Department of Chemistry and Chemical Biology, Indiana University-Purdue University Indianapolis, 402 N. Blackford Street, Indianapolis 46202, Indiana, United States.
Integrated Nanosystems Development Institute, Indiana University-Purdue University Indianapolis 46202, Indiana, United States.
Anal Chem. 2021 Feb 2;93(4):2578-2588. doi: 10.1021/acs.analchem.0c04643. Epub 2021 Jan 12.
Surface-enhanced Raman scattering (SERS) is an ultrasensitive analytical technique, which is capable of providing high specificity; thus, it can be used for toxicological drug assay (detection and quantification). However, SERS-based drug analysis directly in human biofluids requires mitigation of fouling and nonspecificity effects that commonly appeared from unwanted adsorption of endogenous biomolecules present in biofluids (e.g., blood plasma and serum) onto the SERS substrate. Here, we report a bottom-up fabrication strategy to prepare ultrasensitive SERS substrates, first, by functionalizing chemically synthesized gold triangular nanoprisms (Au TNPs) with poly(ethylene glycol)-thiolate in the solid state to avoid protein fouling and second, by generating flexible plasmonic patches to enhance SERS sensitivity via the formation of high-intensity electromagnetic hot spots. Poly(ethylene glycol)-thiolate-functionalized Au TNPs in the form of flexible plasmonic patches show a twofold-improved signal-to-noise ratio in comparison to triethylamine (TEA)-passivated Au TNPs. Furthermore, the plasmonic patch displays a SERS enhancement factor of 4.5 ×10. Utilizing the Langmuir adsorption model, we determine the adsorption constant of drugs for two different surface ligands and observe that the drug molecules display stronger affinity for poly(ethylene glycol) ligands than TEA. Our density functional theory calculations unequivocally support the interaction between drug molecules and poly(ethylene glycol) moieties. Furthermore, the universality of the plasmonic patch for SERS-based drug detection is demonstrated for cocaine, JWH-018, and opioids (fentanyl, despropionyl fentanyl, and heroin) and binary mixture (trace amount of fentanyl in heroin) analyses. We demonstrate the applicability of flexible plasmonic patches for the selective assay of fentanyl at picogram/milliliter concentration levels from drug-of-abuse patients' blood plasma. The fentanyl concentration calculated in the patients' blood plasma from SERS analysis is in excellent agreement with the values determined using the paper spray ionization mass spectrometry technique. We believe that the flexible plasmonic patch fabrication strategy would be widely applicable to any plasmonic nanostructure for SERS-based chemical sensing for clinical toxicology and therapeutic drug monitoring.
表面增强拉曼散射（SERS）是一种超灵敏的分析技术，能够提供高特异性；因此，它可用于毒理学药物分析（检测和定量）。然而，直接在人体生物流体中进行基于 SERS 的药物分析需要减轻常见的非特异性效应和污垢效应，这些效应通常是由于生物流体（例如血浆和血清）中存在的内源性生物分子不受欢迎地吸附在 SERS 基底上而引起的。在这里，我们报告了一种自下而上的制备策略，首先通过在固态下用聚乙二醇-硫醇对化学合成的金三角纳米棱镜（Au TNPs）进行功能化，以避免蛋白质污垢，其次通过生成灵活的等离子体贴片来增强 SERS 灵敏度，通过形成高强度的电磁热点。与三乙胺（TEA）钝化的 Au TNPs 相比，形成灵活的等离子体贴片的聚乙二醇-硫醇功能化的 Au TNPs 的信号与噪声比提高了两倍。此外，等离子体贴片的 SERS 增强因子为 4.5×10。利用朗缪尔吸附模型，我们确定了两种不同表面配体的药物的吸附常数，并观察到药物分子对聚乙二醇配体的亲和力强于 TEA。我们的密度泛函理论计算明确支持药物分子与聚乙二醇部分之间的相互作用。此外，还证明了等离子体贴片在可卡因、JWH-018 和阿片类药物（芬太尼、去丙氧芬太尼和海洛因）以及二元混合物（海洛因中痕量芬太尼）分析中用于基于 SERS 的药物检测的通用性。我们证明了从药物滥用患者的血浆中以皮克/毫升浓度水平选择性检测芬太尼的柔性等离子体贴片的适用性。从 SERS 分析中计算出的患者血浆中的芬太尼浓度与使用纸喷雾电离质谱技术确定的值非常吻合。我们相信，灵活的等离子体贴片制造策略将广泛适用于任何基于 SERS 的化学传感的等离子体纳米结构，用于临床毒理学和治疗药物监测。
