The ability to manipulate therapeutic agents in fluids is of interest to improve the efficiency of targeted drug delivery. Ultrasonic manipulation has great potential in the field of therapeutic applications as it can trap and manipulate micro-scale objects. Recently, several methods of ultrasonic manipulation have been studied through standing wave, traveling wave, and acoustic streaming. Among them, the traveling wave based ultrasonic manipulation is showing more advantage for in vivo environments. In this paper, we present a novel ultrasonic transducer (UT) array with a hemispherical arrangement that generates active traveling waves with phase modulation to manipulate a micromotor in water. The feasibility of the method could be demonstrated by in vitro and ex vivo experiments conducted using a UT array with 16 transducers operating at 1 MHz. The phase of each transducer was controlled independently for generating a twin trap and manipulation of a micromotor in 3D space. This study shows that the ultrasonic manipulation device using active traveling waves is a versatile tool that can be used for precise manipulation of a micromotor inserted in a human body and targeted for drug delivery.

Targeted drug delivery using microrobots manipulated by an external actuator has significant potential to be a practical approach for wireless delivery of therapeutic agents to the targeted tumor. This work aimed to develop a novel acoustic manipulation system and macrophage-based microrobots (Macbots) for a study in targeted tumor therapy. The Macbots containing superparamagnetic iron oxide nanoparticles (SPIONs) can serve as drug carriers. Under an acoustic field, a microrobot cluster of the Macbots is manipulated by following a predefined trajectory and can reach the target with a different contact angle. As a fundamental validation, we investigated an in vitro experiment for targeted tumor therapy. The microrobot cluster could be manipulated to any point in the 4 × 4 × 4 mm region of interest with a position error of less than 300 μm. Furthermore, the microrobot could rotate in the O-XY plane with an angle step of 45 degrees without limitation of total angle. Finally, we verified that the Macbots could penetrate a 3D tumor spheroid that mimics an in vivo solid tumor. The outcome of this study suggests that the Macbots manipulated by acoustic actuators have potential applications for targeted tumor therapy.

Compared to other actuating methods, acoustic actuators offer the distinctive capability of the contactless manipulation of small objects, such as microscale and nanoscale robots. Furthermore, they have the ability to penetrate the skin, allowing for the trapping and manipulation of micro/nanorobots that carry therapeutic agents in diverse media. In this review, we summarize the current progress in using acoustic actuators for the manipulation of micro/nanorobots used in various biomedical applications. First, we introduce the actuating method of using acoustic waves to manipulate objects, including the principle of operation and different types of acoustic actuators that are usually employed. Then, applications involving manipulating different types of devices are reviewed, including bubble-based microrobots, bubble-free robots, biohybrid microrobots, and nanorobots. Finally, we discuss the challenges and future perspectives for the development of the field.

Acoustic tweezers provide unique capabilities in medical applications, such as contactless manipulation of small objects (e.g., cells, compounds or living things), from nanometer-sized extracellular vesicles to centimeter-scale structures. Additionally, they are capable of being transmitted through the skin to trap and manipulate drug carriers in various media. However, these capabilities are hindered by the limitation of controllable degrees of freedom (DoFs) or are limited maneuverability. In this study, we explore the potential application of acoustical tweezers by presenting a five-DoF contactless manipulation acoustic system (AcoMan). The system has 30 ultrasound transducers (UTs) with single-side arrangement that generates active traveling waves to control the position and orientation of a fully untethered nanocarrier clusters (NCs) in a spherical workspace in water capable of three DoFs translation and two DoFs rotation. In this method, we use a phase modulation algorithm to independently control the phase signal for 30 UTs and manipulate the NCs’ positions. Phase modulation and switching power supply for each UT are employed to rotate the NCs in the horizontal plane and control the amplitude of power supply to each UT to rotate the NCs in the vertical plane. The feasibility of the method is demonstrated by in vitro and ex vivo experiments using porcine ribs. A significant portion of this study could advance the therapeutic application such a system as targeted drug delivery.

This study introduces a tunable acoustic tweezer system designed for precise three-dimensional particle trapping and manipulation. The system utilizes a dual-liquid-layer acoustic lens, which enables the dynamic control of the focal length through the adjustable curvature of a latex membrane. This tunability is essential for generating the acoustic forces necessary for effective manipulation of particles, particularly along the direction of acoustic wave propagation ($z$-axis). Experiments conducted with spherical particles as small as 1.5 mm in diameter demonstrated the system’s capability for stable trapping and manipulation. Performance was rigorously evaluated through both $z$-axis and 3D manipulation tests. In the z-axis experiments, the system achieved a manipulation range of 33.4–53.4 mm, with a root-mean-square error and standard deviation of 0.044 ± 0.045 mm, which highlights its precision. Further, the 3D manipulation experiments showed that particles could be accurately guided along complex paths, including multilayer rectangular and helical trajectories, with minimal deviation. A visual feedback-based particle navigation system significantly enhanced positional accuracy, reducing errors relative to open-loop control. These results confirm that the tunable acoustic tweezer system is a robust tool for applications requiring precise control of particles with diameter of 1.5 mm in three-dimensional environments. Considering its ability to dynamically adjust the focal point and maintain stable trapping, this system is well suited for tasks demanding high precision, such as targeted particle delivery and other applications involving advanced material manipulation.

Microrobots driven by multiple external power sources have emerged as promising tools for targeted drug and stem cell delivery in tissue regeneration. However, navigating and imaging these devices within a complex colloidal vascular system at a clinical scale is challenging. Ultrasonic actuators have gained interest in the field of non-contact manipulation of micromachines due to their label-free biocompatible nature and safe operation history. This research presents experimentally validated simulation results of ultrasonic actuation using a novel ultrasonic transducer array with a hemispherical arrangement that generates active traveling waves with phase modulation. Blood flow is used as a carrier force while the direction and path are controlled by blocking undesirable paths using a highly focused acoustic field. In the experiments, the microrobot cluster was able to follow a predefined trajectory and reach the target. The microrobot size, maximum radiation pressure, and focus position were optimized for certain blood flow conditions. The outcomes suggest that this acoustic manipulation module has potential applications in targeted tumor therapy.