Monitoring of HTS Compound Library Quality via a High-Resolution Image Acquisition and Processing Instrument

Monitoring of HTS Compound Library Quality via a High-Resolution Image Acquisition and Processing Instrument
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DOI:
10.1016/j.jala.2011.02.004
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发表时间:
2011-06-01
期刊:
影响因子:
--
通讯作者:
Hodder, Peter
Hodder, Peter
中科院分区:
医学2区
文献类型:
--
作者:
Baillargeon, Pierre;Scampavia, Louis;Hodder, Peter

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本报告介绍了用于化合物管理应用的高分辨率图像采集和处理仪器(HIAPI-CM)。HIAPI-CM结合了成像光谱和机器视觉分析,可对高通量筛选(HTS)化合物库质量进行快速评估。它已被定制为检测和分类HTS化合物库微量滴定板(MTP)中发现的典型伪影。这些伪影包括(1)液体化合物样品体积不足,(2)化合物沉淀,以及(3)干扰HTS测定检测格式读数的有色化合物。HIAPI-CM还配置为自动查询并将其分析结果与存储在LIMS或公司数据库中的数据进行比较,以帮助检测化合物配准错误。为了证明其能力,通过自动HIAPI-CM分析测量了含有不同伪影的几个化合物平板(共n = 5760个威尔斯孔),并将结果与手动(目视)检查获得的结果进行了比较。在所有情况下,仪器均显示出高保真度(99.8%空威尔斯孔; 100.1%填充威尔斯孔; 94.4%部分填充威尔斯孔; 94.0%含有色化合物的威尔斯孔),在沉淀物检测情况下,HIAPI-CM结果显著超过目视观察的保真度(220.0%)。如上所述,HIAPI-CM允许以每板约1分钟的诊断通量进行非侵入性、非破坏性MTP评估,从而降低分析费用并提高HTS化合物文库的质量和管理。(JALA 2011;16:197-203)
This report presents the high-resolution image acquisition and processing instrument for compound management applications (HIAPI-CM). The HIAPI-CM combines imaging spectroscopy and machine-vision analysis to perform rapid assessment of high-throughput screening (HTS) compound library quality. It has been customized to detect and classify typical artifacts found in HTS compound library microtiter plates (MTPs). These artifacts include (1) insufficient volume of liquid compound sample, (2) compound precipitation, and (3) colored compounds that interfere with HTS assay detection format readout. The HIAPI-CM is also configured to automatically query and compare its analysis results to data stored in a LIMS or corporate database, aiding in the detection of compound registration errors. To demonstrate its capabilities, several compound plates (n = 5760 wells total) containing different artifacts were measured via automated HIAPI-CM analysis, and results compared with those obtained by manual (visual) inspection. In all cases, the instrument demonstrated high fidelity (99.8% empty wells; 100.1% filled wells; 94.4% for partially filled wells; 94.0% for wells containing colored compounds), and in the case of precipitate detection, the HIAPI-CM results significantly exceeded the fidelity of visual observations (220.0%). As described, the HIAPI-CM allows for noninvasive, nondestructive MTP assessment with a diagnostic throughput of about I min per plate, reducing analytical expenses and improving the quality and stewardship of HTS compound libraries. (JALA 2011;16:197-203)