Li Yuzhu, Ding Zhongxiang, Wang Hongyan, Qu Cheng, Li Guangping, Liu Honglin
Anhui Provincial International Science and Technology Cooperation Base for Major Metabolic Diseases and Nutritional Interventions, China Light Industry Key Laboratory of Meat Microbial Control and Utilization, School of Food and Biological Engineering, Engineering Research Center of Bio-process, Ministry of Education, Hefei University of Technology, Hefei 230601, P. R. China.
Department of Radiation Oncology, The First Affiliated Hospital of Anhui Medical University, Hefei 230022, China.
Anal Chem. 2025 Feb 18;97(6):3579-3588. doi: 10.1021/acs.analchem.4c05999. Epub 2025 Feb 5.
In clinical diagnostics, human breath presents an alternative and more convenient sample than biofluids for detecting the ingestion of nonvolatile drugs. Surface-enhanced Raman spectroscopy (SERS) is a powerful vibrational spectroscopy technique with high sensitivity based on molecular fingerprinting. However, the low affinity of traditional SERS substrates for aerosols and the stochastic fluctuation of the SERS signal at low concentrations limit their application in breath aerosol analysis. In this study, we synthesized hydrogel microsphere SERS substrates with highly reversible swelling/shrinking properties that enhance target analyte accumulation in breath aerosols and promote plasmonic nanoparticle aggregation for intense Raman hotspot formation. Furthermore, these hydrogel microsphere SERS substrates function as a three-in-one system, enabling multilevel selectivity based on size, charge, and hydrophilicity for target molecules simultaneously without pretreatment. Notably, by "digitizing" the SERS signal of each individual hydrogel microsphere and calculating the proportion of positive microspheres, the hydrogel microspheres can serve as a digital SERS platform that circumvents the low stability issues resulting from fluctuations in SERS signal intensity. Consequently, the digital SERS platform achieved a detection limit of 0.5 ppm for fentanyl in simulated breath aerosols. This innovative sensing strategy not only demonstrates a promising approach for screening nonvolatile drugs but also simplifies the sampling process, holding great potential for clinical diagnosis of breath aerosols.
在临床诊断中，与生物流体相比，人体呼出气体是一种用于检测非挥发性药物摄入情况的更便捷的替代样本。表面增强拉曼光谱（SERS）是一种基于分子指纹识别的具有高灵敏度的强大振动光谱技术。然而，传统SERS底物对气溶胶的低亲和力以及低浓度下SERS信号的随机波动限制了它们在呼气气溶胶分析中的应用。在本研究中，我们合成了具有高度可逆溶胀/收缩特性的水凝胶微球SERS底物，其可增强目标分析物在呼气气溶胶中的积累，并促进等离子体纳米颗粒聚集以形成强烈的拉曼热点。此外，这些水凝胶微球SERS底物作为一个三合一系统，无需预处理即可同时基于尺寸、电荷和亲水性对目标分子实现多级选择性。值得注意的是，通过“数字化”每个单独水凝胶微球的SERS信号并计算阳性微球的比例，水凝胶微球可作为一个数字SERS平台，规避了因SERS信号强度波动而导致的低稳定性问题。因此，该数字SERS平台在模拟呼气气溶胶中对芬太尼的检测限达到了0.5 ppm。这种创新的传感策略不仅展示了一种用于筛查非挥发性药物的有前景的方法，还简化了采样过程，在呼气气溶胶的临床诊断中具有巨大潜力。
