隨著奈米科技(Nanotechnology)的不斷進步，近年來已有許多研究以奈米製程技術製作感測器，特別在製作生醫感測(Biomedical Sensing)晶片上，已投入大量心力進行研究，相較於現在醫院所使用之檢測機台，生醫晶片更可以達到定點照護(Point of care)，對於病患的症狀可以即時的偵測，有助於落實預防醫學之目的。本研究是以奈秒雷射微細加工技術(Nanosecond laser micromachining technique)，在網版印刷多層石墨烯製作電極(Screen-printed multilayered graphene electrode)，該研究探討其能量密度(Fluence)和脈衝重疊率(Pulsed overlap)於材料之加工深度與線寬之影響。本研究採以紫外光波段之奈秒雷射，可製作出之最小電極間距為60 μm。結合靜電紡絲技術(Electrospinning technique)製作聚乙烯醇(Polyvinyl alcohol, PVA)複合葡萄糖氧化酶(Glucose oxidase)之奈米線薄膜於電極結構上，藉由加入不同濃度之葡萄糖氧化酶觀察其電性變化，可以得到當葡萄糖濃度僅有0.011 mM時以具有明顯的電阻變化，且在葡萄糖濃度為0.011 mM - 0.41 mM之區間具有一趨近線性之電流變化，推測此方法對於低濃度之葡萄糖檢測具有良好的價值，並有機會應用於生醫晶片製作且進行大量生產。

With the progress of nanotechnology, there are a great amount of researches about fabricating sensors by means of nano processes techniques in recent years, especially for biomedical sensing devices. Compared with the testing machine in the hospital, biochips can achieve point of care. The disease can be analyzed instantaneously for patient that can be helpful to the goal of preventive medicine. Our research is to use the nanosecond laser micromachining techniques for fabricating the screen-printed multilayered graphene electrodes. The experimental conditions based on the laser fluence and pulsed overlap can affect the width and depth of multilayered graphene. This study uses the nanosecond laser pulses with the ultraviolet (UV) wavelength that can fabricate the minimum electrode distance of 60 μm. Combined with the electrospinning technique, the nanofiber membrane which is made by polyvinyl alcohol (PVA) and glucose oxidase is fabricated on the surface of electrodes. The resistance response is measured through the different concentration of glucose. It can be found that there is the obvious change for the electrical resistance when the glucose concentration is 0.011 mM. In addition, the current response approaches a linear behavior when the glucose concentration is ranging between 0.011 mM and 0.41 mM. It can demonstrate that a prospective value for detection of the lower glucose concentration. Therefore, the study will be a possible opportunity for applying in manufacturing biochip and mass production.

[1] R. P. Feynman, “There’s plenty of room at the bottom” (1959)
[2] E. Primiceri, M. S. Chiriaco`, R. Rinaldi and G. Maruccio, “Cell chips as new tools for cell biology – results, perspectives and opportunities”, Lab on a chip, Vol. 13, pp 3789-3802 (2013).
[3] R. Sista, Z. Hua, P. Thwar, A. Sundarsan, V. Srinivasan, A. Eckhardt, M. Pollack, V. Pamula, “Development of a digital microfluidic platform for point of care testing”, Lab on a chip, Vol. 8, pp. 2091-2104 (2008).
[4] A. K. Yetisen, M.S. Akram, C. R. Lowe, “Paper-based microfluidic point-of-care diagnostic devices”, Lab on a Chip, Vol. 13, pp. 2210-2251 (2013).
[5] R Thusu, “Strong growth predicted for biosensors market”, Frost&Sullivan (2010).
[6] A. Formhals, “Process and apparatus for preparing artificial threads”, United States Patent (1934).
[7] A. L. Yarin, S. Koombhongse, D. H. Reneker, “Taylor cone and jetting from liquid droplets in electrospinning of nanofiber”, Journal of Applied Physics, Vol. 90, pp. 4836-4846 (2001)
[8] V. Pillay, C. Dott, Y. E. Choonara, C. Tyagi, L. Tomar, P. Kumar, L. C. du Toit, V. M. K. Ndesendo, “A review of the effect of processing variables on the fabrication of electrospun nanofibers for drug delivery applications”, Journal of Nanomaterials, Vol. 2013, pp. 1-22 (2013).
