Lipid shedding from single oscillating microbubbles

Ying Luan*, Guillaume Lajoinie, Erik Gelderblom, Ilya Skachkov, Antonius F.W. van der Steen, Hendrik J. Vos, Michel Versluis, Nico de Jong

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

69 Citations (Scopus)
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Lipid-coated microbubbles are used clinically as contrast agents for ultrasound imaging and are being developed for a variety of therapeutic applications. The lipid encapsulation and shedding of the lipids by acoustic driving of the microbubble has a crucial role in microbubble stability and in ultrasound-triggered drug delivery; however, little is known about the dynamics of lipid shedding under ultrasound excitation. Here we describe a study that optically characterized the lipid shedding behavior of individual microbubbles on a time scale of nanoseconds to microseconds. A single ultrasound burst of 20 to 1000 cycles, with a frequency of 1 MHz and an acoustic pressure varying from 50 to 425 kPa, was applied. In the first step, high-speed fluorescence imaging was performed at 150,000 frames per second to capture the instantaneous dynamics of lipid shedding. Lipid detachment was observed within the first few cycles of ultrasound. Subsequently, the detached lipids were transported by the surrounding flow field, either parallel to the focal plane (in-plane shedding) or in a trajectory perpendicular to the focal plane (out-of-plane shedding). In the second step, the onset of lipid shedding was studied as a function of the acoustic driving parameters, for example, pressure, number of cycles, bubble size and oscillation amplitude. The latter was recorded with an ultrafast framing camera running at 10 million frames per second. A threshold for lipid shedding under ultrasound excitation was found for a relative bubble oscillation amplitude >30%. Lipid shedding was found to be reproducible, indicating that the shedding event can be controlled.
Original languageEnglish
Pages (from-to)1834-1846
Number of pages13
JournalUltrasound in medicine and biology
Issue number8
Publication statusPublished - 2014


  • Microbubbles
  • Lipid shedding
  • Fluorescence imaging
  • High-speed imaging
  • Controlled drug delivery
  • Microstreaming
  • 2023 OA procedure


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