Expert Insight: Automation-enabled assay development for high-throughput screening

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Dr. Nina Grossman and Adrian Schoen, Discovery Pharmacology at Merck, Darmstadt

At Merck, a proprietary library of roughly one million drug-like compounds is screened in 10-15 high-throughput screening (HTS) campaigns per year. Respective assays range from simple binding analysis to complex phenotypic assays with multiple read-out parameters.  

In this on-demand webinar, Dr. Nina Grossmann and Adrian Schoen of Discovery Pharmacology at Merck, Darmstadt, reveal how they use SPT Labtech’s novel dragonfly discovery dispensing technology to set up robust high-throughput assays in a short timeframe. Also, hear about how the system enables the team to speed up assay development, multiplex assays, and save reagents.

Read on for highlights from the live Q&A session or watch the full webinar on demand.

Q: Comparing traditional assay development to assay development assisted by the dragonfly discovery, how much time would you save in hours?

NG: This depends on the assay and what you are going to set up. But using an example from the webinar, if you performed the kinase assay, which is comprised of multiple experiments in one on the dragonfly discovery, it would save you at least two days.

Q: Would you recommend the dragonfly discovery for screening applications?

NG: This also depends on the assay. If you have an assay that has complicated kinetics, for example, an assay where the reaction is still going on while dispensing, I would not recommend the dragonfly discovery. This is because if you compare the time it takes to dispense one plate, it is much longer compared to a multidrop system. By using the dragonfly you would start to see drifts on the plate. 

Q: What is the advantage of working in 1536-well plates? When would you not use this format?

NG: The advantage of the 1536-well plate is simply the throughput and the lower volume of reagents needed due to the wells being much smaller. In terms of not using it, I would choose another instrument if I predicted I would have problems with the volumes. For example, if you are using a detection reagent where you need higher volumes, then you cannot use it. I think cell-based assays are often tricky in this, especially if you are doing co-culture assays or are working with primary cells. Then the 1536 might be tricky. 

Q: Have you used the instruments to run cell-based assays?

AS: Yes, indeed we have. Also, since the dragonfly works rapidly you do not have to be cautious of the cells settling in the cylinders. 

Q: Are there dragonfly tips available that have low protein-binding properties?

NG: Only one generation of tips are now available to use. These have low protein-binding properties. However, Adrian (Schoen) has previously mentioned that it is good to saturate the syringes with DSA so you can get rid of any nonspecific binding to the syringes and such. Because we had some issues with the old generation of tips, we have coated them with silicone spray. 

Q: Can assays done on the dragonfly be performed on other liquid handlers as well?

NG: Yes of course, there are different liquid handlers out there. We have a couple of different ones here in our labs. Each of these different benchtop devices have their pros and cons. We also have bigger systems such as the Beckman systems which perform these assays. However, the programming of these assays is then much more complicated. 

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