Ultrasound trapping and navigation of microrobots in the mouse brain vasculature.

The intricate and delicate anatomy of the brain poses significant challenges for the treatment of cerebrovascular and neurodegenerative diseases. Thus, precise local drug delivery in hard-to-reach brain regions remains an urgent medical need. Microrobots offer potential solutions; however, their functionality in the brain remains restricted by limited imaging capabilities and complications within blood vessels, such as high blood flows, osmotic pressures, and cellular responses. Here, we introduce ultrasound-activated microrobots for in vivo navigation in brain vasculature. Our microrobots consist of lipid-shelled microbubbles that autonomously aggregate and propel under ultrasound irradiation. We investigate their capacities in vitro within microfluidic-based vasculatures and in vivo within vessels of a living mouse brain. These microrobots self-assemble and execute upstream motion in brain vasculature, achieving velocities up to 1.5 µm/s and moving against blood flows of ~10 mm/s. This work represents a substantial advance towards the therapeutic application of microrobots within the complex brain vasculature.

Acoustic microbubble propulsion, train-like assembly and cargo transport.

Achieving controlled mobility of microparticles in viscous fluids can become pivotal in biologics, biotechniques, and biomedical applications. The self-assembly, trapping, and transport of microparticles are being explored in active matter, micro and nanorobotics, and microfluidics; however, little work has been done in acoustics, particularly in active matter and robotics. This study reports the discovery and characterization of microbubble behaviors in a viscous gel that is confined to a slight opening between glass boundaries in an acoustic field. Where incident waves encounter a narrow slit, acoustic pressure is amplified, causing the microbubbles to nucleate and cavitate within it. Intermittent activation transforms microbubbles from spherical to ellipsoidal, allowing them to be trapped within the interstice. Continuous activation propels ellipsoidal microbubbles through shape and volume modes that is developed at their surfaces. Ensembles of microbubbles self-assemble into a train-like arrangement, which in turn capture, transport, and release microparticles.