Microfluidic Fabrication of Silica Microspheres Infused with Positron Emission Tomography Imaging Agents

Abstract

Selective internal radiation therapy (SIRT) is a treatment which delivers radioactive therapeutic microspheres via the hepatic artery to destroy tumorigenic tissue of the liver. However, the dose required varies significantly from patient to patient due to nuances in individual biology. Therefore, a positron emission tomography (PET) imaging surrogate, or radiotracer, is used to predict in vivo behavior of therapeutic Y-90 spheres. The ideal surrogate should closely resemble Y-90 microspheres in morphology for highest predictive accuracy. This work presents the fabrication of positron-emitting silica microspheres infused with PET radiotracers copper, fluorine, and gallium. A quick one-pot synthesis is used to create precursor sol, followed by droplet formation with flow-focusing microfluidics, and finally thermal treatment to yield 10–50 μm microspheres with narrow size distribution. Loading of the infused element is controllable in the sol synthesis, while the final sphere size is tunable based on microfluidic flow rates and device channel width. The system is then employed to make radioactive Ga-68 microspheres, which are tested for radioactivity and stability. The fabrication method can be completed within a few hours, depending on the desired microsphere quantity. A microfluidic system is applied to fabricate silica particles loaded with diverse elemental infusions, including radioactive Ga-68.