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基于导电金属有机骨架的无标记电化学检测循环肿瘤 DNA。

Conductive metal-organic framework based label-free electrochemical detection of circulating tumor DNA.

机构信息

Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing, 400044, People's Republic of China.

College of Chemistry and Chemical Engineering, Chongqing University, Chongqing, 400044, People's Republic of China.

出版信息

Mikrochim Acta. 2022 Sep 23;189(10):391. doi: 10.1007/s00604-022-05482-4.

Abstract

An ultrasensitive electrochemical biosensor was designed for the rapid label-free detection of circulating tumor DNA (ctDNA, EGFR 19 Dels for non-small cell lung cancer, NSCLC). We linked the highly conjugated tricatecholate, 2,3,6,7,10,11-hexahydroxytriphenylene (HHTP) with Ni(II) ions into the two-dimensional porous conductive metal-organic frameworks (MOFs), which is termed Ni-catecholates (Ni-CAT). Then, the AuNPs/Ni-catecholates/carbon black/polarized pencil graphite electrode (AuNPs/Ni-CAT/CB/PPGE) was obtained by electrodeposition of AuNPs on the surface of PPGE modified with Ni-CAT/CB composite materials. The AuNPs/Ni-CAT/CB/PPGE were used for label-less detection of ctDNA, with a total detection time of only 30 min. Under optimal detection conditions, the AuNPs/Ni-CAT/CB/PPGE sensor exhibited excellent detection performance with good linear response to ctDNA over a wide concentration range and the detection limit down to the femtomolar level. The sensor was applied to the determination of ctDNA in serum samples with high sensitivity. This simple, efficient, and expeditious method has practical value in liquid biopsy of ctDNA and has potential for development in early detection, treatment, and prognosis of tumors. Herein, an ultrasensitive electrochemical biosensor was designed for the rapid label-free detection of ctDNA (EGFR 19 Dels for non-small cell lung cancer, NSCLC). We linked the highly conjugated tricatecholate, 2,3,6,7,10,11-hexahydroxytriphenylene (HHTP) with Ni(II) ions into the two-dimensional porous conductive metal-organic frameworks (MOFs), which is termed as Ni-catecholates (Ni-CAT). Then, the AuNPs/Ni-catecholates/carbon black/polarized pencil graphite electrode (AuNPs/Ni-CAT/CB/PPGE) was obtained by electrodeposition of AuNPs on the surface of PPGE modified with Ni-CAT/CB composite materials. The AuNPs/Ni-CAT/CB/PPGEs were used for label-less detection of ctDNA, with a total detection time of only 30 min. Under optimal detection conditions, the AuNPs/Ni-CAT/CB/PPGE sensor exhibited excellent detection performance with good linear response to ctDNA in the concentration range of 1 × 10 M to 1 × 10 M and with a detection limit as low as 0.32 fM. The sensor was applied for determination of ctDNA in serum samples and gave high sensitivity. This simple, efficient and expeditious method has practical value in liquid biopsy of ctDNA and has potential for development in early detection, treatment and prognosis of tumors.

摘要

一种超灵敏的电化学生物传感器被设计用于快速无标记检测循环肿瘤 DNA(ctDNA,非小细胞肺癌的 EGFR 19 缺失)。我们将高度共轭的三亚苯,2,3,6,7,10,11-六羟基三亚苯(HHTP)与 Ni(II) 离子链接到二维多孔导电金属有机骨架(MOFs)中,称为 Ni-儿茶酸盐(Ni-CAT)。然后,通过在 Ni-CAT/CB 复合材料修饰的 PPGE 表面电沉积 AuNPs,获得 AuNPs/Ni-CAT/CB/PPGE。AuNPs/Ni-CAT/CB/PPGE 用于无标记检测 ctDNA,总检测时间仅为 30 分钟。在最佳检测条件下,AuNPs/Ni-CAT/CB/PPGE 传感器对 ctDNA 表现出优异的检测性能,在 1×10-1 M 至 1×10-7 M 的宽浓度范围内具有良好的线性响应,检测限低至 0.32 fM。该传感器用于测定血清样品中的 ctDNA,具有较高的灵敏度。这种简单、高效、快捷的方法在 ctDNA 的液体活检中具有实用价值,有望用于肿瘤的早期检测、治疗和预后。

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