Title

整合微流體系統與表面電漿光柵晶片於醣化血紅素量測

Translated Titles

On-Chip HbA1c Detection Utilizing a Compact Surface Plasmon Grating Sensor Integrated on a Microfluidic System

Authors

周煥庭

Key Words

表面電漿 ; Aptamer ; 表面電漿 ; 適體

PublicationName

清華大學光電工程研究所學位論文

Volume or Term/Year and Month of Publication

2014年

Academic Degree Category

碩士

Advisor

李明昌

Content Language

繁體中文

Chinese Abstract

表面電漿生物感測技術擁有比其他生物感測方法有更高的靈敏度,如今已經發展出很多不同的表面電漿生物感測方法。本論文主要是利用光柵式表面電漿感測方法偵測生物檢體。此方法最主要是藉由觀察反射頻譜的變化量,而去感測光柵表面物質的變異。我們利用有限時域分析法 (Finite Difference Time Domain)這個方法去模擬後發現改變光柵表面形貌會影響反射頻譜的特性。接著我們將表面電漿晶片整合在微流道上利用微流道能夠大幅減少檢體用量和使液體傳輸自動化的特性使整個偵測流程更加快速方便。再來我們利用整合微流道的表面電漿晶片偵測糖尿病的指標HbA1c 生物檢體。一開始我們先利用螢光標定的方式確認第一層的適體(aptamer)有最好的自組裝,確認好最佳濃度和時間後,我們分別通入0~3 μg/μl 的HbA1c 接著在通入0.025 μg/μl 糖化血紅素抗體(HbA1c antibody),而我們可以看到HbA1c的訊號偏移量會隨著濃度改變而有不同、而HbA1c antibody 雖然是注入的相同濃度,但會因為HbA1c 的鍵結量不同而有線性變化。

English Abstract

Surface plasmon utilized for biosensing applications has been demonstrated with high sensitivity. There are many types of surface plasmon biosensors today. In this research, we focus on a grating-based surface plasmon biosensor. The grating-based SP biosensor detects the biomolecule through interrogating the shift of the reflection spectrum. According to the simulation result by Finite Difference Time Domain (FTDT) method, we found that the bandwidth is generally related to the profile of the grating. In addition, we integrate microfluidic systems into the SPR chip. Microfluidic systems have the advantage of reducing the usage of specimen and facilitating the delivery of liquid through the entire detection process quickly and easily. After optimizing the concentration and process time of applying HbA1c-specific aptamers, we passed through 0~3 μg/μl of HbA1c, followed by injecting 0.025 μg/μl of HbA1c antibody. We observed the SPR wavelength shifts along with the concentrations of HbA1c, showing a good linear correlation. We also demonstrated that the detection system can be miniaturized for a portable apparatus.

