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：微阵列技术为功能基因组学、蛋白质组学、表观遗传学、医学诊断学甚至组织工程学的各种关键研究提供了一个高通量的平台。结合先进的生化检测、成像和生物信息学技术，现在可以经济有效地监测基因、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含量，芯片上的药物分析甚至检测单核苷酸多态性。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，这些实验有助于我们了解纳米尺度上发生的细胞、基因组和蛋白质组过程。在这项提案中，我们的目标是创建下一代微阵列技术，以实现前所未有的百万通量，即，每秒对数百万个DNA/蛋白质微点的无标记成像将是可行的。我们把这些革命性技术的广泛保护伞称为纳米等离子体LUCAS。具体而言，我们的目标是实现>120 cm 2/s或> 450万个点/s的DNA/蛋白质微阵列的高灵敏度和无标记成像，与现有技术相比，这构成了>3个数量级的速度改进。无标记成像对于不干扰原始感兴趣分子的天然生物化学，物理和结构性质特别重要。它还使测量更加定量，显著提高了数据质量;消除了不方便的标记步骤，进一步降低了成本;并避免了二级探针之间的交叉反应性问题，这可以显著提高弱或过渡分子相互作用的检测。这种超大通量能力将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，用于对抗以前难以解决的生物医学问题和包括癌症在内的各种疾病。此外，Nano-plasmonic LUCAS平台不需要任何透镜、显微镜物镜或其他体光学组件，因此提供了一个非常紧凑的芯片平台，可以很容易地与微流体系统合并，以允许即时操作。 公共卫生相关性：在这个高风险高回报的提案中，我们的目标是创建下一代微阵列技术，以革命性地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治疗方法，以解决以前难以解决的生物医学问题和包括癌症在内的各种疾病。