在複雜生物環境中，生物分子會貼附在不具抗生物沾黏能力的材料表面，若生物分子貼附於表面增強拉曼散射(surface-enhanced Raman scattering, SERS)基板上，則會使SERS基板的熱點區域(hot spot zone)失去活性，因此本研究使用雙離子共聚高分子作為抗生物沾黏層以保護SERS基板的熱點區域，並於人類血清中進行孔雀綠分子的拉曼訊號量測。
本研究包含兩個部分，第一部分合成聚(甲基丙烯酸縮水甘油酯-甲基丙烯酸硫代甜菜鹼)雙離子共聚高分子、銀奈米立方體粒子與製備銀基板，並組裝成雙離子共聚高分子激活之SERS基板，接著進行相關的性質分析。由紫外光/可見光光譜分析得知以不同高分子濃度接枝後，會使SERS基板的表面電漿共振波長產生位移，進而影響SERS基板的增顯能力。由酵素連結免疫吸附測試可知以雙離子共聚高分子修飾後的SERS基板，其Fibrinogen蛋白質相對吸附量皆明顯降低。
第二部分使用已製備的雙離子共聚高分子激活之SERS基板在視為無生物分子干擾環境的磷酸鹽緩衝生理食鹽水(phosphate buffered saline, PBS)以及複雜生物分子環境的人類血清(platelet-rich plasma, PRP)中進行孔雀綠的拉曼訊號偵測，並以未修飾之SERS基板作為對照組。藉由分析PBS環境中孔雀綠拉曼強度對測量時間的趨勢可知高分子層有助於孔雀綠分子的吸附，於是隨著時間的增加其拉曼強度也隨之增強，等到高分子層中的孔雀綠分子達飽和吸附時其拉曼強度開始維持定值；由PRP環境中的實驗結果可知未修飾之SERS基板無法獲得明顯的孔雀綠拉曼訊號，然而以雙離子共聚高分子激活之SERS基板因為有抗生物沾黏層的保護，於是在持續測量2小時內皆可獲得穩定的孔雀綠拉曼訊號，其中5 mg/ml之SERS基板顯現出較穩定的性能。
本研究成功地使用雙離子共聚高分子激活在人類血清中的SERS基板，並克服蛋白質與血小板等生物分子貼附現象對於SERS基板增顯能力的影響，達成於體外人類血清中孔雀綠之拉曼訊號偵測。

Surface-enhanced Raman scattering (SERS) substrates with hot spots generating from large-scale massive nanogaps between silver nanocubes and the silver film via 1, 2-ethanedithiol monolayer as a linkage are fabricated. In complex biological media such as human blood serum, Raman signals can be greatly interfered by biological substance adsorption which impedes analyte molecules and generates background noise. Therefore, the hydrophilic zwitterionic copolymers, poly(glycidyl methacrylate)-r-poly(sulfobetaine methacrylate), PGMA-r-PSBMA is synthesized and grafted-onto the as-prepared SERS substrates. The sulfobetaine headgroup of zwitterionic copolymers can bind water molecules, and thus resist biological adsorption. The zwitterionic copolymers activating SERS substrates are used to detect the Raman signals of malachite green (MG) in phosphate buffered saline (PBS) and human blood serum (platelet-rich plasma, PRP) solution, compared with the unmodified SERS substrates. UV-Vis analysis shows that the zwitterionic copolymers can make the surface plasmon resonance (SPR) wavelength of the SERS substrates shift. ELISA analysis shows that zwitterionic copolymers can effectively reduce relative fibrinogen adsorption. For Raman detection of MG in PBS solution, its intensity increases with time and then reaches stable because MG molecules adsorbed on the zwitterionic copolymer layer gradually become saturated. For Raman detection of MG in PRP, the SERS substrates without anti-fouling property fail to detect MG Raman signals. By grafting zwitterionic copolymer layer, the SERS substrates can resist the nonspecific adsorption of biomolecules of PRP and detect MG Raman signals for at least 2 hours, showing excellent detection ability and better life time in complex biological media.

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