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An electrochemical aptasensor for amyloid-β oligomer based on double-stranded DNA as “conductive spring”

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Abstract

In order to overcome the antibody-based sensor’s shortcomings, an electrochemical aptamer (Apt)-based sensor was developed for amyloid-β40 oligomer (Aβ40-O). The aptasensor was constructed by locating Apt and ferrocence (Fc) on streptavidin-modified gold (SA-gold) nanoparticles. The obtained AptFc@SA-gold nanoparticles were linked onto the Au electrode via the connection of double-stranded DNA (dsDNA) as a “conductive spring.” The determination of Aβ40-O was performed with square-wave voltammetry (SWV). Upon bio-recognition between Apt and Aβ40-O, the conformation of Apt changed and the formed Apt/Aβ40-O complex separated from the SA-gold surface. As a result, the surface charge of SA-gold positively shifted, weakening the electrostatic attraction between the SA-gold and the positively charged Au electrode surface (at potential range of 0.1~0.5 V, corresponding to the Fc redox transformation), and stretching the dsDNA chain. Based on the exponential decay of dsDNA’s electron transfer efficiency on its chain stretching, the oxidation current density from Fc decreased and displayed linear correlation to the concentration of Aβ40-O. A wide linear range of 0.100 nM to 1.00 μM with a low detection limit of 93.0 pM was obtained. The aptasensor displayed excellent selectivity toward Aβ40-O in contrast to other possible interfering analogs (Aβ40 monomer, Aβ42 monomer, and oligomer) at × 100 higher concentrations. The recoveries for Aβ40-O-spiked artificial cerebrospinal fluid and healthy human serum were 94.0~104% and 92.8~95.4%, respectively. The electrochemical aptasensor meets the demands of clinic determination of Aβ40-O, which is significant for the early diagnosis of AD.

Schematic representation of the electrochemical aptasensor for amyloid-β oligomer based on the surface charge change induced by target binding.

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Funding

This work was financially supported by the National High Technology Research and Development Program of China (2015AA020502), the National Key Basic Research Program of China (2014CB744502), the National Natural Science Foundation of China (21727810, 21573290, 21005090), and Hunan Provincial Natural Science Foundation of China (13JJ3004), Hunan Provincial Science and Technology Plan Project, China (2016TP1007), and the China Postdoctoral Science Foundation (2012M510136, 2013T60774).

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Authors and Affiliations

  1. Hunan Provincial Key Laboratory of Micro & Nano Materials Interface Science, College of Chemistry and Chemical Engineering, Central South University, Changsha, 410083, People’s Republic of China

    Chunyan Deng, Hui Liu, Shihui Si & Juan Xiang

  2. School of Information Science and Technology, Nantong University, Nantong, 226019, Jiangsu, People’s Republic of China

    Xiaojun Zhu

  3. Department of Geratology, The Third Xiangya Hospital, Central South University, Changsha, 410013, People’s Republic of China

    Qiuyun Tu & Yan Jin

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  1. Chunyan Deng
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  2. Hui Liu
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  3. Shihui Si
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  4. Xiaojun Zhu
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  6. Yan Jin
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  7. Juan Xiang
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Correspondence to Juan Xiang.

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Deng, C., Liu, H., Si, S. et al. An electrochemical aptasensor for amyloid-β oligomer based on double-stranded DNA as “conductive spring”. Microchim Acta 187, 239 (2020). https://doi.org/10.1007/s00604-020-4217-8

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