Surface-enhanced Raman spectroscopy (SERS) has demonstrated potential for various biomedical applications. However, when these sensors/substrates are exposed for analysis of complex biological fluids, their sensitivity is gradually decreased due to fouling of proteins on the plasmonic substrates, leading to hotspot blockade. To overcome this limitation, immense efforts have been devoted in recent times to develop stealth SERS substrates to maintain sensing capabilities in clinical samples. Two important methods have been proposed for developing stealth SERS with the use of zwitterionic molecules and nanoshearing force. These stealth modification strategies help reduce the background noise and enhance the sensing capability with their antifouling features for point-of-care-testing (POCT). Additionally, we have highlighted some of the recent SERS developments that demonstrate reliable stealth and sensitivity when employed for diagnosis or personalized treatment. Herein, we concisely review and discuss the future of SERS for investigations in complex clinical samples.

表面增强拉曼光谱（SERS）已显示出在各种生物医学应用中的潜力。但是，当这些传感器/底物暴露出来以分析复杂的生物流体时，由于等离子底物上蛋白质的结垢，其灵敏度逐渐降低，从而导致了热点阻塞。为了克服该限制，近来已付出巨大努力来开发隐形SERS基底以维持临床样品中的传感能力。已经提出了使用两性离子分子和纳米剪切力来开发隐形SERS的两种重要方法。这些隐身修改策略通过即时检验（POCT）的防污功能，有助于降低背景噪声并增强感应能力。另外，我们重点介绍了SERS的最新发展，这些新技术在用于诊断或个性化治疗时表现出可靠的隐身性和敏感性。在这里，我们简要地回顾和讨论SERS在复杂临床样品中研究的未来。