Reconfigurable microfluidic assay platform for molecula*

可重构的分子微流控分析平台*

• 批准号: 7318327
• 负责人: PETER Russell Charles GASCOYNE
• 金额: $ 64.98万
• 依托单位: UNIVERSITY OF TX MD ANDERSON CAN CTR
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-02-01 至 2010-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7318327
• 关键词: Archives; Biochemical; Biological Assay; Blood capillaries; Communities; Computer software; Consumption; Detection; Enzyme Inhibitor Drugs; Enzyme Inhibitors; Goals; Health; Human; Individual; Libraries; Liquid substance; Luminescent Measurements; Maintenance; Mechanics; Methods; Microcomputers; Microfluidics; Molecular; Molecular Bank; Numbers; Optics; Performance; Phase; Process; Reaction; Reagent; Research; Research Personnel; Research Project Grants; Sampling; Screening procedure; Solutions; Structure; Surface; System; Technology; Testing; Therapeutic Agents; Validation; Work; assay development; base; capillary; cost; design; detector; drug discovery; high throughput screening; improved; instrument; instrumentation; programs; prototype; size; small molecule libraries

Improved instrumentation for high-throughput screening of molecular compound libraries has the potential to advance human health by accelerating the drug-discovery process. Current mechanized screening approaches suffer from several drawbacks, including bottlenecks in compound maintenance and disbursement, as well as assay rapidity, accuracy, and content. We propose a microfluidic solution to this problem; we will use a reconfigurable fluidic processor as the basis for a biochemical assay engine to perform screening reactions against libraries of test compounds. Technology developed in our lab currently allows the programmable manipulation of nL-scale droplets of reagents for sample analysis on a 0.4 cm2 reaction surface. We plan to combine these assay capabilities with a molecular library archiving and dispensing system to yield a complete prototype screening platform; stored screening libraries will be dispensed onto the reaction platform from individual capillaries (for small libraries) or from capillary channels in credit-card sized library cartridges (for large libraries). Improvements over existing screening methods will include decreased reagent and compound consumption; decreased platform size, cost, and power usage; and greater instrument reliability due to an almost complete absence of moving parts. The system should be ideal for molecular library screening because it can be easily programmed as needed to perform different sets of assays with an arbitrary number of reaction steps. Furthermore, the compound archiving system will provide a convenient way for researchers to store libraries of test agents in a small format that is robust and can be readily disbursed to various screening centers. The specific aims of this design-driven research are to develop a molecular library archiving and dispensing system; develop a microfluidic assay engine with integrated components for molecular screening; and validation of the performance of the molecular library screening platform using test assays. We plan to collaborate with a molecular assay development lab to demonstrate molecular screening using the prototype platform and have structured our project plan to facilitate this. The goal of this project is to build an assay platform that can be used to screen large libraries of chemical compounds for various biologically-relevant activities. This approach is one of the first steps in identifying candidate therapeutic agents for further research and testing. The assay platform described in this proposal has the potential to accelerate the drug discovery process by enabling more efficient and cost-effective compound screening.

改进的仪器以高通量筛选分子化合物库有可能 通过加速药物发现过程来提高人类健康。当前的机械化筛选 方法遭受了几个缺点，包括复合维护中的瓶颈和 支出以及测定的速度，准确性和内容。我们为此提出了一个微流体解决方案 问题;我们将使用可重新配置的流体处理器作为生化测定引擎的基础 对测试化合物的库进行筛查反应。目前在我们的实验室中开发的技术 允许对试剂的NL尺度液滴进行可编程操作，以在0.4 cm2上进行样品分析 反应表面。我们计划将这些测定功能与分子库存档相结合，然后 分配系统以产生完整的原型筛选平台；存储的筛选库将是 从单个毛细血管（对于小文库）或毛细管通道分配到反应平台上 在信用卡大小的图书馆墨盒中（用于大型图书馆）。对现有筛查方法的改进将 包括减少的试剂和复合消耗；平台尺寸，成本和电力使用量降低； 以及由于几乎完全没有运动部件而导致的仪器可靠性更大。系统应该是 非常适合分子库筛选，因为它可以根据需要轻松编程 具有任意数量反应步骤的测定集。此外，复合档案系统将 为研究人员提供一种方便的方式，以较小的格式存储测试代理的库，该格式很强，并且 可以很容易地将各种筛查中心支付。这项以设计为驱动的研究的具体目的是 开发分子库存档和分配系统；开发带有微流体测定引擎 用于分子筛选的集成成分；和验证分子文库的性能 使用测试分析的筛选平台。我们计划与分子测定开发实验室合作 使用原型平台展示分子筛选，并将我们的项目计划构建 促进这一点。 该项目的目的是建立一个可用于筛选大型化学库的测定平台 各种与生物学相关的活性的化合物。这种方法是识别的第一步之一 候选治疗剂进行进一步研究和测试。本提案中描述的测定平台 有可能通过提高效率和成本效益来加速药物发现过程 复合筛选。

项目成果

Quantitative detection of bioassays with a low-cost image-sensor array for integrated microsystems.

• DOI: 10.1002/anie.200901814
• 发表时间: 2009
• 期刊: Angewandte Chemie (International ed. in English)
• 作者: Vykoukal DM;Stone GP;Gascoyne PR;Alt EU;Vykoukal J
• 通讯作者: Vykoukal J

A High-Voltage Integrated Circuit Engine for a Dielectrophoresis-based Programmable Micro-Fluidic Processor.

用于基于介电泳的可编程微流体处理器的高压集成电路引擎。

• DOI: 10.1109/icmens.2005.15
• 发表时间: 2005
• 期刊: Proceedings ... International Conference on MEMS, NANO, and Smart Systems. International Conference on MEMS, NANO, and Smart Systems
• 作者: Current,KWayne;Yuk,Kelvin;McConaghy,Charles;Gascoyne,PeterRC;Schwartz,JonA;Vykoukal,JodyV;Andrews,Craig
• 通讯作者: Andrews,Craig