隨著電路設計以及半導體製程技術發展成熟，感測器的應用也越來越多樣化，生醫感測晶片將微機電系統與生醫晶片结合，可用來感測特定生物分子。在進行生物樣品分析之前，通常需要對樣品進行前處理、分離、純化、混合、運輸等一系列步驟，若能將細胞操控功能與生醫感測功能整合至同一晶片上，將可以降低實驗的成本與對儀器的需求，並提高實驗效率。
本篇論文提出將CMOS指叉式電容感測電路與介電泳技術結合，使單個晶片可同時具有細胞操控與感測的功能，透過這種晶片，我們能夠在不直接接觸目標物的情況下操控大量微粒，並藉由陣列高效率分析樣品。利用自組裝單層膜(self-assembled monolayers, SAMs)技術將抗小鼠免疫球蛋白G（anti-mouse IgG）修飾於感測電極表面上，對驅動電極施以特定頻率的交流電壓，即可以介電泳力驅動外層包裹小鼠免疫球蛋白G(mouse IgG)的微粒至感測電極上並使兩者產生專一鍵結。位於感測電極表面的微粒會改變電極的等效電容值，此電容變化可透過電路轉換成電壓變化讀出。實驗結果成功的將微粒以介電泳力操控至目標處，並量測到微粒造成的訊號變化。

As circuit design and semiconductor manufacturing technologies mature, the applications of sensors continue to diversify. Biomedical sensing chips, integrating microelectromechanical systems (MEMS) with biomedical chips, have emerged for the detection of specific biomolecules. Prior to analyzing biological samples, a series of steps such as pre-processing, separation, purification, mixing, and transportation are typically required. Integrating cell manipulation and biomedical sensing functions onto a single chip has the potential to reduce experimental costs, instrumentation requirements, and improve experimental efficiency.
This paper proposes the combination of a CMOS integrated capacitive sensing circuit with dielectrophoresis technology, enabling a single chip to possess cell manipulation and sensing functions. Through this chip, manipulation of a large number of particles without direct contact with the target substance is achievable, facilitating efficient sample analysis through an array. Utilizing self-assembled monolayers (SAMs) technology, anti-mouse IgG is modified on the sensing electrode surface. By applying a specific frequency of alternating voltage to the driving electrode, dielectrophoretic force can drive particles coated with mouse IgG to the sensing electrode, creating a specific binding. The particles on the sensing electrode surface alter the electrode's equivalent capacitance, and this capacitance change is converted into a voltage change through the circuit for readout. Experimental results successfully demonstrate the manipulation of particles to the target location using dielectrophoretic force and the measurement of signal changes caused by the particles.

摘要 I
Abstract II
致謝 III
目錄 IV
圖目錄 VI
表目錄 X
第一章 緒論 1
1-1 研究動機 1
1-2 文獻回顧 3
第二章 介電泳操控 6
2-1 介電泳理論分析 6
2-2 驅動功能設計與介電泳模擬 9
第三章 電路設計與模擬 23
3-1 電路架構 23
3-2 感測電容設計 34
3-3 電路模擬 38
第四章 生醫實驗介紹 40
4-1 待測生物分子介紹 40
4-2 表面固定化步驟 41
第五章 量測結果與分析 44
5-1 量測設備介紹 44
5-2 晶片結構檢視與PCB板封裝 48
5-3 晶片量測結果與分析 53
5-3-1 初始電容值量測 53
5-3-2 液體中電容值量測 55
5-3-3 微粒操控與感測實驗 57
5-3-4 抗體鍵結實驗 61
5-3-5 Allan方差量測 66
第六章 結論與未來工作 69
參考文獻 71

[1] A. Ashkin and J. M. Dziedzic, "Optical trapping and manipulation of viruses and bacteria," Science, vol. 235, no. 4795, pp. 1517-1520, 1987.
[2] Y. Tan, D. Sun, J. Wang, and W. Huang, "Mechanical characterization of human red blood cells under different osmotic conditions by robotic manipulation with optical tweezers," IEEE Transactions on biomedical engineering, vol. 57, no. 7, pp. 1816-1825, 2010.
[3] D. Huh et al., "Use of air-liquid two-phase flow in hydrophobic microfluidic channels for disposable flow cytometers," Biomedical Microdevices, vol. 4, pp. 141-149, 2002.
[4] H. A. Pohl, "Dielectrophoresis," The behabior of neutral matter in nonuniform electric fields, 1978.
[5] G. Medoro, N. Manaresi, A. Leonardi, L. Altomare, M. Tartagni, and R. Guerrieri, "A lab-on-a-chip for cell detection and manipulation," IEEE Sensors Journal, vol. 3, no. 3, pp. 317-325, 2003.
