Surface-enhanced Raman scattering (SERS) is a powerful analytic tool that can provide information of molecular structures and composition of analytes. The application of SERS for ultrasensitive detection of chemical and biological molecules has attracted particular interests in recent years. Here, a novel type of three-dimensional SERS substrate with uniform hierarchical nanoflower structures was fabricated by growing dense ZnO nanowires (ZnO NWs) on ordered vertically aligned Si nanorods (Si NRs) through a chemical hydrothermal (HT) method. After being decorated with Ag nanoparticles (Ag NPs), such branched nanostructure exhibits greatly improved SERS signals with a detection limit of Rhodamine 6 G (R6 G) down to 1 pM and an excellent uniformity (relative standard deviation lowered to about 6%). Furthermore, this SERS-active substrate is successfully applied to investigate the aggregation status of human islet amyloid polypeptides (hIAPP). The structural change of amyloid aggregates can be detected from SERS spectra at a single aggregate level, providing useful information for the prevention and treatment of protein conformation diseases. Therefore, our studies not only demonstrate a promising type of SERS substrates for highly uniform, reproducible and ultrasensitive molecular detection, but also suggest a potential method for label-free detection on conformation change of amyloid peptides in aggregation process.

表面增强拉曼散射（SERS）是一种功能强大的分析工具，可以提供分子结构和分析物组成的信息。近年来，SERS在化学和生物分子超灵敏检测中的应用引起了特别的兴趣。在这里，通过化学水热（HT）方法在有序的垂直排列的硅纳米棒（Si NRs）上生长致密的ZnO纳米线（ZnO NWs），制造出具有均匀的多层纳米花结构的新型三维SERS衬底。用Ag纳米颗粒（Ag NPs）修饰后，这种分支的纳米结构显示出极大改善的SERS信号，若丹明6 G（R6 G）的检出限低至1 pM，并且具有出色的均匀性（相对标准偏差降低至6％）。此外，该SERS活性底物已成功应用于研究人胰岛淀粉样多肽（hIAPP）的聚集状态。淀粉样蛋白聚集体的结构变化可以在单个聚集体水平上从SERS光谱中检测到，为蛋白质构象疾病的预防和治疗提供有用的信息。因此，我们的研究不仅证明了用于高度均匀，可重现和超灵敏分子检测的SERS底物类型，而且还提出了一种潜在的方法，可用于在聚集过程中对淀粉样肽的构象变化进行无标记检测。为预防和治疗蛋白质构象疾病提供有用的信息。因此，我们的研究不仅证明了用于高度均匀，可重现和超灵敏分子检测的SERS底物类型，而且还提出了一种潜在的方法，可用于在聚集过程中对淀粉样肽的构象变化进行无标记检测。为预防和治疗蛋白质构象疾病提供有用的信息。因此，我们的研究不仅证明了用于高度均匀，可重现和超灵敏分子检测的SERS底物类型，而且还提出了一种潜在的方法，可用于在聚集过程中对淀粉样肽的构象变化进行无标记检测。