Ultrafast dynamics of the acoustic vaporization of phase-change microdroplets

Shpak, Oleksandr; Stricker, Laura; Kokhuis, Tom J. A.; Liu, Ying; Fowlkes, J. Brian; Fabiilli, Mario L.; Lohse, Detlef; Jong, Nico de; Versluis, Michel

doi:10.1121/1.4800334

Cited by 7 publications

(14 citation statements)

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“…The acoustic pressure amplitudes required to nucleate the droplet have been observed to be very high. In a typical ADV experiment, before impinging on the droplet the ultrasound wave from a focused transducer travels a distance on the order of a few centimeters (7,(17)(18)(19)(22)(23)(24). Under these conditions the wave that arrives at the focus of the transducer can be highly distorted owing to nonlinear propagation (25,26).…”

Section: Theorymentioning

confidence: 99%

“…There is also an unexplained decrease of the threshold pressure with increasing size of the droplets (20,21). Finally, ultrahigh-speed imaging has allowed for the construction of spatial and temporal nucleation maps (22). This showed that the nucleation spots inside the droplets were highly localized for some bubbles, whereas other bubbles had nucleation spots at random positions throughout the droplet.…”

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confidence: 99%

“…This showed that the nucleation spots inside the droplets were highly localized for some bubbles, whereas other bubbles had nucleation spots at random positions throughout the droplet. The authors suggested that the location of such spots may be a function of the droplet size (22). The authors also pointed out that temporally the initiation of the nucleation is shifted toward the end of the rarefactional half cycle of the ultrasound pulse.…”

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confidence: 99%

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Acoustic droplet vaporization is initiated by superharmonic focusing

Shpak

Verweij

Vos

et al. 2013

The Journal of the Acoustical Society of America

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Acoustically sensitive emulsion droplets composed of a liquid perfluorocarbon have the potential to be a highly efficient system for local drug delivery, embolotherapy or for tumor imaging. The physical mechanisms underlying the acoustic activation of these phase-change emulsions into a bubbly dispersion, termed acoustic droplet vaporization, have not been well understood. The droplets have a very high activation threshold, its frequency dependence does not comply with homogeneous nucleation theory and focusing spots have been observed. We showed that acoustic droplet vaporization is initiated by a combination of two phenomena: highly nonlinear distortion of the acoustic wave before it hits the droplet, and focusing of the distorted wave by the droplet itself. At high excitation pressures, nonlinear distortion causes significant superharmonics with wavelengths below the diameter of the droplet. Because these superharmonics strongly contribute to the focusing effect, the mechanism also explains pressure thresholding effects. In an accompanying paper, mathematical modeling aspects are presented. A proposed model is validated with experimental data captured with an ultra high-speed camera on the positions of the nucleation spots. Moreover, the presented mechanism explains the hitherto counterintuitive dependence of the nucleation threshold on the ultrasound frequency.

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Section: Theorymentioning

confidence: 99%

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confidence: 99%

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confidence: 99%

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Acoustic droplet vaporization is initiated by superharmonic focusing

Shpak

Verweij

Vos

et al. 2013

The Journal of the Acoustical Society of America

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“…The microtripsymediated droplet transition threshold increases with frequency (Vlaisavljevich et al 2015a), in contrast to measurements with non-histotripsy insonations (Kripfgans et al 2000). For nanodroplet-mediated histotripsy (NMH), homogenous nucleation of the perfluorocarbon liquid occurs via homogenous tensile nucleation (Vlaisavljevich et al 2015a), whereas heating via superharmonic focusing is a mechanism for non-histotripsy droplet transition (Li et al 2014a;Shpak et al 2013). Liquefaction of agar phantoms (Vlaisavljevich et al 2013a) and cancer tumor spheroids (Aydin et al 2016) can be achieved with NMH.…”

Section: Change Thy Liquidmentioning

confidence: 99%

For Whom the Bubble Grows: Physical Principles of Bubble Nucleation and Dynamics in Histotripsy Ultrasound Therapy

