target discovery – simple answers from complex biology!
In past years, the majority of assays approved for use within the drug discovery industry relied heavily upon the creation of stable mammalian cell lines, which over-expressed the target of interest, or upon the over-expression and purification of recombinant proteins to establish biochemical assays. However, in recent years, there has been a shift to working with more physiologically relevant culture systems, like primary cells or iPSC derived cellular models. Typically, cell-based assays have been applied to target classes such as membrane receptors, ion channels and nuclear receptors, and usually employ a functional read-out as a consequence of compound activity. In contrast, biochemical assays, which have been applied to both receptor and enzyme targets often measure the affinity of the test compound for the target protein. Both assay types have been used successfully to identify hits and candidate molecules.
find out how we can help you optimise your:
The complexities of assay development and challenges associated with validating and transferring assays into HTS are well-known bottlenecks in the drug discovery process. TTP Labtech have sought to address this with the application of a novel liquid handling technology within a range of user-friendly, low volume liquid handling instruments that significantly reduce assay development time and greatly improve assay robustness in screening. Our liquid handlers provide you with precise and repeatable nanolitre pipetting, every time, irrespective of liquid viscosity or environmental conditions.
- guaranteed zero cross-contamination
- accurate sample placement for perfect drop dispensing every time
- cost-savings from optimised sample use and reduced waste
- proven suitability for multiple-user environments – just walk up and use it
dragonfly discovery is a very innovative liquid handling instrument, which uses a unique combination of positive displacement and non-contact pipetting to provide reliable, fast, broad dynamic range dispensing, which is agnostic of liquid class.
dragonfly discovery enables:
- design and development of complex assays directly in 384 or 1,536 well plate format
- dispense a variety of sample types including cells and/or beads
- simultaneous dispensing from up to 10 independently controlled channels
- DoE through intuitive user interface
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mosquito can be employed for a wide range of chemical and biological-based applications; including compound and small molecule screening, cell- or bead-based assays, enzyme kinetic assays, ELISAs, and molecular biology applications including rtPCR/qPCR set-up, RNAi screening and SNP genotyping.
Application areas include:
- serial dilutions
- plate reformatting and replication
- acoustic plate source creation
- next generation sequencing
- high-throughput MALDI-TOF MS
multiplex immune & cell health assays
Compound screening is an essential part of the early stage of the drug discovery process, to identify molecules that have activity on specific drug targets. Compounds identified as “hits” are further optimised using traditional medicinal chemistry to determine chemical groups responsible for evoking a target biological effect or structure-activity-relationships (SAR).
- multiplex hit identification and counter-screens into one assay
- use adherent cells, suspension cells, or sol-R beads
- gain throughput advantages with simple automation and gain more stringent results by screening out non-specific and non-selective hits in the same sample
- assay miniaturisation using high-density sol-R microplates
- visual confirmation of your results using an image for QC
RNAi has become a valuable research tool, both in cell culture and in living organisms, because synthetic dsRNA introduced into cells can selectively induce suppression of specific genes of interest. By identifying gene products whose knockdown is associated with phenotypic changes, large-scale RNA-mediated interference screens have demonstrated previously unknown components of biological pathways.
The acumen Cellista laser-scanning imaging cytometer is ideal for RNAi studies both in cell culture, and in whole organisms such as C. elegans or drosophila.
- single-shot whole well scanning
- the ability to analyse multiple parameters in a single assay
- the ability to perform genome wide phenotypic screens in hours not weeks
With over 40% of therapeutic drugs targets currently being membrane-associated proteins, the study of monoclonal antibodies for both immunodiagnostic biomarkers and therapies is a large growth area in the pharmaceutical industry.
Key applications for mirrorball include:
- biologics screening: hybridoma, phage display, B-cell cloning, antibody fragments, peptides, scFv, Fab
- binding characterisation: Bmax and Kd determination
- functional assays: cell cycle, cell signalling & proliferation
- quantification of soluble proteins: cytokines, hormones, growth factors
sample and compound management
Sample and compound storage and delivery are critical to assay development and reproducibility. Compound screening assays for hit discovery are typically run at 1–10 µM compound concentration. At these concentrations compounds with activities of up to 40 µM can be identified. The test concentration can be varied to identify compounds with higher or lower activity.
Our instrumentation is ideally suited to the storage and processing of biological and chemical reagents, including solubilised chemical compounds in DMSO and water, purified DNA, RT-PCR primers, proteins and antibodies.
- reduce potential damage to stocks by only cherry-picking the samples you need
- ensure sample integrity with temperature controlled, dry, inert, hermetically sealed environment
- ensure throughput grows with your library by processing samples in parallel
- never lose a sample
Secure, random access storage of compounds, antibodies, recombinant proteins (-20°C).
comPOUND sample storage system gives you the ability to:
- match storage capacity to current needs. Additional modules can be integrated in response to growing library size
- easily integrate with LIMS for robust sample tracking
- maximise efficiency of downstream automation with custom arraying of selected libraries
arktic is a compact, high density -80°C storage system with rapid random access of stored samples.
Unique pneumatic transport eliminates the need for robotics in the cold zone, combined with extensive monitoring and fail-safe back-up systems resulting in unrivalled reliability. Rackless storage increases density and removes rack edge effects ensuring all samples are treated equally. Tube only cherry picking ensures the integrity of innocent samples.
- easy and rapid sample access
- stable and reliable -80°C storage
- simple user interface
- full LIMS compatibility
- custom sample arraying for more efficient workflows
- sophisticated monitoring and back-up systems for fail-safe operation