奈米壓痕技術(Nanoindentation)是一種有效的方法應用於表面增顯拉曼散射(Surface-Enhanced Raman Scattering, SERS)，此技術可以製作出較深的角錐之圖形表面，基板製備參數容易調整，本論文使用一種簡單的物理性的奈米壓痕技術，在金薄膜表面製作出奈米壓痕金孔洞陣列基板(triangular Au nano-cavities arrayed, nAu)。在先前研究中，以單分子層 2-巰基-5-硝基苯甲酸(2-nitro-5-thiobenzoic acid, NTB)實驗發現以633 nm波長之拉曼雷射最具有拉曼增顯效果，並且在檢測病毒上面確認到不同尺寸病毒對應最適合的壓痕深度才能夠產生最佳增顯效果。
本論文將接續先前研究，以造成全球大流行之呼吸道感染新型冠狀病毒(Severe acute respiratory syndrome coronavirus 2, SARS-CoV-2)與兩種A型流行性感冒病毒(H1N1、H3N2)作為檢測標的，製作適合病毒大小的nAu基板來檢測病毒。探討壓痕深度為90 nm、120 nm及140 nm這三種基板之效能，經過R6G作為分子探針評估增顯因子(enhancement factor, EF)均可達106。
以三種nAu基板檢測SARS-CoV-2-S pseudovirus及VSV-G pseudovirus分析其SARS-CoV-2 S蛋白之光譜作為檢測SARS-CoV-2病毒參考。並檢測SARS-CoV-2及A型流感病毒及三種SARS-CoV-2 (B.1.1.7、B.1.1、A.3)，分析結果顯示，以nAu基板檢測病毒SERS圖譜訊號範圍在800 ~1800 cm-1 之間，大部分為胺基酸的特徵鋒。我們以nAu基板偵測其SERS圖譜可以區分3種不同SARS-CoV-2病毒，其中B.1.1.7濃度至105 copies/mL也可以被檢測出。並且以SARS-CoV-2-S pseudovirus及兩種A型流感病毒進行雙病毒混和分析，SERS光譜上的特徵鋒亦在特定的區域。因此，以nAu SERS-active基板作為無標記檢測平台能夠快速確認SARS-CoV-2與流感病毒株，有潛力作為體外病毒檢測之工具。

The current pandemic urges the extremely sensitive and prompt detection of SARS-CoV-2 virus and influenza A virus. In this study, we present a inverted triangular Au nano-cavities arrayed (nAu) nanostructure as an extremely sensitive Surface-Enhanced Raman Scattering biosensor. Through the induction of the electromagnetic effect with various indentation depths (Dv) by the substrate, the virus can be distinguished from the amino acids on its surface. The nAu substrate was evaluated using rhodamine 6G (R6G) as a probe molecule at low concentration, and the enhancement factor (EF) reaching 5.5×107. SERS spectra of S protein of SARS-CoV-2 were obtained by SERS spectra of SARS-CoV-2 pseudovirus and VSV-G pseudovirus. Multiple detection of SARS-CoV-2 pseudovirus and influenza A virus were also demonstrated with characteristic peaks of individual viruses. In addition, analysis of the Raman spectra of SARS-CoV-2 viruses (A.3, B.1.1 and B.1.1.7) of three lineages, in addition to the characteristic peaks of the S protein exhibited by the SARS-CoV-2 pseudovirus, also obtained Other characteristic peaks and subtle changes in spectra of different ancestry are observed. The detectable concentration for SARS-CoV-2 is 105 copies/ml. The nAu substrate has thus demonstrated a high potential in the fast-screening detection of viruses.

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