A terahertz metamaterial biosensor for sensitive detection of microRNAs based on gold-nanoparticles and strand displacement amplification
A terahertz metamaterial biosensor for sensitive detection of microRNAs based on gold-nanoparticles and strand displacement amplification
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基于金纳米颗粒和链位移放大的太赫兹超材料生物传感器，用于灵敏检测 microRNA
DOI：
10.1016/j.bios.2020.112874
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发表时间：
2021-01-04
影响因子：
12.6
通讯作者：
Fu, Weiling
中科院分区：
文献类型：
--
作者：
Yang, Ke;Li, Jining;Fu, Weiling
太赫兹（THz）光谱引起了核酸功能和构象研究的极大兴趣，但其固有的敏感性阻碍了潜在的生物传感应用。在此，开发了一种新型太赫兹生物传感器，用于检测基于超材料、纳米颗粒和链位移放大 (SDA) 的 microRNA (miRNA) 样品。在此方法中，SDA 反应放大目标 miRNA 并产生大量的次级 DNA 分子（触发 DNA），随后将其与金属纳米颗粒缀合，形成纳米颗粒-触发 DNA 复合物。当这些复合物与大折射率金属纳米粒子（如金）连接时，会产生显着的超材料频移。通过实验和理论研究了超材料共振对纳米颗粒直径和金属类型的依赖性。在最佳条件下，太赫兹超材料生物传感器具有良好的检测灵敏度，检测限为14.54 aM，并且在1 fM至10 pM的浓度范围内对miRNA-21表现出线性响应。通过测量加标临床血清样品中的 miRNA-21，样品回收率确定在 90.92% 至 107.01% 之间。这些发现表明，新型太赫兹生物传感器具有高灵敏度 miRNA 检测的能力，在核酸分析和癌症诊断方面具有值得注意的潜在应用。
Terahertz (THz) spectroscopy has drawn great interest for the functional and conformational investigations of nucleic acids, but its intrinsic sensitivity hinders potential bio-sensing applications. Here, a novel THz biosensor was developed for detecting microRNA (miRNA) samples based on metamaterials coupled with nanoparticles and strand displacement amplification (SDA). In this method, the SDA reaction amplifies the target miRNA and generates copious yields of secondary DNA molecules (Trigger DNA), which are subsequently conjugated to metallic nanoparticles that form nanoparticle-Trigger DNA complexes. These complexes produce remarkable frequency shifts of metamaterials when linked to a large refractive index metallic nanoparticle like Au. The dependence of the metamaterial resonance on the nanoparticle diameter and metal type was investigated experimentally and theoretically. Under optimal conditions, the THz metamaterial biosensor presents good detection sensitivity with a limit of detection of 14.54 aM and exhibits a linear response for miRNA-21 at a concentration range from 1 fM to 10 pM. By measuring the miRNA-21 in spiked clinical serum samples, the sample recoveries were determined to be in the range between 90.92% and 107.01%. These findings demonstrate that the novel THz biosensor offers the capability for highly sensitive miRNA detection, with noteworthy potential applications in nucleic acid analysis and cancer diagnosis.