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Manufacture Analytical Science, Technology and Equipment

Think Fast, Screen Faster

Combinatorial chemistry and other procedures have produced large libraries of chemical compounds – the (re)activity of which need to be assessed. High throughput screening (HTS) is already an important component of the drug discovery toolbox, but could it be improved? Graham Cooks, Henry B. Hass Distinguished Professor of Analytical Chemistry at Purdue University, Indiana, USA, certainly thinks so.

Cooks’ team has developed an even faster HTS process by coupling desorption electrospray ionization mass spectrometry (DESI-MS) with robotic sampling technologies. “We started with the observation that ordinary organic reactions, carried out in small droplets, are accelerated over bulk rates by several orders of magnitude, depending (inversely) on the size of the droplets – and this is now a well-established phenomenon,” explains Cooks.

“When we received funding in 2016 from the US Defense Advanced Research Projects Agency, we set out not merely to perform high throughput screening but to react and screen at high speed.” The team ended up using very small amounts of reaction solution in spots separated by about 1 mm on Teflon plates the size of a standard microtiter plate but without the wells, resulting in 6,144 discrete samples rather than 96 or 386. “We found that we could run this set of reactions in about one and a half hours, or at a rate a little over 1 second per spot. We made this our aim when our project manager said – although not in so many words – that she wanted 10,000 reactions per hour, or else!

The fastest current (non-optical) screening methods take about 8 seconds per sample; if Cooks’ technique proves itself to be robust and reliable, it would reduce analysis time for 100,000 reactions from more than a week down to a day.

Now, the team has its sights set on extending the method to bioactivity screening, and also aims to use the approach to improve the design and production of new synthetic molecules.

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  1. M Wleklinski et al., “High throughput reaction screening using desorption electrospray ionization mass spectrometry”, Chem Sci, 9, 1647–1652 (2018). DOI:10.1039/C7SC04606E.
About the Author
Roisin McGuigan

I have an extensive academic background in the life sciences, having studied forensic biology and human medical genetics in my time at Strathclyde and Glasgow Universities. My research, data presentation and bioinformatics skills plus my ‘wet lab’ experience have been a superb grounding for my role as a Deputy Editor at Texere Publishing. The job allows me to utilize my hard-learned academic skills and experience in my current position within an exciting and contemporary publishing company.

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