Biosensing with Engineered Nanostructures

9821049 Halas提出了一种利用具有专门设计的电磁共振的纳米颗粒进行生物传感的新方法。有两个具体的目标是：（1）制造和演示的全光学体内葡萄糖传感器，和（2）开发一个流线型的，全光学生物测定检测全血中的血浆蛋白。金属纳米壳是由介电核和金壳组成的复合纳米粒子，具有很强的等离子体激元激发，其共振频率受粒子核直径和壳厚度的控制。 通过改变纳米颗粒的核/壳比率，这种共振可以位于光谱的可见光和近红外区域的任何波长处。当纳米壳等离子体与拉曼激发激光共振时，从吸附到单个纳米壳的分子中观察到了巨大的表面增强拉曼散射（Sers）增强。这些增强的发生没有来自纳米颗粒聚集的贡献，这是典型的固体金属纳米Sers增强。这种效应提供了在悬浮于溶液或其他介质中的单个纳米颗粒的局部附近的分子种类的高灵敏度、高信息含量的全光学探针。此外，等离子体共振可以放置在生物流体和组织中的高红外透射率的光谱“水窗”中，从而促进简单的体外和体内感测设计。蛋白质缀合的纳米壳物种，使用免疫金的许多成熟的协议合成，将被用作特定的功能剂在新的基于光学的生物传感应用的开发。这两个传感器项目包括生物共轭纳米壳附着和活性研究，一系列的纳米壳SERS增强的拉曼光谱研究的生化物种和反应的兴趣，和表征的拉曼为基础的监测器与标准校准方法。 在葡萄糖传感器开发的情况下，这些研究之后将是将生物缀合物-纳米壳物质掺入水凝胶介质中并在最后阶段体内。该项目提供了一个令人兴奋的，以目标为导向的跨学科系列研究，结合了纳米颗粒合成，免疫化学，拉曼和红外光谱，定量和统计分析的专业知识。本提案中描述的工作与两位主要研究者已证明的专业知识一致。 该项目将激励和团结电气工程，应用物理，生物工程和生物化学学科的研究生，以实现重大技术和社会影响的目标。

9821049HalasA new approach to biosensing utilizing nanoparticles with specifically engineered electromagnetic resonances is proposed. Two specific goals are targeted: (I) the fabrication and demonstration of an all optical in vivo glucose sensor, and (2) The development of a streamlined, all optical bioassay for the detection of plasma proteins in whole blood. Metal Nanoshells, composite nanoparticles consisting of a dielectric core and an ultrathin gold shell, possess a strong plasmon excitation whose resonant frequency is controlled by the particle core diameter and shell thickness. By varying the nanoparticle's core/shell ratio, this resonance may be positioned at any wavelength across much of the visible and near infrared regions of the spectrum. When the nanoshell plasmon is resonant with a Raman excitation laser, enormous surface enhanced Raman scattering (SERS) enhancements have been observed from molecules adsorbed to the individual nanoshells. These enhancements occur without contributions from nanoparticle aggregation, as is typical with solid metal nanoparticle SERS enhancements. This effect provides a highly sensitive, high information content all-optical probe of molecular species in the local vicinity of individual nanoparticles suspended in a solution or other media. In addition, the plasmon resonance may be placed in a spectral "water window" of high infrared transmissivity in biological fluids and tissue, facilitating simple in vitro and in vivo sensing designs. Protein-conjugated nanoshell species, synthesized using the many well-established protocols of immunogold, will be utilized as specific functional agents in the development of new optically-based biosensing applications. Both sensor projects consist of bioconjugate-nanoshell attachment and activity studies, a series of nanoshell SERS-enhanced Raman spectroscopic studies for the biochemical species and reactions of interest, and characterization of the Raman-based monitors versus standard calibration methods. In the case of the glucose sensor development these investigations will be followed by incorporation of the bioconjugate-nanoshell species into hydrogel media and in viva in the final stage. This project provides an exciting, goal oriented interdisciplinary series of studies that combines expertise in nanoparticle synthesis, immunochemistry, Raman and infrared spectroscopy, and quantitative and statistical analysis. The work described in this proposal is consistent with the demonstrated expertise of the two Principal Investigators. This project will stimulate and unite graduate students in the disciplines of electrical engineering, applied physics, bioengineering and biochemistry toward goals of major technical and societal impact.***