Remote manipulation of cells with ultrasound and microbubbles

Annemieke van Wamel, Ayache Bouakaz, Michel Versluis, Nico de Jong

Research output: Chapter in Book/Report/Conference proceedingConference contributionAcademic

3 Citations (Scopus)


Ultrasound in combination with contrast microbubbles has been shown to alter the permeability of cell membranes. This permeabilization feature is used to design new drug delivery systems using ultrasound and contrast agents. Although the exact underlying mechanisms are still unknown, one hypothesis is that oscillating microbubbles cause cell deformation resulting in enhanced cell membrane permeability. In this paper we show the actions of oscillating microbubbles on cultured cells under a microscope recorded with a fast framing camera at 10 million frames per second. Optical observations of microbubbles and cultured cells is possible through the use of a microscope mounted in front of the fast framing camera Brandaris128. The Brandaris128 is capable of recording a sequence of 128 images with a frame rate up to 25 million frames per second. Pig aorta endothelial cells were grown on the inside of an Opticell/spl trade/ container. A diluted suspension of experimental agents BR14 (Bracco Research, Geneva, Switzerland) was added. Ultrasound exposure consisted of one burst of 6 cycles at a frequency of 1 MHz and a P/spl of 0.5 MPa. During ultrasound transmission, the interactions between BR14 microbubbles and cultured cells were recorded using a frame rate of 10 million frames per second. Cell deformation as a result of vibrating microbubbles is studied. Cell deformation is quantified through measuring the displacement of the cells. Microbubble vibration is quantified by measuring its initial, maximal, and minimal radii. We observed that upon ultrasound arrival and microbubble oscillations, the cell membrane deforms up to a few micrometers in length as a result of the oscillation of the microbubble. The membrane deformation rate changes with the oscillation strength of the microbubble. During the sonication, changes in the cross-sectional distance of the cultured cells were observed due to microbubble vibrations. Depending on the maximal vibrations of the microbubble and the distance between the microbubble and the cell, the displacement of the cells varied form 0 to 20% of the cell size. This study reveals the action of oscillating microbubbles on cells. It is known that living cells sense mechanical forces thus there is no doubt that perturbation of the oscillating microbubbles results in profound alterations in the cellular content. This study is the beginning of revealing the functional relationships that lie beyond the remote manipulation of cells and ultrasound microbubble induced permeabilization of the cell membrane.
Original languageEnglish
Title of host publication2004 IEEE Ultrasonics Symposium
Place of PublicationPiscataway, NJ
ISBN (Print)0-7803-8412-1
Publication statusPublished - 2004
Event2004 IEEE Ultrasonics Symposium - Montreal, Canada
Duration: 23 Aug 200427 Aug 2004


Conference2004 IEEE Ultrasonics Symposium


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