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

Abstract

In this work is demonstrated the use of droplet microreactors 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 is achieved by modulating only the composition and the pH of a buffer stream without disturbing the flow regime and the continuous opeation of the system. Temperature and residence time have been proved key variables to control the properties of the resulted particles. Moving from 25 to 37 oC resulted in more crystaline material while by increasing residence time from 2 to 10 min bigger particles were obtained. Comparing with the standard batch synthesis, in microfluidics crystalisation seems to take place much faster and the crystals are less aggragated. During μ-LIF measurements it was confirmed that the formation of the crystals affects 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 microreactros as a versatile “factory-on-chip” toll for continuous production of biomaterials. Beyond calcium phosphates, the sama approach provides a scalable route to precision synthesis of multiphase and composite materials, enabling new frontiers in biomedical translation and advanced manufacturing.