簡易檢索 / 詳目顯示

回結果列表
研究生： 林晏筠
Lin, Yan-Yun
論文名稱： 金屬-絕緣體-金屬表面電漿共振結構應用於生物分子檢測
Biomolecular Sensing Platform Based on a Metal-Insulator-Metal Plasmonic Structure
指導教授： 林俊宏
Lin, Chun-Hung
學位類別： 碩士
Master
系所名稱： 理學院 - 光電科學與工程學系
Department of Photonics
論文出版年： 2021
畢業學年度： 109
語文別： 中文
論文頁數： 110
中文關鍵詞： 侷域性表面電漿共振 、金屬-絕緣體-金屬結構 、生物分子檢測
外文關鍵詞： Localized surface plasmon resonance, metal-insulator-metal structure, biomolecular sensing
相關次數： 點閱：142  下載：0 
分享至:
查詢本校圖書館目錄 查詢臺灣博碩士論文知識加值系統 勘誤回報

    • 表面電漿子(Surface plasmon，SP)的共振行為會隨著周遭的環境折射率改變而改變，根據表面電漿共振所產生的電磁場特性再分為表面電漿共振(Surface plasmon resonance，SPR)與侷域性表面電漿共振(Localized surface plasmon resonance，LSPR)，由於兩者在產生共振的金屬界面上都有電場增益的現象，所以對周遭的環境折射率的改變非常敏感，再加上可即時檢測的特性，其在檢測生物分子相關的應用上非常廣泛。
    在本研究中，我們利用奈米轉印微影術將奈米金圓盤陣列轉移至塗佈上光阻的金薄膜上製作金屬-絕緣體-金屬(Metal-Insulator-Metal，MIM)表面電漿共振結構，藉由底層金的加入使奈米金圓盤的LSPR模態達到更強的電場增益效果，相較於單純的奈米金圓盤陣列，其更適合應用於生物小分子的量測；因此最後以DNA與玻尿酸分子(Hyaluronic acid，HA)作為檢測的目標分子，且更進一步以HA分子為橋梁外接奈米金粒子，使量測訊號產生放大的效果，使量測HA的偵測極限降低至7.9010-8 g/mL。

    關鍵字：侷域性表面電漿共振、金屬-絕緣體-金屬結構、生物分子檢測

    In this study, we fabricated metal-insulator-metal(MIM) plasmonic structure with nano-transfer printing (nTP). With the three-layered structure, the LSPR mode of gold nanodisk could be strongly confined in the structure when light was incident. Therefore, the field in the SU-8 spacer and the field around the gold nanodisk could be strongly enhanced. Because of the strong field enhancement of MIM structure, the structure was highly sensitive to the refractive index of the surrounding material and was suitable for biomolecular sensing. Furthermore, the MIM plasmonic structure was applied to detect DNA and hyaluronic acid (HA) respectively. Due to too much redundant gold regions on MIM structure, they competed with the regions of electric-field enhancement for target sensing. By adding Au NPs as an enhance factor, we amplified the signal of HA and finally improved the detection limit of HA to 7.9010-8 g/mL.
