醫學領域上精確且快速之診斷感染疾病方式一直以來為研究之重要方向，而利用表面電漿共振(SPR)現象之技術發展越來越受人矚目，特別是表面增顯拉曼散射(SERS)之應用逐漸成熟並開始運用在致病物種之檢測，現今SERS領域上開始發展利用具微奈米結構修飾之SERS效應基板方式來增強待測物訊號，並解決傳統以奈米粒子膠體溶液增顯會有再現性不足之問題。本研究利用聚焦離子束(FIB)方式在鍍金基材表面上直接進行微奈米結構陣列之製作來排除化學微影製程之化學汙染與步驟繁瑣費時之缺點，並藉由聚焦離子束可程式化精準製作出微奈米即結構之特色製作出不同特性之微奈米結構，來對影響SERS之結構上的幾何參數進行靈敏度之探討。研究中，先利用FIB製作出不同尺寸、間距與幾何形狀之微奈米結構陣列，且利用羅丹明6G(R6G)分子探針進行利用微拉曼光譜儀進行SERS效應之檢測與評估，結果顯示對於結構尺寸從300, 250 , 200和150 nm縮小時，150 nm尺寸大小之位於檢測區內結構數越多相對增加熱區之範圍使得訊號增強，而結構彼此間距從83, 58 ,45, 31, 26減少至22 nm時，結構間越近會引發熱區(hot spot)來提升電磁效應之貢獻使訊號增強；當變化微結構本身形狀所引發之避雷針效應(lightning rod effect)也會加強電磁效應使SERS效果加強，研究中具最多邊角之六邊形有較佳之SERS效果；在幾何參數之變化下，對其SERS之影響程度也有所差異，SERS之靈敏度為改變結構間距遠近較高，其次為形狀，而結構尺寸影響程度較小。利用所製作之SERS效應基板進行A型流行性感冒H1N1亞型病毒作拉曼光譜之檢測，得到胺基酸如苯丙胺酸與色胺酸以及蛋白質之資訊，推測訊號來自病毒外層包膜之蛋白質等結構，顯示以SERS效應基板方式能有效檢測出致病物種，達到快速精確檢測之目的。

The study of rapid and accurate diagnosis is of infectious diseases important in the medical field. The development of techniques using surface plasmon resonance (SPR) has become popular and has been applied in the detection of pathogens. Especially the application of surface enhanced Raman scattering (SERS) grows up and begins to be used for the detection of pathogens. Compared with traditional nanoparticles, micro/nanostructures on specific substrate have potentials to be used as SERS-active substrates, which are used to enhance the signal of species. In this study, we used focused ion beam (FIB) to fabricate micro/nanostructures array on the Au film directly to avoid chemical pollution and save time. Besides, several parameters, such as dimension and space were also designed to study their effects on SERS. Finally, this SERS-active substrate was used to diagnose viruses.
In this study, the micro/nanostructure with different dimensions, space and geometry (shape) in array were fabricated by FIB. Moreover R6G as a molecular probe was chosen to estimate the effect of SERS. Based on the results, it indicated higher intensity appeared as dimension and space were decreased because of more hot spot areas. In addition, we also found lightning rod effect induced by varying geometry of micro/nanostructure can also raise EM effect to enhance the signal. Taken together, SERS was affected by space, followed by geometry and finally by dimension.
In the end of the study, we tried to detect the Raman spectra of influenza A virus WSN/33 (H1N1) through our SERS-active substrate. Raman spectra revealed the information of amino acids, phenylalanine and tryptophan, and proteins, indicated the information come from envelope and matrix proteins of virus. It was proved to be a new diagnostic method that is much sensitive and simple and able to detect viruses.

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