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Integrated Digital Microfluidic Platforms for Next-Generation Glycomics

用于下一代糖组学的集成数字微流控平台

基本信息

批准号：
9323361
负责人：
Yong Zeng
金额：
$ 29.27万
依托单位：
UNIVERSITY OF KANSAS LAWRENCE
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-08-01 至 2019-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9323361
关键词：
Address Anabolism Antibodies Antigens Automation Benign Biological Biological Assay Biological Markers Blood Plasma Volume Blood specimen Cancer Patient Carbohydrates Clinical Complex DNA Microarray Chip Detection Development Disease Early Diagnosis Engineering Enzymatic Biochemistry Enzyme-Linked Immunosorbent Assay Genomics Glycoproteins Goals Heterogeneity Human Investigation Laboratories Lectin Life Light Malignant Neoplasms Malignant neoplasm of ovary Mass Spectrum Analysis Measurement Mechanics Methods Microfluidics Molecular Neoplasm Metastasis Oils Operative Surgical Procedures Ovarian Serous Adenocarcinoma Pathologic Patients Pattern Performance Phase Physiological Plasma Polysaccharides Post-Translational Protein Processing Predisposition Protein Glycosylation Protein Microchips Proteins Proteomics Regulation Reproducibility Research Role STEM research Sampling Speed Statistical Data Interpretation Surface System Techniques Technology Time Tissues Variant Western Blotting Work analog base carcinogenesis clinically significant comparative design digital glycosylation high throughput technology improved innovative technologies instrument instrumentation interest microsystems new technology next generation novel optical fiber point of care profiles in patients screening single molecule stem success tool

项目摘要

Abstract Protein glycosylation is ubiquitously involved in all domains of life and holds the key to elucidating molecular mechanisms underpinning disease. Despite the biomedical and clinical significance of glycans, progress in glycomics has considerably lagged behind genomics and proteomics, owing to enormous structural diversity and dynamic alternation of glycans arising from complex non-template driven biosynthesis. Thus it is imperative to develop innovative technologies and instrumentation that can catalyze key breakthroughs in glycomic analysis. This proposal intends to address the urgent need of the next-generation glycomics technologies by leveraging on new microfluidic platforms stemming from research in the PI's laboratory. Specifically, the PI proposes to develop a novel microfluidic actuator-based single-molecule analysis method that can substantially improve the analytical performance of lectin microarray. Moreover, the PI seeks to integrate sample processing functionalities with the digital lectin-antibody barcode array system to construct a “sample-in-answer-out” digital microfluidic lectin array platform for sensitive and quantitative targeted glycomic profiling in a high-throughput manner. The project consists of three aims: 1) develop a digital microfluidic approach for single-molecule quantification of low-abundance glycoproteins; 2) develop a fully integrated microsystem for multiplexed, quantitative targeted glycomic profiling; and 3) demonstrate quantitative comparative glycomic profiling of plasma from ovarian cancer patients. This research, if successful, will yield a key transformative tool for systems glycomics and allow the PI to pursue the long-term interest in biomedical investigation of pathological roles of protein glycosylation through obtaining dynamic overview of human plasma glycome.

摘要蛋白质糖基化广泛存在于生命的各个领域，是阐明蛋白质糖基化的分子机制的关键。疾病的基础机制。尽管聚糖具有生物医学和临床意义，但在由于结构上的巨大差异，糖组学已经大大落后于基因组学和蛋白质组学以及由复杂的非模板驱动的生物合成产生的聚糖的动态变化。因此必须开发创新技术和仪器，以促进关键突破，糖组学分析该提案旨在解决下一代糖组学的迫切需求通过利用PI实验室研究的新微流体平台，具体来说，PI建议开发一种新的基于微流体致动器的单分子分析方法这可以显著提高凝集素微阵列的分析性能。此外，PI旨在将样品处理功能与数字凝集素-抗体条形码阵列系统集成，以构建用于敏感和定量靶向糖组学的“样品输入-应答输出”数字微流控凝集素阵列平台以高通量的方式进行分析。该项目包括三个目标：1）开发数字微流体低丰度糖蛋白的单分子定量方法; 2）开发完全集成的用于多重、定量靶向糖组学谱分析的微系统;以及3）展示定量靶向糖组学谱分析的方法。卵巢癌患者血浆的比较糖组学分析。这项研究如果成功，系统糖组学的关键变革工具，并允许PI追求生物医学领域的长期利益通过获得人体动态概况研究蛋白质糖基化的病理作用血浆糖组。