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基于场效应晶体管器件的无标记全电子核酸检测系统。

Labelfree fully electronic nucleic acid detection system based on a field-effect transistor device.

作者信息

Uslu F, Ingebrandt S, Mayer D, Böcker-Meffert S, Odenthal M, Offenhäusser A

机构信息

Institute for Thin Films & Interfaces, Institute for Bio and Chemosensors (ISG-2), Forschungszentrum Jülich, D-52425 Juelich, Germany.

出版信息

Biosens Bioelectron. 2004 Jul 15;19(12):1723-31. doi: 10.1016/j.bios.2004.01.019.

Abstract

The labelfree detection of nucleic acid sequences is one of the modern attempts to develop quick, cheap and miniaturised hand-held devices for the future genetic testing in biotechnology and medical diagnostics. We present an approach to detect the hybridisation of DNA sequences using electrolyte-oxide-semiconductor field-effect transistors (EOSFETs) with micrometer dimensions. These semiconductor devices are sensitive to electrical charge variations that occur at the surface/electrolyte interface, i.e. upon hybridisation of oligonucleotides with complementary single-stranded (ss) oligonucleotides, which are immobilised on the oxide surface of the transistor gate. This method allows direct, time-resolved and in situ detection of specific nucleic acid binding events without any labelling. We focus on the detection mechanism of our sensors by using oppositely charged polyelectrolytes (PAH and PSS) subsequently attached to the transistor structures. Our results indicate that the sensor output is charge sensitive and distance dependent from the gate surface, which pinpoints the need for very defined surface chemistry at the device surface. The hybridisation of natural 19 base-pair sequences has been successfully detected with the sensors. In combination with nano-transistors a PCR free detection system might be feasible in future.

摘要

核酸序列的无标记检测是为生物技术和医学诊断中的未来基因检测开发快速、廉价且小型化手持设备的现代尝试之一。我们提出了一种使用具有微米尺寸的电解质-氧化物-半导体场效应晶体管(EOSFET)来检测DNA序列杂交的方法。这些半导体器件对在表面/电解质界面处发生的电荷变化敏感,即在寡核苷酸与固定在晶体管栅极氧化物表面的互补单链(ss)寡核苷酸杂交时。该方法允许直接、时间分辨和原位检测特定核酸结合事件,无需任何标记。我们通过使用随后附着在晶体管结构上的带相反电荷的聚电解质(PAH和PSS)来关注我们传感器的检测机制。我们的结果表明,传感器输出对电荷敏感且与栅极表面的距离有关,这突出了在器件表面需要非常明确的表面化学。利用这些传感器已成功检测到天然19个碱基对序列的杂交。与纳米晶体管相结合,未来可能会实现无PCR检测系统。

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