A Droplet-Based Microfluidic Platform for Rapid Optical Detection of Bacteria: Proof-of-Concept for Radiopharmaceutical Sterility Testing

Rapid sterility testing of radiopharmaceuticals is essential due to their short half-lives and strict safety requirements. Conventional culture-based methods require several days and are not compatible with clinical workflows. In this work, we present a proof-of-concept droplet-based microfluidic platform for rapid optical detection of bacterial contamination through optical extinction analysis of microdroplets. Monodisperse water-in-oil microdroplets were generated and optically interrogated using a fiber-based detection system. Calibration was first performed using 500 nm polystyrene nanoparticles to establish the relationship between particle concentration and optical extinction. Subsequently, Staphylococcus aureus suspensions were analyzed under aerobic and anaerobic conditions at concentrations ranging from 0 to 230 CFU/mL. The system demonstrated reliable detection of bacterial contamination with estimated limits of detection of ~15 CFU/mL (aerobic) and ~7.5 CFU/mL (anaerobic). The platform enables real-time, high-throughput analysis with minimal sample handling and reduced analysis time compared to conventional sterility tests. This study validates the feasibility of microdroplet-based optical detection as a rapid quality control strategy specifically suited for radiopharmaceutical production, where the short half-lives of common radiotracers impose strict time constraints incompatible with conventional 14-day culture-based sterility tests. The results provide a proof-of-concept foundation for future integration into automated sterility testing workflows, with further validation on real radiopharmaceutical matrices planned as the next step.