表面增强拉曼散射（Surface-enhanced Raman scattering, SERS）是一种新兴的光谱技术，用于检测和表征靠近等离子纳米结构的化学或生物结构。胶体、固态和可变形纳米结构广泛应用于SERS实验中以增强拉曼强度。SERS中使用的纳米结构是影响参数之一，也是一个不断发展的研究领域。希望制备简单廉价的高增强因子SERS基底。在本研究中，我们利用层层自组装方法，将天然硅藻土（生物硅）涂覆上银纳米颗粒（AgNPs），制备了具有可复制、廉价和可变形的SERS活性条，该条用于无标记识别循环癌蛋白生物标志物。制备了具有不同层数AgNP层的SERS活性条，并使用X射线衍射（XRD）、扫描电子显微镜（SEM）和紫外-可见吸收光谱技术等综合表征技术进行表征。根据与4-氨基硫酚（4-aminothiophenol, 4-ATP）和罗丹明6G（Rh6G）分子的接触来评估不同层数的SERS条的SERS活性。我们发现SERS强度强烈依赖于AgNP层数，其中具有5层AgNPs的条具有最大的SERS强度，增强因子为2.0 × 105。具有最高SERS活性的条用于无标记识别循环癌蛋白生物标志物（HER2、CA15-3、PSA、MUC4和CA27-29）。结果表明，制备的条能够有效地无标记识别循环蛋白生物标志物，并为基于SERS的无标记生物传感应用开辟了新的方向。

Surface-enhanced Raman scattering (SERS) is an emerging spectroscopy technique for detecting and characterizing chemical or biological structures in the vicinity of plasmonic nanostructures. Colloidal, solid, and flexible nanostructures are widely used in SERS experiments to enhance the Raman intensity. The nanostructure used in SERS is one of the main influencing parameters and a growing research area. Fabrication of simple and cheap SERS substrates with a high enhancement factor is desired. In this study, we fabricated a reproducible, cheap, and flexible SERS active strip by coating natural diatomite (biosilica) with silver nanoparticles (AgNPs) using the layer-by-layer assembly method and the fabricated strip is used for the label-free identification of circulating cancer protein biomarkers. SERS active strips were fabricated having different numbers of AgNP layers on natural diatomite and comprehensive characterization techniques such as X-ray diffraction (XRD), scanning electron microscopy (SEM), and UV/vis absorption spectrophotometry were used. SERS activities of the strips depending on the number of layers were evaluated using 4-aminothiophenol (4-ATP) and rhodamine 6G (Rh6G) molecules. We found that the SERS intensity is strongly dependent on the number of AgNP layers, with the maximum SERS intensity obtained from the strip with 5 layers of AgNPs, having a 2.0 × 105 enhancement factor. The strip with the highest SERS activity was used for the label-free identification of circulating cancer protein biomarkers (HER2, CA15-3, PSA, MUC4, and CA27-29). The results demonstrate that the fabricated strip can help in the effective label-free identification of circulating protein biomarkers and open new directions for SERS-based label-free biosensing applications.