Surface-enhanced Raman spectroscopy (SERS) is an ultrasensitive analytical technique with molecular specificity, making it an ideal candidate for therapeutic drug monitoring (TDM). However, in critical diagnostic media including blood, nonspecific protein adsorption coupled with weak surface affinities and small Raman activities of many analytes hinder the TDM application of SERS. Here we report a hierarchical surface modification strategy, first by coating a gold surface with a self-assembled monolayer (SAM) designed to attract or probe for analytes and then by grafting a non-fouling zwitterionic polymer brush layer to effectively repel protein fouling. We demonstrate how this modification can enable TDM applications by quantitatively and dynamically measuring the concentrations of several analytes-including an anticancer drug (doxorubicin), several TDM-requiring antidepressant and anti-seizure drugs, fructose and blood pH-in undiluted plasma. This hierarchical surface chemistry is widely applicable to many analytes and provides a generalized platform for SERS-based biosensing in complex real-world media.

中文翻译：

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SERS底物的两性离子两性修饰可实现对血浆中药物的实时监控。

表面增强拉曼光谱（SERS）是具有分子特异性的超灵敏分析技术，使其成为治疗药物监测（TDM）的理想候选者。但是，在包括血液在内的关键诊断介质中，非特异性蛋白质吸附以及弱的表面亲和力和许多分析物的小拉曼活性，阻碍了SERS的TDM应用。在这里，我们报告了一种分层的表面修饰策略，首先在金表面涂上一层自组装的单层膜（SAM），该层旨在吸引或探测分析物，然后通过接枝不结垢的两性离子聚合物刷层有效地排斥蛋白结垢。我们展示了这种修饰如何通过定量和动态地测量几种分析物（包括抗癌药（阿霉素），在未稀释血浆中需要几种TDM的抗抑郁药和抗癫痫药，果糖和血液pH值。这种分层的表面化学方法广泛适用于许多分析物，并为复杂的现实世界介质中基于SERS的生物传感提供了一个通用平台。