本研究以水電漿鍵合製程，對PMMA和Silicon進行表面改質技術使 (PMMA/Silicon/PMMA) 鍵合為一體，使用水電漿製程使(PMMA/Silicon/PMMA) 介面處形成Si–O–Si共價鍵達成異質鍵合的效果，目的是改良傳統的鍵合製程，由於傳統的鍵合製程只能使用同質性材料，若將PMMA和Silicon使用傳統鍵合製程容易在鍵合過程中產生極大的內應力集中和晶格錯位間接造成矽晶層破裂，造成此現象原在於不同種材料其熱膨脹係數和晶格常數排列皆不同，故透過水電漿鍵合製程就能改善此缺點，而後使用蝕刻過後的矽基板搭配熱壓印法技術製作 (PMMA/Silicon/PMMA) 微流道裝置，並透過電子顯微鏡(SEM) 觀察鍵合介面處。最後使用拉曼光譜儀搭配微流道裝置對血液、血漿和血清進行檢測，可以透過不同的血液樣本來觀察生物訊息的差異性。

In this study, the H2O plasma bonding process was used to modify the surface of PMMA and Silicon to make them bond as a whole, and the Si–O–Si covalent bond was formed at the interface using the atmospheric H2O plasma process (PMMA/Silicon/PMMA). To achieve the effect of heterogeneous bonding, the purpose is to improve the traditional bonding process. Since the traditional bonding process can only use homogeneous materials, if PMMA and Silicon are used in the traditional bonding process, it is easy to produce great internal stress during the bonding process. Concentration and lattice dislocation indirectly cause the silicon crystal layer to crack. The reason for this phenomenon is that the thermal expansion coefficient and lattice constant arrangement of different materials are different, so this shortcoming can be improved by the H2O plasma bonding process. Next, the etched silicon substrate is used with hot embossing technology to fabricate a (PMMA/Silicon/PMMA) micro-channel device, and the bonding interface is observed through an electron microscope (SEM). Finally, blood, plasma and serum are detected by Raman spectrometer with microfluidic device, and the difference of biological information can be observed through different blood samples.

[1] S. Gupta, K. Ramesh, S. Ahmed, & V. Kakkar, "Lab-on-Chip Technology: A Review on Design Trends and Future Scope in Biomedical Applications," International Journal of Bio-Science and Bio-Technology, Vol. 8, no. 5, pp. 311-322, 2016.

[2] S. K. Tang, R. Derda, Q. Quan, & M. Lončar, "Continuously tunable microdroplet-laser in a microfluidic channel," Optics express, Vol. 19, no. 3, pp. 2204-2215, 2011.

[3] D. Y. Fedyanin, & Y. V. Stebunov, "All-nanophotonic NEMS biosensor on a chip," Scientific reports, vol. 5, no. 1, pp. 1-12, Jun. 2015.

[4] T. Claes, W. Bogaerts, & P. Bienstman, "characterization of a silicon photonic biosensor consisting of two cascaded ring resonators based on the Vernier-effect and introduction of a curve fitting method for an improved detection limit," Optics express, vol. 18, no. 22, pp. 22747-22761, 2010.

[5] W. R. Zeng, S. F. Li, & W. K. Chow, "Review on chemical reactions of burning poly (methyl methacrylate) PMMA," Journal of Fire Sciences, vol. 20, no. 5, pp.401-433, Sep. 2020.

[6] C. C. Chiang, P. N. Immanuel, & S. J. Huang, "Heterogeneous Bonding of PMMA and Double-Sided Polished Silicon Wafers through H2O Plasma Treatment for Microfluidic Devices," Coatings, Vol. 5, no. 11, pp. 580, May. 2021.

[7] 血氧數據如何幫助提早發現快樂缺氧的存在。取自Garmin健康新知網址：
https://www.garmin.com/zh-TW/blog/healthandnews/covid-19-about-happy-hypoxia-and-pulse-ox/

[8] A. M. Enejder, T. W. Koo, J. Oh, M. Hunter, S. Sasic, M. S. Feld, & G. L. Horowitz, "Blood analysis by Raman spectroscopy," Optics letters, vol. 27, no. 22, pp. 2004-2006, 2002.

[9] B. Baumann, B. Potsaid, M. F. Kraus, J. J. Liu, D. Huang, J. Hornegger, & J. G. Fujimoto, "Total retinal blood flow measurement with ultrahigh speed swept source/Fourier domain OCT," Biomedical optics express, vol. 2, no. 6, pp. 1539-1552, May. 2011.

