Holographic Acoustic Tweezers for 5-DoF Manipulation of Nanocarrier Clusters toward Targeted Drug Delivery

Abstract

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.

Acoustically Driven Cell-Based Microrobots for Targeted Tumor Therapy

“…The proposed transducer array contains 30 transducers that can be set in 8 angular steps for the twin-trap phase. The Macbot is thus free to rotate in the O-XY plane by 360°/8 = 45° for each step [ 36 ]. The current position of the Macbots in the O-XY plane was captured by a CCD camera mounted on the top, whereas that of the Macbots in the O-XZ plane was captured by a CCD camera mounted on the side.…”

“…Second, the acoustic manipulation method can trap a nanometer- to millimeter-sized object at a specific point; thus, it can gather or separate objects without requiring the specific characteristic of object materials. Third, acoustic energy usage has a long history, and it is a safe technology for the human body as well as a biocompatible energy source [ 7 , 34 , 35 , 36 ]. Table 1 shows the summary of previously reported external powered platforms for wireless particle manipulation with certain operating parameters and system requirements.…”

“…Acoustic actuation generally consists of one to multiple piezoelectric transducers that generate a pressure field to trap and manipulate the object in low acoustic impedance media, commonly known as acoustic tweezers. Considering the ability to precisely control a single agent [ 37 , 38 , 39 ] as well as a cluster of agents [ 31 , 36 , 40 ] at different length scales, safety, and biocompatibility, acoustically-powered systems are becoming versatile and efficient platforms in diverse applications. Many approaches have been reported for levitating and manipulating an object in air [ 34 , 41 ], microfluidic channels [ 42 , 43 , 44 ], and in vitro experiments [ 40 , 45 , 46 , 47 , 48 ].…”

Fabrication, Acoustic Characterization and Phase Reference-Based Calibration Method for a Single-Sided Multi-Channel Ultrasonic Actuator

“…To generate an acoustic twin trap, the phase of each transducer was estimated as the sum of the focus phase and twin trap phase. The π radian difference (0.5 in phase offset value) was used to divide the array into two sides [29]. The phase of each transducer is given in (7), as shown below:…”

“…Marzo et al presented 3D holographic patterns for trapping (i.e., twin, bottle, and vortex traps) based on this approach [22,27,28]. All these can trap and manipulate some targeted particles with any hemispherical arrangement of multiple transducers, but the twin trap is considered a suitable pattern for providing two extra rotational motions for the acoustic tweezer [29].…”