本研究目標要發展一系列光學檢測微流道系統(series of optical biosensor in micro-fluidic system) 置入具有微型化、表面奈微級結構的光學元件作為一基因快速檢測平台：GMR(guided-mode resonance)，本元件利用半導體技術，製作一次波長光柵結構，並利用其產生的窄帶高反射率之效果，及其光柵表面區域之高敏感度，應用於共種生化反應，並設計一系列表面改質於晶片表面，使生物分子以共價鍵鍵結固定於晶片表面,並成功的以此光學即時量測系統即時監測整個反應過程，觀測是否有雜交反應。本光學式檢測系統具有以下優點：免標定(label free)、微型化(mini size)、可高通量(high through put)、易與其它半導體元件接合、高訊雜比(high quality)、高穩定性、即時偵測(real time)之優點。

We used the guided-mode resonance (GMR) device to achieve the real-time detection on DNA hybridization process. The bulk-shift sensitivity is about 200 (nm/RIU) of the biosensor in the sandwich types of micro-fluidic system, and the detection limit is approximately 10-5 refraction index unit (RIU). We proposed a novel method to detect the different length of DNA hybridizations of DNA attached the chip surface respectively. Obviously, this optical biosensor shows its promising role in developing a real-time testing system which is with the most benefits of label free, high throughput, small size, and high sensitivity, etc.

[1] H.G. van der Poel, “ Review Smart Drugs in Prostate Cancer, ” European Urology 45, 1–17 (2004).
[2] 黃國華, “基因晶片與生物醫學, ”科學發展 381,64-69 (2004).
[3] S. K. Arya, M. Datta and B. D. Malhotra, “Recent advances in cholesterol biosensor, ” Biosensors and Bioelectronics 23, 1083–1100 (2008).
[4] X.J. Liang, P.H. Yap, “Determining refractive index of single living cell using an integrated microchip, ” Sensors and Actuators A 133, 349–354 (2007).
[5] 朱杰,王国栋,National Natural Science Foundation of China, 20572067.
[6] F. A. Schabert and J. P. Rabe,“ Vertical Dimension of Hydrated Biological Samples in Tapping Mode Scanning Force Microscopy, ” Biophysical Journal 70, 1514-1520 (1996).
[7] L. J. C. Jeuken,“ AFM Study on the Electric-Field Effects on Supported Bilayer Lipid Membranes, ” Biophysical Journal 94, 4711–4717 (2008).
[8] V. L. Berre, E. T. visiol, and J. FrancËois,“ Dendrimeric coating of glass slides for sensitive DNA microarrays analysis, ”Nucleic Acids Research, 31, No. 16 e88 (2003).
[9] S. J. OH, J. W. Park, “Surface Modification for DNA and Protein Microarrays,” OMICS A Journal of Integrative Biology 10, Number 3 (2006).
[10] S. E.-Martı’n and J. Salgado,“ Self-Assembling of Peptide/Membrane Complexes by Atomistic Molecular Dynamics Simulations, ”Biophysical Journal 92, 903–912 (2007).
[11] M. Samoc, A. Samoc and J. G. Grote, “Complex nonlinear refractive index of DNA, ” Chemical Physics Letters 431, 132–134 (2006).
[12] S. Niu, R. F. Saraf, “Label-less fluorescence-based method to detect hybridization with applications to DNA micro-array, ”Biosensor and Bioelectronics 23, 714-720 (2007).
[13] A. Nabok, S. P.J. Higson, “ The study of genomic DNA adsorption and subsequent interactions using total internal reflection ellipsometry, ” Biosensors and Bioelectronics 23 ,377–383 (2007).
[14] G. Demirel, E. P. kin, “ A novel DNA biosensor based on ellipsometry, ”Surface Science 602, 952-959 (2008).
[15] “ Imaging ellipsometry, ”Optrel GbR www.optrel.de.
[16] A. Eing and M. Vaupel, “Imaging Ellipsometry in Biotechnology, ”ISBN 3-9807279-6-3, www.nanofilm.de.
[17] J. Homola, and G. Gauglitz, “Surface plasmon resonance sensors: review, ”Sensors and Actuators B 54, 3–15 (1999).
[18] C. T. Campbell, G. Kim, “ Review: SPR microscopy and its applications to high-throughput analyses of biomolecular binding events and their kinetics, ”Biomaterials 28, 2380–2392 (2007).
[19] J. Mavri, M. Franko, “Application of chromogenic reagents in surface plasmon resonance (SPR), ”Biosensors and Bioelectronics 22, 1163–1167 (2007).
[20] B.N. Feltis, T.J. Davis, “A hand-held surface plasmon resonance biosensor for the detection of ricin and other biological agents, ”Biosensors and Bioelectronics 23, 1131–1136 (2008).
[21] Y. Lei, H. Chen, D. Pang, “ Electroless-plated gold films for sensitivity surface Plasmon resonance detection of white spot syndrome virus, ”Biosensor and Bioelectronics 23, 1200-1207 (2008).