[9] A. Greiner, J.H. Wendorff, “Electrospinning: a fascinating method for the prepa-ration of ultrathin fibers”, Angewandte Chemie International Edition, Vol. 46 pp.5670-5703 (2007).
[10] P. Lu, B. Ding,"Applications of electrospun fibers", Recent Patents on Nanotechnology, Vol. 2 pp. 169-182 (2008)
[11] W. E. Teo, “Introduction to electrospinning parameters and fiber control” , ElectrospinTech.
[12] E. S. Medeiros, L. H. C. Mattoso, E.N. Ito, K. S. Gregorski, G. H. Robertson, R. D. Offeman, D. F. Wood, W. J. Orts, S. H. Imam, “Electrospun nanofibers of poly(vinyl alcohol) reinforced with cellulose nanofibrils”, Journal of Biobased Materials and Bioenergy, Vol. 2, pp. 1-12 (2008).
[13] S.Kaur, S. Sundarrajan, D. Rana, R. Sridhar, R. Gopal, T. Matsuura, S. Ramakrishna, “Review: the characterization of electrospun nanofibrous liquid filtration membranes ”, Journal of Material Sciences, Vol. 49, pp. 6143-6159 (2014).
[14] J. He, T. Qin, Y. Liu, X. Li, D. Li, Z. Jin, “Electrospinning of nanofibrous scaffolds with continuous structure and material gradients”, Materials letters, Vol. 137, pp. 393-397 (2014).
[15] N. Wang, K. Burugapalli, W. Song, J. Halls, F. Moussy, A. Ray, Y. Zheng, “Electrospun fibro-porous polyurethane coatings for implantable glucose biosensors”, Biomaterials, Vol. 34, pp888-901 (2013).
[16] Z. M. Huang, Y. Z. Zhang, M. Kotaki, S. Ramakrishna, “A review on polymer nanofibers by electrospinning and their applications in nanocomposites”, Composites Science and Technology, Vol. 63, pp. 2223-2253 (2003).
[17] 國人十大死因統計，行政院衛生福利部報告 (2014)
[18] J. H. Yoo, J. B. In, J. B. Park, H. Jeon, C. P. Grigoropoulos, “Graphene folds by femtosecond laser ablation”, Applied Physics Letters, Vol. 100, 233124 (2012)
[19] F. Wakaya, T. Teraoka, T. Kisa, T. Manabe, S. Abo, M. Takai, “Effect of ultra-violet laser irradiation on graphene”, Microelectronic Engineering, Vol. 97, pp. 144-146 (2012)
[20] V. Kiisk, T. Kahro, J. Kozlova, L. Matisen, H. Alles, “Nanosecond lasertreatment of graphene”, Applied Surface Science, Vol. 276, pp. 133-137 (2013)
[21] H.Y. Chen, D. Han, Y. Tian, R. Shao, S. Wei, “Mask-free and programmable patterning of graphene by ultrafast laser direct writing”, Chemical Physics, Vol.430, pp. 13-17 (2014)
[22] R. Sahin, E. Simsek, S. Akturk, “Nanoscale patterning of graphene through femtosecond laser ablation”, Applied Physics Letters, Vol.104, 053118 (2014)
[23] V. D. Frolov, P. A. Pivovarov, E. V. Zavedeev, A. A. Khomich, A. N. Grigorenko, V. I. Konov, “Laser-induced local profile transformation of multilayered graphene on a substate”, Optics & Laser Technology, Vol. 69, pp. 34-38 (2015)
[24] Z. Lin, T. Huang, X. Ye, M. Zhong, L. Li, J.Jiang, W. Zhang, L. Fan, H. Zhu, “Thinning of large-area graphene film from multilayer to bilayer with a low-power CO2 laser”, Nanotechnology, Vol. 24, 275302 (2013)
[25] M. Currie, J. D. Caldwell, F. J. Bezares, J. Robinson, T. Anderson, H. Chun, M. Tadjer,“Quantifying pulsed laser induced damage to graphene”, Applied Physics Letters, Vol. 99, 211909 (2011)
[26] T. Huang, J. Long, M. Zhong, J. Jiang, X. Ye, Z. Lin,L. Li, “The effect of low power density CO2 laser irradiation on graphene properties”, Applied Surface Science, Vol. 273, pp. 502-506 (2013)
[27] F. Wakaya, T. Kurihara, S. Abo, M. Takai, “Ultra-violet laser processing of graphene on SiO2/Si”, Microelectronic Engineering, Vol. 110, pp. 358-360 (2013)
[28] A. Koski, K. Yim, S. Shivkurmar, “Effect of molecular weight on fibrous PVA produced by electrospinning”, Materials Letters, Vol. 58, pp. 493-497 (2004).
