Early lung cancer screening by computed tomography is hampered by pulmonary nodules caused by massive COVID‐19 infections, necessitating an ultrasensitive approach for the early diagnosis of lung cancers at the single‐base level from circular tumor DNAs (ctDNAs). This study introduces an approach that merges DNA origami and DNA scissors technologies in a framework of surface plasmon resonance (SPR) biosensors. By combining the precision of DNA origami probes with the inherent single‐base resolution of DNA scissors, this method systematically addresses the limitations of conventional SPR techniques, resulting in enhanced detection accuracy. The synergistic interplay between DNA scissors and DNA origami enables the SPR biosensors to achieve unprecedented levels of sensitivity, precision, and practical utility. This efficacy allows the precise identification of mutations, demonstrated here by detection of the T790M mutation in the EGFR gene and the G12C mutation in the KRAS gene of non‐small cell lung cancer patients. With this technique, single‐base resolution as well as near zeptomolar‐level sensitivity is achieved. As a result, this discovery holds significant potential to advance the field of precision diagnostics.

中文翻译：

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用于精确检测循环肿瘤 DNA 的超灵敏 DNA 折纸等离子体传感器

通过计算机断层扫描进行的早期肺癌筛查受到大规模 COVID-19 感染引起的肺部结节的阻碍，因此需要一种超灵敏的方法，通过环状肿瘤 DNA (ctDNA) 在单碱基水平上早期诊断肺癌。本研究介绍了一种将 DNA 折纸和 DNA 剪刀技术融合在表面等离子共振 (SPR) 生物传感器框架中的方法。通过将 DNA 折纸探针的精度与 DNA 剪刀固有的单碱基分辨率相结合，该方法系统地解决了传统 SPR 技术的局限性，从而提高了检测精度。 DNA 剪刀和 DNA 折纸之间的协同相互作用使 SPR 生物传感器能够达到前所未有的灵敏度、精度和实用性水平。这种功效可以精确识别突变，这里通过检测 T790M 突变来证明这一点。表皮生长因子受体基因和G12C突变克拉斯非小细胞肺癌患者的基因。通过这种技术，可以实现单碱基分辨率以及接近 zeptomolar 水平的灵敏度。因此，这一发现具有推动精准诊断领域发展的巨大潜力。