High Throughput Screening

High Throughput Screening - An Introduction

MOT head/Janus

High throughput screening (HTS) is a popular approach to target validation as it allows the assaying of a large number of potential biological modulators against a chosen set of defined targets.

HTS brings together expertise in liquid handling and robotic automation, multi-platform plate readers and more recently high content imaging, this combinatorial approach means that complex, content rich data set can be produced over a relatively short space of time. The advantage of miniaturisation and automated liquid handling allows rapid, inexpensive and effective up-scaling of small scale bench top assays to large scale assay formats.

Screening large numbers of biological modulators across a panel of targets produces a number of ‘active hits’, this is usually somewhere in the region of 2% of the total number screened. These ‘actives’ can then be interrogated in much finer detail through secondary hit validation and selection of potentially potent modulators for progression to much more in-depth study. Screening a wide range of constructs in such a way can provide detailed information into the interaction of biological processes.

High throughput screening can be seen as a quick scan of biological actives, meaning compounds with poor or no effect can rapidly be dropped from investigation and a portfolio of biologically relevant compounds can quickly be built up. This promotes a much more structured and focused approach to latter stage screening.

Full scale HTS libraries generally extend into many thousands of constructs. Libraries are initially divided into biological activity approach – e.g. Small compound, siRNA, shRNA.

Each of these libraries is further sub-divided into smaller libraries according to biological family or target specificity. All libraries are arrayed into micro-well plates enabling screening in a miniaturised form – either in 96, 384 and in some cases 1536 well plates.

The high throughput screening approach accelerates target interrogation, meaning large scale libraries can be screened both quickly and relatively cost effectively.

High Throughput Screening at the TDI

TDI _ Barcoded Plates

The TDI offers a wide range of expertise gained from both industrial and academic backgrounds. This means we are able to offer a wide range of screens across a number of platforms as well as being able to offer technical and scientific advice for the development and execution of you assays form the earliest stage of development through to completion and data analysis.

A brief introduction to small compound and siRNA high throughput screening at the TDI can be found using the links at the top of this page.

Details of screens run in the TDI

High Throughput Screening - Further Reading

Eli Lilly/NIH Centre for Clinical Excellence Guidance for Assay Development and HTS

A review of high throughput screening for drug discovery