High-throughput screening strategies have traditionally focused on identifying compounds that modify the activity of a specific molecular protein target. This molecular target approach to screening is widely used as information regarding protein structure and small molecule-protein interactions is readily available for many protein targets.
However, when prerequisite knowledge of a target’s function and structure is unknown or a single target cannot be identified, cellular imaging assays can be used to screen chemical libraries for a desired phenotype, and these assays more accurately reflect the complex biology of tissues. Recent efforts have focused on screening in microtissues, which can provide a more valid model of disease.
High-Throughput Screening (HTS) for Molecular Targets
The screening of specific molecular targets is the most straightforward method for identifying small molecule drugs with a specific, desired mechanism-of-action. This not only facilitates hit identification, but can also speed drug approval at later stages. A key goal of HTS campaigns is to develop a robust, functional assay that is easily automated and provides good signal-to-background and Z’ scores. This increases objectivity and reduces subjectivity in data evaluation, providing easier identification of true hits.
PerkinElmer provides robust cellular and biochemical screening reagents and assays for proven and novel target classes, including:
PerkinElmer’s plate readers, high-throughput radiometric detectors, and automated liquid handling workstations allow you to customize screening operations to meet your throughput and application needs.
- The EnVision® Multilabel Plate Reader uses an enhanced luminescence technology to increase the sensitivity of HTS assays, a laser option for TR-FRET that allows savings on reagent costs and increased throughput, and offers the fastest speed for reading 384- and 1536- well AlphaScreen® assays.
- TopCount NXT™ and MicroBeta2 detectors can count beta, gamma, and luminescent labels in 24-, 96-, and 384-well microplates and utilize plate stackers for unattended counting.
- For increased laboratory efficiency, our plate readers and detectors can be integrated with JANUS®, Sciclone, or Zephyr® liquid handling workstations to facilitate volume miniaturization for cost-effective use of reagents, greater reproducibility and data consistency, and elimination of hands-on, manual processes.
High Content Screening (HCS) Using Cellular ModelsHigh content screening
utilizes cellular assay models that more accurately reflect the complex biology of disease, permits measurement of multiple complex phenotypic parameters, and enables screening in situations where a specific molecular target cannot or has not been identified. The large amount of image data generated, as well as challenges in automated, quantitative analysis of phenotypic data, can hinder the screening process.
PerkinElmer’s Operetta® High Content Imaging System enables researchers to quickly image samples and analyze complex phenotypic parameters in cellular imaging assays. The Operetta is an easy to operate system well-suited for multi-user, multi-department environments, and includes Harmony® high content analysis software that facilitates the translation of image data to unbiased quantitative data. For high-volume image data storage, our Columbus™ Image Data Storage and Analysis System enables users to analyze, access, view and store high content images from almost any system.
High Content Analysis of Microtissues
Cells are traditionally grown in monolayers for high content imaging and cell-based assays. However, cells behave very differently in three dimensions. Three-dimensional microtissues provide an environment where cells more closely retain their physiological properties, and are amenable to high-throughput applications. Screening in microtissues can result in lower incidence of false positives and allows early elimination of toxic compounds during the screening process.
The use of microtissues can present challenges in imaging due to their density. PerkinElmer’s Operetta High Content Imaging System has a confocal imaging option that enables imaging of dense microtissues, while providing the throughput necessary for screening large or small compound libraries. For easier workflows, our JANUS® Automated Liquid Handling Workstation facilitates handling of microtissues in large screens. Microtissues can be used in conjunction with our near-infrared (NIR) fluorescence imaging agents, which ensure low light absorption and scattering in tissue for easier phenotypic measurement of complex biological processes including angiogenesis, cardiovascular disease, hypertension, inflammation, and oncology.