US scientists have used a microfluidic device to perform over 1000 click chemistry reactions at once. The device could speed up the discovery of new enzyme inhibitors for treating diseases such as cancer.

1000 reactions in a hand

Hsian-Rong Tseng, at the University of California, Los Angeles, and colleagues purified all 1024 reactions using solid phase extraction and analysed them using mass spectrometry.

In situ click chemistry uses azide and alkyne building blocks that react (click) to form triazoles inside the binding pocket of an enzyme. This acts as a template and guides the product formation. Because the resulting triazoles fit well into the binding pocket, they are potential inhibitors of the enzyme.

Tseng explains that the traditional way of screening libraries found using in situ click reactions is time-consuming and uses a lot of reagents. 'Our system enables large-scale screening with minimum sample consumption,' he says - the device mixes tiny amounts of reactants with great precision and without cross contamination. Many more reactions can be performed at once and more quickly, he adds.

Andrew deMello, an expert in microfluidic devices at Imperial College London, UK, says, 'this is a great example of how miniaturisation can transform the process of library screening. What's especially clever is how they have integrated their microfluidic platform with both sample clean up and mass spectrometry analysis. This drastically reduces both analysis times and sample requirements.'

'We hope to explore the use of our microchip for other screening reactions where reagents and samples are in limited supply,' comments Tseng. This includes a class of enzymes called kinases, which play critical roles in the malignant transformation of cancer, he says.

Fay Nolan-Neylan

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