Towards Mega-Throughput, Label-free Genomics and Proteomics: Revolutionizing Micr

迈向高通量、无标记基因组学和蛋白质组学：彻底改变微生物学

• 批准号: 7846673
• 负责人: Aydogan Ozcan
• 金额: $ 231万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-30 至 2014-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7846673
• 关键词: Arts; Behavior; Binding; Biochemical; Bioinformatics; Biological Markers; Cell Line; Chemicals; Data Quality; Detection; Development; Diagnostic; Disease; Epigenetic Process; Gene Proteins; Genetic Research; Genome; Genomics; Image; Label; Lead; Light; Malignant Neoplasms; Measurement; Medical; Microscope; Monitor; Operative Surgical Procedures; Optics; Pharmaceutical Preparations; Process; Property; Proteins; Proteome; Proteomics; Screening procedure; Single Nucleotide Polymorphism; Speed; Spottings; System; Technology; Tissue Engineering; abstracting; combat; cost; cross reactivity; functional genomics; high risk; high throughput screening; improved; interest; lens; nano; nanoscale; next generation; point of care; public health relevance; research study

DESCRIPTION (Provided by the applicant) Abstract: Micro-arrays provide a high-throughput platform for various key studies in functional-genomics, proteomics, epigenetics, medical-diagnostics and even tissue-engineering. Together with advanced biochemical detection, imaging and bioinformatics technologies, it is now possible to cost-effectively monitor the expression behavior of genes, proteins or other biomarkers, as well as screening the genome and proteome content of various cell lines, on-chip drug profiling or even detection of single-nucleotide-polymorphism. Therefore, micro-array technologies provide a vital platform for performing high-throughput screening experiments that shed light on our understanding of cellular, genomic, and proteomic processes occurring at the nano-scale. In this proposal, we aim to create the next-generation of micro-array technologies to achieve an unprecedented mega-throughput, i.e., label-free imaging of millions of DNA/protein microspots would be feasible per second. We term the broad-umbrella of these revolutionary technologies as Nano-plasmonic LUCAS. Specifically, we aim achieve a throughput of >120 cm2/second or >4.5 million spots/second for highlysensitive and label-free imaging of DNA/protein micro-arrays, which constitutes a speed improvement of >3 orders-of-magnitude when compared to the state-of-the-art. Label-free imaging is especially important not to perturb the natural bio-chemical, physical and structural properties of the original molecule-of-interest. It also makes the measurements much more quantitative, significantly improving the data quality; eliminates inconvenient labeling steps which further reduces the cost; and avoids cross-reactivity issues among secondary-probes which can significantly improve the detection of weak or transitional molecular interactions. This mega-throughput capability will revolutionize the speed of progress that is taken in proteomics/genetics research by orders-of-magnitude that could eventually lead to the development of improved strategies/therapies for combating previously intractable bio-medical problems and various diseases including cancer. Furthermore, the Nano-plasmonic LUCAS platform does not require any lenses, microscope-objectives or other bulk optical components, and therefore offers an extremely compact on-chip platform that can easily be merged with micro-fluidic systems to permit point-of-care operation. Public Health Relevance: In this high-risk high pay-off proposal, we aim to create the next generation of micro-array technologies to revolutionize the speed of progress that is taken in proteomics and genetics research by orders of magnitude that could eventually lead to the development of improved strategies and therapies for combating previously intractable bio-medical problems and various diseases including cancer.

描述（由申请人提供） 摘要：微阵列为功能基因组学、蛋白质组学、表观遗传学、医学诊断甚至组织工程的各种关键研究提供了高通量平台。结合先进的生化检测、成像和生物信息学技术，现在可以经济高效地监测基因、蛋白质或其他生物标志物的表达行为，以及筛选各种细胞系的基因组和蛋白质组内容、芯片上药物分析甚至单核苷酸多态性的检测。因此，微阵列技术为进行高通量筛选实验提供了一个重要的平台，这有助于我们了解纳米级发生的细胞、基因组和蛋白质组过程。在本提案中，我们的目标是创建下一代微阵列技术，以实现前所未有的超大通量，即每秒对数百万个 DNA/蛋白质微点进行无标记成像是可行的。我们将这些革命性技术的总称称为纳米等离子体 LUCAS。具体来说，我们的目标是实现 >120 cm2/秒或 >450 万个点/秒的吞吐量，以实现 DNA/蛋白质微阵列的高灵敏度和无标记成像，与相比，这构成了 > 3 个数量级的速度提升达到最先进的水平。无标记成像对于不干扰原始目标分子的天然生化、物理和结构特性尤其重要。它还使测量更加定量，显着提高数据质量；消除了不方便的贴标步骤，进一步降低了成本；并避免二级探针之间的交叉反应问题，这可以显着改善弱或过渡分子相互作用的检测。这种超大通量能力将以数量级彻底改变蛋白质组学/遗传学研究的进展速度，最终可能导致开发改进的策略/疗法，以对抗以前棘手的生物医学问题和包括癌症在内的各种疾病。此外，纳米等离子体 LUCAS 平台不需要任何透镜、显微镜物镜或其他大体积光学元件，因此提供了一个极其紧凑的片上平台，可以轻松与微流体系统合并，以实现即时护理手术。 公共卫生相关性：在这个高风险高回报的提案中，我们的目标是创造下一代微阵列技术，以彻底改变蛋白质组学和遗传学研究的进展速度，最终可能导致开发改进的策略和疗法来对抗以前棘手的生物医学问题和包括癌症在内的各种疾病。