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研究生: 龔柏誠
Kung, Po-Cheng
論文名稱: 以CMOS為主的離子感測場效電晶體微系統之特性探討及其尿液檢測之應用
CMOS-based ISFET microsystem characteristic study for urine sensing application
指導教授: 蘇炎坤
Su, Yan-Kuin
學位類別: 碩士
Master
系所名稱: 電機資訊學院 - 微電子工程研究所
Institute of Microelectronics
論文出版年: 2010
畢業學年度: 98
語文別: 英文
論文頁數: 78
中文關鍵詞: 酸鹼值白蛋白溫度互補式金屬-氧化層-半導體
外文關鍵詞: ph, albumin, temperature, cmos
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  •  本論文利用CMOS BioMEMS微系統技術,將多功能的生物感測器和一個環境溫度監控整合於單一感測系統中。以CMOS為主的離子感測場效電晶體微系統能夠準確的檢測出白蛋白分子和連續式的酸鹼度量測。這微系統的感測薄膜可以自然形成於最頂層,不需要額外的後製程處理。為了達到整體系統的微小化,這微系統以固態的參考電極取代傳統式的商用型參考電極。從結果顯示這一個微系統最後可以應用於尿液白蛋白檢測。
      根據實驗的架設是以氧化鋁和金的感測薄膜做為離子感測場效電晶體感測器結構的感測材料,並進行了白蛋白與酸鹼值感測器之特性比較和評估:
    1. 對於一個BioFET白蛋白晶片製造之可以簡易檢測白蛋白及其特點進行了研究。因此,這個BioFET的電流訊號變化是靠不同濃度的白蛋白吸附在金表上。根據實驗結果可知,這一個白蛋白感測器對於不同的白蛋白濃度可以檢測的線性範圍在14 μg/ml到28 μg/ml之間。所以這個白蛋白感測器可以實際應用於尿液的檢測。
    2. 我們使用pH-ISFET去感測酸鹼值濃度的變化,感測薄膜由自然形的氧化鋁它位於在最頂端的金屬層。針對其靈敏度、線性度、可逆性與遲滯現象做探討與比較兩種參考電極的特性。從實驗結果可知pH-ISFET的酸鹼值靈敏度最高可達到53.2 mV/pH,檢測範圍位於pH 6到pH 8之間。除此之外,溫度感測器也一併做探討,對於溫度感測器檢測範圍在25 ℃到60 ℃之間,對溫度的靈敏度是每度可以變化0.152歐姆。
    3. 最後我們整合白蛋白感測器、酸鹼值感測器、溫度感測器和一個固態的參考電極,它們被整合在一個玻璃基板上。從實驗結果明確的指出我們可以成功的檢測出白蛋白濃度、酸鹼值和溫度的變化。因此這一個以CMOS為主的離子感測場效應電晶體之微系統有能力實際應用於尿液的感測。

    This thesis reports a CMOS BioMEMS (biological micro-electromechanical system) microsystem for monolithically integrated multi-type biosensors and environment temperature monitor. CMOS-based ISFET microsystem is capable of precise detection albumin and continuous pH measurements. Without any deposition layer, the sensing membrane is formed naturally on the top of metal. To minimize the whole system size, the commercial Ag/AgCl electrode is replaced by pseudo electrode. The test results showed the applicability of the microsystem as a urinary albumin monitor.
    From the experimental setup, using native aluminum oxide and gold membrane to be the material of ISFET detecting device structure, and then comparing and estimating characteristic of albumin and pH sensor:
    1. A BioFET albumin chip for the easy detection of albumin was fabricated and its characteristics were investigated. As such, the drain current of the BioFET albumin chip can be varied by albumin absorbed on the gate (Au) surface. According to experiment results, it is shown that a linear curve from 14 μg/ml to 28 μg/ml for the different albumin concentrations. Therefore, it can be used as urinary albumin sensor in real applications.
