Acoustic bubble-based drug manipulation: Carrying, releasing and penetrating for targeted drug delivery using an electromagnetically actuated microrobot

Abstract This paper presents a new type of microrobotic drug delivery technology where an electromagnetically actuated untethered microrobot swimming inside human blood vessels performs targeted drug delivery operations: carrying, releasing, and penetrating drugs to target tissues using acoustic excitation of bubbles. The novel microrobot is capable of not only transporting liquid forms of drugs in an aqueous medium but also wirelessly manipulating drugs without using complex mechanical parts. For the electromagnetic actuation of a microrobot, an electromagnetic system consisting of a pair of Helmholtz and Maxwell electric coils is fabricated. Using the developed electromagnetic system, the actuation of the microrobot made of a cylindrical neodymium magnet is successfully demonstrated in a T-shaped channel. For the drug manipulation, selective acoustic excitation of bubbles is investigated. The drug release actuation is studied using a microtube which is a drug container consisting of two bubbles with different volumes. Then, the effect of acoustic bubble-induced microstreaming on the drug penetration to tissues is investigated for three different conditions: pure diffusion, penetration with an acoustic wave, and microstreaming using an agarose gel. As a proof of concept, the proposed sequential drug manipulation (carrying, releasing, and penetrating) is experimentally demonstrated using the prototype of a microrobot enabling propulsion in a low Reynolds number environment using an electromagnetic system and drug manipulation using acoustic bubbles in a C-shaped channel filled with liquid. The proposed microrobot can be applied to various biomedical applications such as targeted drug delivery, cell manipulation, and microsurgery.