Researchers at the Korea Advanced Institute of Science and Technology (KAIST) have developed an unmanned synthesis platform that uses synthesis robots and light to automatically carry out everything from mixing raw materials to synthesis and analysis. The system is expected to help secure a wider range of drug candidate compounds by reducing the burden of repetitive experiments.
KAIST said on the 18th that a team led by Park Yun-soo, a professor in the department of chemistry, built the unmanned synthesis platform by combining visible light with a continuous-flow process. Using the platform, the team synthesized the N-methyl pyrrole skeleton, a basic molecular framework used in drug development, and demonstrated the potential to scale up output through continuous production.
In drug development, molecules that have been designed must actually be produced so that their efficacy and safety can be tested. But new synthesis conditions have to be found for each compound, even when structures differ only slightly.
The team linked a raw-material preparation robot, automated pumps, a light-irradiation reactor and analytical equipment into a single system. Once a researcher sets up the equipment and the conditions, the robot mixes the raw materials and the pumps send the solution at a steady rate through a narrow tube. Visible light is shone on the tube to drive the chemical reaction. That delivers light evenly through the solution, allowing output to increase.
The solution is automatically transferred to the analytical equipment once the reaction is complete. The equipment checks whether the target compound was properly produced and how much of it was made. Rather than having a researcher move the solution for measurement each time, the process runs automatically from mixing the raw materials through confirming the results.
"How quickly and reliably designed molecules can be synthesized will determine the pace of drug development going forward," Park said. "We expect the platform we have built to serve as a foundation for moving into an era of automated organic synthesis, because it allows reaction conditions to be quantified and reproduced."