Abstract
Application of microfluidics offers numerous advantages in the field of radiochemistry and could enable dramatic reductions in the cost of producing radiotracers for positron emission tomography (PET). Droplet-based microfluidics, in particular, requires only microgram quantities of expensive precursors and reagents (compared to milligram used in conventional radiochemistry systems), and occupies a more compact footprint (potentially eliminating the need for specialized shielding facilities, i.e. hot cells). However, the reported platforms for droplet radiosynthesis have several drawbacks, including high cost/complexity of microfluidic reactors, requirement for manual intervention (e.g. for adding reagents), or difficulty in precise control of droplet processes. We describe here a platform based on a particularly simple chip, where reactions take place atop a hydrophobic substrate patterned with a circular hydrophilic liquid trap. The overall supporting hardware (heater, rotating carousel of reagent dispensers, etc.) is very simple and the whole system could be packaged into a very compact format (about the size of a coffee cup). We demonstrate the consistent synthesis of [18F]fallypride with high yield, and show that protocols optimized using a high-throughput optimization platform we have developed can be readily translated to this device with no changes or re-optimization. We are currently exploring the use of this platform for routine production of a variety of 18F-labeled tracers for preclinical imaging and for production of tracers in clinically-relevant amounts by integrating the system with an upstream radionuclide concentrator.