On-chip fabrication of calcium carbonate nanoparticles loaded with various compounds using microfluidic approach

Engineered calcium carbonate (CaCO₃) particles are extensively used as drug delivery systems due to their availability, biological compatibility, biodegradability, and cost-effective production. The synthesis procedure of CaCO₃ particles, however, suffers from poor reproducibility. Furthermore, reducing the size of CaCO₃ particles to <100 nm requires the use of additives in the reaction, which increases the total reaction time. Here we propose on-chip synthesis and loading of nanoscaled CaCO₃ particles using microfluidics. After the development and fabrication of a microfluidic device, we optimized the synthesis of CaCO₃ NPs by varying different parameters such as flow rates in the microfluidic channels, concentration of reagents, and the reaction time. To prove the versatility of the used synthesis route, we performed single and double loading of CaCO₃ NPs with various compounds (Doxorubicin, Cy5 or FITC conjugated with BSA, and DNA) using the same microfluidic device. Further, the on-chip loaded CaCO₃ NPs were used as carriers to transfer compounds to model cells. We have developed a microfluidic synthesis method that opens up a new pathway for easy on-chip fabrication of functional nanoparticles for clinical use.