Magnetic Navigation of Collective Cell Microrobots in Blood Under Ultrasound Doppler Imaging

We propose a strategy for magnetic navigation of collective stem cell microrobots in blood environments under ultrasound Doppler imaging. The cell microrobots are fabricated through a coculture process of stem cells and iron microparticles, they have spheroidal structures and are actuated under external magnetic fields. The collective cell microrobots can be reversibly gathered and spread by adjusting the magnetic interaction, and these microrobots are able to exhibit collective motion in whole blood under rotating magnetic fields. Simulation results indicate that the induced blood flow around the collective pattern affects the motion of red blood cells, and experimental results show that Doppler signals are observed when emitting ultrasound waves to the microrobots. Due to the induced three-dimensional blood flow, Doppler signals can also be observed when the imaging plane is above the collective microrobots, which enables indirect localization when performing navigation on uneven surfaces. Moreover, collective patterns of different numbers of microrobots are formed in flowing conditions, and these collective biohybrid agents are actively navigated against flowing blood with a flow rate up to 4.5 mL/min (mean velocity: 5.97 mm/s). Our study investigates a strategy for pattern formation and navigation of collective microrobots under ultrasound Doppler imaging, demonstrating the integration of collective control approach and medical imaging holds great potential for real-time active delivery tasks.

I. Introduction

Untethered microrobots offer promising capabilities in micromanipulation, biosensing, targeted delivery, and minimally invasive surgery [1]–[5]. Driven by external fields, these remotely actuated micromachines are able to be navigated in complex media to perform demanding tasks, such as active delivery in bovine vitreous humor, blood, peritoneal cavity, and gastrointestinal tract [6]–[9]. However, the tiny size and volume of a single microrobot limit the delivery capability, thus, repeated delivery procedures are required. Recently, introducing collective behaviors of microrobots holds great potential in tackling these challenges [10], [11]. Compared to the application of individual microrobot, the usage of collective microrobots enables controlled delivery in a batch (e.g., materials, drugs, and energy) [12]–[14], and the gathering of microrobots also enhances the contrast of medical imaging [15]. However, the navigation of collective microrobots in dynamic environments (e.g., blood vessels) encounters challenges, which are mainly caused by the impact of fluid flow and the heterogeneous fluidic environment [16]. The collective pattern may be disrupted by fluidic drag, challenging navigation efficiency, and access rate.