臺灣博碩士論文加值系統

本研究成功地利用低溫多晶矽（LTPS，LOW TEMPERATURE POLYCRYSTALLINE SILICON）製程技術，設計並製作出一個利用介電泳力進行細胞操控之生醫感測晶片，此製程比起以CMOS製程做出的生醫晶片最大的好處之一為省去後製程這道步驟，除此之外，大面積與較低的成本都是極大的優勢，但此製程也不是這樣完好無缺點，最需要改進的就是製程的穩定度。
在本文的研究中首先詳細的介紹介電泳力的基本原理，並對其數學模型進行推導，之後利用CFD-RC模擬軟體將各項實驗條件參數帶入，可成功的設計出以介電泳力原理來操控微粒的模擬結果。而在晶片感測部份，使用在CMOS製程中發展應用成熟的3T影像感測電路來進行細胞感測，並用H-spice電路模擬軟體來進行設計驗證其可行性。最後下線回來的晶片需先在表面濺鍍一層氧化矽以進行生醫實驗，實驗結果可成功的將表面有修飾過抗體在其上的微粒以介電泳力操控在目標處並與表面有修飾抗原的晶片進行專一性抗體抗原鍵結，之後利用下方的影像感測器讀出訊號來判斷。

This study has successfully used LTPS TFT process technology to design a bio chip that can perform dielectrophoretic (DEP) manipulation and optical detection. The LTPS process has the benefit of less post-processing steps required than the CMOS (complementary metal oxide semiconductor) process to realize the chip. In addition, the process can provide a large chip area at low cost. Reliability, however, is the main issue that the LTPS process has to improve.
The basic principle of DEP force and its mathematical model will be presented. CFD-RC software is utilized for simulation to ensure microbeads can be successfully moved to the target electrodes based on our design. Bio-detection is achieved by using image sensors. H-spice simulation is used to verify the feasibility of the circuit design. In the experiments, a thin layer of silicon dioxide is deposited on chip surface for surface functionalization and biomolecule immobilization. Immobilized microbeads can be moved to the target microelectrodes by DEP and produce specific bindings with the immobilized biomolecules on sensor surface. Those beads are successfully detected by the optical sensors underneath microelectrodes to validate the bio-recognition event.

Abstract i
中文摘要 ii
誌謝 iii
目錄 iv
圖目錄 vi
第一章 序論 .1
1-1 研究動機 1
1-2 文獻回顧 3
1-2-1 光夾箝(optical tweezers) 3
1-2-2 流體動力（Hydrodynamics） 5
1-2-3 介電泳 (dielectrophoresis) 7
1-3 細胞操控與感測的LTPS晶片系統架構 13
第二章 介電泳操控 15
2-1 理論分析 15
2-2 CFD-RC模擬與設計 21
2-3 DEP微粒實驗 30
第三章 LTPS影像感測電路 34
3-1 製程簡介 34
3-2 理論分析與研究 37
3-2-1 影像感測器簡介 37
3-2-2 光二極體 39
3-3 HSPICE電路設計與模擬 43
3-3-1 主動式影像感測器 43
3-3-2 感測電路設計與模擬 46
3-4 LTPS製程與CMOS製程的影像感測器比較 49
第四章 晶片量測與生醫實驗結果 51
4-1 3T影像感測器量測結果 51
4-2 微粒操控與感測實驗 53
4-3 生醫晶片應用之1-抗體抗原鍵結實驗 56
4-4 生醫晶片應用之2-PSA鍵結實驗 61
第五章 結論與未來工作 64
附錄A 65
參考文獻 67

