(46e) Multimodal Microwheel Swarms Targeting in Three-Dimensional Networks

Traditional drug delivery requires high systemic concentrations that limit therapeutic benefit due to harmful side effects. A promising alternative is using drug-laden microscale bots that deliver a high local drug concentration directly to a target location. We have previously demonstrated that magnetically actuated colloidal microwheels (µwheels) reversibly assembled from superparamagnetic 4.5 µm beads can translate rapidly and be well directed. Here we show that swarms of µwheels, depending on their cooperative motion, can achieve high velocities (~200µm/s), steep climbing ability (80°), local mechanical action, or bead deposition. Characteristic “fingerprints” for these µwheel swarms are obtained using particle tracking image analysis and a custom rotating microscope/magnetic actuation system. In addition, we demonstrate the ability of swarms to navigate complex three-dimensional branching microenvironments. Taking inspiration from cerebrovascular stroke models, swarms are actively driven through 3D printed murine middle cerebral artery scale models. A targeting efficiency, defined as the number of beads captured in a target vascular branch divided by the total number of beads injected, of ~54% was achieved in branching arterial networks with multiple turns. This demonstrates reliable targeting of colloidal payloads with weak magnetic fields (5 mT) over macroscale length scales (40 mm). Lastly, targeting efficiency is predicted by simulating swarm translation in the network, allowing application to arbitrary vascular networks and paving the way to µwheel targeting in vivo.

Fig 1. (A) Optical microscopy of four swarm modes after ~15 s of magnetic actuation. Scale = 1 mm. (B) Predicted mass transport of swarms based on measured velocity distributions. Colors correspond to swarm modes in A, and the shaded areas under each swarm curve are equal. (C) 3D model of branching vascular network. (D) Fluorescence microscopy of printed device after targeting µwheel swarm to branch 1.