In-situ Measurements of Activity in Microliter Droplets

Imaging of tracers labeled with positron emitters is a powerful tool that enables understanding the initiation and progression of disease and the creation of novel therapeutics. Development and validation of new PET tracers takes years of research, in part due to the complexity, cost and limited throughput of conventional radiochemistry. To address this limitation, we are constructing a high-throughput radiochemistry system for the rapid development of radio-tracers for molecular imaging. The core of the system is a silicon wafer "chip" that contains a 4x4 array of 3mm diameter microdroplet reaction sites that allow performing simultaneous droplet-based radiosynthesis. A critical requirement for these systems is that the activity of the microliter droplets must be repeatedly and accurately measured to monitor the efficacy of each radiosynthesis step. To perform rapid and non-destructive in situ measurements of radioactivity at each droplet reaction site, two optical methods based on imaging via an overhead camera are considered: (a) measuring the intrinsic but weak Cerenkov light produced by positrons (<1 ph/e+) inside droplets and (b) measuring the much stronger (~103 ph/e+) scintillation light generated above the reaction sites from positrons that exit the droplets and interact in an organic scintillator. Absolute quantification of radioactivity in droplets is complicated by variations in overall positron energy deposition depending on the stage of synthesis, including the volume (and thus "thickness") of the droplet. We sought to determine the sensitivity of these methods to droplet geometry via Monte Carlo simulations of radiation emanating from arrays of droplets. We examined which of the imaging methods would provide better signal-to-noise, minimum crosstalk between droplets, minimum impact of background radiation and more consistent measurements for different experimental conditions.