全球糖尿病的病患逐年增加，糖尿病容易引發許多併發症致死率相當高，現今的檢測方式多為侵入式，為了免去病人其痛苦，建立一個非侵入式的檢測平台，透過奈米矽結構結合奈米金粒子，製作一個奈米尺度的化學反應與質譜分析的快速檢測平台，本文以奈米矽結構為基材沉積奈米金粒子，利用奈米矽結構本身的吸附性，吸附葡萄糖進入奈米矽，接觸金產生還原氧化反應，反應完的樣本留在晶片上，使用MALDI-TOF質譜儀將雷射打在晶片上，讓樣本脫附飛梭進入檢測器，以達到反應檢測的效果。
由於要建立的平台為非侵入式，因此以檢測病患的尿液為的目標，在人體的尿液中有相當多的雜質及鹽分，這對於檢測分析而言具有相當大的干擾性，本人參考了氧化酶電極法的催化機制，透過具有高度的專一性的酶，將催化機制應用於奈米矽結構上，本人使用金觸媒取代一般傳統葡萄糖氧化酶作為催化物。
經過實驗發現奈米尺度的金具有良好的催化能力，再加上質譜分析儀的應用提高整個平台的靈敏性，以標準品葡萄糖為檢測對象可以檢測至10-8M，之後將此高靈敏性的平台應用於尿液的檢測上，使用正常人的尿液混合加入10-3M的葡萄糖，進行檢測分析具有良好的訊號強度，此結果證實奈米金的應用有助於分析葡萄糖，並且提高其專一性及靈敏性。

Diabetic patients increases ni the global year by year. The disease is that easy to trigger many complicating disease and have high fatality rate. Recently , detect it has many method , but mostly method is invasive. We want to establish a non-invasive detection platform by nanostructure silicon (nSi) surface combination gold nanoparticle(AuNPs) for less patient pain. This detection platform have nano-scale,chemical reaction and rapid analysis with Mass Spectrometry.
In this study, Depositing AuNPs on nSi surface,we call it sd-nSi chip. Use the chip surface properties absorption glucose to inside to oxidation reaction with AuNPs. After the oxidation reaction, employ MALDI-TOF mass spectography laser hit sd-nSi surface let the sample shuttle into a detector to achieve the detection. Because of our method is invasive,so we chose human urine detected. But in human urine have many impurity and salt that for detect is not easy. As a result we use catalytic mechanism on nSi by enzymes and take AuNPs replace GOx. In our experiment,finding that the platform combine AuNPs have high sensitivity for standard glucose even to clinical test still have good sensitivity.

[1] 陳信典, "糖尿病人的自我偵測," 2006.
[2] I. I. o. B. Science), "A history of urine tests in the investigation
of human disease," 2005.
[3] A. H. F. a. H. M. Flee, "Self Testing, An Emerging Component of Clinical Chemistry," 1984.
[4] D. K. A. E. F. HARTREE, "Properties of Glucose Oxidase (Notatin)," 1948.
[5] E. C. A. Alfred H. Free, Mary Lou Kercher, Helen M. and a. M. H. C. Free, "Simple Specific Test for Urine Glucose," 1957.
[6] B. M. J. E. MJDDLETON, M.R.C.P., AND, and P. D. W. J. GRIFFITHS, B.Sc., A.R.I.C., "Rapid colorimetric micro-method
For estimating glucose in blood
And c.s.f. using glucose oxidase," 1957.
[7] A. D. ASSOCIATION, "Tests of Glycemia in Diabetes," 2004.
[8] H. M. Free and A. H. Free, "Analytical Chemistry in the Conquest Daibet," 1984.
[9] J. A. W. JOHN T. HAYFORD, AND ROBERT G. THOMPSON, "V.alidity of Urine Glucose Measurements for
Estimating Plasma Glucose Concentration," 1983.
[10] R. D. Cheeley and S. M. Joyce, "A clinical comparison of the performance of four blood glucose reagent strips," The American Journal of Emergency Medicine, vol. 8, pp. 11-15, 1990.
[11] U. P. D. S. U. Group, "Intensive blood-glucose control with sulphonylureas or insulin
compared with conventional treatment and risk of complications
in patients with type 2 diabetes (UKPDS 33)," 1998.
[12] P. C. ed, "Diabetes in the 80s," New York: Praeger, 1982.
[13] P. P. Ferguson SD, "Are reflectance meters necessary for
home blood glucose monitoring?," 1980.
[14] M. D., "History of blood glucose meters: transcripts of
interviews," 2006(www.mendosa. com/history/htm).
[15] T. L. R. Stephen F. Malin, Thomas B. Blank, Suresh N. Thennadil, and and S. L. Monfre, "Noninvasive Prediction of Glucose by Near-
Infrared Diffuse Reflectance Spectroscopy," 1999.
[16] S. K. Vashist, "Non-invasive glucose monitoring technology in diabetes management: a review," Anal Chim Acta, vol. 750, pp. 16-27, Oct 31 2012.
