Drug-Loaded IRONSperm clusters: modeling, wireless actuation, and ultrasound imaging

Individual biohybrid microrobots have the potential to perform
biomedical in vivo tasks such as remote-controlled drug and cell delivery and
minimally invasive surgery. This work demonstrates the formation of biohybrid
sperm-templated clusters under the influence of an external magnetic field and
essential functionalities for wireless actuation and drug delivery. Ferromagnetic
nanoparticles are electrostatically assembled around dead sperm cells, and
the resulting nanoparticle-coated cells are magnetically assembled into threedimensional biohybrid clusters. The aim of this clustering is threefold: First, to
enable rolling locomotion on a nearby solid boundary using a rotating magnetic
field; second, to allow for noninvasive localization; third, to load the cells inside
the cluster with drugs for targeted therapy. A magneto-hydrodynamic model
captures the rotational response of the clusters in a viscous fluid, and predicts an
upper bound for their step-out frequency, which is independent of their volume
or aspect ratio. Below the step-out frequency, the rolling velocity of the clusters
increases nonlinearly with their perimeter and actuation frequency. During rolling
locomotion, the clusters are localized using ultrasound images at a relatively
large distance, which makes these biohybrid clusters promising for deep-tissue
applications. Finally, we show that the estimated drug load scales with the
number of cells in the cluster and can be retained for more than 10 hours.
The aggregation of microrobots enables them to collectively roll in a predictable
way in response to an external rotating magnetic field, and enhances ultrasound
detectability and drug loading capacity compared to the individual microrobots.
The favorable features of biohybrid microrobot clusters place emphasis on the
importance of the investigation and development of collective microrobots and
their potential for in vivo applications.