Novel 3-dimensional (3-D) platform for high-throughput glycomics analysis

用于高通量糖组学分析的新型 3 维 (3-D) 平台

基本信息

批准号：
8068769
负责人：
Jian Zhang
金额：
$ 35.92万
依托单位：
ADA TECHNOLOGIES, INC.
依托单位国家：
美国
项目类别：
财政年份：
2007
资助国家：
美国
起止时间：
2007-02-01 至 2012-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8068769
关键词：
3-Dimensional Address Adhesions Antibodies Antibody Formation Antibody Specificity Antigens Autoantibodies Avidity Binding Biochemical Biological Assay Biological Markers Carbohydrate Biochemistry Carbohydrate Sequence Carbohydrates Cells Chemicals Chemistry Clinical Research Collaborations Communities Comparative Study Complex Custom Data Dendrimers Detection Development Diagnosis Diagnostics Research Disease Enzymes Epitopes Event Exhibits Fc Receptor Film Foundations Funding Genomics Glass Goals Gold Human body Image Immobilization In Vitro Industry International Investigation Iowa Knowledge Label Laboratories Ligands Malignant Neoplasms Malignant neoplasm of prostate Manufacturer Name Marketing Measures Methodology Methods Microarray Analysis Modeling Modification Molecular Monitor Monitoring for Recurrence Mono-S National Center for Research Resources Nature Noise Nucleic Acids Nucleotides Oligosaccharides Pattern Performance Pharmaceutical Preparations Phase Plasma Polysaccharides Population Positioning Attribute Process Prostatic Neoplasms Protein Microchips Protein-Carbohydrate Interaction Proteins Proteomics Reaction Reagent Reporting Research Research Personnel Screening for cancer Screening procedure Sequence Analysis Signal Transduction Site Slide Small Business Innovation Research Grant Solid Solutions Source Specificity Structure Surface Surveys System Systems Analysis Techniques Technology Testing Time Tumor-Derived United States National Institutes of Health Universities Viral Work analytical tool base biological research cancer microarray cancer risk carbohydrate binding protein commercialization cost cost effective density design disease diagnosis drug mechanism follow-up high throughput screening inhibitor/antagonist innovation medical schools meetings microwave electromagnetic radiation neoplastic cell novel novel strategies outcome forecast preconditioning prevent prototype public health relevance receptor response success sugar tool transcriptomics tumor

项目摘要

DESCRIPTION (provided by applicant): Glycan (carbohydrate microarrays), carrying tens or hundreds of different sugars that are immobilized on solid surfaces in a spatially discrete pattern, possess a wide variety of potential applications in glycomics including rapid determination of the binding profile of carbohydrate-binding proteins, detection of specific antibodies for the diagnosis of diseases, characterization of carbohydrate-cell recognition events and the high-throughput screening of inhibitors to prevent carbohydrate-protein interactions. However, platforms that would enable construction of high quality carbohydrate microarrays and sensitive and rapid determination and characterization of carbohydrate-protein interactions have not kept pace with, for example, equivalent technology in genomic and proteomic research. To address this need, we have developed a unique novel 3-dimensional platform which we have demonstrated successfully for fabrication of high sensitive carbohydrate microarray in Phase I research; this platform could potentially allow us to screen thousands of different carbohydrate probes for binding to proteins including receptors and antibodies. In the Phase II project, we propose to build on our feasibility work to develop advanced carbohydrate microarray platform for high throughput glycan analysis. Specifically, we propose to (1) optimize a 3D glass-substrate microarray platform that will function with the existing fluorescent-based glycan analysis methods; (2) systematically compare of the effect of platform surface chemistry to glycan functions and epitope-displays; (3) develop epitope-defined high avidity N-glycan microarray for prostate cancer glycan-based biomarkers discovery, and (4) to develop 3D SPR substrate platform and a label-free surface plasma resonance (SPR) carbohydrate microarray system. The Phase II project results and deliverables will support the Phase II commercialization goals for implementing a Supercarbohydrate glass substrate for carbohydrate microarray fabrication that the fluorescent detection can be applied for the glycan analysis, and a Gold SPR platform substrate for carbohydrate microarray fabrication that the label-free detection can be applied for the glycan analysis. Follow-on products will include well-defined carbohydrate microarray for tumor biomarkers, and a label-free SPR imaging system for high throughput glycan analysis. The value of the platform substrates and the microarray system will bring to both the primary and secondary markets should attract large corporations as partners to support commercial development, marketing, and distribution. PUBLIC HEALTH RELEVANCE: Interactions between carbohydrates and proteins define a wide range of biochemical mechanisms in the human body. At present there is no commercially viable tool for rapid screening and investigation of these carbohydrate interactions. The proposed work will develop and demonstrate a microarray tool to allow researchers to probe carbohydrate biochemistry to elucidate disease and drug mechanisms and identify cancer biomarkers.

描述（由申请人提供）：聚糖（碳水化合物微阵列），携带数十种或数百种不同的糖，这些糖以空间离散的模式固定在固体表面上，具有多种潜在的应用，在糖中具有多种潜在的应用事件和对抑制剂的高通量筛选，以防止碳水化合物 - 蛋白质相互作用。但是，将能够构建高质量碳水化合物微阵列的平台以及碳水化合物 - 蛋白质相互作用的敏感和快速测定以及表征，例如基因组和蛋白质组学研究中的等效技术并没有跟上加速。为了满足这一需求，我们开发了一个独特的新型三维平台，我们已经成功地证明了在I期研究中制造高灵敏碳水化合物微阵列的。该平台有可能使我们能够筛选数千种不同的碳水化合物探针，以与包括受体和抗体在内的蛋白质结合。在II阶段项目中，我们建议建立在可行性工作的基础上，以开发高级碳水化合物微阵列平台，以进行高吞吐量聚糖分析。具体而言，我们建议（1）优化一个将与现有的基于荧光的聚糖分析方法一起起作用的3D玻璃基层微阵列平台；（2）系统地比较平台表面化学的影响与聚糖功能和表位分配；（3）为前列腺癌聚糖的生物标志物发现开发表位定义的高潮N-聚糖微阵列，以及（4）开发3D SPR底物平台和无标签的表面等离子体共振（SPR）碳水化合物碳水化合物微阵列系统。 II期项目的结果和可交付成果将支持II期商业化目标，用于实施碳水化合物微阵列制造的超碳水化合物玻璃基质，以便将荧光检测应用于聚糖分析，并且用于碳水化合物的微阵列制造的金SPR平台底物，可用于无标记的检测可用于glycul分析。后续产品将包括定义明确的碳水化合物微阵列，用于肿瘤生物标志物，以及用于高吞吐量聚糖分析的无标签SPR成像系统。平台基板和微阵列系统的价值将带给主要和二级市场，应吸引大型公司作为合作伙伴支持商业开发，营销和分销。公共卫生相关性：碳水化合物和蛋白质之间的相互作用定义了人体中广泛的生化机制。目前，还没有可以快速筛选和研究这些碳水化合物相互作用的商业可行工具。拟议的工作将开发并展示一种微阵列工具，使研究人员能够探测碳水化合物生物化学以阐明疾病和药物机制并鉴定癌症生物标志物。