    Key words: Localized surface plasmon resonance, metal-insulator-metal structure, biomolecular sensing

    摘要 i 誌謝 ix 目錄 x 表目錄 xiii 圖目錄 xiv 第一章 緒論 1 1.1 研究背景與動機 1 1.2論文架構 3 第二章 理論原理與文獻回顧 5 2.1 MIM奈米結構的分析 5 2.1.1 MIM結構的設計原理 6 2.1.2 SPP原理 6 2.1.3 LSPR原理 7 2.2 不同訊號轉換模式下的生物感測器 8 2.2.1 機械式生物感測器 9 2.2.2 電化學式生物感測器 10 2.2.3 光學式生物感測器 11 2.3 奈米金粒子的耦合與應用 12 第三章 研究方法 22 3.1 MIM結構數值模擬方法 22 3.2 MIM結構製作方法 22 3.2.1 矽母模具的製作 22 3.2.2 PFPE軟模具製作 24 3.2.3 製作MIM結構前的材料製備 26 3.2.4 利用奈米轉印微影術製作MIM結構 28 3.3 折射率靈敏度量測架構及方法 29 3.3.1 實驗材料 29 3.3.2 實驗儀器 30 3.3.3 反射頻譜與靈敏度的量測 30 3.4 DNA分子量測 31 3.4.1 實驗材料 31 3.4.2 實驗儀器 31 3.4.3 實驗材料製備 32 3.4.4 MIM結構直接應用於tDNA分子量測 32 3.4.5 修飾上pDNA分子的MIM結構進行去雜合化反應後，再應用於tDNA分子量測 33 3.4.6 MIM結構預先進行去雜合化加熱處理 34 3.4.7 去雜合化加熱處理的MIM結構進行tDNA的檢測 34 3.5 HA分子檢測 35 3.5.1 實驗材料 35 3.5.2 實驗儀器 35 3.5.3 實驗材料製備 36 3.5.4 HA分子量測 36 3.6 利用奈米金粒子放大量測到的HA訊號 37 3.6.1 奈米金粒子的合成 37 3.6.2 利用奈米金粒子放大HA訊號 38 3.7 生物分子量測方法 40 第四章 模擬與實驗結果分析 49 4.1 MIM結構之光學模擬分析 49 4.1.1 MIM結構在不同金圓盤厚度下的光學模擬分析 49 4.1.2 MIM結構在不同中間層SU-8厚度下的光學模擬分析 50 4.1.3 MIM結構中間層SU-8蝕刻前後的光學模擬分析 51 4.1.4 MIM結構與奈米金圓盤陣列結構光學模擬分析之比較 52 4.2 MIM結構製程結果 53 4.2.1 MIM結構在不同參數下的初步轉印結果 53 4.2.2 不同氧電漿蝕刻參數下的MIM結構 55 4.2.3 MIM結構與奈米金圓盤陣列結構實際結果之比較 57 4.3 MIM結構應用於DNA分子檢測 57 4.3.1 不同雜合溫度下對於檢測tDNA的影響 58 4.3.2 去雜合化過程對於MIM結構的影響 61 4.3.3 利用去雜合化加熱處理的MIM結構進行tDNA的檢測 63 4.4 MIM結構應用於HA分子檢測 66 4.4.1 MIM結構對於HA分子的檢測 66 4.4.2 利用奈米金粒子增強MIM結構的感測能力 67 第五章 結論與未來展望 99 5.1 結論 99 5.2 未來展望 100 第六章 參考文獻 105

    1. L. Tribolet, E. Kerr, C. Cowled, A. G. D. Bean, C. R. Stewart, M. Dearnley, and R. J. Farr, "MicroRNA Biomarkers for Infectious Diseases: From Basic Research to Biosensing," Frontiers in Microbiology 11(2020).
    2. M. D. Jansson and A. H. Lund, "MicroRNA and cancer," Mol Oncol 6, 590-610 (2012).
    3. J. C. Dudley, J. Schroers-Martin, D. V. Lazzareschi, W. Y. Shi, S. B. Chen, M. S. Esfahani, D. Trivedi, J. J. Chabon, A. A. Chaudhuri, H. Stehr, C. L. Liu, H. Lim, H. A. Costa, B. Y. Nabet, M. L. Y. Sin, J. C. Liao, A. A. Alizadeh, and M. Diehn, "Detection and Surveillance of Bladder Cancer Using Urine Tumor DNA," Cancer Discov 9, 500-509 (2019).
    4. D. Peruzzi, F. Mori, A. Conforti, D. Lazzaro, E. De Rinaldis, G. Ciliberto, N. La Monica, and L. Aurisicchio, "MMP11: a novel target antigen for cancer immunotherapy," Clin Cancer Res 15, 4104-4113 (2009).
    5. D. Lima, A. C. M. Hacke, J. Inaba, C. A. Pessôa, and K. Kerman, "Electrochemical detection of specific interactions between apolipoprotein E isoforms and DNA sequences related to Alzheimer’s disease," Bioelectrochemistry 133, 107447 (2020).
