With high-throughput screening (HTS), pharmaceutical laboratories can boost their output whilst reducing their experiment timescales and costs. HTS is an automated drug discovery process that enables large volumes of compounds to be tested at any one time for a specific target. Various methods exist and these are used widely across pharma businesses; using automation and robotics to rapidly test the biochemical or biological activity of molecules at volume (usually drugs).
The approach is particularly useful for:
- Accelerating the analysis of targets, as compound libraries can be rapidly and cost-effectively screened at a large scale.
- Identifying biological ‘leads’ and generating insights for their optimisation – usually as a starting point for the development of new drugs, or to understand how different biochemical agents interact.
- Providing a rapid scan for biological processes, so that compounds with a null of limited effect can be rapidly removed from the subsequent analysis.
How does High-throughput screening work?
From a tech perspective, there are three main points in the approach: 1) miniaturisation, automation and assay readout. The screening will typically incorporate four steps.
- Preparing samples and compound libraries
- Devising a suitable lab automation method
- Programming the robotic workstation
- Planning how to handle the gathered data and doing so.
Key points to note:
– Miniaturisation is a key issue as samples have to be small enough to manage costs, but significant enough to provide valid results. This means that the microplate reader’s sensitivity and ability to measures samples in a reliable way is hugely important.
– Depending on the assay, the samples will usually be biochemical or cellular. The microplate acts as the sample carrier, and its choice of colour and format depends on the nature of the detection assay and the sample.
– Automation is critical for success, as the process relies on high-throughput screening which forces a series of specific constraints. Key issues when preparing the automated screen are the quality control method and the establishment of a stringent essay. High-quality data can be more reliably gathered where distinctions between positive and negative controls are clear.
– The robotic platform will need to manage a large number of plates simultaneously in order to facilitate rapid data gathering. This could range from simple liquid handling through to multiple functions across multidimensional workstations, using a series of mechanical arms. Robotic systems will manage station microplates for steps that include adding reagents, mixing, incubating and detecting.
Limitations of high-throughput screening
These processes aren’t usually able to identify drugs, as compound library screening isn’t able to identify a number of properties that are key to new drug development. For example, HTS cannot measure bioavailability or toxicity. The cost of this approach can also be prohibitive, as HTS needs expensive and highly specialised screening services that are beyond the resources of many labs.
Some labs instead use CRO third party services or the facilities of academic environments. Interested in finding out more? Visit bmglabtech.com for the latest news and updates in the field of microplate reader instrumentation innovations, and their varied applications.
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