[17] P. KIRILL V. LARIN, M. MOHSEN S. ELEDRISI, P. MASSOUD MOTAMEDI, and P. RINAT O. ESENALIEV, "Noninvasive Blood Glucose Monitoring
With Optical Coherence Tomography," 2002.
[18] C. F. H. Shu-jen Yeh, and Omar S. Khalil*, "Monitoring Blood Glucose Changes in Cutaneous
Tissue by Temperature-modulated Localized
Reflectance Measurements," 2003.
[19] D. I. Ellis and R. Goodacre, "Metabolic fingerprinting in disease diagnosis: biomedical applications of infrared and Raman spectroscopy," Analyst, vol. 131, pp. 875-85, Aug 2006.
[20] 刘. 蓉. 徐. 陈. 马. 真, "光学无创血糖检测中的主要问题及研究进展," 2007.
[21] 王玫君, "<血糖檢測之古往今來.pdf>," 2000.
[22] L. C. Clark and C. Lyons, "ELECTRODE SYSTEMS FOR CONTINUOUS MONITORING IN CARDIOVASCULAR SURGERY," Annals of the New York Academy of Sciences, vol. 102, pp. 29-45, 1962.
[23] S. J. Updike and G. P. Hicks, "The Enzyme Electrode," Nature, vol. 214, pp. 986-988, 1967.
[24] M. F. Burrltt, "Current Analytical Approaches to Measuring Blood Analytes," 1990.
[25] D. Ross, L. Heinemann, and E. A. Chantelau, "Short-term evaluation of an electro-chemical system (ExacTech™) for blood glucose monitoring," Diabetes Research and Clinical Practice, vol. 10, pp. 281-285, 1990.
[26] J. Wang, "Electrochemical Glucose Biosensors," 2008 American Chemical Society, 2008.
[27] 陳藹然, "糖醇(Sugar alcohol)、醣酸(Saccharinic acid)與胺醣(Amino
sugar)."
[28] A. Heller and B. Feldman, "Electrochemical Glucose Sensors and Their Applications in Diabetes Management," Chemical Reviews, vol. 108, pp. 2482-2505, 2008/07/01 2008.
[29] W. Chen, H. Yao, C. H. Tzang, J. Zhu, M. Yang, and S.-T. Lee, "Silicon nanowires for high-sensitivity glucose detection," Applied Physics Letters, vol. 88, p. 213104, 2006.
[30] W. C. Todd Strother , † Xinsheng Zhao ,‡ Robert J. Hamers ,† and Lloyd M. Smith *†, "Synthesis and Characterization of DNA-Modified Silicon (111) Surfaces," J. Am. Chem. Soc., 2000.
[31] S. Su, Y. He, S. Song, D. Li, L. Wang, C. Fan, and S. T. Lee, "A silicon nanowire-based electrochemical glucose biosensor with high electrocatalytic activity and sensitivity," Nanoscale, vol. 2, pp. 1704-7, Sep 2010.
[32] M. A. Posthumus, P. G. Kistemaker, H. L. C. Meuzelaar, and M. C. Ten Noever de Brauw, "Laser desorption-mass spectrometry of polar nonvolatile bio-organic molecules," Analytical Chemistry, vol. 50, pp. 985-991, 1978/06/01 1978.
[33] M. M. JOHN B. FENN, CHIN KAI MENG, SHEK Fu WONG, and C. M. WHITEHOUSE, "Electrospray Ionization for Mass Spectrometry
of Large Biomolecules," 1989.
[34] V. F. Taylor, R. E. March, H. P. Longerich, and C. J. Stadey, "A mass spectrometric study of glucose, sucrose, and fructose using an inductively coupled plasma and electrospray ionization," International Journal of Mass Spectrometry, vol. 243, pp. 71-84, 2005.
[35] Q. He, S. Chen, J. Wang, J. Hou, S. Xiong, and Z. Nie, "1-naphthylhydrazine hydrochloride: a new matrix for the quantification of glucose and homogentisic acid in real samples by MALDI-TOF MS," Clin Chim Acta, vol. 420, pp. 94-8, May 2013.
[36] J. Sunner, E. Dratz, and Y.-C. Chen, "Graphite surface-assisted laser desorption/ionization time-of-flight mass spectrometry of peptides and proteins from liquid solutions," Analytical Chemistry, vol. 67, pp. 4335-4342, 1995/12/01 1995.
[37] J. Wei, J. M. Buriak, and G. Siuzdak, "Desorption-ionization mass spectrometry on porous silicon," Nature, vol. 399, pp. 243-246, 1999.
[38] S. A. Trauger, E. P. Go, Z. Shen, J. V. Apon, B. J. Compton, E. S. P. Bouvier, M. G. Finn, and G. Siuzdak, "High Sensitivity and Analyte Capture with Desorption/Ionization Mass Spectrometry on Silylated Porous Silicon," Analytical Chemistry, vol. 76, pp. 4484-4489, 2004/08/01 2004.
