病毒感染是導致人類發病和死亡的主要原因之一，在臨床診斷領域上，精確且快速診斷病原體的方式一直為學術研究之重要方向，而利用表面電漿共振現象之技術發展逐漸受人矚目，其中表面拉曼增顯散射技術已逐漸成熟並運用於致病物種之檢測，透過具電漿子效應的材料所構成的奈米結構產生震盪耦合，在有效距離內能產生局域表面電漿共振(LSPR)的位置稱為熱點(hot spot)，而目前多數研究皆致力於將熱點的分布最佳化以產生更強的SERS 效應。本研究係以本實驗室先前研究之熱區聚集放大(collective amplification)試片為基礎，以三種尺寸之自組裝單層聚苯乙烯微球作為犧牲輔助模板，利用溶膠-凝膠法製備ZrO2 介電層，經熱處理後形成奈米碗型陣列的結構，並藉熱蒸鍍製備金奈米粒子於有序多孔的ZrO2 中，形成Au/pZrO2 (150), Au/pZrO2 (250)和Au/pZrO2 (350)三種孔徑大小的SERS 基板，利用多孔結構的凹面性質使得入射雷射光散射與表面電磁場互相疊加，進而增顯待測物質之拉曼訊號。
本研究以R6G 及DTNB 兩種分子探針進行基板效能評估，確認以奈米金顆粒結合ZrO2 孔洞陣列結構作為SERS 活性基板的可行性，其中以Au/pZrO2 (250)增顯效果最佳，EF 值最高分別可以達4.3 × 10^7 及1.3 × 10^7；有序陣列的結構得以使量測具有良好的重複性(RSD < 15%)，Au/pZrO2 (x)基板的SERS 增顯效來自於金奈米粒子間產生的熱點效應，加上金屬與ZrO2 層的交界面電荷轉移而產生的電磁增顯效應；此外，也利用了Au/pZrO2 (x)針對實驗室培養的偽病毒及A 型流感病毒進行拉曼光譜測定，透過來自病毒外膜結構所得之色胺酸及蛋白質訊號，得到特徵光譜並對病毒進行定性描述。藉由所設計的奈米孔洞陣列基板對不同分子探針及病毒的量測，探討奈米結構與待測物尺寸間的對應關係；此外也透過混合病毒的光譜量測探討基板對於個別病毒的鑑別力，以期對於建立病毒之拉曼光譜資料庫並應用於未來醫療檢測能有所幫助。

Surface-enhanced Raman spectroscopy (SERS) has shown great potential in the sensitive and rapid detection of various molecules including viruses, through the identification of characteristic peaks of their outer membrane proteins. In this study, Au nanoparticles upon three differently sized ZrO2 nanopores (Au/pZrO2) were tested and used as SERS-active substrates in detecting SARS-CoV-2 S pseudovirus, VSV-G (vesicular stomatitis virus G) pseudovirus, and influenza A viruses to demonstrate their virus detection capability. The substrates were then verified by examining the repetition of measurement, reproducibility, and detection limit. Due to the difference in pore size and depth of the substrates, the characteristic peaks of pseudoviruses and influenza A viruses in the obtained Raman spectra vary. Besides, Au/pZrO2 (250) also showed the effectiveness of distinguishing between two viruses under mixed conditions. Due to competitive adsorption, an unequal reduction in peak intensity ratios under mixed conditions was observed. Based on the experimental results, SERS mechanism to detect virus is proposed. There were three factors that contribute to the SERS effect in Au/pZrO2 (x): EM effect (Au nanoparticles), geometrical effect (pore structure) and CT effect between ZrO2 and Au nanoparticles. The formation of hot spots brought by the synergistic integration effect among substrate, analyte, and laser induction may result differences in the obtained SERS spectra.

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