[1] W. Y. Tadir, O. Vafa, T. Ord, R. H. Asch, M. W. Berns, Fertility and Sterility “Micromanipul-
ation of sperm by a laser generated optical trap.” NCBI, Vol.52, No.5, 870-873, Nov 1989
[2] M. W. Berns “Laser scissors and tweezers.” Scientific American Magazine, Vol.278,52-57
Apr 1998.
[3] A. A. and J. M. Dziedzic "Optical trapping and manipulation of Viruses and Bacteria." Sci-
ence, vol. 235, 1517-1520, Mar 1987.
[4] D. Hun, Y. C. Tung, H. H. Wei, J. B. Grotberg, S. J. Skerlos, K. Kurabayashi and S. Taka-
yama “Use of Air-Liquid two-phase flow in hydrophobic micro-fluidic channels for dispos-
able flow cytometers.” Biomedical Microdevices, Vol.4, No.2, 141-149, 2002.
[5] H. A. Pohl “Dielectrophoresis.” Cambridge University Press, 1978.
[6] G. Medoro, N. Manaresi, A. Leonardi, L. Altomare, M. Tartagni, R. Guerrieri and I. Bologn-
a “A lab-on-a-chip for cell detection and manipulation.” IEEE Sensors Journal, Vol.3, No3
317-325, 2003.
[7] T. Matsue, N. Matsumoto. and I. Uchida “Rapid micro-patterning of living cells by repulsiv-
e dielectrophoretic force.” Electrochimica Acta, Vol.42, No.20, 3251-3256, 1997.
[8] J. Suehiro and R. Pethig “The dielectrophoretic movement and positioning of a biological
cell using a three-dimensional grid electrode system.” J. Phys. D, Vol.31,3298-3305,1998
[9] M. Suzuki, T. Yasukawa, H. Shiku and T. Matsue “Negative dielectrophoretic patterning with colloidal particles and encapsulation into a hydrogel.” Langmuir, Vol.27, No.3, Feb 2007
[10] G. Medoro, C. Nastruzzi, R. Guerrieri, R. Gambari and N. Manaresi “Lab on a Chip for Live-Cell Manipulation.” IEEE Design & Test of Computers, Vol.24, No.1, 26-36, 2007
[11] S. Masuda, M. Washizu and I. Kawabata "Movement of Blood Cells in Liquid by Non-un-
fo- orm Travelling Field," IEEE Trans.LAS, 217–222, 1988.
[12] W. Choi, S. Kim, J. Jang “A new micro-particle manipulation platform using a Liquid Cry-
stal Display(LCD).” Microfluidics and MicroNanofluidics, Vol.3, No.2, 217-225, Apr 2007.
[13] Y. S. Lu, Y. P. Huang, J. A. Yeh and C. Lee " Image Driven Cell Manipulation using Optical Dielectrophoresis (ODEP) ," Proceedings of the Second Asian and Pacific Rim Symposium on Biophotonics, 238-240, 2004
[14] A. Ashkin and J. M. Dziedzic "Optical trapping and manipulation of Viruses and Bacteria." Science, vol.235, 1517-1520, Mar 1987
[15] M. Ozkan, J. Scheel, C. Barlow, S. Esener and S. N. Bhatia “Electro-Optical Platform for
the Manipulation of Live Cells.” Langmuir, Vol.19, No.5, 1532-1538, Mar 2003.
[16] K. C. Neuman, G. F. Liou, S. M. Block and K. Bergman " Characterization of Photodam-
age In- duced by Optical Tweezers” Lasers and Electro-Optics, 1998. CLEO98. Technical Digest. S- ummaries of papers presented at the Conference on May1998, 203-204, 1998.
[17] P. Y. Chiou, Z. Chang and M. C. Wu " A Novel Optoelectronic Tweezer Using A Light
Induced Dielectrophoresis" Proceedings of IEEE/LEOS International Conf. Optical ME-
MS, 8-9, 2003
[18] M. P. Hughes ”Nanoelectromechanics in Engineering and Biology.” CRC Press, 2003.
[19] T. B. Jone “Electromechanics of particles.” Cambridge University Press, 1995.
[20] J. Ohta ”Smart CMOS Image Sensors and Applications.” CRC Press 2001
[21] Y. H. Tai, S. C. Huang, C. W. Lin and H. L. Chiu “Degradation of the Capacitance-Volt-
age behaviors of the low-temperature poly-silicon TFTs under DC stress.”Journal of The
Electrochemical Society, Vol.154, No.7, 611-618, 2007.
[22] Y. Urkako, M. Miyashita, Y. Sugawara, H. Yano, T. Hatayama, T. Fuyuki and T. Sames-
hima “Improvement of reliability in low-temperature polycrystalline silicon thin-film trans-
istors by water vapor annealing.” Japanese Journal of Applied Physics, Vol.45, No.7 56
57–5661, 2006.
[23] Y. Uraoka, M. Miyashita, Y. Sugawara, H. Yano, T. Hatayama and T. Fuyuki “Hot carrier effect in low-temperature poly-Si TFTs with sputtered Gate SiO2 films.” Journal of the Korean Physical Society, Vol.49, No.4, 1477-1481, Oct 2006.
[24] C. Xu, J. Li, Y. Wang, L. Cheng, Z. Lu and M. Chan “A CMOS-compatible DNA microarray using optical detection together with a highly sensitive nanometallic particle protocol.” IEEE Electron Device Letters, Vol.26, No.4, 240-242, Apr 2005.
[25] E. H. Tay, L. Yu, A. J. Pang ”Electrical and thermal characterization of a dielectrophoretic chip with 3D electrodes for cells manipulation.” Electrochimica Acta, Vol.52, No.8, 2862-2868, Feb 2007.
[26] H. Lee, A. M. Purdon and R. M. Westervelt “Manipulation of biological cells using a micro-electromagnet matrix.” Applied Physics Letters, Vol.85, No.6, 1063-1065, Aug 2004
[27] J. M. Dziedzic “Optical trapping and manipulation of Viruses and Bacteria.” Science, Vol.235, 1517-1520, Mar 1987.
[28] C. J. Kim, A. P. Pisano and R. S. Muller “Silicon-processed overhanging micro-gripper.” Microelectromechanical Systems, Vol.1, No.1, 31-36, Mar 1992.