Saving an Enzymatic HTS Assay with Sound

Written by Bioscribe on July 30, 2018

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In theory, it shouldn’t have presented much of a challenge, but trying to automatize a classic enzymatic assay based on the use of a substrate that becomes fluorescent after saponification proved more difficult.

The problem?

A strong adsorption of the substrate and stop compound on silicon tubes and tips, as well as a strong line effect on the experimental plates.

The solution? The Echo 550.

Dr. Céline Legros, a research scientist at Servier, shares her experience using an integrated Echo to rub out the phenomena of adsorption and line effect during HTS and H2L screenings in a recent Nature webcast.

Dr. Legros and her team made two attempts to automate their drug screening process with other liquid handling systems, but faced frustration as they encountered problems with adsorption, solubility, stability, and precipitation.

“I have to be honest with you, this project started to be a nightmare for me,” Legros said. “But, as I was working—fighting — with the automation, we installed in the lab a big robotic platform designed around an Echo 550.”

The custom-designed system, HEIDI (High Efficiency Investigation Drugs Instrument) includes two Echo Liquid Handlers (550 and 525), as well as cell washers, centrifuges, incubators, and other robotic components.

Legros, who had previously borrowed time on an Echo Liquid Handler to help with compound preparation, was happy to incorporate the technology in her third attempt at automating the screening process. She used it to dispense her enzyme substrate, and the results were much more robust, with more stable compounds and no line effect.

“With this new design of the assay, we were able to run up to 60 plates a day,” Legros said. “We were very happy with the result. Definitely the Echo 550 was a major improvement in the process.”

The gains were also seen in subsequent H2L tests, which involved six different proteins. The Echo automation not only saved the experiments, but also saved significant time and money: 1.5 technician working days, rather than the 6 days it previously took to carry out each protein screen separately.

“This assay was in theory easy to run, but classical dispensing instruments were not the solution and I was maybe too optimistic at the beginning of the project,” Legros said. “Echo technology arrived just in time in the lab to save the project and to avoid any more delay. Echos are now in the central position in our assay development strategies.”

Watch the webcast HERE.

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