Congratulations to Mark Mc Veigh and the Bellan group! Mark’s paper, 鈥淯nderstanding the Compatibility of Fluoride-Based Radiopharmaceutical Reaction Solutions and PDMS鈥� has been featured as a VINSE Spotlight publication and published in ACS Applied Materials and Interfaces.
Nuclear medicine has become an integral tool for physicians to diagnose and treat cancer and various other diseases. This growth has been enabled by the ongoing development of thousands of targeted radiopharmaceuticals (RPs) designed to track specific biological processes. Currently, production methods rely on economies of scale to reduce costs, meaning lesser used but more targeted RPs are prohibitively expensive for the patient. Microfluidics has been identified as a key technology that can reduce this cost barrier by enabling decentralized dose-on-demand RP production. Using a microfluidic synthesis platform, PET scan facilities and radiopharmacies can produce single doses of RPs and directly distribute them to patients. This eliminates the waste associated with large batches and reduces cost for patients. As these systems transition from research to commercialization, understanding material compatibility has become a critical concern. In particular, polydimethylsiloxane (PDMS), a material widely used to fabricate microfluidic devices, has been the subject of significant debate due to conflicting reports on its interaction with 18F, with some studies reporting severe activity losses and others reporting minimal effects.
In this work, scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDS), profilometry, and gas chromatography mass spectrometry (GC-MS) were used to directly probe the interaction between fluoride-based reaction solutions and PDMS. SEM-EDS revealed that fluoride does not significantly diffuse into PDMS and can largely be removed by washing with appropriate solvents. However, images showed significant damage to the surface if the reaction solution was completely evaporated on the surface (a necessary step in many radiofluorination processes). The damage was confirmed and quantified with profilometry which provided further insight that substantial surface etching occurred only after complete solvent evaporation (when crystallized salts contact the PDMS surface). GC-MS identified several volatile compounds that are created during this interaction including the F-containing species trimethylfluorosilane. Together, these results reconcile previously conflicting reports by showing that PDMS remains largely stable during exposure to liquid-phase reaction solutions but degrades to form F-containing volatile species once the solution is fully evaporated, resulting in significant activity loss.
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Authors: Mark Mc Veigh, Charles Frech, Mai Lin, Robert Ta, H. Charles Manning, and Leon M. Bellan
Abstract: Microfluidic devices offer unique and exciting benefits when applied to radiopharmaceutical manufacturing, and these platforms are now starting to be integrated into commercial products. The field has strayed away from the use of polydimethylsiloxane (PDMS), the most common microfluidic device material, due to its suspected incompatibility with 18F, the most commonly used radionuclide. However, existing literature provides conflicting conclusions as to the existence and extent of this incompatibility. In this study, we use several analytical instruments to uncover the underlying interaction between fluoride and PDMS. SEM imaging and profilometry confirm the reactive relationship between the two materials and suggest that this interaction only occurs when the reaction solution is fully evaporated and crystallized salts are in contact with PDMS. Furthermore, GC-MS identifies fluoride-containing volatile species that can account for loss of fluoride in previous studies and additionally reveals an incompatibility between PDMS and K2CO3 (a commonly used component of radiofluorination reaction solutions). These results confirm the need for microfluidic radiofluorination devices to avoid the use of PDMS in most contexts but may allow for inexpensive design and testing of liquid state operations (such as concentration, purification, and mixing) using the material.