Highly sensitive and reliable detection of microRNA for clinically disease surveillance using SERS biosensor integrated with catalytic hairpin assembly amplification technology
Highly sensitive and reliable detection of microRNA for clinically disease surveillance using SERS biosensor integrated with catalytic hairpin assembly amplification technology
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DOI：
10.1016/j.bios.2022.114236
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发表时间：
2022-04-02
影响因子：
12.6
通讯作者：
Feng，Shangyuan
中科院分区：
文献类型：
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作者：
Weng，Shuyun;Lin，Duo;Feng，Shangyuan
microRNA（miRNAs）在多种疾病中发挥着重要的调控作用，尤其是作为一类有希望的肿瘤诊断和预后的生物标志物。本研究基于表面增强拉曼光谱（Sers）结合催化发夹组装（CHA）扩增技术，构建了一种用于乳腺癌血清中miRNA-21和miRNA-155超灵敏检测的生物传感器。通过使用CHA策略，可以通过与数千个发夹探针的再杂交来触发扩增循环，从而显著扩增人血清中极低浓度的目标microRNA。此外，通过二维Au-Si基底与上层Ag@4-MBA@Au核壳纳米粒子的连接，构建了具有多热点和信号自校准的夹心Sers传感芯片。使用这种专门设计的生物传感平台，对于miRNA-21和miRNA-155的检测，可以分别实现0.398 fM和0.215 fM的低检测限，动态范围从1 fM到10 nM。此外，对血清样本中这两种miRNA的分析能够以100%的准确度将乳腺癌受试者与正常受试者区分开来，并可能评估乳腺癌的分子类型和预后。这些结果表明，提出的Sers与CHA技术将是一种替代方法，用于高灵敏度和可靠的检测有助于乳腺癌诊断和预后的miRNA生物标志物。
MicroRNAs (miRNAs) play an important regulatory role in several diseases, especially as a class of promising biomarkers for cancer diagnosis and prognosis. Here, a biosensor based on surface enhanced Raman spectroscopy (SERS) combined with catalytic hairpin assembly (CHA) amplification technology was developed for ultra-sensitive detection of miRNA-21 and miRNA-155 in breast cancer serum. By using CHA strategy, the extremely low concentration of target microRNA in human serum can be significantly amplified through the re-hybridization with thousands of hairpin probes to trigger amplification cycles. Besides, a sandwich SERS sensing chip with numerous hot spots and signal self-calibration was built through the linkage between two-dimensional Au–Si substrate and upper Ag@4-MBA@Au core-shell nanoparticles. Using this specially-designed biosensing platform, a low detection limit of 0.398 fM and 0.215 fM with a dynamic range from 1 fM to 10 nM can be achieved for the detection of miRNA-21 and miRNA-155, respectively. Additionally, the analysis of these two miRNAs in serum samples is capable of identifying the breast cancer subjects from normal ones with 100% of accuracy, as well as potentially evaluating the molecular types and prognosis for breast cancer. These results demonstrate that the proposed SERS with CHA technology would be an alternative method for highly sensitive and reliable detection of miRNA biomarkers contributing to breast cancer diagnosis and prognosis.