[29] N. Liu, G. Fang, J. Wan, H. Zhou, H. Long, X. Zhao,“Electrospun PEDOT:PSS-PVA nanofiber based ultrahigh-strain sensors with controllable electrical conductivity”, Journal of Materials Chemistry, Vol. 21, pp. 18962-18966 (2011)
[30] D. Cho, N. Hoepker, M. W. Frey, “Fabrication and characterization of conducting polyvinyl alcohol nanofibers”, Materials Letter, Vol. 68, pp. 293-295 (2012)
[31] B. C. Okeke, G. Ma, Q. Cheng, M. E. Losi, and W. T. Frankenberger Jr., “Development of perchlorate reductase based biosensor for real time analysis of perchlorate in water”, Journal of Microbiological Methods, Vol. 68, Issue. 1, pp. 69-75 (2007)
[32] E. Liaudet, S. Hatz, M. Droniou, N. Dale, “Microelectrode biosensor for real-time measurement of ATP in biological tissue”, Analytical Chemistry, Vol. 77, pp. 3267-3273 (2005)
[33] Y. Zhang, A. Heller, “Reduction of the nonspecific binding of a target antibody and of Its enzyme-labeled detection probe enabling electrochemical immunoassay of an antibody through the 7 pg/mL-100 ng/mL (40 fM–400 pM) range”, Analytical Chemistry, Vol.77, pp. 7758-7762 (2005)
[34] G. Ren, X. Xu, Q. Liu, J. Cheng, X. Tuan, L. Wu, Y. Wan, “Electrospun poly(vinyl alcohol)/glucose oxidase biocomposite membranes for biosensor application”, Reactive & Functional Polymers, Vol. 66, pp. 1559-1564 (2006)
[35] R. Antiochia, L. Gorton, “A new osmium-polymer modified screen-printed graphene electrode for fructose detection”, Sensors and Actuators B:Chemical, Vol. 195, pp. 287-293 (2014)
[36] F. Y. Kong, S. X. Gu, W. W. Li, T. T. Chen, Q. Xu, W. Wang, “A paper disk equipped with graphene/polyaniline/Aunanoparticles/ glucose oxidase biocomposite modified screen-printed electrode: Toward whole blood glucose determination”, Biosensors and Bioelectronics, Vol. 56, pp. 77-82 (2014)
[37] E. P. Randviir, D. A. C. Brownson, J. P. Metters, R. O. Kadara, C. E. Banks, “The fabrication, characterization and electrochemical investigation of screen-printed graphene electrodes”, Physical Chemistry Chemical Physics, Vol. 16, pp. 4598-4611 (2014)
[38] W. Pacquentin, N. Caron, R. Oltra, “Nanosecond laser surface modification of AISI 304L stainless steel: Influence the beam overlap on pitting corrosion resistance”, Applied Surface Science, Vol. 288, pp. 34-39 (2014)
[39] S. Martin, A. Hertwig, M. Lenzner, J. Kruger, W. Kautek, “Spot-size dependence of ablation threshold in dielectrics for femtosecond laser pulses”, Applied Physics A, Vol. 77, pp. 883-884 (2003)
[40] C. Shao, H. Y. Kim, J. Gong, B. Ding, D. R. Lee, S. J. Park, “Fiber mats of poly(vinyl alcohol)/silica composite via electrospinning”, Materials Letters, Vol. 57, pp. 1579-1584 (2003)
[41] C. Tang, C. D. Saquing, J. R. Harding, S. A. Khan, “In situ cross-linking of poly(vinyl alcohol) nanofibers”, Macromolecules, Vol. 43, pp. 630-637 (2010)
[42] K. Schrote, M. W. Frey, “Effect of irradiation on poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) nanofiber conductivity ”, Polymer, Vol. 54, pp. 737-742 (2013)
[43] Y. Piao, D. J. Han, T. S. Seo, “Highly conductive graphite nanoparticles based enzyme biosensor for electrochemical glucose detection”, Sensors and Actuators B: Chemical, Vol. 194, pp. 454-459 (2014)