Efficient finite element modeling of radiation forces on elastic particles of arbitrary size and geometry.

A finite element based method is presented for calculating the acoustic radiation force on arbitrarily shaped elastic and fluid particles. Importantly for future applications, this development will permit the modeling of acoustic forces on complex structures such as biological cells, and the interactions between them and other bodies. The model is based on a non-viscous approximation, allowing the results from an efficient, numerical, linear scattering model to provide the basis for the second-order forces. Simulation times are of the order of a few seconds for an axi-symmetric structure. The model is verified against a range of existing analytical solutions (typical accuracy better than 0.1%), including those for cylinders, elastic spheres that are of significant size compared to the acoustic wavelength, and spheroidal particles.

Acoustofluidics 9: Modelling and applications of planar resonant devices for acoustic particle manipulation.

This article introduces the design, construction and applications of planar resonant devices for particle and cell manipulation. These systems rely on the pistonic action of a piezoelectric layer to generate a one dimensional axial variation in acoustic pressure through a system of acoustically tuned layers. The resulting acoustic standing wave is dominated by planar variations in pressure causing particles to migrate to planar pressure nodes (or antinodes depending on particle and fluid properties). The consequences of lateral variations in the fields are discussed, and rules for designing resonators with high energy density within the appropriate layer for a given drive voltage presented.

HeLa cell transfection using a novel sonoporation system.

Sonoporation has been shown to have an important role in biotechnology for gene therapy and drug delivery. This paper presents a novel microfluidic sonoporation system that achieves high rates of cell transfection and cell viability by operating the sonoporation chamber at resonance. The paper presents a theoretical analysis of the resonant sonoporation chamber design, which achieves sonoporation by forming an ultrasonic standing wave across the chamber. A piezoelectric transducer (PZT 26) is used to generate the ultrasound and the different material thicknesses have been identified to give a chamber resonance at 980 kHz. The efficiency of the sonoporation system was determined experimentally under a range of sonoporation conditions and different exposures time (5, 10, 15, and 20 s, respectively) using HeLa cells and plasmid (peGFP-N1). The experimental results achieve a cell transfection efficiency of 68.9% (analysis of variance, ANOVA, p < 0.05) at the resonant frequency of 980 kHz at 100 V(p-p) (19.5 MPa) with a cell viability of 77% after 10 s of insonication.

Contrast agent-free sonoporation: The use of an ultrasonic standing wave microfluidic system for the delivery of pharmaceutical agents.

Sonoporation is a useful biophysical mechanism for facilitating the transmembrane delivery of therapeutic agents from the extracellular to the intracellular milieu. Conventionally, sonoporation is carried out in the presence of ultrasound contrast agents, which are known to greatly enhance transient poration of biological cell membranes. However, in vivo contrast agents have been observed to induce capillary rupture and haemorrhage due to endothelial cell damage and to greatly increase the potential for cell lysis in vitro. Here, we demonstrate sonoporation of cardiac myoblasts in the absence of contrast agent (CA-free sonoporation) using a low-cost ultrasound-microfluidic device. Within this device an ultrasonic standing wave was generated, allowing control over the position of the cells and the strength of the acoustic radiation forces. Real-time single-cell analysis and retrospective post-sonication analysis of insonated cardiac myoblasts showed that CA-free sonoporation induced transmembrane transfer of fluorescent probes (CMFDA and FITC-dextran) and that different mechanisms potentially contribute to membrane poration in the presence of an ultrasonic wave. Additionally, to the best of our knowledge, we have shown for the first time that sonoporation induces increased cell cytotoxicity as a consequence of CA-free ultrasound-facilitated uptake of pharmaceutical agents (doxorubicin, luteolin, and apigenin). The US-microfluidic device designed here provides an in vitro alternative to expensive and controversial in vivo models used for early stage drug discovery, and drug delivery programs and toxicity measurements.

Mode-switching: a new technique for electronically varying the agglomeration position in an acoustic particle manipulator.

Acoustic radiation forces offer a means of manipulating particles within a fluid. Much interest in recent years has focussed on the use of radiation forces in microfluidic (or "lab on a chip") devices. Such devices are well matched to the use of ultrasonic standing waves in which the resonant dimensions of the chamber are smaller than the ultrasonic wavelength in use. However, such devices have typically been limited to moving particles to one or two predetermined planes, whose positions are determined by acoustic pressure nodes/anti-nodes set up in the ultrasonic standing wave. In most cases devices have been designed to move particles to either the centre or (more recently) the side of a flow channel using ultrasonic frequencies that produce a half or quarter wavelength over the channel, respectively. It is demonstrated here that by rapidly switching back and forth between half and quarter wavelength frequencies - mode-switching - a new agglomeration position is established that permits beads to be brought to any arbitrary point between the half and quarter-wave nodes. This new agglomeration position is effectively a position of stable equilibrium. This has many potential applications, particularly in cell sorting and manipulation. It should also enable precise control of agglomeration position to be maintained regardless of manufacturing tolerances, temperature variations, fluid medium characteristics and particle concentration.