Acoustic Metastructure-Lensed Multi-Focal Sonicator Designs for High-Throughput Therapeutic Ultrasound Testing In Vitro

We developed a custom multi-focal sonicator for high-throughput in vitro benchtop testing for micro/nanoagent-mediated ultrasound therapies. As biocompatible micro/ nanoagents show significant therapeutic potential, optimizing ultrasound excitation conditions is essential. Traditional single-focus ultrasound setups face issues like beam alignment errors, long test times, and condition variations. To address these limitations, we designed a multi-focal sonicator generating uniform pressure across a 4×4 circular array. Using the acoustic hologram technique and iterative angular spectrum approach, we created a lens-interchangeable sonicator adaptable to different test plate sizes. After 70 iterations, simulations revealed a precise 4×4 focal array with a -6 dB lateral beam size of 1.4 mm. We prototyped both the lens and a sonicator bath with a flat-aperture transducer. Hydrophone measurements confirmed a multi-focal pressure pattern similar to simulations, with a structural similarity of 0.45 and cross-correlation of 0.78. The peak-negative pressures ranged from 1.5 to 1.7 MPa, averaging 1.62 MPa under an 800 V (peak-to-peak) burst input. Output intensities (SPTA) ranged from 0.5 W/cm<sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sup> to 10.2 W/cm<sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sup> with duty cycles from 0.5% to 12%. This device offers precise control and uniformity, enabling high-throughput benchtop studies on sonoporation and ultrasound-triggered drug release.