技术进步在循环肿瘤DNA（ctDNA）的检测方面提供了新的诊断、分类、生物研究和治疗选择的方法。然而，对于分析这一新兴生物标记物的有效和实用方法仍然缺乏。在本研究中，设计了一种用于无标记检测ctDNA（非小细胞肺癌EGFR 19 del型，NSCLC）的荧光生物传感器。该生物传感器基于MnO2纳米片（MnO2 NSs）对单链DNA（ssDNA）具有比双链DNA（dsDNA）更强的亲和力这一事实。作为高性能纳米酶，MnO2 NSs能将多巴胺（DA）氧化为荧光聚多巴胺纳米颗粒（FL-PDA NPs），可用作荧光信号。探针ssDNA能通过π-π堆积吸附在MnO2 NSs表面，使活性位点被遮盖，导致较低的荧光。当目标与探针ssDNA结合形成dsDNA后，其对MnO2 NSs的亲和力降低，活性位点恢复，导致荧光增强。实验证明，Mn离子、•OH自由基和电子转移是DA催化氧化中的重要因素。在最佳实验条件下，该生物传感器具有380 pM的检测限和25-125 nM的线性范围，能在短时间（45分钟）内提供可靠的测量结果。该传感器具有出色的特异性、稳定性和重复性。此外，该传感器应用于血清样品和细胞裂解液中ctDNA的检测。实验证明，FL-PDA NPs可用作无标记易于快速检测ctDNA的荧光信号，无需其他扩增策略，该策略在液体活检领域的生物标志物检测具有巨大潜力。

Technological advances in the detection of circulating tumor DNA (ctDNA) have made new options available for diagnosis, classification, biological studies, and treatment selection. However, effective and practical methods for analyzing this emerging class of biomarkers are still lacking. In this work, a fluorescent biosensor was designed for the label-free detection of ctDNA (EGFR 19 del for non-small cell lung cancer, NSCLC). The biosensor was based on the fact that MnO2 nanosheets (MnO2 NSs) have stronger affinity towards single-stranded DNA (ssDNA), as compared with double-stranded DNA (dsDNA). As a high-performance nanoenzyme, MnO2 NSs could oxidize dopamine (DA) into fluorescent polydopamine nanoparticles (FL-PDA NPs), which could be used as a fluorescence signal. The probe ssDNA could be adsorbed on the surface of MnO2 NSs through π-π stacking, and the active site would be masked, causing a lower fluorescence. After the targets were recognized by probe ssDNA to form dsDNA, its affinity for MnO2 NSs decreased and the active site recovered, causing a restored fluorescence. It was verified that Mn ions, •OH radicals and electron transfer were the important factors in the catalytic oxidation of DA. Under the optimal experimental conditions, this biosensor exhibited a detection limit of 380 pM and a linear range of 25-125 nM, providing reliable readout in a short time (45 min). This sensor exhibited outstanding specificity, stability and reproducibility. In addition, this sensor was applied to the detection of ctDNA in serum samples and cell lysates. It is demonstrated that FL-PDA NPs can be used as a fluorescence signal for easy, rapid and label-free detection of ctDNA without any other amplification strategies, and the proposed strategy has great potential for biomarker detection in the field of liquid biopsy.