The ability to precisely transport and position individual cells and microscopic particles in fluids could provide a powerful tool for a wide range of biomedical applications, including targeted drug delivery, nanomedicine and tissue engineering. With this goal, scientists in the USA and China have created acoustically powered bubble-based microswimmers that can manipulate individual particles and cells in a crowded environment without affecting nearby objects (Sci. Adv. 5 eaax3084).
The microswimmers comprise a 7.5-µm long, half-capsule-shaped polymer structure, with an outer diameter of 5 µm and a shell thickness of 500 nm. The researchers coated the capsules with a 10 nm layer of magnetic nickel, enabling them to be steered with magnets, followed by a 40 nm gold layer. They then modified the inner surface to be hydrophobic, such that when submerged in fluid, an air bubble is spontaneously trapped inside each capsule.
When exposed to a megahertz acoustic field, the encapsulated bubble pulsates and the microswimmers align themselves normal to a nearby boundary and statically hover on it. Applying an external magnetic field initiates translational motion, with both the direction and speed of this motion precisely regulated by the direction of the applied magnetic field.
“These microswimmers provide a new way to manipulate single particles with precise control and in three dimensions, without having to do special sample preparation, labelling or surface modification,” says Joseph Wang from UC San Diego, a senior author along with Thomas Mallouk from the University of Pennsylvania and Wei Wang from Harbin Institute of Technology.
The researchers tested the microswimmers in an acousto-fluidic chamber, with the acoustic field generated by a piezoelectric ceramic transducer and an external magnetic field provided by a cylindrical magnet (with a pulling force of 200 N) held next to the chamber. They showed that placing the magnet by the chamber caused the microswimmers to move in the direction of their closed ends.
At an acoustic pressure of 4 kPa, a level that does not generate obvious acoustic bulk streaming or trap passive particles, the microswimmers could be propelled at speeds as fast as 2.6 mm/s. When the acoustic field was turned off, they stopped moving immediately. The team notes that capsules without a trapped air bubble neither self-rotated nor translated in the acoustic field.
This strong propulsion and precise directional control enabled the microswimmers to selectively pick up individual particles and relocate them to arbitrary positions. For example, the researchers used an acoustic pressure of 300 Pa to propel a microswimmer through a collection of 4-mm diameter silica particles and steer it to push a target particle. The microswimmer separated its target from an adjacent particle, indicating fine control over individual particle manipulation in a crowded group.
At higher acoustic pressures, an attractive force can occur between the microswimmer and a particle. The researchers demonstrated particle transport via this pulling mode at an acoustic pressure of 1 kPa. Using a combination of the push and pull manipulation modes, they moved particles into arbitrary shapes, creating the letters “PSU”, for example.
To validate potential utility in bioanalytical applications, the researchers used a microswimmer to move HeLa cells in culture medium. The HeLa cell, which at 20 µm diameter is significantly larger than the microswimmer, could be transported to contact another cell in the medium without disturbing neighbouring cells. Finally, the team demonstrated that the microswimmers can climb up micro-sized blocks and stairs or swim in free space, allowing them to operate robustly and reliably in complex 3D environments.
The researchers conclude that the bubble-based acoustic microswimmers exhibited controllable 3D motion and precise particle manipulation and patterning in crowded environments – feats that have not been achieved with other microswimmer designs. Future improvements will include making the microswimmers more biocompatible, such as building them from biodegradable polymers, for example, and replacing nickel with a less toxic magnetic material such as iron oxide.
