The words 'organic chemistry' tend to conjure up images of large bubbling flasks, brightly coloured test tubes and explosive reagents. Although most chemists still use flasks for their reactions, a growing number of them make their molecules using miniaturized devices. These 'labs on chips' require only tiny quantities of reagents, thus reducing cost, producing less waste and cutting down the time needed to perform a reaction and to analyse its products.

Although it is quite easy to perform a single reaction on a chip, it is much harder to carry out multiple reactions in the same device, making several different molecules. But now Hartmuth C. Kolb, Hsian-Rong Tseng and their colleagues have developed a device (pictured) that can perform 32 reactions at the same time. The group reports its results in Angewandte Chemie (doi:10.1002/anie.200601677).

Credit: WILEY-VCH

The authors miniaturized a technique known as 'in situ click chemistry', which can be used to identify high-affinity inhibitors for enzymes. These inhibitors can then be used in other biological experiments: for example, the molecules can be used to block the enzyme's 'active site' to see how it works, or to elucidate its cellular role.

Two compounds — one containing an azide group, and another containing an acetylene group — are combined in a reaction vessel with the target enzyme. Molecules of both compounds may enter the enzyme's active site, and orient themselves so that the azide group and the acetylene group fit comfortably inside. If the two groups align favourably, then 'click', they react to form a five-membered ring. Because this click reaction occurs in the active site of the enzyme, the product usually binds very tightly to that enzyme.

By miniaturizing this process on a chip, the authors were able to run 32 reactions at the same time to find inhibitors for a well-known target enzyme (bovine carbonic anhydrase II) using much less of the protein than would have been needed in a traditional, microtitre-based procedure.

Many interesting proteins are notoriously difficult to obtain in large quantities, preventing their use in biochemical assays for inhibitors. This chip enables such proteins to be screened at last, and may open up many areas for biological and medicinal study.