Performing multi-step chemical reactions in microliter-sized droplets by leveraging a simple passive transport mechanism

Despite the increasing importance of positron emission tomography (PET) imaging in research and clinical management of disease, access to myriad new radioactive tracers is severely limited due to their short half-lives (which requires daily production) and the high cost and complexity of tracer production. The application of droplet microfluidics based on electrowetting-on-dielectric (EWOD) to the field of radiochemistry can significantly reduce the amount of radiation shielding necessary for safety and the amount of precursor and other reagents needed for the synthesis. Furthermore, significant improvements in the molar activity of the tracers have been observed. However, widespread use of this technology is currently hindered in part by the high cost of prototype chips and the operating complexity. To address these issues, we developed a novel microfluidic device based on patterned wettability for multi-step radiochemical reactions in microliter droplets and implemented automated systems for reagent loading and collection of the crude product after synthesis. In this paper, we describe a simple and inexpensive method for fabricating the chips, demonstrate the feasibility of prototype chips for performing multi-step radiochemical reactions to produce the PET tracers [F-18]fallypride and [F-18]FDG, and further show that synthesized [F-18]fallypride can be used for in vivo mouse imaging.