    6. A. Roointan, T. Ahmad Mir, S. Ibrahim Wani, R. Mati Ur, K. K. Hussain, B. Ahmed, S. Abrahim, A. Savardashtaki, G. Gandomani, M. Gandomani, R. Chinnappan, and M. H. Akhtar, "Early detection of lung cancer biomarkers through biosensor technology: A review," J Pharm Biomed Anal 164, 93-103 (2019).
    7. S. D. Selcuklu, Mark T. A. Donoghue, and C. Spillane, "miR-21 as a key regulator of oncogenic processes," Biochemical Society Transactions 37, 918-925 (2009).
    8. M. Lai and G. Slaughter, "Label-Free MicroRNA Optical Biosensors," Nanomaterials (Basel) 9, 1573 (2019).
    9. B. Purohit, P. R. Vernekar, N. P. Shetti, and P. Chandra, "Biosensor nanoengineering: Design, operation, and implementation for biomolecular analysis," Sensors International 1, 100040 (2020).
    10. S. Kasani, K. Curtin, and N. Wu, "A review of 2D and 3D plasmonic nanostructure array patterns: fabrication, light management and sensing applications," Nanophotonics 8, 2065-2089 (2019).
    11. A. Tadimety, Y. Zhang, K. M. Kready, T. J. Palinski, G. J. Tsongalis, and J. X. J. Zhang, "Design of peptide nucleic acid probes on plasmonic gold nanorods for detection of circulating tumor DNA point mutations," Biosens Bioelectron 130, 236-244 (2019).
    12. O. A. Sadik, A. O. Aluoch, and A. Zhou, "Status of biomolecular recognition using electrochemical techniques," Biosens Bioelectron 24, 2749-2765 (2009).
    13. J. Liu, M. Jalali, S. Mahshid, and S. Wachsmann-Hogiu, "Are plasmonic optical biosensors ready for use in point-of-need applications?," Analyst 145, 364-384 (2020).
    14. L. Zeni, C. Perri, N. Cennamo, F. Arcadio, G. D’Agostino, M. Salmona, M. Beeg, and M. Gobbi, "A portable optical-fibre-based surface plasmon resonance biosensor for the detection of therapeutic antibodies in human serum," Scientific Reports 10, 11154 (2020).
    15. J. Pollet, F. Delport, K. P. Janssen, D. T. Tran, J. Wouters, T. Verbiest, and J. Lammertyn, "Fast and accurate peanut allergen detection with nanobead enhanced optical fiber SPR biosensor," Talanta 83, 1436-1441 (2011).
    16. J. Wang, D. Song, L. Wang, H. Zhang, H. Zhang, and Y. Sun, "Design and performances of immunoassay based on SPR biosensor with Au/Ag alloy nanocomposites," Sensors and Actuators B: Chemical 157, 547-553 (2011).
    17. D. Li, Q. He, Y. Cui, L. Duan, and J. Li, "Immobilization of glucose oxidase onto gold nanoparticles with enhanced thermostability," Biochem Biophys Res Commun 355, 488-493 (2007).
    18. W. H. Chang, Z. Y. Yang, T. W. Chong, Y. Y. Liu, H. W. Pan, and C. H. Lin, "Quantifying Cell Confluency by Plasmonic Nanodot Arrays to Achieve Cultivating Consistency," ACS Sens 4, 1816-1824 (2019).
    19. P. P. Austin Suthanthiraraj and A. K. Sen, "Localized surface plasmon resonance (LSPR) biosensor based on thermally annealed silver nanostructures with on-chip blood-plasma separation for the detection of dengue non-structural protein NS1 antigen," Biosens Bioelectron 132, 38-46 (2019).
    20. S. Chen, Y. Liu, Q. Yu, and W. Peng, "Self-referencing SPR biosensing with an ultralow limit-of-detection using long-wavelength excitation," Sensors and Actuators B: Chemical 327(2021).
    21. L. Soares, A. Csaki, J. Jatschka, W. Fritzsche, O. Flores, R. Franco, and E. Pereira, "Localized surface plasmon resonance (LSPR) biosensing using gold nanotriangles: detection of DNA hybridization events at room temperature," Analyst 139, 4964-4973 (2014).
