Surface-enhanced Raman scattering (SERS) is emerging as a novel strategy for biofluid analysis. In this review, we delineate four experimental SERS protocols that are frequently used for the profiling of biofluids: 1) liquid SERS for the detection of purine metabolites; 2) iodide-modified liquid SERS for the detection of proteins; 3) dried SERS for the detection of both purine metabolites and proteins; 4) resonant Raman for the detection of carotenoids. To explain the selectivity of each experimental SERS protocol, we introduce a heuristic model for the chemisorption of analytes mediated by adsorbed ions (adions) onto the SERS substrate. Next, we show that the promising results of SERS liquid biopsy stem from the fact that the concentration levels of purine metabolites, proteins and carotenoids are informative of the cellular turnover rate, inflammation, and oxidative stress, respectively. These processes are perturbed in virtually every disease, from cancer to autoimmune maladies. Finally, we review recent SERS liquid biopsy studies and discuss future steps that are required for translating SERS in the clinical setting.

表面增强拉曼散射 (SERS) 正在成为生物流体分析的新策略。在这篇综述中，我们描述了四种常用于生物流体分析的实验性 SERS 方案：1) 用于检测嘌呤代谢物的液体 SERS；2）用于蛋白质检测的碘化物修饰的液体SERS；3) 用于检测嘌呤代谢物和蛋白质的干燥 SERS；4) 共振拉曼检测类胡萝卜素。为了解释每个实验 SERS 协议的选择性，我们引入了一个启发式模型，用于由吸附离子（adions）介导的分析物化学吸附到 SERS 基材上。接下来，我们表明 SERS 液体活检的有希望的结果源于这样一个事实，即嘌呤代谢物、蛋白质和类胡萝卜素的浓度水平可以提供细胞更新率的信息，分别是炎症和氧化应激。这些过程在几乎所有疾病中都会受到干扰，从癌症到自身免疫性疾病。最后，我们回顾了最近的 SERS 液体活检研究，并讨论了在临床环境中转化 SERS 所需的未来步骤。