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基于核酸适体的电化学传感器用于检测血清 P-tau231 及阿尔茨海默病的即时筛查测试。

Nucleic acid aptamer-based electrochemical sensor for the detection of serum P-tau231 and the instant screening test of Alzheimer's disease.

机构信息

School of Basic Medical Sciences, Harbin Medical University, Harbin, 150081, China.

The Heilongjiang Provincial Joint Laboratory of Basic Medicine and Multiple Organ System Diseases (International Cooperation), Harbin, Heilongjiang, 150086, China.

出版信息

Mikrochim Acta. 2024 May 14;191(6):328. doi: 10.1007/s00604-024-06395-0.

DOI:10.1007/s00604-024-06395-0
PMID:38743383
Abstract

The instant screening of patients with a tendency towards developing Alzheimer's disease (AD) is significant for providing preventive measures and treatment. However, the current imaging-based technology cannot meet the requirements in the early stage. Developing biosensor-based liquid biopsy technology could be overcoming this bottleneck problem. Herein, we developed a simple, low-cost, and sensitive electrochemical aptamer biosensor for detecting phosphorylated tau protein threonine 231 (P-tau231), the earliest and one of the most efficacious abnormally elevated biomarkers of AD. Gold nanoparticles (AuNPs) were electrochemically synthesized on a glassy carbon electrode as the transducer, exhibiting excellent conductivity, and were applied to amplify the electrochemical signal. A nucleic acid aptamer was designed as the receptor to capture the P-tau231 protein, specifically through the formation of an aptamer-antigen complex. The proposed biosensor showed excellent sensitivity in detecting P-tau 231, with a broad linear detection range from 10 to 10 pg/mL and a limit of detection (LOD) of 2.31 pg/mL. The recoveries of the biosensor in human serum ranged from 97.59 to 103.26%, demonstrating that the biosensor could be used in complex practical samples. In addition, the results showed that the developed biosensor has good repeatability, reproducibility, and stability, which provides a novel method for the early screening of AD.

摘要

对有发生阿尔茨海默病(AD)倾向的患者进行即时筛查对于提供预防措施和治疗非常重要。然而,目前基于成像的技术无法满足早期阶段的要求。开发基于生物传感器的液体活检技术可能是克服这一瓶颈问题的方法。在这里,我们开发了一种简单、低成本且灵敏的电化学适体生物传感器,用于检测磷酸化 tau 蛋白苏氨酸 231(P-tau231),P-tau231 是 AD 最早和最有效的异常升高生物标志物之一。金纳米粒子(AuNPs)作为传感器在玻碳电极上电化学合成,具有出色的导电性,并用于放大电化学信号。设计了一种核酸适体作为受体来捕获 P-tau231 蛋白,具体通过适体-抗原复合物的形成。所提出的生物传感器在检测 P-tau 231 方面表现出优异的灵敏度,具有从 10 到 10 pg/mL 的宽线性检测范围和 2.31 pg/mL 的检测限(LOD)。该生物传感器在人血清中的回收率范围为 97.59%至 103.26%,表明该生物传感器可用于复杂的实际样本。此外,结果表明,所开发的生物传感器具有良好的重复性、重现性和稳定性,为 AD 的早期筛查提供了一种新方法。

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