蛋白質的瓜胺酸化與人類許多的疾病息息相關，例如: 炎症、自體免疫性疾病、神經退化性疾病和癌症等，因為被瓜胺酸化後，蛋白質的結構和電性都會出現變化，導致失去原本的功能和與其他分子的交互作用，甚至影響到周圍的蛋白質或是細胞，也因此瓜胺酸化蛋白質的變化對於許多的疾病都具有做為診斷指標或治療標靶的潛力，但是目前對於瓜胺酸化蛋白質在各種疾病之中的所扮演的角色和實際的作用都尚未釐清，針對它的檢測技術如果要被應用到臨床醫學的檢測上也仍有不足，因此為了更精準的分析瓜胺酸化蛋白質分子以利了解與疾病之間的關聯，檢測方法的優化也勢在必行。現今瓜胺酸化蛋白質的檢測方式主要有試劑顯色法、利用抗體捕捉瓜胺酸化蛋白質的檢測法以及螢光化學探針，但這些方法都有各自的優缺點和侷限性。
表面增強拉曼散射(Surface-enhanced Raman Scattering, SERS)是現今被廣泛應用在各個領域的分析檢測方法，有著高靈敏度、量測方式簡便、檢測快速等優點。在使用實驗室團隊所開發的具有單層金奈米粒子的奈米柱陣列SERS基板量測不同濃度的羅丹明-苯乙二醛(Rhodamine-phenylglyoxal, Rh-PG)分子後，確認Rh-PG具有自身特定的拉曼光譜，因此能夠做為SERS標籤使用拉曼光譜量測的方式進行觀察。本研究利用Rh-PG作為瓜胺酸化蛋白質的SERS標籤與本實驗室團隊製作出的SERS基板配合，使用修飾在結構表面的抗體捕捉已經與Rh-PG反應了的瓜胺酸化組蛋白H3(Citrullinated Histone H3, CitH3)，而後量測SERS結構上Rh-PG的拉曼光譜的訊號來檢測被捕捉到的CitH3。根據得到的光譜顯示，Rh-PG的拉曼訊號強度確實會隨著瓜胺酸化蛋白質的濃度而改變，能夠檢測到的量測極限濃度為2.18×10^-8 g/ml，在將訊號強度和CitH3的濃度做出關係圖以及線性回歸分析後，能夠得到相關係數(R^2)為0.995，此外也使用非瓜胺酸化的組蛋白(Histone H3)進行測試，從而確認了Rh-PG和檢測方法針對瓜胺酸胺基酸的專一性。綜上所述，使用SERS結構捕捉瓜胺酸化蛋白質並量測與其結合的Rh-PG的SERS訊號強度是能夠用於檢測蛋白質瓜胺酸化的方法，也是具有專一性以及定量分析能力的檢測方法。

In this study, we using rhodamine−phenylglyoxal (Rh−PG), a citrulline-specific chemical probe, as a Surface-enhanced Raman scattering (SERS) tag combined with Raman measurement to detect citrullinated Histones H3 (CitH3). We used photoreduction to growing gold nanoparticle (AuNP) monolayers uniformly on SU-8 nanopillars array patterned by nanoimprint as SERS substrate [1]. The SERS structure of the modified antibody will capture the citrullinated protein previously bound to Rh-PG, and then observe the concentration of citrullinated protein based on the measurement results of the Raman spectrum. The detection limit of CitH3 can be reduced to 2.18×10^−8 g/ml. Perform linear regression analysis on the logarithm of CitH3 concentration and the SERS intensity of Raman shift 1357cm^-1 peak, and can obtain the correlation coefficient R^2 as 0.995, indicating that quantitative analysis is possible. Compared with other citrullination detection methods, our detection method has lower cost, faster detection speed, strong specificity and ability of quantitative analysis.

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