Localized micro‐scale disruption of cells using laser‐generated focused ultrasound

Abstract

We utilize laser-generated focused ultrasound (LGFU) to create targeted mechanical disturbance on a few cells. The LGFU is transmitted through an optoacoustic lens that converts laser pulses into focused ultrasound. The tight focusing (<100 µm) and high peak pressure of the LGFU produces cavitational disturbances at a localized spot with micro-jetting and secondary shock-waves arising from micro-bubble collapse. We demonstrate that LGFU can be used as a non-contact, non-ionizing, high-precision tool to selectively detach a single cell from its culture substrate. Furthermore, we explore the possibility of biomolecule delivery in a small population of cells targeted by LGFU at pressure amplitudes below and above the cavitation threshold. We experimentally confirm that cavitational disruption is required for delivery of propidium iodide, a membrane-impermeable nucleic acid-binding dye, into cells.

Micro-ultrasonic cleaving of cell clusters by laser-generated focused ultrasound and its mechanisms

“…In addition, micro-jetting can be formed as the merged bubble cloud is collapsed. This produces local stresses towards the focal center [15,18]. Since all these effects are concentrated at the focal center, the single cells could be individually and sharply detached from the cluster.…”

“…High peak pressures of tens of MPa could be tightly focused onto a spot diameter of <100 μm due to inherent high-frequency characteristics of the optoacoustic generation (centered at ~15 MHz with a 6-dB cutoff around 30 MHz). Thus, LGFU-induced disruptions could be demonstrated in a micro-scale regime, enabling single-cell detachment and trans-membrane delivery over a few cells [17,18]. Particularly, acoustic cavitation under LGFU could be delicately controlled with pressure amplitudes near a cavitation threshold.…”

“…Particularly, acoustic cavitation under LGFU could be delicately controlled with pressure amplitudes near a cavitation threshold. This allowed a tightly confined impact only at the focal center (<60 μm in diameter for a given 6-dB focal spot of 100 μm), barely affecting the peripheral region [18]. Such focal disruption mechanism was partly clarified as originated from micro-jet formation upon bubble collapse.…”

“…1(a)) [17,18]. The pulsed laser beam (initially, 5-mm diameter) was expanded by 5-fold and collimated.…”

Highly Efficient Photoacoustic Conversion by Facilitated Heat Transfer in Ultrathin Metal Film Sandwiched by Polymer Layers

“…In addition to the carbon‐based broadband absorbers, a metal‐based PDMS composite consisting of gold nanoparticles was developed, showing high PA conversion efficiency compared to aluminum thin film . Beyond imaging and sensing applications, such highly efficient PA materials have allowed new applications, e.g., PA cavitation therapy capable of selectively removing biomaterials, cells or tissues …”