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通过利用单捕获现象的适体功能化纳米线传感器检测淀粉样β肽。

Amyloid-beta peptide detection via aptamer-functionalized nanowire sensors exploiting single-trap phenomena.

机构信息

Bioelectronics (ICS-8), Forschungszentrum Jülich, 52425, Jülich, Germany.

Fraunhofer Institute for Cell Therapy and Immunology, Branch Bioanalytics and Bioprocesses (IZI-BB), 14476, Potsdam, Germany.

出版信息

Biosens Bioelectron. 2020 Apr 15;154:112053. doi: 10.1016/j.bios.2020.112053. Epub 2020 Jan 28.

Abstract

New highly sensitive direct methods for the early detection of peptides involved in Alzheimer's disease (AD) are required in order to prolong effective and healthy memory and thinking capabilities and also to stop the factors resulting in AD. In this contribution, we report the successful demonstration of a label-free approach for the detection of amyloid-beta (Aβ) peptides by highly selective aptamers immobilized onto the SiO surface of the fabricated sensors. A modified single-stranded deoxyribonucleic acid (ssDNA) aptamer was specially designed and synthesized to detect the target amyloid beta-40 sequence (Aβ-40). Electrolyte-insulator-semiconductor (EIS) structures as well as silicon (Si) nanowire (NW) field-effect transistors (FETs) covered with a thin SiO dielectric layer have been successfully functionalized with Aβ-40-specific aptamers and used to detect ultra-low concentrations of the target peptide. The binding of amyloid-beta peptides of different concentrations to the surface of the sensors varied in the range from 0.1 pg/ml to 10 μg/ml resulting in a change of the surface potential was registered by the fabricated devices. Moreover, we show that the single-trap phenomena observed in the novel Si two-layer (TL) NW FET structures with advanced characteristic parameters can be effectively used to increase the sensitivity of nanoscale sensors. The obtained experimental data demonstrate a highly sensitive and reliable detection of ultra-low concentrations of the Aβ-40 peptides. This opens up prospects for the development of real-time electrical biosensors for studying and understanding different stages of AD by utilizing Si TL NW FET structures fabricated on the basis of cost-efficient CMOS-compatible technology.

摘要

为了延长有效的健康记忆和思维能力,并阻止导致阿尔茨海默病(AD)的因素,需要新的高度敏感的直接方法来早期检测涉及 AD 的肽。在本贡献中,我们成功地展示了一种无标记方法,用于通过固定在制造的传感器的 SiO 表面上的高度选择性适体来检测淀粉样β(Aβ)肽。专门设计和合成了一种改良的单链脱氧核糖核酸(ssDNA)适体,以检测目标淀粉样β-40 序列(Aβ-40)。已经成功地将电解质-绝缘体-半导体(EIS)结构以及覆盖有薄 SiO 介电层的硅(Si)纳米线(NW)场效应晶体管(FET)用 Aβ-40 特异性适体功能化,并用于检测超低浓度的目标肽。不同浓度的淀粉样β肽与传感器表面的结合在 0.1 pg/ml 至 10 μg/ml 的范围内变化,导致由所制造的器件记录到表面电位的变化。此外,我们表明,在具有先进特性参数的新型 Si 双层(TL)NW FET 结构中观察到的单陷波现象可以有效地用于提高纳米级传感器的灵敏度。获得的实验数据表明对 Aβ-40 肽的超低浓度具有高度敏感和可靠的检测。这为利用基于成本效益的 CMOS 兼容技术制造的 Si TL NW FET 结构来开发用于研究和理解 AD 不同阶段的实时电生物传感器开辟了前景。

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