On-demand synthesis of calcium phosphate crystals in droplet micro-reactors of continuous operation

In this work, the use of droplet microreactors is demonstrated for the on-demand synthesis of three calcium phosphate minerals. In a simple three-inlet, flow focusing design, microdroplets serve as isolated reactors where crystals are formed under controlled conditions. Selective production of brushite, hydroxyapatite, or fluorapatite was achieved by modulating only the composition and the pH of a buffer stream without disturbing the flow regime and the continuous operation of the system. Temperature and residence time have been proved as key variables to control the properties of the resulted particles. Moving from 25 to 37 °C resulted in a more crystalline material, while by increasing the residence time from 2 to 10 min, bigger particles were obtained. Compared to the standard batch synthesis, in microfluidics, crystallisation crystals were less aggregated and smaller in size. During μ-LIF measurements, it was confirmed that the formation of the crystals affects the mixing quality within the droplets and this can be a field of improvement in order to get particles with more consistent properties. Overall, this work shows the potential of droplet microreactors as a versatile "factory-on-chip" tool for continuous production of biomaterials. Beyond calcium phosphates, the same approach provides a scalable route to precision synthesis of multiphase and composite materials, enabling new frontiers in biomedical translation and advanced manufacturing.