[22] A. Tsortos, E. Gizeli, “Quantitative Determination of Size and Shape of Surface-Bound DNA Using an Acoustic Wave Sensor, ”Biophysical Journal 94, 2706–2715 (2008).
[23] R. W. Wood, “On a remarkable case of uneven distribution of light in a diffraction grating spectrum, ”Phil. Mag. 4, 396-408 (1902).
[24] S. S. Wang and R. Magnusson, “New principle for optical filters, ” Appl. Phys. Lett. 61, 1022-1024 (1992).
[25] S. S. Wang and R. Magnusson, “Theory and applications of guided-mode resonance filters, ”Appl. Opt., 32 ,2606-2613 (1993).
[26] J. N. Yih, Y. M. Chu, Y. C. Mao, W. H. Wang, F. C.Chien, C. Y. Lin, K. L. Lee, P. K. Wei ,and S. J. Chen, “ Optical waveguide biosensors constructed with subwavelength gratings, ”Appl. Opt. 45, 1938-1942 (2006).
[27] B. Cunningham, B. Lin, J. Qiu, P. Li, J. Pepper and B. Hugh, “A plastic colorimetric resonant optical biosensor for multiparallel detection of label-free biochemical interactions, ” Sensors and Actuators B 85, 219-226 (2002).
[28] B. Cunningham, P. Li, “Colorimetric resonant reflection as a direct biochemical assay technique, ” Sensors and Actuators B 81, 316-328 (2002).
[29] B. Lin, P. Li, B. Cunningham, “A label-free optical technique for detecting small molecule interactions, ”Biosensors and Bioelectronics 17, 827-834 (2002).
[30] B. Cunningham, J. Qiu, P. Li, “Enhancing the surface sensitivity of colorimetric resonant optical biosensor, ”Sensors and Actuators B 87, 365-370 (2002).
[31] B. Cunningham, J. Qiu, P. Li, “Self-referenced assay method for photonic crystal biosensors:Application to small molecule analytes, ” Appl. Phys. Lett. 89, 123113 (2006).
[32] N. Ganesh, I. D. Block, and B. T. Cunningham, “Near ultraviolet-wavelength photonic-crystal biosensor with enhanced surface-to-bulk sensitivity ratio,” Appl. Phys. Lett. 89, 023901 (2006).
[33] K. Cottier, M. Wiki, R. E. Kunz, “Label-free highly sensitive detection of (small) molecules by wavelength interrogation of integrated optical chips,” Sensors and Actuators B 91, 241-251 (2003).
[34] I. D. Block, and B. T. Cunningham, “Photonic crystal optical biosensor in corporating structured low-index porous dielectric, ” Sensors and Actuators B 120, 187-193 (2006).
[35] Nikhil Ganesh and Brian T. Cunningham, “Photonic-crystal near-ultraviolet reflectance filters fabricated by nanoreplica molding, ” Appl. Phys. Lett. 88 , 071110 (2006).
[36] N. Ganesh, A. Xiang, and B. T. Cunningham, “Compact wavelength detection system incorporation a guided-mode resonance filter,” Appl. Phys. Lett. 90 , 081103 (2007).
[37] Y. Feng, A. M. Ferrie, and J. Balkrishnan, “Resonant Waveguide Grating Biosensor for Living Cell Sensing, ” Biophysical Journal 91, 1925-1940 (2006).
[38] L. L. Chan, B. Cunningham, P. Li, “Self-referenced assay method for photonic crystal biosensor: Application to small molecule analytes, ” Sensors and Actuators B 120, 392-398 (2007).
[39] F. Wei, B. Sun, W. Liao and X. S. Zhao, “Achieving differentiation of single-base mutations through hairpin oligonucleotide and electric potential control, ” Biosensors and Bioelectronics 18, 1149-1155 (2003).
[40] D. Rekesh, Y. Lyubchenko, and S. M. Lindsay, “Scanning Tunneling Microscopy of Mercapto-Hexyl-Oligonucleotides Attached to Gold, ” Biophysical Journal 71, 1079-1086 (1996).
[41] A. Nabok, and S. P. J. Higson, “The study of genomic DNA adsorption and subsequent interactions using total internal refraction ellipsometer, ”Biosensor and Bioelectronics 23, 377-383 (2007).
[42] A. Ulman, “Formation and Structure of Self-Assembled Monolayers, ” Chem. Rev. 96, 1533-1554 (1996).
[43] G. Rong, A. Najmaie and S. M. Weiss, “ Nanoscale porous silicon waveguide for label-free DNA sensing,” Biosensors and Bioelectronics 23,1572–1576 (2008).
[44] M. R. Vilar, A. M. Botelho do Rego, and R. Naaman, “Interaction of Self-Assembled Monolayers of DNA with Electrons: HREELS and XPS studies,” J. Phys. Chem. B, 112, 6957-6964 (2008).