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基于三螺旋开关与 AuNPs@CuMOF 标记信号置换探针耦联的可切换电化学生物传感器用于检测淀粉样β寡聚体

Switchable electrochemical aptasensor for amyloid-β oligomers detection based on triple helix switch coupling with AuNPs@CuMOF labeled signaling displaced-probe.

机构信息

Key Laboratory of the Environmental Medicine and Engineering, Ministry of Education, School of Public Health, Southeast University, Nanjing, 210009, China.

出版信息

Mikrochim Acta. 2021 Jan 25;188(2):49. doi: 10.1007/s00604-021-04704-5.

Abstract

The aggregation of amyloid-β oligomers (AβOs) with extremely strong neurotoxicity has been proved to be the main pathogenesis of Alzheimer's disease (AD). For sensitive quantification of AβOs, a switchable electrochemical aptasensor is proposed. Metal organic framework carrying Au nanoparticles (AuNPs@CuMOF) has been used to label signaling displaced-probe (SD), which formed triple helix switch (THS) by hybridizing with label-free anti-AβOs aptamer (Apt) on the electrodeposited palladium electrode (EPd). Thus, a relatively strong response of differential pulse voltammetry (DPV) was produced (switch on). With the specific binding between AβOs and Apt, the DPV response obviously decreased, owing to destroyed structure of THS and the separation of AuNPs@CuMOF/SD from the EPd (switch off). The mode of "switch on-off" can dramatically enhance the AβOs-dependent DPV intensity change. As a result, the switchable EA exhibited excellent selectivity and sensitivity with the linear range from 0.5 fM to 500 fM and the detection limit of 0.25 fM. When evaluating the AβOs of artificial cerebrospinal fluid (aCSF) samples, the switchable EA exhibited desirable feasibility, and the results are basically consistent with the enzyme linked immunosorbent assay (ELISA). The work could provide a potential tool of the AD diagnosis and a bright future in clinical applications.

摘要

淀粉样蛋白-β寡聚体 (AβOs) 的聚集具有极强的神经毒性,已被证明是阿尔茨海默病 (AD) 的主要发病机制。为了灵敏地定量检测 AβOs,提出了一种可切换的电化学适体传感器。金属有机骨架负载金纳米粒子 (AuNPs@CuMOF) 用于标记信号置换探针 (SD),SD 与在电沉积钯电极 (EPd) 上未标记的抗 AβOs 适体 (Apt) 杂交形成三螺旋开关 (THS)。因此,产生了相对较强的差分脉冲伏安法 (DPV) 响应 (打开)。由于 THS 结构的破坏和 AuNPs@CuMOF/SD 与 EPd 的分离,AβOs 与 Apt 之间的特异性结合导致 DPV 响应明显降低 (关闭)。“打开-关闭”模式可以显著增强 AβOs 依赖性 DPV 强度变化。结果,可切换的 EA 表现出优异的选择性和灵敏度,线性范围从 0.5 fM 到 500 fM,检测限为 0.25 fM。在评估人工脑脊液 (aCSF) 样品中的 AβOs 时,可切换的 EA 表现出良好的可行性,结果与酶联免疫吸附测定 (ELISA) 基本一致。这项工作为 AD 的诊断提供了一种潜在的工具,并为临床应用带来了光明的前景。

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