[10] 賴彥廷、王捷、楊孝政(民106)。取自微流道的發展與應用網址：
http://cc.ee.ntu.edu.tw/~ultrasound/belab/midterm_oral_files/2018_106_2/106_1_G2.pdf

[11] 微反應晶片與分析。取自國立臺灣師範大學，機電科技研究所網址：http://rportal.lib.ntnu.edu.tw/bitstream/20.500.12235/96978/3/300403.pdf

[12] Microbiologyinfo, Difference between Serum and Plasma, 2020.
Retrieved from https://microbiologyinfo.com/difference-between-
serum-and plasma/

[13] 顏士傑(2013)，反射式雷射光學感測系統應用於凝血檢測研究，國立交通大學機械工程學系碩士論文。

[14] S. Ahlawat, N. Kumar, A. Uppal, & P. K. Gupta, "Visible Raman excitation laser induced power and exposure dependent effects in red blood cells," Jourmal of Biophotonics, vol. 10, no. 6, pp. 1–8, Mar. 2016.

[15] Y. Zou, F. Yang, X. Huang, N. Cai, B. Jiang, X. Zhao, W. Liu, & X. Chen, " Whole blood and semen identification using mid-infrared and Raman spectrum analysis for forensic applications," Analytical Methods, vol. 8, no. 18, pp. 3763–3767, 2016.

[16] K. R. M. Dinesh, A. Maguire, J. Bryant, J. Arm-strong, M. Dunne, M. Finn, F. M. Lyng, & A. D. Meade, "Development of a high throughput (HT) Raman spectroscopy method for rapid screening of liquid blood plasma from prostate cancer patients," The Analyst, vol. 142, no. 8, 2016, pp. 3763, Apr. 2017.

[17] H. Wang, C. Chen, D. Tong, C. Chen, R. Gao, H. Han, & X. Lv, "Serum Raman spectroscopy combined with multiple algorithms for diagnosing thyroid dysfunction and chronic renal failure," Photodiagnosis and Photodynamic Therapy, vol. 34, no. 3, pp.34-102241, Jun. 2021.

[18] P. Amirfeiz, S. Bengtsson, M. Bergh, E. Zanghellini, & L. Börjess-on, "Formation of silicon structures by plasma‐activated wafer bonding," Journal of the Electrochemical Society, vol. 147, no. 7, pp. 2693, 2000.

[19] S. Roy, C. Y. Yue, Z. Y. Wang, & L. Anand, "Thermal bonding of microfluidic devices: Factors that affect interfacial strength of similar and dissimilar cyclic olefin copolymers," Sensors and Actuators B: Chemical, vol. 161, no. 1, pp. 1067-1073, 2012.

[20] L. Brown, T. Koerner, J. H. Horton, & R. D. Oleschuk, "Fabrication and characterization of poly (methyl methacrylate) microfluidic devices bonded using surface modifications and solvents," Lab on a Chip, vol. 6, no. 1, pp. 66-73, 2006.
[21] V. Bagiatis, G. W. Critchlow, D. Price, & S. Wang, "The effect of atmospheric pressure plasma treatment (APPT) on the adhesive bonding of poly (methyl methacrylate) (PMMA)-to-glass using a polydimethylsiloxane (PDMS)-based adhesive," International Journal of Adhesion and Adhesives, vol. 95, Dec. 2019.

[22] W. Pfleging, & O. Baldus, "Laser patterning and welding of transparent polymers for microfluidic device fabrication," In Laser based Micro packaging, International Society for Optics and Photonics, vol. 6107, pp. 610-705, Feb. 2006.

[23] U. Ali, K. J. B. A. Karim, & N. A. Buang, "A review of the properties and applications of poly (methyl methacrylate)(PMMA)," Polymer Reviews, vol. 55, no. 4, pp. 678-705, 2015.

[24] H. D. Lynh, & C. Pin-Chuan, "Novel solvent bonding method for creation of a three-dimensional, non-planar, hybrid PLA/PMMA microfluidic chip," Sensors and Actuators A: Physical," Volume, vol. 280, pp. 350-358, 2018.

[25] A. Annušová, J. Krištof, P. Veis, C. Foissac, & P. Supiot, "Spectroscopic study of an Ar-H2O discharge excited by a RF helical cavity," Proceedings of Contributed Papers, Vol. 12, pp. 99-104, 2012.

[26] R. Q. Frazer, R. T. Byron, P. B. Osborne, & K. P. West, "PMMA: an essential material in medicine and dentistry," Journal of long-term effects of medical implants, vol. 15, no. 6, pp. 629-939, 2005.

[27] 拉曼光譜儀原理。取自利泓科技網址：https://www.rightek.com.tw/product_list/%E6%8B%89%E6%9B%BC%E5%85%89%E8%AD%9C%E5%84%80%E5%88%86%E6%9E%90%E5%8E%9F%E7%90%86%E2%94%82raman-spectrometer-principle/

[28] University of Cambridge, Dissemination of IT for the Promotion of Materials Science, Raman scattering. Retrieved from https://www.doitpoms.ac.uk/tlplib/raman/raman_scattering.php

[29] M. Qin, C. Wang, J. Zhu, L. Yong, H. Wang, & L. Yang, "Synthesis of Differently Sized Gold Nanoparticles for SERS Applications in the Detection of Malachite Green," Journal of Physics: Conference Series, vol. 36, no. 4, pp. 41–46, April. 2021.