Topic Category 電機資訊學院 > 光電工程研究所
工程學 > 電機工程
Reference
  1. [1] C. J. Huang, H. I. Lin, S. C. Shiesh, and G. B. Lee, "An integrated microfluidic system for rapid screening of alpha-fetoprotein-specific aptamers," Biosens Bioelectron, vol. 35, pp. 50-5, May 15 2012.
    連結:
  2. [2] Y. Yang, D. Yang, H. J. Schluesener, and Z. Zhang, "Advances in SELEX and application of aptamers in the central nervous system," Biomol Eng, vol. 24, pp. 583-92, Dec 2007.
    連結:
  3. [3] D. H. Bunka and P. G. Stockley, "Aptamers come of age - at last," Nat Rev Microbiol, vol. 4, pp. 588-96, Aug 2006.
    連結:
  4. [4] P. Grodzinski, R. Liu, J. Yang, and M. D. Ward, "Microfluidic system integration in sample preparation chip-sets - a summary," Proceedings of the 26th Annual International Conference of the Ieee Engineering in Medicine and Biology Society, Vols 1-7, vol. 26, pp. 2615-2618, 2004.
    連結:
  5. [5] R. W. Wood, "On a remarkable case of uneven distribution of light in a diffraction grating spectrum," Philosophical Magazine, vol. 4, pp. 396-402, Jul-Dec 1902.
    連結:
  6. [6] U. Fano, "The theory of anomalous diffraction gratings and of quasi-stationary waves on metallic surfaces (Sommerfeld's waves)," Journal of the Optical Society of America, vol. 31, pp. 213-222, Mar 1941.
    連結:
  7. [7] R. H. Ritchie, "Plasma Losses by Fast Electrons in Thin Films," Physical Review, vol. 106, pp. 874-881, 1957.
    連結:
  8. [8] E. A. Stern and R. A. Ferrell, "Surface Plasma Oscillations of a Degenerate Electron Gas," Physical Review, vol. 120, pp. 130-136, 1960.
    連結:
  9. [9] A. Otto, "Excitation of Nonradiative Surface Plasma Waves by Light," Bulletin of the American Physical Society, vol. 13, pp. 983-&, 1968.
    連結:
  10. [10] B. Liedberg, C. Nylander, and I. Lundstrom, "Surface-Plasmon Resonance for Gas-Detection and Biosensing," Sensors and Actuators, vol. 4, pp. 299-304, 1983.
    連結:
  11. [11] P. Englebienne, A. Van Hoonacker, and M. Verhas, "Surface plasmon resonance: principles, methods and applications in biomedical sciences," Spectroscopy-an International Journal, vol. 17, pp. 255-273, 2003.
    連結:
  12. [12] K. S. Lee, J. M. Son, D. Y. Jeong, T. S. Lee, and W. M. Kim, "Resolution Enhancement in Surface Plasmon Resonance Sensor Based on Waveguide Coupled Mode by Combining a Bimetallic Approach," Sensors, vol. 10, pp. 11390-11399, Dec 2010.
    連結:
  13. [13] B. K. Singh and A. C. Hillier, "Surface plasmon resonance imaging of biomolecular interactions on a grating-based sensor array," Analytical Chemistry, vol. 78, pp. 2009-2018, Mar 15 2006.
    連結:
  14. [14] K. S. Yee, "Numerical Solution of Initial Boundary Value Problems Involving Maxwells Equations in Isotropic Media," Ieee Transactions on Antennas and Propagation, vol. Ap14, pp. 302-&, 1966.
    連結:
  15. [15] 楊自森, 吳見明, 蔡旻龍, 莊淳宇, 崔豫笳, and 許志楧, "分子生醫光電科學與技術," 物理, vol. 27卷, pp. 頁670-686, 200510 2005.
    連結:
  16. [18] H. Raether, "Surface-Plasmons on Smooth and Rough Surfaces and on Gratings," Springer Tracts in Modern Physics, vol. 111, pp. 1-133, 1988.
    連結:
  17. [19] 吳民耀 and 劉威志, "表面電漿子理論與模擬," 物理, vol. 28卷, pp. 頁486-496, 200604 2006.
    連結:
  18. [20] H. W. Gao, W. Zhou, and T. W. Odom, "Plasmonic Crystals: A Platform to Catalog Resonances from Ultraviolet to Near-Infrared Wavelengths in a Plasmonic Library," Advanced Functional Materials, vol. 20, pp. 529-539, Feb 22 2010.
    連結:
  19. [21] G. M. Whitesides, "The origins and the future of microfluidics," Nature, vol. 442, pp. 368-373, Jul 27 2006.
    連結:
  20. [22] K. H. Yoon, M. L. Shuler, and S. J. Kim, "Design optimization of nano-grating surface plasmon resonance sensors," Optics Express, vol. 14, pp. 4842-4849, May 29 2006.
    連結:
  21. [23] R. Zheng, B. W. Park, D. S. Kim, and B. D. Cameron, "Development of a highly specific amine-terminated aptamer functionalized surface plasmon resonance biosensor for blood protein detection," Biomedical Optics Express, vol. 2, pp. 2731-2740, Sep 1 2011.
    連結:
  22. [16] 楊自森, 吳見明, 蔡旻龍, and 許志□, "生醫光電檢測技術," 機械工業, pp. 頁167-187, 200504 2005.
  23. [17] 黃朝均 and 李國賓, ":整合微流體之電化學感測晶片於生醫檢測之應用,":化工技術 卷期:20卷6期總號231, pp. 頁116-129, :201206.