Navigation of microrobots in living vasculatures is essential in realizing targeted drug delivery and advancing non‐invasive surgeries. Acoustically‐controlled “swarmbots” are developed based on the self‐assembly of clinically‐approved microbubbles (MBs). Ultrasound is noninvasive, penetrates deeply into the human body, and is well‐developed in clinical settings. This propulsion strategy relies on two forces: the primary radiation force and the secondary Bjerknes force. Upon ultrasound activation, the MBs self‐assemble into microswarms, which migrate toward and anchor at the containing vessel's wall. A second transducer, which produces an acoustic field parallel to the channel, propels the swarms along the wall. Noting that human arteries have a blood flow 5–19 cm s−1, powerful features of cross‐ and upstream swarmbot navigation are demonstrated against physiologically‐relevant flow rates that reach 16.7 cm s−1. Additionally, controlled navigation of swarmbots is shown within mice blood and under pulsatile flow conditions of 100 beats per minute (bpm); an adult human heart at rest executes between 60 and 100 bpm. This capability represents a much‐needed pathway for advancing preclinical research.

Navigation of microrobots in living vasculatures is essential in realizing targeted drug delivery and advancing non-invasive surgeries. We developed acoustically-controlled swarmbots based on the self-assembly of clinically-approved microbubbles. Ultrasound is noninvasive, penetrates deeply into the human body, and is well-developed in clinical settings. Our propulsion strategy relies in two forces: the primary radiation force and secondary Bjerknes force. Upon ultrasound activation, the microbubbles self-assemble into microswarms, which migrate towards and anchor at the containing vessels wall. A second transducer, which produces an acoustic field parallel to the channel, propels the swarms along the wall. We demonstrated cross- and upstream navigation of the swarmbots at 3.27 mm/s and 0.53 mm/s, respectively, against physiologically-relevant flow rates of 4.2 to 16.7 cm/s. Additionally, we showed swarm controlled manipulation within mice blood and under pulsatile flow conditions of 100 beats per minute. This capability represents a much-needed pathway for advancing preclinical research.

Many cerebrovascular and neurodegenerative diseases are currently challenging to treat due to the complex and delicate anatomy of the brain. The use of microrobots can create new opportunities in brain research due to their ability to access hard-to-reach regions and empower various biological applications; however, little is known about the functionality of microrobots in the brain, owing to their limited imaging modalities and intravascular challenges such as high blood flow velocities, osmotic pressures, and cellular responses. Here, we present an acoustic, non-invasive, biocompatible microrobot actuation system, for in vivo navigation in the bloodstream, in which microrobots are formed by lipid-shelled microbubbles that aggregate and propel under the force of acoustic irradiation. We investigated their capacities in vitro within a microfluidic 3D setup and in vivo in a living mouse brain. We show that microrobots can self-assemble and navigate upstream in the brain vasculature. Our microrobots achieved upstream velocities of up to 1.5 um/s and overcame blood flows of ~10 mm/s. Our results prove that microbubble-based microrobots are scalable to the complex 3D living milieu.

No abstract