Achieving sensitive detection and accurate identification of cancer cells is vital for diagnosing and treating the disease. Here, we developed a logic signal amplification system using DNA tetrahedron-mediated three-dimensional (3D) DNA nanonetworks for sensitive electrochemiluminescence (ECL) detection and subtype identification of cancer cells. Specially designed hairpins were integrated into DNA tetrahedral nanostructures (DTNs) to perform a catalytic hairpin assembly (CHA) reaction in the presence of target microRNA, forming hyperbranched 3D nanonetworks. Benefiting from the “spatial confinement effect,” the DNA tetrahedron-mediated catalytic hairpin assembly (DTCHA) reaction displayed significantly faster kinetics and greater cycle conversion efficiency than traditional CHA. The resulting 3D nanonetworks could load a large amount of Ru(phen)₃²⁺, significantly enhancing its ECL signal, and exhibit detection limits for both miR-21 and miR-141 at the femtomolar level. The biosensor based on modular logic gates facilitated the distinction and quantification of cancer cells and normal cells based on miR-21 levels, combined with miR-141 levels, to further identify different subtypes of breast cancer cells. Overall, this study provides potential applications in miRNA-related clinical diagnostics.

中文翻译：

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用于灵敏电化学发光检测和癌细胞亚型识别的逻辑信号放大系统

实现癌细胞的灵敏检测和准确识别对于诊断和治疗疾病至关重要。在这里，我们开发了一种逻辑信号放大系统，利用 DNA 四面体介导的三维 (3D) DNA 纳米网络进行灵敏的电化学发光 (ECL) 检测和癌细胞亚型识别。特别设计的发夹被整合到 DNA 四面体纳米结构 (DTN) 中，在目标 microRNA 存在的情况下进行催化发夹组装 (CHA) 反应，形成超支化 3D 纳米网络。受益于“空间限制效应”，DNA四面体介导的催化发夹组装（DTCHA）反应比传统的CHA表现出明显更快的动力学和更高的循环转换效率。由此产生的3D纳米网络可以负载大量的Ru(phen) ₃ ²⁺，显着增强其ECL信号，并在飞摩尔水平上表现出miR-21和miR-141的检测限。基于模块化逻辑门的生物传感器有助于根据miR-21水平区分和定量癌细胞和正常细胞，结合miR-141水平，进一步识别乳腺癌细胞的不同亚型。总体而言，这项研究为 miRNA 相关的临床诊断提供了潜在的应用。