    22. L. G. Carrascosa, A. Calle, and L. M. Lechuga, "Label-free detection of DNA mutations by SPR: application to the early detection of inherited breast cancer," Analytical and Bioanalytical Chemistry 393, 1173 (2008).
    23. S. Mohseni, T. T. Moghadam, B. Dabirmanesh, S. Jabbari, and K. Khajeh, "Development of a label-free SPR sensor for detection of matrixmetalloproteinase-9 by antibody immobilization on carboxymethyldextran chip," Biosensors and Bioelectronics 81, 510-516 (2016).
    24. P. L. Truong, B. W. Kim, and S. J. Sim, "Rational aspect ratio and suitable antibody coverage of gold nanorod for ultra-sensitive detection of a cancer biomarker," Lab on a Chip 12, 1102-1109 (2012).
    25. Y. Yanase, H. Suzuki, T. Tsutsui, I. Uechi, T. Hiragun, S. Mihara, and M. Hide, "Living cell positioning on the surface of gold film for SPR analysis," Biosensors and Bioelectronics 23, 562-567 (2007).
    26. S. Zeng, D. Baillargeat, H.-P. Ho, and K.-T. Yong, "Nanomaterials enhanced surface plasmon resonance for biological and chemical sensing applications," Chemical Society Reviews 43, 3426-3452 (2014).
    27. L. Hong, M. Lu, M. P. Dinel, P. Blain, W. Peng, H. Gu, and J. F. Masson, "Hybridization conditions of oligonucleotide-capped gold nanoparticles for SPR sensing of microRNA," Biosens Bioelectron 109, 230-236 (2018).
    28. T. Zhang, H. Li, S. Hou, Y. Dong, G. Pang, and Y. Zhang, "Construction of Plasmonic Core-Satellite Nanostructures on Substrates Based on DNA-Directed Self-Assembly as a Sensitive and Reproducible Biosensor," ACS Appl Mater Interfaces 7, 27131-27139 (2015).
    29. C.-Y. Chang, H.-T. Lin, M.-S. Lai, T.-Y. Shieh, C.-C. Peng, M.-H. Shih, and Y.-C. Tung, "Flexible Localized Surface Plasmon Resonance Sensor with Metal–Insulator–Metal Nanodisks on PDMS Substrate," Scientific Reports 8, 11812 (2018).
    30. G. Duffett, R. Wirth, M. Rayer, E. R. Martins, and T. F. Krauss, "Metal-insulator-metal nanoresonators – strongly confined modes for high surface sensitivity," Nanophotonics 9, 1547-1552 (2020).
    31. E. N. Economou, "Surface Plasmons in Thin Films," Physical Review 182, 539-554 (1969).
    32. R. H. Ritchie, "Surface plasmons in solids," Surface Science 34, 1-19 (1973).
    33. N. L. Kazanskiy, S. N. Khonina, and M. A. Butt, "Plasmonic sensors based on Metal-insulator-metal waveguides for refractive index sensing applications: A brief review," Physica E: Low-dimensional Systems and Nanostructures 117, 113798 (2020).
    34. R. Nicolas, G. Lévêque, J. Marae-Djouda, G. Montay, Y. Madi, J. Plain, Z. Herro, M. Kazan, P.-M. Adam, and T. Maurer, "Plasmonic mode interferences and Fano resonances in Metal-Insulator-Metal nanostructured interface," Scientific reports 5, 14419 (2015).
    35. G. Lévêque and O. J. F. Martin, "Optical interactions in a plasmonic particle coupled to a metallic film," Opt. Express 14, 9971-9981 (2006).
    36. J. J. Mock, R. T. Hill, A. Degiron, S. Zauscher, A. Chilkoti, and D. R. Smith, "Distance-Dependent Plasmon Resonant Coupling between a Gold Nanoparticle and Gold Film," Nano Letters 8, 2245-2252 (2008).
    37. M. Tamura and H. Kagata, "Analysis of Metal–Insulator–Metal Structure and Its Application to Sensor," IEEE Transactions on Microwave Theory and Techniques (2010).
    38. W. L. Barnes, A. Dereux, and T. W. Ebbesen, "Surface plasmon subwavelength optics," Nature 424, 824-830 (2003).
    39. D. Zhang, L. Men, and Q. Chen, "Microfabrication and applications of opto-microfluidic sensors," Sensors 11, 5360-5382 (2011).
