EWOD Digital Microfluidics and Its Biomedical Applications Including the Synthesis of PET Radiotracers

Abstract

The reconfigurable microfluidics mechanism of electrowetting-on-dielectric (EWOD) has led to various optical and biological applications. In a typical EWOD device, including commercial ones, aqueous droplets in oil are manipulated by electric signals. If operational in air environment as well (i.e., no oil surrounding the droplets), EWOD would open the door for many additional applications. One example is MALDI-MS, where the aqueous liquid needs to be evaporated prior to sample analysis – this is not possible if in oil. We have demonstrated an integrated EWOD-MALDI-MS chip designed for parallel processing of multiple sample droplets without oil. Leveraging on this success, our team between engineering and medicine at UCLA has been working to synthesize PET tracers on an EWOD digital microfluidic platform. All the key steps have been demonstrated on a single EWOD chip to synthesize a variety of 18F-labeled tracers in the nanomole quantities necessary for PET imaging. The obtained fluorination efficiencies (90-95%) and synthesis times (30-60 min) were comparable to conventional approaches, and overall yields were sufficient for eventual clinical use. Additional techniques, including dose scale-up and product purification, have been developed on chip to move towards the ultimate goal of producing tracers for clinical imaging. The resulting integrated system, being commercialized by Sofie Biosciences, is expected to dramatically reduce radiation shielding and the associated cost, empowering final users to produce radiotracers of their choice locally and eventually making PET imaging as readily available as CT and MRI.