    2. We used the pH-ISFET to detect the variation pH value that sensing membrane is aluminum oxide formed naturally on the top of M4. The discussion is base on the estimating of sensitivity, linearly, reversibility, and comparison commercial and pseudo reference electrode. From the experiment results, it is found that sensitivity of pH-ISFET is maximum 53.2 mV/pH ranging from pH 6 to pH 8. In addition, temperature sensor have estimated, sensitivity is 0.1526 Ω/ ℃ between 25 ℃ and 60 ℃ (step 5 ℃).
    3. Finally, we integrate albumin sensor, pH sensor, and temperature sensor and pseudo reference electrode on a glass substrate. Experimental results definitely indicate that we successfully measure albumin concentration, pH value, and temperature variation. Therefore, this CMOS-based ISFET microsystem is capable application in urine sensing.

    Content Abstract (in Chinese) Ⅰ Abstract (in English) Ⅲ Acknowledgements (in Chinese) V Contents VI Figure caption X Table captions XIII Chapter 1 Introduction 1 1.1 What's biosensor 1 1.2 The composition of Urine 1 1.2.1 Introduction of albumin 2 1.3 Motivation 3 1.4 Method of this research 4 1.5 Literature review 4 1.5.1 Ion sensitive field effect transistor 5 1.5.2 Albumim sensor 6 1.6 Organization and arrangement of thesis 7 1.7 References 9 Chapter 2 Theory description 11 2.1 FET-based sensor 11 2.1.1 pH-ISFET 12 2.1.1.1 Site-Binding Model 15 2.1.1.2 Electrical double layer 16 2.1.1.3 Helmholtz model 16 2.1.1.4 Stern model 17 2.1.2 BioFET sneosr 18 2.1.2.1 Principles of protein adsorption 18 2.2 Temperature sensor 19 2.2.1 Temperature coefficient of resistance 20 2.3 Concept of reference electrode 21 2.3.1 pH electrode 22 2.3.1 Silver-silver chloride reference electrode 23 2.3.1 Pseodo reference electrode 23 2.4 Relationship of temperature and pH 24 2.5 Reference 34 Chapter 3 Design and fabrication for multi-functional sensors on glass substrate 36 3.1 FET-based sensors 36 3.2 Design concept for pH-ISFET sensors 37 3.2.1 Native aluminum oxide as sensing membrane 37 3.2.2 Considerations for reference electrode 38 3.3 BioFET albumin sensor 39 3.4 Temperature sensor 40 3.5 Fabrication for multi-functional sensors on glass substrate 41 3.5.1 Fabrication for CMOS BioMEMS process in CIC 41 3.5.2 Fabrication for glass substrate 42 3.5.3 Biochip package 44 3.6 References 52 Chapter 4 Results and Discussion 54 4.1 BioFET albumin sensor 54 4.1.1 Preparation for solution 54 4.1.2 Experimental setup for BioFET albumin sensor 55 4.1.3 Results for BioFET albumin sensor 55 4.2 pH-ISFET sensor 57 4.2.1 Preparation for solution 57 4.2.2 Continuous step injection method for measuring pH level 58 4.2.3 Experimental setup for pH-ISFET 58 4.2.4 Results of pH-ISFET 59 4.2.4.1 The reversible testing for native Al2O3 sensing membrane 60 4.2.4.2 pH-ISFET with different kinds of reference electrode 61 4.2.4.3 The sensitivity by different reference voltage 61 4.3 Temperature sensors 62 4.4 Results for multi-functional sensors on glass substrate 63 4.5 References 76 Chapter 5 Conclusion and future work 77 5.1 Conclusion 77 5.2 Future work 78

    chapter 1 :
    References
    [1] http://en.wikipedia.org/wiki/Human_serum_albumin.
    [2] P. Bergveld, “Development of an ion-sensitive solid-state device for neurophysiological measurements”, IEEE Trans. Biomed. Eng. Vol. 17, 70(1970).
    [3] P. Bergveld, “Development, operation, and application of the ion-sensitive field-effect transistor as a tool for electrophysiology”, IEEE Trans. Biomed. Eng. Vol. 19, 342(1972).
