Institute of Fundamental Technological Research

Manipulating particles in the blood pool with noninvasive methods has been of great interest in therapeutic delivery. Recently, it was demonstrated experimentally that red blood cells can be forced to translate and accumulate in an ultrasound field. This acoustic response of the red blood cells has been attributed to sonophores, gas pockets that are formed under the influence of a sound field in the inner-membrane leaflets of biological cells. In this paper, we propose a simpler model: that of the compressible membrane. We derive the spatio-temporal cel dynamics for a spherically symmetric single cell, whilst regarding the cell bilayer membrane as two monolayer Newtonian viscous liquids, separated by a thin gas void. When applying the newly-derived equations to a red blood cell, it is observed that the void inside the bilayer expands to multiples of its original thickness, even at clinically safe acoustic pressure amplitudes. For causing permanent cell rupture during expansion, however, the acoustic pressure amplitudes needed would have to surpass the inertial cavitation threshold by a factor 10. Given the incompressibility of the inner monolayer, the radial oscillations of a cell are governed by the same set of equations as those of a forced antibubble. Evidently, these equations must hold for liposomes under sonication, as well.

spatio-temporal cell dynamics, Rayleigh-Plesset equation, spherical cell, red blood cell, erythrocyte

The bilayer sonophore model suggests that ultrasound induces a pulsating structure in the intra-membrane hydrophobic space between the two lipid monolayer lea ets of the cell membrane, assembled by dissolved gas of the surrounding area, which absorbs acoustic energy and transforms it by creating intra-cellular structural changes. This void has been referred to as a bilayer sonophore. The bilayer sonophore in ates and de ates periodically when exposed to ultrasound and may itself radiate acoustic pressure pulses in the surrounding medium in the same way a gas bubble does: once exposed to ultrasound the bilayer sonophore becomes a mechanical oscillator and a source of intracellular cavitation activity. In this paper, we describe observations of the clustering behaviour of living cells and several other particles in a standing sound eld generated inside a ring transducer. Upon sonication, blood cells and monodisperse polystyrene particles were observed to have been trapped in the same locations, corresponding to nodes of the ultrasound eld. Because polystyrene is hydrophobic, it behaves like a particle trapped inside a thin gas shell. In fact, the sonophore model treats biological cells in a similar way. Microbubbles that form the ultrasound contrast agent Quantison behave di erently, however. These microbubbles accumulated in circles faster than blood cells and polystyrene particles. In addition, they form tightly packed clusters at the nodes, indicating very strong secondary Bjerknes forces. Cluster formation is not to be expected in cells with predicted sonophore sizes on the order of 10 - 100 nm.