Droplet-based microfluidic production of soft alginate microrobots for magnetically targeted cargo delivery

Abstract

The development of microrobotic drug delivery systems capable of active navigation offers significant advantages over conventional passive and ligand-based targeting approaches. In this study, we present the high-yield fabrication of soft, magnetically actuated alginate microrobots via a droplet-based microfluidic method. Using a 5% sodium alginate solution and internal gelation strategy with calcium-EDTA (Ca-EDTA), we successfully overcame the challenges associated with high-viscosity materials and microchannel clogging. The resulting microrobots, loaded with either ferromagnetic iron-platinum (FePt) nanoparticles or superparamagnetic iron oxide nanoparticles (SPIONs), exhibited uniform spherical morphology, magnetic responsiveness, and tunable mechanical properties. Fluorescent labeling with Nile red enabled effective optical tracking. Atomic force microscopy (AFM) analysis confirmed that the alginate microrobots were significantly softer than well-known silica-based microrollers, suggesting enhanced deformability. A comprehensive evaluation of their physical stability in different buffer systems revealed that HEPES buffer was the only medium that preserved structural integrity over time, highlighting its critical role in in vitro release studies and in selecting an appropriate storage solution. Under homogeneous and permanent magnetic fields, both FePt nanoparticles- and SPIONs-loaded microrobots exhibited directional motion. FePt nanoparticles-loaded microrobots achieved higher velocities under oscillating magnetic fields, while SPIONs-loaded microrobots demonstrated rapid, swarm-like collective behavior under static fields. This work introduces a scalable and soft microrobotic platform with promising potential for precise and magnetically guided therapeutic delivery.