    [4] T. Matsuo and K. D. Wise, “An integrated field-effect electrode for biopotential recording”, IEEE Trans. Biomed. Eng. Vol. 21, 485(1974).
    [5] K. K. Ng, “Complete guide to semiconductor devices”, McGraw-Hill, New York, 517(1995).
    [6] 周榮泉,王彥盛,2002,“離子感測場效電晶體及其應用於酵素感測器之方法與量測”,化工技術,10 卷,8 期,頁142~162(1990)。
    [7] J. C. Chou, H. M. Tasi and Y. F. Wang, “Study on the temperature dependence ofthe hysteresis for the A-Si:H gate pH-ISFET”, The International Symposium on Optoelectronic Materials and Devices. 809(2000).
    [8] H. K. Liao, J. C. Chou, W. Y. Chung, T. P. Sun and S. K. Hsiung, “Study on the interface trap density of the Si3N4/SiO2 gate ISFET”, Proceedings 3nd East Asian Conference on Chemical Sensor. 394(1997).
    [9] J. C. Chou, Y. S. Li and J. L. Chiang, “Simulation of Ta2O5-gate ISFET temperature characteristics”, Sens. Actuators B. Vol . 71, 73(2000).
    [10] S. S. Jan, J. L. Chiang, J. C. Chou and Y. C. Chen, “Temperature effect on PbTiO3 gate pH-ISFET”, Proc. of IEDMS. 242(2000).
    [11] V. Volotovsky, Y. J. Nam and N. Kim, “Urease-based biosensor for mercuric ions determination”, Sens. Actuators B. Vol. 42, 233(1997).
    [12] L. T. Yin, J. C. Chou, W. Y. Chung, T. P. Sun, K. P. Hsiung and S. K. Hsiung, “Glucose ENFET doped with MnO2 powder”, Sens. Actuators B. Vol. 76, 187(2001).
    [13] A. S. Poghossian, “Method of fabrication of ISFETs and CHEMFETs on an Si-SiO2-Si structure”, Sens. Actuators B. Vol. 44, 361-364(1993).
    [14] C. J. Huang, C. C. Lu,T. Y. Lin, T. C. Chou and G. B. Lee, “An electrochemical albumin-sensing system utilizing microfluidic technology”, J. Micromech. Microeng. Vol. 17, 835(2007).
    [15] 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, 1289( 2001).
    [16] MJ Schoning and A. Poghossian, ”Recent advances in biologically sensitive field-effect transistors (BioFETs)”, The Analyst. Vol. 127, 1177( 2002).
    [17] K.Y. Park, Y.S. Sohn, C.K. Kim, H.S. Kim, Y.S. Bae, S.Y. Choi, “Development of FET-type albumin sensor for diagnosing nephritis”, Biosensors and Bioelectronics. Vol. 23, 1904(2008).
    [18] G. Dhawan, G. Sumana, B.D. Malhotra, “Recent developments in urea biosensors”, Biochemical Engineering Journal. Vol. 44, 42(2009).
    chapter 2 :
    References
    [1] P. Bergveld, “Thirty years of ISFETOLOGY What happened in the past 30 years and what happen in the next 30 years”, Sens. Actuators B. Vol. 88, 1(2003).
    [2] D. E. Yates, S. Levine, T. W. Healy, “Site-Binding Model of the Electrical Double Layer at the Oxide/Water Interface”, Chem. Soc. Faraday Trans I. Vol. 70, 1807(1974).
    [3] J. S. Mattson, and Jr. H. B. Mark, “Activated Carbon: Surface Chemistry and Adsorption from Solution”, Wiley-Vch: New York. (1998).
    [4] C. H. Hamann, A. Hamnett, and W. Vielstich, “Electrochemistry”, Wiley-Vch: New York. (1998).
    [5] P. Ying, A. S. Viana, L. M. Abrantes, G. Jin, “Adsorption of human serum albumin onto gold: a combined electrochemical and ellipsometric study”, J Colloid. Interface Sci. Vol. 279, 95(2004).
