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基于金纳米粒子功能化的硅纳米线场效应晶体管的生物传感器,用于前列腺特异性抗原的高灵敏测定。

Biosensor based on a silicon nanowire field-effect transistor functionalized by gold nanoparticles for the highly sensitive determination of prostate specific antigen.

机构信息

Chemistry Faculty, M.V. Lomonosov Moscow State University, Leninskie gori, Moscow, 119991 Russia.

Skobeltsyn Institute of Nuclear Physics, M.V. Lomonosov Moscow State University, Leninskie gori, Moscow, 119991 Russia; Faculty of Physics, M.V. Lomonosov Moscow State University, Leninskie gori, Moscow, 119991 Russia.

出版信息

Biosens Bioelectron. 2017 Feb 15;88:283-289. doi: 10.1016/j.bios.2016.08.054. Epub 2016 Aug 18.

Abstract

We have demonstrated label-free and real-time detection of prostate specific antigen (PSA) in human serum using silicon nanowire field effect transistors (NW FETs) with Schottky contacts (Si-Ti). The NW FETs were fabricated from SOI material using high-resolution e-beam lithography, thin film vacuum deposition and reactive-ion etching processes eliminating complicated processes of doping and thermal annealing. This allowed substantial simplifying the transistors manufacturing. A new method for covalent immobilization of half-fragments of antibodies on silicon modified by 3-glycidopropyltrimethoxysilane with thiol groups and 5nm gold nanoparticles (GNPs) was established. NW FETs functionalized by GNPs revealed extremely high pH sensitivity of 70mV/pH and enhanced electrical performance in the detection of antigen due to enhanced surface/volume ratio, favorable orientation of antibody active sites and approaching the source of the electric field close to the transistor surface. Si NWFETs were applied for quantitative detection of PSA in a buffer and human serum diluted 1/100. Response time was about 5-10s, and analysis time per sample was 1min. The limit of PSA detection was of 23fg/mL, concentration range of 23fg/mL-500ng/mL (7 orders of magnitude). The PSA concentrations determined by the NW FETs in serum were compared with well-established ELISA method. The results matched well with the correlation coefficient of 0.97.

摘要

我们已经证明了使用肖特基接触硅纳米线场效应晶体管(Si-Ti)对人血清中的前列腺特异性抗原(PSA)进行无标记和实时检测。纳米线场效应晶体管是使用高分辨率电子束光刻、薄膜真空沉积和反应离子刻蚀工艺从 SOI 材料制造的,消除了掺杂和热退火等复杂工艺。这使得晶体管的制造大大简化。建立了一种新的方法,通过 3-缩水甘油丙基三甲氧基硅烷将巯基和 5nm 金纳米粒子(GNPs)修饰的硅进行半抗体的共价固定化。由于增强了表面/体积比、有利于抗体活性位点的取向以及接近电场源靠近晶体管表面,因此功能化的 GNPs 的 NW FET 表现出极高的 pH 灵敏度(70mV/pH)和增强的电导率,从而提高了抗原检测的性能。Si NWFET 用于在缓冲液和稀释 1/100 的人血清中定量检测 PSA。响应时间约为 5-10s,每个样品的分析时间为 1min。PSA 的检测极限为 23fg/mL,浓度范围为 23fg/mL-500ng/mL(7 个数量级)。通过 NW FET 在血清中测定的 PSA 浓度与已建立的 ELISA 方法进行了比较。结果与相关系数为 0.97 的结果非常吻合。

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