[30] X. Ma, R. Li, Z. Jin, Y. Fan, X. Zhou, & Y. Zhang, "Injection molding and characterization of PMMA-based microfluidic device. " Microsystem Technologies, vol. 26, no. 4, pp.1317-1324, 2020.

[31] 宋旺洲、馬康柏、陳淑慧(民98)。具長效親水性之聚雙甲基矽氧烷基材之蛋白質抗體晶片。

[32] 科普講堂。生物晶片的奧妙。取自國家實驗研究院網址：
https://www.narlabs.org.tw/xcscience/cont?xsmsid=0I148638629329404252&sid=0J282408310587446584

[33] 楊崇榮 (2021)，通過大氣電漿處理與低溫退火對聚甲丙烯酸甲酯(PMMA)微流道進行表面活化鍵合暨血液檢測之研究，國立臺灣科技大學機械工程學系碩士論文。

[34] M. M. R. Howlader, S. Suehara, H. Takagi, T. H. Kim, R. Maeda, & T. Suga, "Room-temperature microfluidics packaging using sequential plasma activation process," IEEE transactions on advanced packaging, vol. 29, no. 3, pp. 448-456, 2006.

[35] P. N. Immanuel, C. C. Chiang, T. H. Lee, S. D. Midyeen, & S. J. Huang, "Utilization of Low Wavelength Laser Linking with Electrochemical Etching to Produce Nano-Scale Porous Layer on p-Type Silicon Wafer with High Luminous Flux," ECS Journal of Solid-State Science and Technology, vol. 10, no.1, 2021.

[36] P. N. Immanuel, C. C. Chiang, C. R. Yang, M. Subramani, T. H. Lee, & S. J. Huang, "Surface activation of poly (methyl methacrylate) for microfluidic device bonding through a H2O plasma treatment linked with a low-temperature annealing," Journal of Micromechanics and Microengineering, vol. 31, no. 5, 2021.

[37] H. H. Tran, & W. Wu, "Ethanol and UV-assisted instantaneous bonding of PMMA assemblies and tuning in bonding reversibility," Sensors and Actuators B: Chemical, vol. 181, pp. 955-962, 2013.

[38] N. Huang, M. Short, J. Zhao, H. Wang, H. Lui, M. Korbelik, & Haishan Zeng, "Full range characterization of the Raman spectra of organs in a murine model," Optics Express, vol. 19, no. 23, Nov. 2011.

[39] N. Huang, H. Zeng, & M. Korbelik, " Full range characterization of the Raman spectra of organs in a murine model," Optics Express, vol.19, no. 23, 2011.

[40] D. Williams, "The Effect of Red Blood Cell Velocity on Oxygenation Measurements using Resonance Raman Spectroscopy," Physiology, 2005.

[41] 什麼是貧血。取自康健知識庫網址:
https://kb.commonhealth.com.tw/library/283.html

[42] Lactate acid乳酸鹽。取自花蓮慈濟醫院網址：
https://hlm.tzuchi.com.tw/mt/index.php/item/2019-03-16-05-32-05/262-item-lac

[43] Lactate(Blood)檢驗查詢。取自嘉義基督教醫院網址: https://www.cych.org.tw/lab/6_%E9%A0%85%E7%9B%AE%E6%9F%A5%E8%A9%A2/find.asp?sh1=0481~

[44] A. Bankapur, E. Zachariah, S. Chidangil, M. Valiathan, & D. Mathur, "Raman Tweezers Spectroscopy of Live, Single Red and White Blood Cells," PLOS ONE, vol. 5, no. 4, Apr. 2010.

[45] H. Li, Q. Wang, J. Tang, N. Gao, X. Yue, & T. Wang, "Establishment of a reliable scheme for obtaining highly stable SERS signal of biological serum," Biosensors & Bioelectronics, vol. 189, no. 2, pp. 113315, May. 2021.

[46] H. Lin, J. Zhou, Q. Wu, T. M. Hung, W. Chen, Y. Yu, J. T. C. Chang, J. Pan, S. Qiu, & R. Chen, "Human blood test based on surface-enhanced Raman spectroscopy technology using different excitation light for nasopharyngeal cancer detection," IET Nanobiotechnology, vol. 13, no. 9, pp. 942-945, Dec. 2019.

[47] B. Long, W. Zheng, M. Schweitzer, & H. Hallen, "Resonance Raman imagery of semi-fossilized soft tissues," Ultrafast Nonlinear Imaging and Spectroscopy, vol. 10753, pp. 1075310, Sep. 2018.

[48] M. Casellaa, A. Lucotti, M. Tommasini, M. Bedoni, E. Forvi, F. Gramaticac, & G. Zerbi, " Raman and SERS recognition of β-carotene and haemoglobin," Volume, vol. 79, no. 5, pp. 915-919, Sep. 2011.