Continuous-Imaging HT Screening Instrument(RMI)

连续成像高通量筛选仪(RMI)

• 批准号: 7125565
• 负责人: JEFFREY H PRICE
• 金额: $ 39.94万
• 依托单位: SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INSTITUTE
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-09-23 至 2009-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7125565
• 关键词: NIH Roadmap Initiative tag; bioimaging /biomedical imaging; biomedical equipment development; biotechnology; charge coupled device camera; computer program /software; computer system hardware; high throughput technology; image enhancement; robotics

DESCRIPTION (provided by applicant): Completion of the genomes of humans and several other organisms creates the foundation for translating this rich knowledge base into new products for the improvement of human medicine. A critical component of realizing the promise of genomics efforts is access to well-characterized chemical compounds that bind to and alter the activities of specific gene products. To this end, modern technologies for genome-wide expression profiling and high throughput proteomics provide the enabling foundation for large-scale chemical biology initiatives, using chemical compounds as discovery tools to probe biological pathways, thereby revealing new protein targets that alter cellular phenotypes in potentially beneficial or insightful ways. It is becoming recognized that many critical points of biological pathway regulation are predicated on protein-protein interactions rather than enzyme-based catalysis of cellular products to substrates. Thus, traditional methods of drug discovery are limited in the scope of targets they can adequately address. Screening scientists are finding that elucidation of cellular responses to chemical compounds at critical points of biological pathway regulation can be enabled by image-based cellular assays that automatically measure protein dynamics via computer vision of pattern and organelle translocations. Subunits of membrane and intracellular receptors often respond by reorganization or translocation. In addition, cellular heterogeneities that are both physiological (e.g., cell division cycle phase-specific) or apparently random can overwhelm whole-well conventional high throughput screening HTS readouts. These are examples of the ways that cell-image-based instruments can dramatically increase the information content of automated assays. The drawback of cell-image-based screening has been that instruments imaging at medium microscopy resolution (approximately 0.5 - 2.0 mu/m with 10-40x objectives) are typically limited to about 25,000 wells per day as compared with rates of 100,000 or more wells/per day for HTS conventional whole-well plate-reader HTS systems. While higher rates have been reported, these increases have been typically achieved by sacrificing resolution (e.g., even lower magnification objectives or substantial camera binning). Here we propose to increase the fundamental image scanning bandwidth (measured in pixels/s) by 10- fold over the current Beckman Coulter IC-100 instrument, the prototype of which was developed in Dr. Price's academic laboratory and first commercialized by Q3DM Inc. This increase will be gained by application of fundamentally new principles that parallelize auto-focus and image acquisition to scan slides and microtiter plates in long, unbroken continuous-motion multi-color strips. This will result in screening speeds of over 100,000 wells per day using medium resolution objectives (10-40x dry magnification).

描述（由申请人提供）：人类和其他几种生物的基因组的完成为将这种丰富的知识基础转化为新产品以改善人类医学的基础。意识到基因组学努力的希望的关键组成部分是获得与特征化的化合物结合并改变特定基因产物活性的良好化合物。为此，用于全基因组表达分析和高吞吐量蛋白质组学的现代技术为大规模化学生物学计划提供了促成基础，使用化学化合物作为发现生物学途径的发现工具，从而揭示了在潜在有益或有见识的方式中改变细胞表型的新蛋白质靶标。人们认识到，生物途径调节的许多临界点是基于蛋白质 - 蛋白质相互作用而不是基于酶的细胞产物催化对底物的。因此，传统的药物发现方法的限制是可以充分解决目标的范围。 筛选科学家发现，可以通过基于图像的细胞测定法来启动细胞对化合物对化合物的反应，从而通过基于图像的细胞测定方法来自动测量蛋白质动力学，这是通过模式和细胞器易位的计算机视觉。膜和细胞内受体的亚基通常通过重组或易位反应。此外，既有生理学的细胞异质性（例如细胞分裂循环阶段特异性）或显然随机的，可能会淹没全孔的常规高吞吐量筛选HTS读数。这些是基于细胞图像的仪器可以显着增加自动化测定的信息内容的示例。基于细胞图像的筛选的缺点是，中等显微镜分辨率的仪器成像（大约0.5-2.0 mu/m，目标为10-40x目标）通常限于每天约25,000孔，而HTS常规全玻璃板板系统的每天100,000或更多井/多个井/更多。虽然已经报道了较高的速率，但是这些增加通常是通过牺牲分辨率来实现的（例如，较低的放大目标或实质性的摄像机箱）。 在这里，我们建议将基本图像扫描带宽（以像素/s的衡量测量）提高10-折叠，而不是当前的贝克曼·库尔特IC-100乐器，该乐器的原型是在Price博士的学术实验室中开发的，并首先由Q3DM Inc. Inc. Inc.首先通过Q3DM INC进行商业化。将通过将基本原理应用于自动化的基本原理和图像 - 备用量的整个图像，并与图像相似，并将图像与图像相似，并将图像与图像相似。连续运动多色条。这将通过中等分辨率目标（10-40倍干放大倍率）每天导致筛查速度超过100,000孔。