Enhanced Molecular Detection and Biosensing of Carbohydrate-Mediated Interactions Through Integrated Silicon Nanophotonics

这个奖项是根据2009年美国复苏和再投资法案(公共法律111-5)资助的。硅光子学揭示了它的潜力，它将彻底改变无标签实时生物传感。通过可以选择性地将氧化硅和氮化硅与蛋白质、DNA、抗体、碳水化合物和小分子配体功能化的化学方法，可以在基于纳米光子波导的芯片规模系统中实现专一性和非凡的灵敏度。硅环谐振器是硅光子学领域出现的最有前途的生物传感结构之一。环形谐振器由一个行波环组成，行波环与附近的硅波导相耦合。与传统的表面等离子体共振(SPR)类似，表面功能化环形谐振器(SFRR)的响应是谐振器上方折射率的函数，使其能够灵敏而特异地检测设备表面或附近的细胞和生物分子。文献报道表明，这些和其他共振装置可以用来检测与蛋白质、DNA、病毒和细菌的相互作用。初步研究表明，对于相同的表面化学成分，SFRR具有超过SPR的灵敏度-检测限低到足以潜在地检测单个小分子结合事件。因此，在表面科学和生物传感领域使用了几十年的共轭方法现在可以与硅光子学相结合，显著增强生物传感器的能力。该方案的目标是开发基于新型集成硅纳米光子器件和用于呈现生物分子配体的优化的表面化学相结合的新一代超灵敏生物传感器。这项提案将侧重于使用合成碳水化合物作为模型配体，以促进这一生物传感平台的设计和制造。选择碳水化合物用于这一应用是因为它们参与了一系列高亲和力和低亲和力结合事件，包括与其他碳水化合物、蛋白质、核酸、细胞、细菌和病毒的相互作用。碳水化合物和糖共轭化合物也与多种重要的生物过程有关，实时无标记的葡聚糖生物传感器对于宿主-病原体相互作用和疫苗设计的生物医学研究将是非常有价值的。

0930411Ratner"This award is funded under the American Recovery and Reinvestment Act of 2009 (Public Law 111-5)."Silicon photonics has revealed its potential to revolutionize label-free real-time biosensing. Through chemistries that can selectively functionalize both oxidized silicon and silicon nitride with protein, DNA, antibody, carbohydrate and small molecule ligands, it is possible to achieve both specificity and extraordinary sensitivity in a chip-scale system based on the use of nanophotonic waveguides. Among the most promising biosensing structures to emerge from the silicon photonics community is the silicon ring resonator. The ring resonator consists of a travelling-wave ring that is coupled to a nearby silicon waveguide. Analogous to conventional Surface Plasmon Resonance (SPR), the surface functionalized ring resonator's (SFRR) response is a function of the refractive index above the resonator - permitting it to sensitively and specifically detect cells and biomolecules at or near the surface of the device. Literature reports have demonstrated that these and other resonant devices can be used to detect interactions with proteins, DNA, viruses and bacteria. Preliminary studies indicate that the SFRR possesses sensitivities that exceed that of SPR for identical surface chemistries - with limits of detection low enough to potentially detect individual small-molecule binding events. As such, conjugation methods that have been used for decades within the surface science and biosensing communities can now be leveraged, with silicon photonics, to significantly enhance biosensor capabilities. The objective of this proposal is to develop a new generation of ultrasensitive biosensors based on the combination of novel integrated silicon nanophotonic devices and optimized surface chemistries for the presentation of biomolecular ligands. This proposal will focus on the use of synthetic carbohydrates as model ligands to facilitate the design and fabrication of this biosensing platform. Carbohydrates were selected for this application based on the fact that they are involved in a range of high-affinity and lowaffinity binding events, including interactions with other carbohydrates, proteins, nucleic-acids, cells, bacteria, and viruses. Carbohydrates and glycoconjugates are also implicated in a variety of vital biological processes, and real-time label-free glycan biosensors would be invaluable to biomedical research in host-pathogen interactions and vaccine design.