3D-PRINTED MICROFLUIDIC CAPILLARIC CIRCUITS FOR THE AUTOMATION OF RADIOPHARMACEUTICAL SYNTHESIS

Abstract

Positron emission tomography (PET) offers a powerful means of tracking transplantedmesenchymal stem cells in vivo, but the radiopharmaceuticals required for PET-based tracking, such as [89Zr]Zr-SCN-Bn-DFO, are currently synthesized and handled manually. This manual process exposes laboratory personnel to prolonged, close-proximity radiation during pipetting, mixing, and incubation, approaching regulatory dose limits under ALARA guidelines. This thesis presents the design, fabrication, and experimental validation of a novel capillaric microfluidic circuit platform for autonomous, pump-free radiopharmaceutical synthesis, distinguished from prior sequential-release, absorption-based capillary circuit systems by its simultaneous-release, product-recovery architecture. Two capillaric chip designs, Chip 1 and Chip 2, were developed and independently fabricated for two fluid systems, fluorescent surrogate dyes and radioactive synthesis reagents, yielding four unique chip geometries validated across this work. Chip geometries were derived from governing capillary pressure, hydraulic resistance, and diffusion-based mixing equations, using fluid properties obtained from literature and, where unavailable, experimentally back-calculated using the chips themselves as tensiometers. Chips were fabricated via LCD-based vat photopolymerization on an Elegoo Mars 5 printer using biocompatible Liqcreate Bio-Med Clear resin, with fabrication accuracy validated through SEMbased feature characterization and surface wettability confirmed through contact angle measurements following oxygen plasma treatment and Pluronic F-108 functionalization. Chip performance was first validated using fluorescent surrogate fluids, confirming simultaneous reservoir release and diffusion-driven mixing via fluorescence imaging. Radioactive synthesis was subsequently evaluated across four test sessions alongside conventional cuvette controls. In final testing, the chip platform achieved radiolabeling efficiencies exceeding 94% within 5 minutes, compared to 20 minutes required by the cuvette method to reach comparable efficiency, a fourfold reduction in synthesis time. MSC labeling was additionally demonstrated with cell viability comparable to unlabeled controls, confirming the biocompatibility of the platform and its potential to substantially reduce radiation exposure while maintaining clinically relevant synthesis performance.