CEGSTech: Integrated Biologically-Active Microsystems

原核生物和真核生物基因组序列的可用性为一场革命奠定了基础，这场革命最终将使生物学从主要是描述性和还原性的预测科学转变为科学。基于基因组信息分析整个生物系统的能力日益增强，这在转录和翻译水平上创造了细胞快照，这为细胞复杂性提供了初步的见解。然而，为了理解复杂的分子结果，如细胞增殖、分化、凋亡和发病机制，有必要确定这些部分如何在时间和空间上整合以形成复杂的、动态的细胞功能，以及细胞相互作用如何创造高阶功能。这种分析需要同时实时测量许多变量，并且由于细胞群体的异质性，这些分析需要对单个细胞进行。因此，实现这一目标的主要障碍是缺乏基于基因组信息在单个细胞水平上进行高度多变体动态分析的可用技术。第二个主要障碍是缺乏基于基因组信息处理单个细胞的技术。第二个主要障碍是缺乏处理基于基因组的表达分析的微样本的可用技术，允许比较主动性是与来自基因组科学，微分析化学和微系统工程的跨学科专家团队一起应对这些挑战，他们将开发和应用使能技术来分析和处理单个细胞。我们建议设计和建造完全集成和自动化的微系统来审问单个细胞。这一核心技术随后将转化为为特定应用而设计的模块，这将把检测的限制推到最低限度，在某些情况下，达到单分子水平。这一使能技术将针对两个主要领域的特定研究问题：1)细胞群体中稀有细胞的自动检测，以及2)单个细胞代谢的实时分析。这两个领域都适用于真核生物和原核生物，并且依赖于基因组序列数据的可用性，但不需要完整的基因组。我们开发的集成生物活性微系统将突破检测的极限，解决所有集成微系统中普遍存在的模块到模块的互连问题，强调整体系统集成，并使综合数据集的产生成为可能。最终，这些微系统将在生物医学系统生物学的广泛领域的基础和应用研究中具有深远的应用。

The availability of genome sequences for both prokaryotes and eukaryotes is laying the foundation for a revolution that will ultimately transform biology from a largely descriptive and reductionist predictive science. The growing ability to analyze whole biological systems based on genomic information is creating snapshots of cells at the transcriptional and translational level, which are providing preliminary insights into cellular complexity. However, to understand complex molecular outcomes such as cell proliferation, differentiation, apoptosis, and pathogenesis, it will be necessary to determine how the parts are integrated in time and space to form complex, dynamic cellular functions, and how cellular interactions create higher-order functions. Such analyses require the simultaneous measurement of many variable sin real-time, and due to heterogeneity in cellular populations, these analyses need to be carried out for individual cells. Therefore, a major barrier to achieving this objective is the lack of available technology for carrying out highly multi-variant, dynamic analyses at the level of individual cells, based on genomic information. A second major barrier is the lack of available technology for processing individual cells, based on genomic information. A second major barrier is the lack of available technology for processing microsamples for genome-based expression analysis, to allow comparative initiative is to meet these challenges with an interdisciplinary team of experts from genomic sciences, microanalytical chemistry, and microsystems engineering who will develop and apply enabling technology for analysis and processing of individual cells. We propose to design and build fully integrated and automated microsystems for the interrogation of individual cells. This core technology will then be converted into modules designed for specific applications, which will push the limits of detection to the minium, in some cases, to single molecule levels This enabling technology will be directed towards specific research problems in two main areas: 1) automated detection of rare cells in cell populations, and 2) real-time analysis of metabolism in individual cells. Both areas are applicable to eukaryotes and prokaryotes, and depend on availability of genome sequence data, but not necessary complete genomes. The integrated biologically-active microsystems we develop will push the limits of detection, tackle the module-to-module interconnect problem that is ubiquitous in all integrated microsystems, emphasize overall systems integration, and enable the production of comprehensive data sets. Ultimately, these microsystems will have far- reaching applications for both basic and applied research in broad areas of biomedical systems biology.