Induction of Microstreaming by Nonspherical Bubble Oscillations in an Acoustic Levitation System

Summary

A fast and reliable technique is proposed to control the shape oscillations of a single, trapped acoustic bubble that is based on coalescence technique between two bubbles. The steady-state, symmetry-controlled bubble shape oscillations allow analysis of the fluid flow generated in the vicinity of the bubble interface.

Abstract

When located near biological barriers, oscillating microbubbles may increase cell membrane permeability, allowing for drug and gene internalization. Experimental observations suggest that the temporary permeabilization of these barriers may be due to shear stress that is exerted on cell tissues by cavitation microstreaming. Cavitation microstreaming is the generation of vortex flows which arise around oscillating ultrasound microbubbles. To produce such liquid flows, bubble oscillations must deviate from purely spherical oscillations and include either a translational instability or shape modes. Experimental studies of bubble-induced flows and shear stress on nearby surfaces are often restricted in their scope due to the difficulty of capturing shape deformations of microbubbles in a stable and controllable manner. We describe the design of an acoustic levitation chamber for the study of symmetry-controlled nonspherical oscillations. Such control is performed by using a coalescence technique between two approaching bubbles in a sufficiently intense ultrasound field. The control of nonspherical oscillations opens the way to a controlled cavitation microstreaming of a free surface-oscillating microbubble. High-frame rate cameras allow investigating quasi-simultaneously the nonspherical bubble dynamics at the acoustic timescale and the liquid flow at a lower timescale. It is shown that a large variety of fluid patterns may be obtained and that they are correlated to the modal content of the bubble interface. We demonstrate that even the high-order shape modes can create large-distance fluid patterns if the interface dynamics contain several modes, highlighting the potential of nonspherical oscillations for targeted and localized drug delivery.

Introduction

In medicine, an administered drug must penetrate many obstacles in the living system before reaching the desired targets. However, most drugs are rapidly cleaned away from the blood stream. The targeting efficiency is low and they cannot easily cross cell membranes, leading to ineffective drug delivery. Currently, the use of microbubbles in combination with ultrasound has been proposed as an innovative method for noninvasive, precise and targeted delivery of drugs and genes to pathological tissues and cells¹. In this approach, microbubbles can play a role as carriers where free drugs are either co-injected with a gas bubble suspension or loaded....

Protocol

1. Design of the acoustic levitation chamber

1. Design an optically transparent (PMMA-like) cubic tank (8 cm edge and 2.8 mm thickness per face) with the geometry module of a multiphysics simulation software (Table of Materials).
2. Insert a cylindrical surface (Ø = 35 mm) centered at the bottom of the tank, to model the ultrasonic transducer.
3. Set the boundary conditions to zero pressure on each wall with a normal displacement of amplitude 1 µm at the transducer surface.
4. Using a Frequency domain module, simulate the Frequency Response Function (FRF) of the tank in the frequency range [10 - 40] kHz, at the ....

Results

A complete sequence of bubble coalescence leading to time-stable, symmetry-controlled nonspherical oscillations is presented in Figure 9. The approaching phase of two spherically-oscillating bubbles ends when the thin liquid film between the two bubbles is ruptured. It is worth noting that, at the last stage prior to the coalescence, the bubble interfaces deviate from sphericity. Both bubbles elongate on an ellipsoidal shape along the path of the rectilinear .......

Discussion

The presented procedure consists of using bubble coalescence in order to trigger steady-state, symmetry-controlled bubble shape oscillations, allowing the study of the long-term fluid flow induced by these oscillations. The main challenge in the technique is the control of nonspherical oscillations for a bubble being trapped, far from any boundaries.

Most of the existing techniques proposed in the literature focused on substrate-attached bubbles^7,

Materials

List of materials used in this article

Name	Company	Catalog Number	Comments
Aspherical lens	Thorlabs	AL4050	Lens of focus 40 mm
Continuous wave laser source	CNI	MLL6FN	DPSS laser of wavelength 532nm, energy 400 mW
Cylindrical plano-concave lens	Thorlabs	LJ1277L1-A	lens of focus -25?4mm
Cylindrical plano-concave lens	Thorlabs	LK1900L1	lens of focus 250 mm
Fluorescent particles	Duke Scientific	R700	Red polymer fluorescent microspheres
Function generator	Agilent	HP33120	Generator of function feeding the ultrasound transducer
High-speed camera	Vision Research	Phantom v12.0	High-speed recording up to 1 Mfps
Liquid medium	Carlo Erba	Water for analysis	Demineralized, undegassed water
Multiphysics software	Comsol	None	Softwate for simulating the acoustic field of the levitation chamber
Nd:Yag pulsed laser	New Wave Research	Solo III-15	5 ns pulse duration, λ=532 nm, 3.5 mm beam diameter, up to 50 mJ
Plano-concave lens	Thorlabs	N-BK7	lens of focus 125 mm
Spherical concave lens	Thorlabs	N-SF11	Bi-concave lens of focus -25mm
Ultrasound transducer	SinapTec	Custom-made	Nominal frequency 31kHz, active area 35mm diameter
Visualization software	NIH	ImageJ	Software for image processing and analysis in Java
XY Linear stage	Newport	M-406	Displacement stage with micrometric screw
Z-axis linear stage	Edmund Optics	62-299	Vertical displacement stage with micrometric screw