Computational fluid dynamics study of the synthesis process for a PET radiotracer compound, [11C]raclopride on a microfluidic chip

Recent synthetic applications conducted on microfluidic chips have shown improved yields and shorter reaction times as compared to conventional methods. These have generated great interest in the microfluidic synthesis of radiotracer compounds with short lived radioisotopes, such as carbon-11 (t1/2 – 20.4 min). For the purpose of microreactor design optimization and to predict synthetic behavior, we launched a study of the radiosynthesis of [11C]raclopride on three different microchip designs by computational fluid dynamics, using COMSOL Multiphysics®. COMSOLʹs Reaction Engineering Lab® tool and convection and diffusion models were used first to investigate the “ideal” reactor and then to study reaction progress in the microchip geometry. Examining the concentration distribution within the microchannel geometry, it was clear that the microchannel length can predict passive mixing and higher product generation than microchannel length. Reducing the flow rate of reagents, premixing the reagents, and increasing reagent concentrations also increased product generation due to increased space times and molecular interactions. For the purpose of simulation, the yield is undesirably reduced by decreasing the diffusion coefficient and the reaction rate constant. This study provides the optimized parameters to redesign the microchip in order to increase the efficiency of micromixing within the microchannels and, therefore, increase the reaction yield.