High Throughput Screening
Cellomatics offer a range of high throughput screening services that can be applied to a wide variety of projects. High throughput screening facilitates the interrogation of hundreds to thousands of chemical or biological compounds in a single automated or semi-automated experimental set-up.
For more information on how Cellomatics Biosciences can assist with your high throughput screening requirements, please contact us or request a consultation.
High throughput screening (HTS) is a technique employed for accelerated lead generation in early phase drug discovery. High throughput screening facilitates the interrogation of hundreds to thousands of chemical or biological compounds in a single automated or semi-automated experimental set-up. Careful selection of an appropriate biochemical or cell-based assay(s) is essential, either focusing on a specific cellular target/process or broad physiological and metabolic changes in the presence of compound. Our team of scientists, bring expertise across the fields of molecular and cellular biology, immunology, oncology, immune-oncology, respiratory, and inflammation to tailor screening cascades to your specific requirements. Strategic HTS approaches can significantly streamline downstream functional investigations through the removal of compounds inviable due to unwanted cytotoxicity, poor solubility, lack of target engagement, and poor efficacy. Ultimately, HTS reduces the potential risk of both time and financial loss, whilst maximising success rates by investing in only the most promising leads.
Operating from a standard 3-step workflow, Cellomatics will guide you through primary lead generation, IC50/EC50 determination, and mode of action (MoA) investigation/confirmation. A typical HTS workflow investigating potential anti-inflammatory compounds might consist of an initial single high-dose screen in a relevant cell line to identify and exclude cytotoxic compounds and compounds displaying undesirable effects on physiological and metabolic functions. Suitable compounds are progressed for IC50/EC50 determination. This step can be conducted within the same assay, with relevant reference compounds, or in a phenotypic assay, using an appropriate disease background to determine changes in cytokines associated with inflammation. Finally, a selection of the most promising compounds can be investigated using functional molecular cell-based assays to confirm the biological relevance of these potential leads.
Our equipment for high throughput screening
To best support HTS at Cellomatics, we have continued to invest in state-of-the-art automated liquid handling systems, sample processors, and multimode analysis equipment. Our automated liquid handling system (Integra ASSIST PLUS) facilitates accurate, robust, and reproducible miniaturised assays in 96 or 384 microwell formats. Our multimode plater reader platform (VICTOR Nivo™) can analyse Absorbance, Luminescence, HTRF or TR-FRET up to a 1536-well scale. Recently we have doubled our throughput for phenotypic screening with the addition of the CytKick™ Autosampler to complement our existing Attune Nxt Flowcytometer. Finally, Cellomatics also provides High content screening/imaging services with the ImageXpress® Pico featuring the ImageXpress HCS.ai software.
BrdU assay was performed to investigate the effect of 100 test compounds on proliferation of primary keratinocytes isolated from three donors with skin diseases. The Proliferation (%) of keratinocytes treated with test compounds was determined by normalisation to untreated keratinocytes (dashed line at 100 on y-axis). Compound 17, indicated by the green arrow, was identified to have produced a consistent effect on the proliferation of keratinocytes from all three donors.
Cytokine analysis of the conditioned media taken from each keratinocyte treatment condition was conducted on a Luminex® Multiplex platform. Comparison of treatment conditions and untreated controls (dashed lines) revealed compound specific reduction in three analytes, IL-6, IL-8 and IL-23. Notably, the levels of cytokine release from cells treated with Compound 17 showed an overall reduction for all three analytes, across the three donors (represented with green symbols and arrows).
Compound 17 was investigated further for its effect on gene expression using QuantiGene™ RNA Multiplex assay. Gene expression is represented as fold change to housekeeping gene (HKG) (dotted line at 1). A difference in fold change were observed for genes encoding structural proteins such as Cadherin (CDH1), Involucrin (IVL), Occludin (OCLN), Keratin 10 (KRT10), Kallikrein (KLK 5 and 7). Changes in these genes and the cytokines might be correlated to skin cancer.
Request a consultation with Cellomatics Biosciences today
Our experienced team of in vitro laboratory scientists will work with you to understand your high throughput screening needs and provide a bespoke project plan with a professional, flexible service and a fast turnaround time.
To request a consultation to discuss your exact high throughput screening requirements, please contact Cellomatics Biosciences.
