氮化鋁鎵/氮化鎵(N-HEMT)場效電晶體具有高電子遷移率、高靈敏度、高效率、高選擇性和即時偵測等優點，此類材料對於生物分子的感測方式和製備生物感測器是很重要的一項研究。本研究希望透過半導體生物晶片能在未來應用於居家型快篩生物感測器。
本研究主要分成兩個部分:第一個部分為利用N-HEMT偵測胰臟癌抗原分子(CA19-9 antigen)，並探討不同感測區域大小之電極圖層對其電流-電壓(ID-VDS和ID-VG)的影響。第二部分為利用人類血液和血將加入胰臟癌抗原分子，並透過化學表面修飾和微流道技術進行流體實。
N-HEMT是由三五族氮化物組成，其AlGaN/GaN異質結構的接面處會形成二維電子氣體。由於生物分子修飾在靠近二維電子氣體的表面上時，會改變二維電子氣體的載子分布進而影響載子傳導特性。我們利用Labview軟體結合鎖像放大器測量即時電流曲線圖，來判斷生醫晶片的電導變化。
本實驗製作之生物感測晶片最好的CA19-9 抗原分子在PBS背景溶液中感測極限為15 U/mL。而在血漿與CA19-9抗原混合之溶液下我們發現其偵測極限為30 U/mL。另外，我們製備了不同感測區域大小的生醫晶片，結果顯示感測大小為0.06 mm2 時，電流變化對CA19-9抗原有較高的靈敏性。
 
本論文第一章先做生物感測器之文獻回顧，第二章為儀器介紹和樣品結構分析。生物晶片製程技術則在第三章詳細說明，第四章與第五章則為實驗結果討論和全文總結。

AlGaN/GaN (N-HEMT) field effect transistors have high electron mobility, high sensitivity, high efficiency, high selectively and real-time detection. This kind of material for sensing of biological molecules and preparation of biological sensors is a very important research. This study expects that the semiconductor biochips can be applied for fast screening of home-based biosensors in the future.
The study is divided into two parts: The first part is the use of N-HEMT to detect pancreatic cancer antigen (CA19-9 antigen), and to analyze different sensing area with its current-voltage (ID-VDS and ID-VG) measurements. The second part is the use of human blood and plasma added CA19-9 antigen, and through chemical surface modification and micro-channel technology for fluid experiment.
N-HEMT is a III-V nitride composition, at its junction AlGaN/GaN heterostructures will form a two-dimensional electron gas. Due to the modification of biological molecules near the surface of the two-dimensional electron gas, it will change the carrier distribution thereby affecting the carrier conduction characteristics. We use the software “Labview” and combines with lock-in amplifier to measure real-time current graphs, and analyze the conductance change of biosensors.
 
The experiments produced the best bio-sensing chip CA19-9 antigen at a limit of 15 U/mL, and the detection limit of CA19-9 with background in plasma is 30 U/mL. Also the sensing area of size 0.06 mm2 has higher current reduction, which means this size is more sensitive to concentrations.
In this study, the first chapter we introduce the biosensors literature review, and the second chapter describes the instruments and sample analyses. Biosensor fabrication process is described in chapter III, and chapter IV is the experimental results and discussion. Finally, the summary is in chapter V.

論文審定書 …………………………………………………………………..……...i
Acknowledge ………………………………………………….……...…….…..…...ii
摘要 ………………………………………………………………….…………..…iii
Abstract ……………………………………………………….……………..…...…v
Contents ………………………………………………………….…………..….....vii
Figure list ………………………………………………………….………..…........ix
Table list ……………………………………………………….……………..….xiii
Chapter I: Introduction ………………………………………………………..…...1
1-1 Introduction of biosensor development…………………………………1
1-2 Introduction of high electron mobility transistor (HEMT) ……......…...3
1-3 Introduction of tumor marker, CA19-9 …………………..…….…........5
1-4 Introduction of biomolecule binding technique ………….….…..……..6
Chapter II: Instruments and sample analyses ……………………..…………..…8
2-1 Hall and Van der Pauw measurement results ……….………….….…..8
2-2 Scanning Electron Microscope results ……….………………….……11
2-3 High Resolution X-Ray Diffractometer results ………..…....………..15
2-4 Atomic Force Microscopy results ..……………………………...…...20
Chapter III: Biosensor fabrication process …………………………….…..…..25
3-1 HEMT Mask pattern ………………………………….………...…...25
3-2 Transmission line model …..……………………….………...……...27
3-3 Fabrication steps for HEMT based biosensor ....……….…..….....…31
3-4 Fabrication of microfluidic channel ……………………...…………37
3-5 Au-wire bonding technique ………………………....…....…...…….39
3-6 Chemicals compounds of biological solutions …………...…………41
Chapter IV: Experimental results and discussion ……………………...…...…44
4-1 Id-Vds curve measurement with different contacts configurations ......44
4-2 APTES modification results …..……………………………..…..….48
4-3 CA19-9 antigen microfluidic experiments ……………………..…...53
4-4 Specimen with CA19-9 antigen microfluidic experiments ……...….62
Chapter V: Summary ……………..………………...…………...……...…………67
Chapter VI: Future Outlook ...…………………………………………………..67
Appendix A 電性量測系統介紹 ……………...………….….......……………......71
Appendix B 微流體實驗系統介紹 ……………….……………………………....73
Reference …………………………………………………………...………75