Bader

Vlaisavljevich

Maxwell

2019

Ultrasound in Medicine & Biology

136

114

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Histotripsy is a focused ultrasound therapy for non-invasive tissue ablation. Unlike thermally ablative forms of therapeutic ultrasound, histotripsy relies on the mechanical action of bubble clouds for tissue destruction. Although acoustic bubble activity is often characterized as chaotic, the short-duration histotripsy pulses produce a unique and consistent type of cavitation for tissue destruction. In this review, the action of histotripsyinduced bubbles is discussed. Sources of bubble nuclei are reviewed, and bubble activity over the course of single and multiple pulses is outlined. Recent innovations in terms of novel acoustic excitations, exogenous nuclei for targeted ablation and histotripsy-enhanced drug delivery and image guidance metrics are discussed. Finally, gaps in knowledge of the histotripsy process are highlighted, along with suggested means to expedite widespread clinical utilization of histotripsy.

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“…Ultrasound can induce oscillation, rupture, and collapse of the double emulsion droplets, which releases the payload from the core of the emulsion. [17][18][19] The perfluorohexane shell undergoes a phase change during vaporization causing a change from liquid to gas. [17] It is theorized, due to anisotropic pressures, that inertial cavitation will occur, which can cause transient pores in nearby cell membranes and enable transport of therapeutic compounds directly into the cytoplasm of cells ( fig.…”

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Tumor-targeted double emulsions for ultrasound-triggered delivery of molecular therapeutics.

Centner¹

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Cancer is the second leading cause of death in the United States, with 1.74 million new cancer cases diagnosed and 610,000 cancer deaths expected in 2018 alone. Current treatments often result in negative systemic effects and ineffective treatment of the tumor. Drug delivery vehicles have been developed for more effective local delivery methods, but many drug delivery vehicles lack spatial and temporal control. Targeted double emulsions are a new class of drug delivery vehicles which present a promising option for a high payload and controlled delivery. The purpose of our project was to develop and characterize an aptamer-chelated double emulsion that has the ability to actively target cancer cells and can be activated with ultrasound. AS1411, a 26-base guanine-rich oligonucleotide (GRO), was selected since AS1411 has the ability to target nucleolin surface receptors, which are overexpressed in many cancerous cell lines. Perfluorohexane forms the shell of the drug delivery vehicle since it is ultrasound-responsive in clinically acceptable pressure ranges. Ultrasound applied to double emulsions will cause vaporization of the perfluorocarbon shell, allowing transport of the molecular compound into the cancer cell with a higher efficiency. If a higher concentration is inside the cell than the microenvironment, the transient pores can release the molecular compound from the cytoplasm. This was seen in our static condition (p=0.054). A fluidic model is needed since static conditions doesn't accurate depict conditions that will be seen in vivo. The payload was released from core of the double emulsion. To help reduce the passive release of the payload, different surfactants were testing. FluorN562 showed a slower release profile than FluorN561 and Poloxamer 188 at 4 o C, 21 o C, and 37 o C (p<0.05), with 21 o C being the optimal temperature for storage of double emulsions (p<0.01). Polydispersed double emulsions varied too greatly in size for the double emulsions to be used clinically. To address this issue, a microfluidic device was developed for the creation of monodispersed double emulsions under 10 microns. Double emulsions, once steady state steady flow was reached, were constantly between 1 to 2 µm. Ultrasound-responsive double emulsions could a potential significant impact clinically allowing for therapeutic molecular compounds to enter the cancer cell more easily through the transient pores, which is a distinct advantage to this drug delivery system.

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Ultrafast dynamics of the acoustic vaporization of phase-change microdroplets

Cited by 7 publications

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Acoustic droplet vaporization is initiated by superharmonic focusing

Acoustic droplet vaporization is initiated by superharmonic focusing

For Whom the Bubble Grows: Physical Principles of Bubble Nucleation and Dynamics in Histotripsy Ultrasound Therapy

Tumor-targeted double emulsions for ultrasound-triggered delivery of molecular therapeutics.

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