Biology subjects

Mirkhani, N.

Publications and source records attributed to Mirkhani, N..

2 recordsLinked to original sources

bioRxiv2023

Spatially selective open loop control of magnetic microrobots for drug delivery

Rotating magnetic fields (RMFs), when used to actuate biomedical microrobots for targeted delivery to tumors, have been shown to enable them to overcome physiological barriers and promote their accumulation and penetration into tissue. Nevertheless, directly applying a RMF to a deeply situated target site also leads to off-target actuation in surrounding healthy tissue. Here, we investigate an open-loop control strategy for delivering torque density to diffuse distributions of microrobots at focal points by combining RMFs with magnetostatic gating fields. Taking magnetotactic bacteria (MTB) as a model biohybrid microrobotic system for torque-based actuation, we first use simulation to elucidate off-target torque suppression and find that resolution is set by the relative magnitude of the magnetostatic field and RMF. We study focal torque delivery in vitro, observing off-target suppression of translational velocity of MTB, convection-driven accumulation of companion nanoparticles, and tumor spheroid colonization. We then design, construct, and validate a mouse-scale torque-focusing apparatus incorporating a permanent magnet array, three-phase RMF coils, and offset coils to maneuver the focal point. Our control scheme enables the advantages of torque-based actuation to be combined with spatial targeting, and could be broadly applied to other microrobotic designs for improved drug delivery. One-Sentence SummaryCombining rotating magnetic fields with gating fields enables focused delivery of torque density to dispersed microrobots.

bioengineering↗

bioRxiv2022

Magnetic torque-driven living microrobots for enhanced tumor infiltration

Bacterial microrobots combining self-propulsion and magnetic guidance are increasingly recognized as promising drug delivery vehicles for targeted cancer therapy. Thus far, control strategies have either relied on poorly scalable magnetic field gradients or employed directing magnetic fields with propulsive forces limited by the bacterial motor. Here, we present a magnetic torque-driven actuation scheme based on rotating magnetic fields to wirelessly control Magnetospirillum magneticum AMB-1 bearing versatile liposomal cargo. We observed a 4-fold increase in conjugate translocation across a model of the vascular endothelium and found that the primary mechanism driving this increased transport is torque-driven surface exploration at the cell interface. Using spheroids as a 3D tumor model, fluorescently labeled bacteria colonized their core regions with up to 21-fold higher signal in samples exposed to rotating magnetic fields. In addition to enhanced transport, we demonstrated the suitability of this magnetic stimulus for simultaneous actuation and inductive detection of AMB-1. Finally, we demonstrated that RMF significantly enhances AMB-1 tumor accumulation in vivo following systemic intravenous administration in mice. Our findings suggest that scalable magnetic torque-driven control strategies can be leveraged advantageously with biohybrid microrobots. One-Sentence SummaryMagnetic torque-driven motion enhances infiltration of living microrobots across physiological barriers both in vitro and in vivo.

bioengineering↗