    40. M. Li, S. K. Cushing, and N. Wu, "Plasmon-enhanced optical sensors: a review," Analyst 140, 386-406 (2015).
    41. K. A. Willets and R. P. Van Duyne, "Localized surface plasmon resonance spectroscopy and sensing," Annu Rev Phys Chem 58, 267-297 (2007).
    42. N. S. Fracchiolla, S. Artuso, and A. Cortelezzi, "Biosensors in clinical practice: focus on oncohematology," Sensors (Basel) 13, 6423-6447 (2013).
    43. L. G. Carrascosa, M. Moreno, M. Álvarez, and L. M. Lechuga, "Nanomechanical biosensors: a new sensing tool," TrAC Trends in Analytical Chemistry 25, 196-206 (2006).
    44. W. J. Polacheck and C. S. Chen, "Measuring cell-generated forces: a guide to the available tools," Nature Methods 13, 415-423 (2016).
    45. Jules L. Hammond, N. Formisano, P. Estrela, S. Carrara, and J. Tkac, "Electrochemical biosensors and nanobiosensors," Essays in Biochemistry 60, 69-80 (2016).
    46. M. Pohanka and P. Skládal, "Electrochemical Biosensors-Principles and Applications," Journal of Applied Biomedicine 6(2008).
    47. H. Teymourian, A. Barfidokht, and J. Wang, "Electrochemical glucose sensors in diabetes management: an updated review (2010-2020)," Chem Soc Rev 49, 7671-7709 (2020).
    48. R. Peltomaa, B. Glahn-Martinez, E. Benito-Pena, and M. C. Moreno-Bondi, "Optical Biosensors for Label-Free Detection of Small Molecules," Sensors (Basel) 18(2018).
    49. J. A. Goode, J. V. H. Rushworth, and P. A. Millner, "Biosensor Regeneration: A Review of Common Techniques and Outcomes," Langmuir 31, 6267-6276 (2015).
    50. J. L. Hammond, N. Bhalla, S. D. Rafiee, and P. Estrela, "Localized surface plasmon resonance as a biosensing platform for developing countries," Biosensors (Basel) 4, 172-188 (2014).
    51. T. Schneider, N. Jahr, J. Jatschka, A. Csaki, O. Stranik, and W. Fritzsche, "Localized surface plasmon resonance (LSPR) study of DNA hybridization at single nanoparticle transducers," Journal of Nanoparticle Research 15, 1531 (2013).
    52. W. P. Hall, S. N. Ngatia, and R. P. Van Duyne, "LSPR Biosensor Signal Enhancement Using Nanoparticle−Antibody Conjugates," The Journal of Physical Chemistry C 115, 1410-1414 (2011).
    53. E. Martinsson, B. Sepulveda, P. Chen, A. Elfwing, B. Liedberg, and D. Aili, "Optimizing the Refractive Index Sensitivity of Plasmonically Coupled Gold Nanoparticles," Plasmonics 9, 773-780 (2013).
    54. M. Alvarez and L. M. Lechuga, "Microcantilever-based platforms as biosensing tools," Analyst 135, 827-836 (2010).
    55. M. S. Ozdemir, M. Marczak, H. Bohets, K. Bonroy, D. Roymans, L. Stuyver, K. Vanhoutte, M. Pawlak, and E. Bakker, "A Label-Free Potentiometric Sensor Principle for the Detection of Antibody–Antigen Interactions," Analytical Chemistry 85, 4770-4776 (2013).
    56. A. Csáki, M. Thiele, J. Jatschka, A. Dathe, D. Zopf, O. Stranik, and W. Fritzsche, "Plasmonic nanoparticle synthesis and bioconjugation for bioanalytical sensing," Engineering in Life Sciences 15, 266-275 (2015).
    57. C.-H. Lin, H.-L. Chen, W.-C. Chao, C.-I. Hsieh, and W.-H. Chang, "Optical characterization of two-dimensional photonic crystals based on spectroscopic ellipsometry with rigorous coupled-wave analysis," Microelectronic Engineering 83, 1798-1804 (2006).
