Assays
Figure 2: Change in assay development time over the past two years
Development time decreased 52%
Development time increased 10%
© HighTech Business Decisions
“We start off with a robot-friendly assay so assay development is very fast, and there’s no adapting the assays to the high throughput instrumentation.” HTS laboratory
Development time stayed the same 38%
“It used to be that targets were proposed, approved, and then we would have to wait for reagents and assays to be generated before we could start screening. Now when the target ID group finds a target, they let us know about three months ahead, and we start generating reagents and developing assays ourselves. This has com- pletely eliminated reagents and assays that are inappropriate in a high throughput format, and it has decreased our assay development time by 2.5 months.”
HTS Laboratory
l Experience and knowledge of the target. l Implementing high throughput automation earlier. l New technologies and platform approaches. l Availability of custom or commercial reagents and assays.
Experience with HTS and the target High throughput screening has become a well- established technology in the past decade, and directors and their staff have become experienced meeting the unique miniaturised and automated demands of HTS. Familiarity with a target and knowledge of its active site dynamics and other physical properties of the proteins facilitates assay development. The following comments from the HTS lab directors describe the effect of experience on assay development.
“Assay development time has decreased a little bit because people working with the assays are more knowledgeable.”
HTS laboratory
“When I worked at a small biotech company, assay development time took two to three weeks because we were working on similar target classes.” Non-commercial laboratory
Implementing high throughput automation earlier
HTS directors have seen that it is important to incorporate automation and robust screening assay formats from the beginning of assay development. Early communication with the therapeutic or tar- get identification groups diminishes delays caused by the need to generate reagents. The comments below describe how early implementation of HTS speeds assay development.
52
New technologies and platform approaches
New technology has enhanced screening making it faster with better quality. Liquid handling is more accurate and automated scheduling has improved. One HTS vendor noted: “Most of the mechanical and software problems have been solved, so the challenge isn’t a matter of moving the wells around.” As a consequence of experience and famil- iarity with the targets, lab directors are able to devel- op some standardised approaches to assay develop- ment. The following remarks expand on some of the standardisation directors are implementing.
“Assay development time has decreased because we have set up a process in which we do a full high throughput characterisation of the proteins we use.” HTS laboratory
“Certain parts of our assay development are repeated and we’ve developed sort of a template. We have also limited our target choices to fit into this assay development template.”
HTS laboratory
Availability of custom and commercial reagents and assays
The availability of commercial reagents and assay kits is another time-saving tool that has influenced assay development, as one director commented, the time “depends on the availability of tools. If we can purchase an enzyme commercially, then it may take three to four months”. Custom or commercial assays are enabling labs to save time on internal development thus speeding targets into screening. One director noted below that previously estab- lished assays are helpful.
Drug Discovery World Summer 2010
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