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基于晶体管的 DNA 逻辑计算在癌症分子诊断中的应用

DNA Logical Computing on a Transistor for Cancer Molecular Diagnosis.

机构信息

State Key Laboratory of Molecular Engineering of Polymers, Department of Macromolecular Science, Shanghai, 200433, P. R. China.

Laboratory of Molecular Materials and Devices, Fudan University, Shanghai, 200433, P. R. China.

出版信息

Angew Chem Int Ed Engl. 2024 Oct 7;63(41):e202407039. doi: 10.1002/anie.202407039. Epub 2024 Sep 10.

Abstract

Given the high degree of variability and complexity of cancer, precise monitoring and logical analysis of different nucleic acid markers are crucial for improving diagnostic precision and patient survival rates. However, existing molecular diagnostic methods normally suffer from high cost, cumbersome procedures, dependence on specialized equipment and the requirement of in-depth expertise in data analysis, failing to analyze multiple cancer-associated nucleic acid markers and provide immediate results in a point-of-care manner. Herein, we demonstrate a transistor-based DNA molecular computing (TDMC) platform that enables simultaneous detection and logical analysis of multiple microRNA (miRNA) markers on a single transistor. TDMC can perform not only basic logical operations such as "AND" and "OR", but also complex cascading computing, opening up new dimensions for multi-index logical analysis. Owing to the high efficiency, sensing and computations of multi-analytes can be operated on a transistor at a concentration as low as 2×10 M, reaching the lowest concentration for DNA molecular computing. Thus, TDMC achieves an accuracy of 98.4 % in the diagnosis of hepatocellular carcinoma from 62 serum samples. As a convenient and accurate platform, TDMC holds promise for applications in "one-stop" personalized medicine.

摘要

鉴于癌症高度的可变性和复杂性,精确监测和逻辑分析不同的核酸标志物对于提高诊断精度和患者生存率至关重要。然而,现有的分子诊断方法通常存在成本高、步骤繁琐、依赖专用设备以及数据分析方面的深入专业知识等问题,无法同时分析多个与癌症相关的核酸标志物,并在即时护理点提供结果。在此,我们展示了一种基于晶体管的 DNA 分子计算(TDMC)平台,该平台能够在单个晶体管上同时检测和逻辑分析多个 microRNA(miRNA)标志物。TDMC 不仅可以执行“与”和“或”等基本逻辑运算,还可以进行复杂的级联计算,为多指标逻辑分析开辟了新的维度。由于具有高效性,在晶体管上可以在低至 2×10^-15 M 的浓度下进行多分析物的传感和计算,达到了 DNA 分子计算的最低浓度。因此,TDMC 可以从 62 份血清样本中以 98.4%的准确率诊断肝细胞癌。作为一种方便、准确的平台,TDMC 在“一站式”个性化医疗中有很大的应用潜力。

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