    58. D. P. Edward and I. Palik, "Handbook of optical constants of solids," (Academic, Orlando, Florida, 1985).
    59. K. Van Nguyen and S. D. Minteer, "DNA-functionalized Pt nanoparticles as catalysts for chemically powered micromotors: toward signal-on motion-based DNA biosensor," Chemical Communications 51, 4782-4784 (2015).
    60. N. G. Bastús, J. Comenge, and V. Puntes, "Kinetically Controlled Seeded Growth Synthesis of Citrate-Stabilized Gold Nanoparticles of up to 200 nm: Size Focusing versus Ostwald Ripening," Langmuir 27, 11098-11105 (2011).
    61. T. Cao, C.-w. Wei, R. E. Simpson, L. Zhang, and M. J. Cryan, "Broadband Polarization-Independent Perfect Absorber Using a Phase-Change Metamaterial at Visible Frequencies," Scientific Reports 4, 3955 (2014).
    62. Y.-J. Chen, W.-H. Chang, C.-Y. Li, Y.-C. Chiu, C.-C. Huang, and C.-H. Lin, "Direct synthesis of monolayer gold nanoparticles on epoxy based photoresist by photoreduction and application to surface-enhanced Raman sensing," Materials & Design 197(2021).
    63. S. S. Aćimović, H. Šípová, G. Emilsson, A. B. Dahlin, T. J. Antosiewicz, and M. Käll, "Superior LSPR substrates based on electromagnetic decoupling for on-a-chip high-throughput label-free biosensing," Light: Science & Applications 6, e17042-e17042 (2017).
    64. J. Li, C. Chen, L. Lagae, and P. Van Dorpe, "Nanoplasmonic Sensors with Various Photonic Coupling Effects for Detecting Different Targets," The Journal of Physical Chemistry C 119, 29116-29122 (2015).
    65. Y. S. Lee and A. Dutta, "MicroRNAs in Cancer," Annual Review of Pathology: Mechanisms of Disease 4, 199-227 (2009).
    66. Y. Peng and C. M. Croce, "The role of MicroRNAs in human cancer," Signal Transduct Target Ther 1, 15004-15004 (2016).
    67. V. B. Lokeshwar, C. Öbek, M. S. Soloway, and N. L. Block, "Tumor-associated Hyaluronic Acid: A New Sensitive and Specific Urine Marker for Bladder Cancer," Cancer Research 57, 773-777 (1997).
    68. M. Medina-Sánchez, B. Ibarlucea, N. Pérez, D. D. Karnaushenko, S. M. Weiz, L. Baraban, G. Cuniberti, and O. G. Schmidt, "High-Performance Three-Dimensional Tubular Nanomembrane Sensor for DNA Detection," Nano Letters 16, 4288-4296 (2016).
    69. D. Y. Petrovykh, H. Kimura-Suda, M. J. Tarlov, and L. J. Whitman, "Quantitative Characterization of DNA Films by X-ray Photoelectron Spectroscopy," Langmuir 20, 429-440 (2004).
    70. O. H. Orasan, G. Ciulei, A. Cozma, M. Sava, and D. L. Dumitrascu, "Hyaluronic acid as a biomarker of fibrosis in chronic liver diseases of different etiologies," Clujul Med 89, 24-31 (2016).
    71. Y. Zhou, X. Li, X. Ren, L. Yang, and J. Liu, "Designing and fabricating double resonance substrate with metallic nanoparticles-metallic grating coupling system for highly intensified surface-enhanced Raman spectroscopy," Analyst 139, 4799-4805 (2014).
    72. T. G. Souza, V. S. Ciminelli, and N. D. S. Mohallem, "A comparison of TEM and DLS methods to characterize size distribution of ceramic nanoparticles," in Journal of physics: conference series, (IOP Publishing, 2016), 012039.
    73. L. Zhang, D. Hu, M. Salmain, B. Liedberg, and S. Boujday, "Direct quantification of surface coverage of antibody in IgG-Gold nanoparticles conjugates," Talanta 204, 875-881 (2019).

    下載圖示
    2026-09-23公開
    QR CODE