CEGSTech: Integrated Biologically-Active Microsystems

原核生物和真核生物的基因组序列的可用性正在为一场革命奠定基础，这场革命最终将使生物学从一门主要是描述性和还原论的预测科学转变为一门科学。基于基因组信息分析整个生物系统的能力不断增长，正在转录和翻译水平上创建细胞快照，这为细胞复杂性提供了初步见解。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细胞功能，以及细胞相互作用如何产生高阶功能。这种分析需要实时同时测量许多变量，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，实现这一目标的一个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异的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可用技术。第二个主要障碍是缺乏处理用于基于基因组的表达分析的微量样品的可用技术，以允许比较主动性是通过来自基因组科学、微量分析化学和微系统工程的跨学科专家团队来应对这些挑战，他们将开发和应用使能技术来分析和处理单个细胞。我们建议设计和建立完全集成和自动化的微系统，用于单个细胞的询问。 然后，这一核心技术将被转换成专为特定应用设计的模块，这将把检测的极限推到最低限度，在某些情况下，推到单分子水平。这一技术将针对两个主要领域的具体研究问题：1）自动检测细胞群中的稀有细胞，2）实时分析单个细胞的代谢。这两个领域都适用于真核生物和原核生物，并取决于基因组序列数据的可用性，但不一定是完整的基因组。我们开发的集成生物活性微系统将突破检测极限，解决所有集成微系统中普遍存在的模块到模块互连问题，强调整体系统集成，并实现全面数据集的生成。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.