ECIS-based High Throughput Screening Instrumentation

基于 ECIS 的高通量筛选仪器

• 批准号: 7655548
• 负责人: CHARLES R KEESE
• 金额: $ 32.17万
• 依托单位: APPLIED BIOPHYSICS, INC.
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-02-04 至 2011-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7655548
• 关键词: Achievement; Behavior; Biological Assay; Biophysics; Cell Culture Techniques; Cell physiology; Cells; Complex; Computer software; Cultured Cells; Custom; Cytoskeleton; Data; Data Files; Data Set; Development; Device or Instrument Development; Drug Industry; Electrodes; Electronics; Endothelial Cells; Evaluation; Frequencies; Goals; Grant; Individual; Laboratories; Libraries; Marketing; Measurement; Measures; Mechanics; Methods; Monitor; Permeability; Pharmaceutical Preparations; Phase; Production; Property; Reading; Research; Robotics; Running; Screening procedure; Site; Source; Spectrum Analysis; Speed; System; Techniques; Technology; Testing; Therapeutic; Time; Wound Healing; Writing; base; cell behavior; cell motility; cost; data acquisition; design; electric impedance; high throughput screening; insight; instrument; instrumentation; migration; monolayer; prototype; solid state; success; voltage; wound

DESCRIPTION (provided by applicant): The long-term objective of the research is to develop and fabricate an instrument that can facilitate the discovery of new drugs via high throughput screening (HTS). ECIS (electric cell-substrate impedance sensing) is a technology developed by Applied BioPhysics to study the behavior of cultured cells in real time. Instruments manufactured by the company currently find use in over 150 laboratories world wide to measure such fundamental cell properties as permeability of cell monolayers, cell migration and cell-extra cellular matrix interactions. The ECIS instrumentation had been limited to low throughput research endeavors where a maximum of 16 individual cell cultures could be monitored. Phase I research culminated in the development and fabrication of the first 96 well version of ECIS. This instrument is limited to measurements of simple impedance and has a throughput restricted to a single 96 well plate. In spite of these limitations, the ECIS 9600 instrument is now being successfully marketed primarily to academic laboratories. The objective of the Phase II research is to build upon the success of Phase I and create a truly high throughput ECIS system. The new instrument will be capable of monitoring the complex impedance of ECIS culture wells over a broad spectrum of AC frequencies. Custom electronics will accommodate rapid data acquisition of large numbers of 96 well plates permitting thousands of individual wells to be screened. The instrument will capitalize upon the power of monitoring complex impedance and will be tailored for two important cell-based assays. One of these assays will involve measurement of cell migration based on an automated ECIS-based wound-healing assay. The other will monitor changes in barrier function of cell layers. None of these important measurements can presently be accomplished in a high throughput assay. The achievement of these goals will involve several steps: "development and testing the necessary electronics," design and testing of affordable consumable arrays specifically tailored for each assay, "production of custom software to run assays and manage the large resulting data files, "interfacing the ECIS instrumentation with standard robotic plate handlers. Once a complete prototype instrument has been fabricated, we will establish two beta test sites where the instrumentation and its software will be thoroughly evaluated and changes implemented to yield the final production unit. In Phase III, the instrument will be used in HTS assays in the pharmaceutical industry, where literally tens of thousands of test compounds will be evaluated in the search for modern therapeutic drugs.

描述（由申请人提供）：该研究的长期目标是开发和制造一种可以通过高通量筛查（HTS）促进新药的仪器。 ECIS（电细胞基层阻抗传感）是一种由应用生物物理学实时研究培养细胞的行为开发的技术。该公司生产的仪器目前在全球150多个实验室中使用，以测量诸如细胞单层，细胞迁移和细胞脱离细胞细胞矩阵相互作用等基本细胞特性。 ECIS仪器仅限于低吞吐量研究，其中最多可以监测16个单个细胞培养物。第一阶段的研究最终达到了第一个96井版本的ECIS的开发和制造。该仪器仅限于简单阻抗的测量，并且吞吐量仅限于单个96井板。尽管存在这些局限性，但ECIS 9600仪器现在主要将主要销售给学术实验室。第二阶段研究的目的是建立在第一阶段的成功基础上，并创建一个真正高的吞吐量ECIS系统。该新仪器将能够监测ECIS培养井在广泛的AC频率上的复杂阻抗。定制电子设备将适应大量96个井板的快速数据采集，允许筛选数千个单独的井。该仪器将利用监测复杂阻抗的力量，并针对两个重要的基于细胞的测定法进行量身定制。这些测定法之一将涉及基于基于ECIS的自动伤口治疗测定法测量细胞迁移。另一个将监视细胞层屏障功能的变化。这些重要的测量目前无法在高通量测定中完成。这些目标的实现将涉及多个步骤：“开发和测试必要的电子设备”，专门针对每种测定的负担得起的可消耗阵列的设计和测试，“定制软件的生产来运行测定和管理大型数据文件”，将ECIS仪器与标准的机器人板件将ECIS互动交织在一起。一旦制造了完整的原型仪器，我们将建立两个beta测试站点，其中仪器及其软件将得到彻底评估并进行更改以产生最终的生产单元。在第三阶段中，该仪器将用于制药行业的HTS测定法，从字面上看，在寻找现代治疗药物时，将评估成千上万的测试化合物。