[6] L.-G. Chen, D.-Y. Wu, and M. S. Lu, "An integrated micro-manipulation and biosensing platform built in glass-based LTPS TFT technology," Journal of Micromechanics and Microengineering, vol. 22, no. 9, p. 095010, 2012.
[7] F. Arai et al., "Pinpoint injection of micro tools using dielectrophoresis and hydrophobic surface for minimally invasive separation of microbe," in Technical Digest. MEMS 2002 IEEE International Conference. Fifteenth IEEE International Conference on Micro Electro Mechanical Systems (Cat. No. 02CH37266), 2002: IEEE, pp. 48-51.
[8] X. Hu, P. H. Bessette, J. Qian, C. D. Meinhart, P. S. Daugherty, and H. T. Soh, "Marker-specific sorting of rare cells using dielectrophoresis," Proceedings of the national academy of sciences, vol. 102, no. 44, pp. 15757-15761, 2005.
[9] A. Y. Fu, H.-P. Chou, C. Spence, F. H. Arnold, and S. R. Quake, "An integrated microfabricated cell sorter," Analytical chemistry, vol. 74, no. 11, pp. 2451-2457, 2002.
[10] A. L. Clow, P. T. Gaynor, and B. J. Oback, "A novel micropit device integrates automated cell positioning by dielectrophoresis and nuclear transfer by electrofusion," Biomedical microdevices, vol. 12, pp. 777-786, 2010.
[11] L. A. MacQueen, M. D. Buschmann, and M. R. Wertheimer, "Gene delivery by electroporation after dielectrophoretic positioning of cells in a non-uniform electric field," Bioelectrochemistry, vol. 72, no. 2, pp. 141-148, 2008.
[12] J. Voldman, "A microfabricated dielectrophoretic trapping array for cell-based biological assays," Massachusetts Institute of Technology, 2001.
[13] J. Johari, Y. Hübner, J. C. Hull, J. W. Dale, and M. P. Hughes, "Dielectrophoretic assay of bacterial resistance to antibiotics," Physics in Medicine & Biology, vol. 48, no. 14, p. N193, 2003.
[14] D. Chugh and K. V. Kaler, "Integrated liquid and droplet dielectrophoresis for biochemical assays," Microfluidics and Nanofluidics, vol. 8, pp. 445-456, 2010.
[15] C. Tan et al., "Local secretion of IL-12 augments the therapeutic impact of dendritic cell–tumor cell fusion vaccination," journal of surgical research, vol. 185, no. 2, pp. 904-911, 2013.
[16] M. P. Hughes, R. Pethig, and X.-B. Wang, "Dielectrophoretic forces on particles in travelling electric fields," Journal of Physics D: Applied Physics, vol. 29, no. 2, p. 474, 1996.
[17] C. H. Kua, Y. C. Lam, C. Yang, K. Youcef-Toumi, and I. Rodriguez, "Modeling of dielectrophoretic force for moving dielectrophoresis electrodes," Journal of Electrostatics, vol. 66, no. 9-10, pp. 514-525, 2008.
[18] S. Van den Driesche, V. Rao, D. Puchberger-Enengl, W. Witarski, and M. J. Vellekoop, "Continuous cell from cell separation by traveling wave dielectrophoresis," Sensors and Actuators B: Chemical, vol. 170, pp. 207-214, 2012.
[19] E. Choi, B. Kim, and J. Park, "High-throughput microparticle separation using gradient traveling wave dielectrophoresis," Journal of Micromechanics and Microengineering, vol. 19, no. 12, p. 125014, 2009.
[20] P. Y. Chiou, A. T. Ohta, and M. C. Wu, "Massively parallel manipulation of single cells and microparticles using optical images," Nature, vol. 436, no. 7049, pp. 370-372, 2005.
[21] H. Hwang, D.-H. Lee, W. Choi, and J.-K. Park, "Enhanced discrimination of normal oocytes using optically induced pulling-up dielectrophoretic force," Biomicrofluidics, vol. 3, no. 1, 2009.
[22] S.-B. Huang et al., "High-purity and label-free isolation of circulating tumor cells (CTCs) in a microfluidic platform by using optically-induced-dielectrophoretic (ODEP) force," Lab on a Chip, vol. 13, no. 7, pp. 1371-1383, 2013.
[23] W.-P. Chou et al., "The utilization of optically-induced-dielectrophoresis (ODEP)-based virtual cell filters in a microfluidic system for continuous isolation and purification of circulating tumour cells (CTCs) based on their size characteristics," Sensors and Actuators B: Chemical, vol. 241, pp. 245-254, 2017.
