From trial and error to brute force
A Franco-Japanese research group at the University of Tokyo has developed a new “brute force” technique to test thousands of biochemical reactions at once and quickly home in on the range of conditions where they work best. Until now, optimizing such biomolecular systems, which can be applied for example to diagnostics, would have required months or years of trial and error experiments, but with this new technique that could be shortened to days.
“We are interested in programming complex biochemical systems so that they can process information in a way that is analogous to electronic devices. If you could obtain a high-resolution map of all possible combinations of reaction conditions and their corresponding outcomes, the development of such reactions for specific purposes like diagnostic tests would be quicker than it is today,” explains Centre National de la Recherche Scientifique (CNRS) researcher Yannick Rondelez at the Institute of Industrial Science (IIS).
“Currently researchers use a combination of computer simulations and painstaking experiments. However, while simulations can test millions of conditions, they are based on assumptions about how molecules behave and may not reflect the full detail of reality. On the other hand, testing all possible conditions, even for a relatively simple design, is a daunting job.”
Rondelez and his colleagues at the Laboratory for Integrated Micro-Mechanical Systems (LIMMS), a 20-year collaboration between the IIS and the French CNRS, demonstrated a system that can test ten thousand different biochemical reaction conditions at once. Working with the IIS Applied Microfluidic Laboratory of Professor Teruo Fujii, they developed a platform to generate a myriad of micrometer-sized droplets containing random concentrations of reagents and then sandwich a single layer of them between glass slides. Fluorescent markers combined with the reagents are automatically read by a microscope to determine the precise concentrations in each droplet and also observe how the reaction proceeds.