Plasmonic Glycan Arrays for Highly Sensitive Detection of Glycan-binding Proteins

项目摘要 探索多糖中的生物信息含量代表了当前的 后基因组研究和技术开发的重点。以多糖为基础的高 吞吐量分析(如葡聚糖微阵列)为快速分析提供了巨大的希望 糖类结合蛋白(CBPS)、CBP生物学的阐明及其研究进展 许多疾病的诊断、疫苗和治疗，包括癌症和 神经紊乱。随着糖生物学领域的发展，多糖的重要作用 糖蛋白在健康中的作用越来越受到人们的认可。然而，“国家-- 最先进的“葡聚糖阵列有几个本能的局限性，包括动态范围差，差 敏感性，以及不能轻松地询问多个糖蛋白相互作用 同时在复杂的样品中。因为蛋白质-葡聚糖的相互作用通常很低 亲和力强，临床标本中的许多CBPS和自身抗多糖抗体一般都是 在fg/m L到pg/m L的范围内，目前的多糖阵列的检测灵敏度无法 达到许多CBPS和自身抗多糖抗体生物标志物的临床阈值， 尤其是在疾病的早期，当它们在临床样本中的浓度 非常低。本项目的目标是应用纳米技术攻克重大课题 目前的葡聚糖微阵列的低灵敏度和动态范围的局限性。我们的目标是 多等离子体共振光子增强荧光(MPREF)的开发和商业化 糖链研究用的糖链阵列。通过这个项目，我们希望开发出即用型 产品：1)MPREF系统包括等离子体基板组件和 将作为糖链阵列试剂盒销售的等离子荧光团，2)经过验证的模型 含有50+糖胺多糖的MPREF多聚糖阵列。

Project Summary Exploring the biological information content in glycans represents one of the current focuses of postgenomic research and technology development. Glycan-based high throughput assays (e.g. glycan microarrays) hold great promise for the rapid analysis of carbohydrate binding proteins (CBPs), elucidation of CBP biology, and the development of diagnostics, vaccines, and therapeutics for a number of diseases, including cancer and neurological disorders. As the field of glycobiology grows, the important roles that glycans and glycoproteins play in health are becoming increasingly recognized. However, the “state- of-the-art” glycan arrays have several instinct limitations including poor dynamic range, poor sensitivity, and inability to easily interrogate multiple glycan-protein interactions simultaneously in complex samples. Because protein–glycan interactions are typically of low affinity, and many CBPs and auto-anti-glycan antibodies in clinical samples are generally in the range of fg/mL to pg/mL, the detection sensitivity of current glycan arrays is unable to reach the clinical threshold of many CBPs and auto-anti-glycan antibody biomarkers, especially in the early stages of the diseases when their concentrations in clinical samples very low. The goal of this project is to applied nanotechnology to overcome the major limitations of poor sensitivity and dynamic ranges of current glycan microarrays. We aim to develop and commercialize multi-plasmonic resonant photon enhanced fluorescent (MPREF) glycan array for glycomic research. With this project, we expect to develop ready-to-use products of: 1) the MPREF system include the components of plasmonic substrate and plasmonic fluorophores which will be marketed as glycan array kit, 2) a validated model MPREF glycan array containing 50+ Glycosaminoglycans.