Improving the Limit of Detection of Nanoscale Sensors by Directed Binding to High-Sensitivity Areas
Improving the Limit of Detection of Nanoscale Sensors by Directed Binding to High-Sensitivity Areas
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DOI：
10.1021/nn901457f
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发表时间：
2010-04-01
期刊：
影响因子：
17.1
通讯作者：
Hook, Fredrik
中科院分区：
文献类型：
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作者：
Feuz, Laurent;Jonsson, Peter;Hook, Fredrik
蛋白质相互作用的揭示是蛋白质组学领域的主要关注点之一。纳米等离子体技术已成为一种有吸引力的基于表面的技术，因为它能够以无标记的方式在生理条件下感知蛋白质结合。在这里，我们使用直径约为 150 nm、深度约为 50 nm 的短程有序孔作为纳米等离子体模板。类似 40 nm 高的金圆柱区域仅暴露在孔壁上，而表面的其余部分由 TiO2 组成。由于灵敏度仅限于纳米孔，因此使用两种不同的材料作为传感器基板提供了将蛋白质选择性地结合到传感器表面上最敏感的金区域的机会。这是通过应用基于材料选择性聚乙二醇的表面化学来实现的，限制 NeutrAvidin 仅与 Au 区域上的表面固定生物素结合。我们表明，在质量传输限制条件下（低 nM 体积浓度），与允许蛋白质结合在整个传感器表面的情况相比，吸收的初始时间分辨响应可以增加近 20 倍，并强调了这一概念对于纳米级传感器的一般相关性。在进一步优化传感器结构的检测限（LOD）的范围内，我们提出了有限元（FE）模拟来阐明空间分辨的结合率。这些表明，孔中的结合率以高度不均匀的方式发生，在孔的上边缘观察到最高的结合率，在孔的底部观察到最低的结合率。通过假设 Au-TiO(2) 界面处的等离子体场分布具有增强的灵敏度，有限元模拟定性地再现了实验结果。
The revelation of protein protein-interactions is one of the main preoccupations in the field of proteomics. Nanoplasmonics has emerged as an attractive surface-based technique because of its ability to sense protein binding under physiological conditions in a label-free manner. Here, we use short-range ordered holes with a diameter of similar to 150 nm and a depth of similar to 50 nm as a nanoplasmonic template. A similar to 40 nm high cylindrical region of Au is exposed on the walls of the holes only, while the rest of the surface consists of TiO2. Since the sensitivity is confined to the nanometric holes, the use of two different materials for the sensor substrate offers the opportunity to selectively bind proteins to the most sensitive Au regions on the sensor surface. This was realized by applying material-selective poly(ethylene glycol)-based surface chemistry, restricting NeutrAvidin binding to surface-immobilized biotin on the Au areas only. We show that under mass-transport limited conditions (low nM bulk concentrations), the initial time-resolved response of uptake could be increased by a factor of almost 20 compared with the case where proteins were allowed to bind on the entire sensor surface and stress the generic relevance of this concept for nanoscale sensors. In the scope of further optimizing the limit of detection (LOD) of the sensor structure, we present finite-element (FE) simulations to unravel spatially resolved binding rates. These revealed that the binding rates in the holes occur in a highly inhomogeneous manner with highest binding rates observed at the upper rim of the holes and the lowest rates observed at the bottom of the holes. By assuming a plasmonic field distribution with enhanced sensitivity at the Au-TiO(2)interface, the FE simulations reproduced the experimental findings qualitatively.