High Content Imaging as an Early Discovery Tool
High content imaging allows you to analyze how your compound interacts with a target at the subcellular level, delivering valuable insights that can drive your go/no-go decisions. As a screening tool, you can use multiplex cell painting techniques to analyze multiple profiles at the same time in the same sample well, optimizing your hit identification strategies. As you progress your candidate through lead optimization, you can use high content analysis to monitor compounds in complex cellular systems to predict translational success in vivo.
Cell Painting: Morphological Profiling Using Multiplexed Fluorescent Dyes
Figure 1: HeLa cells stained with multiple fluorescent dyes after exposure to the compounds (a) Cytochalasin (b) Lovastatin (c) Latrunculin (d) Nocodazole.
High Content Screening (HCS)
HCS uses a high-throughput live cell imaging format to screen compounds in complex cellular systems to identify new drug targets or new lead compounds. More predictive than classic plate-reader high-throughput screening (HTS), the high content imaging screening format provides data specifically at the target site, as well as any off-target effects, all in the same assay. Using cell painting multiplex techniques, you can even monitor multiple nodes in a cellular pathway.
With extensive experience in high-throughput screening, in-house image analysis algorithm design, and disease biology, our team can help you select the right cell type and assay parameters before initiating HCS. We develop assays for small molecule screening using our 850,000-compound collection and for RNAi screening using our proprietary adenoviral platform, SilenceSelect®. Current screening assays include apoptosis, protein phosphorylation, receptor degradation, marker expression, and many more.
High Content Analysis (HCA)
As you move further into development, you can use HCA to profile lead compounds in disease-relevant cell-based assays. Detailing cellular physiology in a complex cellular system, live cell imaging delivers predictive, translatable data. HCA monitors phenotypic changes such as morphology, cellular localization and proliferation that can be both visualized and quantified and in real time. HCA has progressed to include multicellular structures such as 3D spheroids and co-cultures as well as multiplexing to monitor multiple features within a microenvironment all in one well.
High Content Imaging (HCI) Assay Development
High content imaging is a powerful tool for drug discovery, but its application requires specialized equipment and expertise that few organizations have in-house. Below are just some of the tools and technologies you’ll find at Charles River.
- GE InCell Analyzer 2200
- GE InCellAnalyzer 6000
- TTP LabTech Acumen Explorer™
- BD Pathway™ 435
- LI-COR Odyssey imager
- 10 TB and 30 TB dedicated image servers
- Cell types
- Anchorage independence (in 3D)
- Autophagy and protein aggregation
- Cell motility and migration
- Epigenetic modifications
- Marker expression
- Protein acetylation and phosphorylation
- Receptor internalization and degradation
- Subcellular localization
- Translocation of transcription factors
- Custom assays
What’s the difference between HCI, HSC, and HCA?
The terms high content imaging (HCI), high content screening (HSC) and high content analysis (HCA) are often used interchangeably. HCI refers to the imaging technology. HCS typically refers to screening targets and compounds in a high-throughput format. HCA is studying cell based-assays, typically for optimizing the hits from a high-throughput or high content screen.
Where can high content imaging be applied in the drug discovery pipeline?
High content imaging can be applied to many steps in the drug discovery workflow. Cellomics starting at the earliest stage, hit identification high content screening can be used to screen targets and compounds. Once a hit has been identified, that compound can lead can be optimized using high content analysis which will provide predictive, translatable data for in vivo studies. High content analysis can also be applied to ex vivo studies before moving into safety assessment. High content imaging has many applications in well planned Integrated Drug Discovery program for therapeutic areas such as Cancer and Neuroscience.
CRISPR-Cas9 used under licenses to granted and pending US and international patents from The Broad Institute and ERS Genomics Limited.