    [6] E.J. Castillo, J.L. Koenig, J.M. Andersen and J. Lo, “Characterization of protein adsorption on soft contact lenses: I. Conformational changes of adsorbed human serum albumin”, Biomaterials. Vol. 5, 319(2004).
    [7] W. Norde, “Adsorption of proteins from solution at the solid-liquid interface”, Adv. Colloid Interface Sci. Vol. 25, 267(1986).
    [8] http://zh.wikipedia.org/zh-tw/%E6%B0%A8%E5%9F%BA%E9%85%B8
    [9] R.L. Smith and D.C. Scott, “An integrated sensor for electrochemical measurements”, IEEE Trans. Biomed. Eng. Vol. 33, 83(1986).
    [10] I.Y. Huang and R.S. Huang, “Fabrication and characterization of a new planar solid-state reference electrode for ISFET sensors”, Thin Solid Films Vol. 406, 255(2002).
    [11] P. Bergveld: Development, “Operation, and Application of the
    Ion-Sensitive Field-Effect Transistor as a tool for electrophysiology”, IEEE Trans. Biomed. Eng. Vol. 19, 255(1972).
    [12] Y. Q. Miao, J. R. Chen and K. M. Fang, “New technology for the detection of pH”, J. Biochem. Biophys. Methods. Vol. 63, 1(2005).
    [13] S. Martinoia and G. Massobrio, “A behavioral macromodel of the ISFET in SPICE”, Sens. Actuators B. Vol. 62, 182(2000).
    [14] L.M. Shepherd, C. Toumazou, “A biochemical translinear principle with
    weak inversion isfets”, IEEE Transactions on Circuits and Systems I. Vol. 52, 2614(2005).
    chapter 3 :
    References
    [1] J. Van Der Spiegel, I. Lauks, P. Chan and D. Babic, “The Extended Gate Chemical Sensitive Field Effect Transistor as Multi-Species Microprobe”, Sens. Actuators B. Vol. 4, 291(1983).
    [2] Hann-Huei Tsai, Chen-Fu Lin, Ying-Zong Juang, I-Long Wang, Yu-Cheng Lin, Ruey-Lue Wang, Hung-Yin Lin, ”Multiple type biosensors fabricated using the CMOS BioMEMS platform”, Sens. Actuators B. Vol. 144, 407 (2009).
    [3] The CIC CMOS MEMS Design Platform for Heterogeneous Integration, Technical Report, CIC-CID-RD-08-01, V1.0, National Chip Implementation Center, Hsinchu, Taiwan. (2008).
    [4] B. Palan, F. V. Santos, J. M. karam, B. Courtois, and M. Husak, “New ISFET sensor interface circuit for biomedical applications”, Sens. Actuators B. Vol. 57, 63(1999).
    [5] P. Ying, A. S. Viana, L. M. Abrantes, G. Jin, “Adsorption of human serum albumin onto gold: a combined electrochemical and ellipsometric study”, J. Colloid Interface Sci. Vol. 279, 95(2004).
    [6] S.H. Tseng, C.L. Fang, P.C.Wu, Y.Z. Juang, M.S.C. Lu, Tech. Digest “A CMOS MEMS thermal sensor with high frequency output”, IEEE Int. Conf. on Sensors. 387(2008).
    [7] 林建甫,”微流體多功能電化學檢測系統”,國立成功大學工程科學系碩士論文. (2005)。
    [8] 武世香,虞惇,王貴華,“化學量傳感器”,傳感器技術,第2期, 58(1990).
    chapter 4 :
    References
    [1] Jin, B.-H., and Lee, G.-S., “Urine chemistry and general test”, Pyeo Naem Hong Publisher. (2003).
    [2] J. L. Chiang, J. C. Chou and Y. C. Chen, “Sensitivity and Hysteresis Properties of a-WO3, a-Ta2O5 and a-Si:H Gate ISFETs”, Optical Engineering. Vol. 41, 2032(2002).

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