One-step generation of luminescent core-shell microspheres for cell encapsulation via pulsed operation in centrifugal microfluidics

Biopolymer core-shell microspheres play a crucial role in various biomedical applications, including drug delivery, tissue engineering, and diagnostics. These applications require microparticles with consistent, well-controlled size and precise shape fidelity. However, achieving high-throughput synthesis of size and shape-controlled core-shell biopolymer microgels remains a significant challenge. Herein, we present a one-step process for the high-throughput generation of monodisperse, luminescent, chitosan alginate core-shell microspheres by a novel manipulation of a centrifugal microfluidic device. We utilized the pH sensitivity of chitosan and the ionic gelation properties of alginate to create well-defined core-shell morphologies. To address particle merging issues and promote uniform particle size generation, we introduced an innovative pulsed mode operation in our centrifugal microfluidics device. We also incorporated fluorescent, nitrogen-functionalized graphene quantum dots into the core-shell structures, thereby rendering them useful for real-time imaging, which is necessary for diagnostic and therapeutic applications. To enhance biocompatibility, the alginate solution was supplemented with fish gelatin (FG). The resulting microspheres exhibited excellent structural integrity maintaining their core-shell structure after 15 days. Biocompatibility was demonstrated by C2C12 cell viability exceeding 88% after 15 days and by bacterial viability reaching the same percentage after 2 days. The system demonstrates considerable scalability, allowing for the consistent production of large quantities of microspheres without compromising functionality. The streamlined and efficient methodology simplifies the production process while unlocking new possibilities in targeted therapies, tissue regeneration, and diagnostics.