1 B. S. Kang, H. T. Wang, F. Ren, and S. J. Pearton, J. Appl. Phys. 104, 031101, (2008).
2 L. Clark Jr., C. Lyons, Ann. NY Acad. Sci. 102, 29, (1962).
3 G. G. Guilbault, and J. G. Montalvo, J. Am. Chem. Soc. 92, Issue 8, 2533, (1970).
4 P. Bergveld, IEEE Trans Biomed Eng. 19, Issue 5, 342, (1972).
5 A. F. Collings, and F. Caruso, Rep. Prog. Phys. 60, 1397, (1997).
6 N. Chaniotakis, and N. Sofikiti, Anal. Chim. Acta. 615, Issue 1, (2008).
7 F. Rückert, C. Pilarsky, and R. Grützmann, Cancers. 2, 1107, (2010).
8 J. L. Magnani, Z. Steplewski, H. Koprowski, and V. Ginsburg, Cancer Res. 43, 5489, (1983).
9 T. Malati, Ind. J. Clinical Biochemistry. 22, Issue 2, 17, (2007).
10 S. Pavai, and S. F. Yap, Med. J. Malaysia. 58, No. 5, 667, (2003).
11 U. K. Ballehaninna, and R. S. Chamberlain, Journal of Gastrointestinal Oncology. 3, No. 2, 105, (2012).
12 A. Ulman, Chem. Rev. 96, 1533, (1996).
13 張哲魁、葛威成、張正宏、陳惠民, 奈米通訊, 14卷, No. 3, (2007).
14 N. K. Chaki, and K. Vijayamohanan, Biosens Bioelectron. 17, No. 1-2, 1, (2002).
15 L. J. Van der Pauw, Philips Res. Repts. 13, 1, (1958)
16 J. I. Goldstein, D. E. Newbury, P. Echlin, D. C. Joy, C. Fiori, and E. Lifshin, “Scanning electron microscopy and X-ray microanalysis. A text for biologists, materials scientists, and geologists”, Plenum Publishing Corporation, N. Y., (1981).
17 B. Lu, E. L. Piner, and T. Palacios, IEEE Electron Device Lett. 31, No.4, (2010).
18 D. H. Kang, I. H. Kim, J. H. Jeong, B. K. Cheong, D. H. Ahn, D. Lee, H. M. Kim, K. B. Kim, and S. H. Kim, J. Appl. Phys. 100, 054506, (2006).
19 G. M. Whitesides, Nature, 442, 368, (2006).
20 O. Israel, and A. Kuten, J. Nucl. Med. 48, No. 1, 28S, (2007).
21 N. Sawabu H. Watanabe, Y. Yamaquchi, K. Ohtsubo, and Y. Motoo, Pancrease. 28, Issue 3, 263, (2004).
22 M. R. C. Marques, R. Loebenberg, and M. Almukainzi, Dissolution Technologies. 18, Issue. 3, 15, (2011).
23 E. H. Williams, A. V. Davydov, A. Motayed, S. G. Sundaresan, P. Bocchini, L. J. Richter, G. Stan, K. Steffens, R. Zangmeister, J. A. Schreifels, and M. V. Rao, Appl Surf Sci. 258, 6056, (2012).
24 G. Yang, “Advanced Materials and Information Technology Processing”, International Materials Science Society. Hong Kong, (2014).
25 呂國豪, 戴達夫, “人類血漿蛋白的診斷”, 化學, 64, No. 1, 119 (2006).
26 H. Morkoc, and J. Leach, ”Polarization in GaN Based Heterostructures and Heterojunction Field Effect Transistors (HFETs)”, Polarization Effects in Semiconductors. 377, (2007).
27 E. F. Schubert, T. Gessmann, and J. K. Kim, “Light Emitting Diodes”, Kirk-Othmer Encyclopedia of Chemical Technology. (2005).
28 B. Baur, G.Steinhoff, J. Hernando, O. Purrucker, M. Tanaka, B. Nickel, M. Stutzmann, and M. Eickhoff, Appl. Phys. Lett. 87, 263901, (2005).
29 O. Ambacher, J. Smart, J. R. Shealy, N. G. Weimann, K. Chu, M. Murphy, W. J. Schaff, L. F. Eastman, R. Dimitrov, L. Wittmer, M. Stutzmann, W. Rieger, and J. Hilsenbeck, J. Appl. Phys. 85, No. 6, (1999).
30 N. L. Anderson, and B. J. Hickman, Analytical Biochemistry. 93, 312, (1979).