[24] T.-K. Chiu et al., "Optically-induced-dielectrophoresis (ODEP)-based cell manipulation in a microfluidic system for high-purity isolation of integral circulating tumor cell (CTC) clusters based on their size characteristics," Sensors and Actuators B: Chemical, vol. 258, pp. 1161-1173, 2018.
[25] J. K. Valley et al., "Preimplantation mouse embryo selection guided by light-induced dielectrophoresis," PloS one, vol. 5, no. 4, p. e10160, 2010.
[26] R. Manczak et al., "UHF-dielectrophoresis crossover frequency as a new marker for discrimination of glioblastoma undifferentiated cells," IEEE Journal of Electromagnetics, RF and Microwaves in Medicine and Biology, vol. 3, no. 3, pp. 191-198, 2019.
[27] Y.-S. Chan, T.-T. Hsu, Y.-P. Chen, H.-M. Wu, Y.-M. Wang, and C.-Y. Lee, "A traveling-wave dielectrophoresis bio-chip for cell manipulation in standard CMOS process," IEEE Transactions on Circuits and Systems II: Express Briefs, vol. 69, no. 3, pp. 1582-1586, 2021.
[28] N. Manaresi et al., "A CMOS chip for individual cell manipulation and detection," IEEE Journal of Solid-State Circuits, vol. 38, no. 12, pp. 2297-2305, 2003.
[29] Y. Demircan et al., "Label-free detection of leukemia cells with a lab-on-a-chip system integrating dielectrophoresis and CMOS imaging," in 2015 Transducers-2015 18th International Conference on Solid-State Sensors, Actuators and Microsystems (TRANSDUCERS), 2015: IEEE, pp. 1589-1592.
[30] K. Park, S. Kabiri, and S. Sonkusale, "Dielectrophoretic lab-on-CMOS platform for trapping and manipulation of cells," Biomedical microdevices, vol. 18, pp. 1-11, 2016.
[31] M. Castellarnau et al., "Integrated microanalytical system based on electrochemical detection and cell positioning," Materials Science and Engineering: C, vol. 26, no. 2-3, pp. 405-410, 2006.
[32] M. Castellarnau et al., "Integrated cell positioning and cell-based ISFET biosensors," Sensors and Actuators B: Chemical, vol. 120, no. 2, pp. 615-620, 2007.
[33] A. Romani et al., "Capacitive sensor array for localization of bioparticles in CMOS lab-on-a-chip," in 2004 IEEE International Solid-State Circuits Conference (IEEE Cat. No. 04CH37519), 2004: IEEE, pp. 224-225.
[34] M. A. Miled and M. Sawan, "A new fully integrated cmos interface for a dielectrophoretic lab-on-a-chip device," in 2011 IEEE International Symposium of Circuits and Systems (ISCAS), 2011: IEEE, pp. 2349-2352.
[35] J. Wei, "Distributed capacitance of planar electrodes in optic and acoustic surface wave devices," IEEE Journal of Quantum Electronics, vol. 13, no. 4, pp. 152-158, 1977.
[36] R. Esfandiari, D. W. Maki, and M. Siracusa, "Design of interdigitated capacitors and their application to gallium arsenide monolithic filters," IEEE Transactions on Microwave Theory and Techniques, vol. 31, no. 1, pp. 57-64, 1983.
[37] S. S. Gevorgian, T. Martinsson, P. L. Linner, and E. L. Kollberg, "CAD models for multilayered substrate interdigital capacitors," IEEE Transactions on microwave theory and techniques, vol. 44, no. 6, pp. 896-904, 1996.
[38] C.-M. Chen and M. S.-C. Lu, "A CMOS capacitive biosensor array for highly sensitive detection of pathogenic avian influenza DNA," in 2017 19th International Conference on Solid-State Sensors, Actuators and Microsystems (TRANSDUCERS), 2017: IEEE, pp. 1632-1635.
[39] H. J. Pandya et al., "Towards an automated MEMS-based characterization of benign and cancerous breast tissue using bioimpedance measurements," Sensors and Actuators B: Chemical, vol. 199, pp. 259-268, 2014.
[40] K. Mohammad, D. A. Buchanan, K. Braasch, M. Butler, and D. J. Thomson, "CMOS single cell dielectrophoresis cytometer," Sensors and Actuators B: Chemical, vol. 249, pp. 246-255, 2017.
[41] M. A. Miled and M. Sawan, "Dielectrophoresis-based integrated lab-on-chip for nano and micro-particles manipulation and capacitive detection," IEEE transactions on biomedical circuits and systems, vol. 6, no. 2, pp. 120-132, 2012.