oxide," Sensors and Actuators B: Chemical, vol. 76, pp. 624-628, 2001.
[16] W. Bigelow, D. Pickett, and W. Zisman, "Oleophobic monolayers* 1:: I. Films adsorbed from solution in non-polar liquids," Journal of Colloid Science, vol. 1, pp. 513-538, 1946.
[17] R. G. Nuzzo and D. L. Allara, "Adsorption of bifunctional organic disulfides on gold surfaces," Journal of the American Chemical Society, vol. 105, pp. 4481-4483, 1983.
[18] K. E. Nelson, L. Gamble, L. S. Jung, M. S. Boeckl, E. Naeemi, S. L. Golledge, T. Sasaki, D. G. Castner, C. T. Campbell, and P. S. Stayton, "Surface characterization of mixed self-assembled monolayers designed for streptavidin immobilization," Langmuir, vol. 17, pp. 2807-2816, 2001.
[19] S. Caras and J. Janata, "Field effect transistor sensitive to penicillin," Analytical Chemistry, vol. 52, pp. 1935-1937, 1980.
[20] J. Van Der Spiegel, I. Lauks, P. Chan, and D. Babic, "The extended gate chemical sensitive field effect transistor as multi-species microprobe," Sensors and Actuators, vol. 4, pp. 1-8, 1983.
[21] P. Bergveld, "Thirty years of ISFETOLOGY* 1:: What happened in the past 30 years and what may happen in the next 30 years," Sensors and Actuators B: Chemical, vol. 88, pp. 1-20, 2003.
[22] P. Bergveld and A. Sibbald, Analytical and biomedical applications of ion-selective field-effect transistors: Elsevier New York, 1988.
[23] M. Schienle, C. Paulus, A. Frey, F. Hofmann, B. Holzapfl, P. Schindler-Bauer, and R. Thewes, "A fully electronic DNA sensor with 128 positions and in-pixel A/D conversion," Solid-State Circuits, IEEE Journal of, vol. 39, pp. 2438-2445, 2004.
[24] R. J. Baker, CMOS: Circuit design, layout, and simulation: Wiley-IEEE Press, 2010.
[25] K. Aslan, C. C. Luhrs, and V. H. Perez-Luna, "Controlled and reversible aggregation of biotinylated gold nanoparticles with streptavidin," The Journal of Physical Chemistry B, vol. 108, pp. 15631-15639, 2004.
[26] I. Huang, "Improvement of integrated Ag/AgCl thin-film electrodes by KCl-gel coating for ISFET applications," Sensors and Actuators B: Chemical, vol. 94, pp. 53-64, 2003.