State Key Laboratory of Molecular Engineering of Polymers, Department of Macromolecular Science, and Laboratory of Advanced Materials, Fudan University, Shanghai 200433, People's Republic of China.
ACS Appl Mater Interfaces. 2013 Jun 26;5(12):5832-44. doi: 10.1021/am401468a. Epub 2013 Jun 17.
Gold nanoparticles (Au NPs) are very attractive candidate nanoparticles in biological assay because of their high chemical stabilities, high homogeneities, good biocompatibilities, and low toxicities. However, molecular beacon assays via encapsulating the combined fluorescence or surface-enhanced Raman scattering (SERS) signals of reporters and Au NPs in nanobarcodes particles usually suffer from fluorescence quenching or weak Raman enhancement when Au NPs are employed (especially with size smaller than 15 nm). Herein, we present a new design of simultaneously realizing metal-enhanced fluorescence and coenhanced surface-enhanced Raman scattering by facilely embedding Ag nanoparticle into the shell of two kinds of Au nanoaggregate (5 and 10 nm), meanwhile, fluorophore is located between the silver core and gold nanoparticle layers and the distance among them is adjusted by SiO2 spacer (Ag@first SiO2 spacer@FiTC+SiO2@second SiO2 spacer@Au nanoaggregate). In this architecture, Ag nanoparticle not only is utilized as an efficient fluorescence enhancer to overcome the common fluorescence quenching around Au nanoaggregates but also behaves like a mirror. Thus, incident light that passes through the SERS-active Au nanoaggregate and the intervening dielectric layer of SiO2 could be reflected multiply from the surface of Ag nanoparticle and coupled with the light at the nanogap between the Au nanoaggregates to further amplify Raman intensity. This results in enhancement factors for fluorescence and SERS ~1.6-fold and more than 300-fold higher than the control samples without silver core under identical experimental conditions, respectively. Moreover, fluorophore and SERS reporters are assembled onto different layers of the concentric hybrid microsphere, resulting in a feasible fabrication protocol when a large number of agents need to be involved into the dual-mode nanobarcodes. A proof-of-concept chip-based DNA sandwich hybridization assay using genetically modified organisms as a model system has been investigated based on the concentric hybrid microsphere. The high specificity and sensitivity of the assays suggest that the new architecture has a potential for various bioanalytical applications and provides opportunities for other similar metal nanoparticles to realize coenhancement effect.
金纳米粒子（Au NPs）由于其高化学稳定性、高均一性、良好的生物相容性和低毒性，是生物测定中非常有吸引力的候选纳米粒子。然而，通过将报告分子和 Au NPs 的荧光或表面增强拉曼散射（SERS）信号结合封装在纳米条码颗粒中进行分子信标分析时，当 Au NPs 被使用时（特别是尺寸小于 15nm 时），通常会受到荧光猝灭或弱拉曼增强的影响。在此，我们提出了一种新的设计，通过简便地将 Ag 纳米粒子嵌入到两种 Au 纳米聚集体（5nm 和 10nm）的壳中，同时实现金属增强荧光和共增强表面增强拉曼散射，同时，荧光团位于银核和金纳米粒子层之间，并且通过 SiO2 间隔物（Ag@first SiO2 spacer@FiTC+SiO2@second SiO2 spacer@Au 纳米聚集体）来调整它们之间的距离。在这种结构中，Ag 纳米粒子不仅用作克服 Au 纳米聚集体周围常见荧光猝灭的有效荧光增强剂，而且还像镜子一样。因此，穿过 SERS 活性 Au 纳米聚集体和 SiO2 介电层的入射光可以从 Ag 纳米粒子的表面多次反射，并与 Au 纳米聚集体之间的纳米间隙中的光耦合，进一步放大拉曼强度。在相同的实验条件下，这分别导致荧光和 SERS 的增强因子提高了 1.6 倍和 300 倍以上，高于没有银核的对照样品。此外，荧光团和 SERS 报告分子组装到同心混合微球的不同层上，当需要将大量试剂组装到双模纳米条码中时，这会产生一种可行的制造方案。基于同心混合微球，已经研究了一种用于模式生物作为模型系统的基于芯片的 DNA 夹心杂交分析的概念验证。该分析具有高特异性和灵敏度，表明该新结构具有用于各种生物分析应用的潜力，并为其他类似金属纳米粒子实现共增强效应提供了机会。
