Flasks, beakers, and hot plates may soon be a thing of the past in medicinal chemistry labs. Instead of handling a few experiments on a benchtop, scientists may simply pop a microchip into a computer and instantly run thousands of chemical reactions, with results literally shrinking the lab down to the size of a thumbnail.
Toward that end, a team of investigators at the University of California, Los Angeles (UCLA), have developed technology to perform more than a thousand chemical reactions at once on a stamp-size, PC-controlled microchip, which could accelerate the identification of potential drug candidates for treating diseases such as cancer. The results of their study appear in the journal Lab on a Chip.
Heading the multidisciplinary were Hsian-Rong Tseng, Ph.D., a member of the Nanosystems Biology Cancer Center, one of eight Centers of Cancer Nanotechnology Excellence created by the National Cancer Institute. Their miniaturized laboratory uses microfluidics to automatically handle and channel tiny amounts of liquids and chemicals. The chemical reactions were performed using in situ click chemistry, a technique often used to identify potential drug molecules that bind tightly to protein enzymes to either activate or inhibit an effect in a cell, and were analyzed using mass spectrometry.
Traditionally, only a few chemical reactions could be produced on a chip, but the research team pioneered a way to instigate multiple reactions, thus offering a new method to quickly screen which drug molecules may work most effectively with a targeted protein enzyme. In this study, scientists produced a chip capable of conducting 1,024 reactions simultaneously, which, in a test system, ably identified potent inhibitors to the enzyme bovine carbonic anhydrase.
A thousand cycles of complex processes, including controlled sampling and mixing of a library of reagents and sequential microchannel rinsing, all took place on the microchip device and were completed in just a few hours. At the moment, the UCLA team is restricted to analyzing the reaction results offline, but in the future, they intend to automate this aspect of the work as well.