[39] E. P. Go, ‡ J. V. Apon,†,‡ G. Luo,§ A. Saghatelian,† R. H. Daniels,| V. Sahi,| R. Dubrow,*,| B. F. Cravatt,† and a. G. S. A. Vertes, †, "Desorption Ionization on Silicon Nanowires," 2005.
[40] C.-W. Tsao, P. Kumar, J. Liu, and D. L. DeVoe, "Dynamic Electrowetting on Nanofilament Silicon for Matrix-Free Laser Desorption/Ionization Mass Spectrometry," Analytical Chemistry, vol. 80, pp. 2973-2981, 2008/04/01 2008.
[41] X. Li and P. W. Bohn, "Metal-assisted chemical etching in HF/H[sub 2]O[sub 2] produces porous silicon," Applied Physics Letters, vol. 77, p. 2572, 2000.
[42] C.-W. Tsao, Z.-J. Yang, and C.-W. Chung, "Preparation of nanostructured silicon surface for mass spectrometry analysis by an all-wet fabrication process using electroless metal deposition and metal assisted etching," International Journal of Mass Spectrometry, vol. 321–322, pp. 8-13, 2012.
[43] J. W. Mirtha Umafia, Mansukh and C. W. Wani, and Edgar Cook, "Enzyme-Enhanced Electrochemical
Immunoassay for Phenytoin," 1988.
[44] D. Zeng, W. Luo, J. Li, H. Liu, H. Ma, Q. Huang, and C. Fan, "Gold nanoparticles-based nanoconjugates for enhanced enzyme cascade and glucose sensing," Analyst, vol. 137, pp. 4435-9, Oct 7 2012.
[45] M. Comotti, C. Della Pina, R. Matarrese, and M. Rossi, "The catalytic activity of "naked" gold particles," Angew Chem Int Ed Engl, vol. 43, pp. 5812-5, Nov 5 2004.
[46] J. T. Miller, A. J. Kropf, Y. Zha, J. R. Regalbuto, L. Delannoy, C. Louis, E. Bus, and J. A. van Bokhoven, "The effect of gold particle size on AuAu bond length and reactivity toward oxygen in supported catalysts," Journal of Catalysis, vol. 240, pp. 222-234, 2006.
[47] M. L. a. Sabine Schimpf a, Christian Mohra, Uwe Rodemerck b, and J. R. b. Angelika Brückner b, Herbert Hofmeister c, Peter Claus a,∗, "Supported gold nanoparticles: in-depth catalyst characterization
and application in hydrogenation and oxidation reactions," 2002.
[48] C. Milone, C. Crisafulli, R. Ingoglia, L. Schipilliti, and S. Galvagno, "A comparative study on the selective hydrogenation of α,β unsaturated aldehyde and ketone to unsaturated alcohols on Au supported catalysts," Catalysis Today, vol. 122, pp. 341-351, 2007.
[49] Y. Sun, "Conversion of Ag Nanowires to AgCl Nanowires Decorated with Au Nanoparticles and Their Photocatalytic Activity," The Journal of Physical Chemistry C, vol. 114, pp. 2127-2133, 2010/02/11 2010.
[50] Z. Peng, H. Hu, M. I. B. Utama, L. M. Wong, K. Ghosh, R. Chen, S. Wang, Z. Shen, and Q. Xiong, "Heteroepitaxial Decoration of Ag Nanoparticles on Si Nanowires: A Case Study on Raman Scattering and Mapping," Nano Letters, vol. 10, pp. 3940-3947, 2010/10/13 2010.
[51] K.-Q. Peng, X. Wang, X.-L. Wu, and S.-T. Lee, "Platinum Nanoparticle Decorated Silicon Nanowires for Efficient Solar Energy Conversion," Nano Letters, vol. 9, pp. 3704-3709, 2009/11/11 2009.
[52] J. K. Hyun and L. J. Lauhon, "Spatially Resolved Plasmonically Enhanced Photocurrent from Au Nanoparticles on a Si Nanowire," Nano Letters, vol. 11, pp. 2731-2734, 2011/07/13 2011.
[53] L. A. Porter, H. C. Choi, A. E. Ribbe, and J. M. Buriak, "Controlled Electroless Deposition of Noble Metal Nanoparticle Films on Germanium Surfaces," Nano Letters, vol. 2, pp. 1067-1071, 2002/10/01 2002.
[54] 羅聖全, "電子顯微鏡介紹."
[55] 黃蔭樨, "生物化學," 1989,九月.
[56] M. Pasta, F. La Mantia, and Y. Cui, "Mechanism of glucose electrochemical oxidation on gold surface," Electrochimica Acta, vol. 55, pp. 5561-5568, 2010.
[57] 梁秀美, "市面上血糖機之比較," 2012 年12 月.
[58] 臨. 孫建峰醫師 and 鏡. 趙少文醫檢師(http://web.it.nctu.edu.tw/~hcsci/hospital/uti/uti0.html), "脊隨損傷醫訊."