Acoustic Characterization of a Vessel-on-a-Chip Microfluidic System for Ultrasound-Mediated Drug Delivery

Ines Beekers (Corresponding Author), Tom van Rooij, Martin D. Verweij, Michel Versluis, Nico de Jong, Sebastiaan J. Trietsch, Klazina Kooiman

Research output: Contribution to journalArticleAcademicpeer-review

14 Citations (Scopus)
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Ultrasound in the presence of gas-filled microbubbles can be used to enhance local uptake of drugs and genes. To study the drug delivery potential and its underlying physical and biological mechanisms, an in vitro vessel model should ideally include 3D cell culture, perfusion flow, and membranefree soft boundaries. Here, we propose an organ-on-a-chip microfluidic platform to study ultrasound-mediated drug delivery: the OrganoPlate. The acoustic propagation into the OrganoPlate was determined to assess the feasibility of controlled microbubble actuation, which is required to study the microbubble-cell interaction for drug delivery. The pressure field in the OrganoPlate was characterized non-invasively by studying experimentally the well-known response of microbubbles and by simulating the acoustic wave propagation in the system. Microbubble dynamics in the OrganoPlate were recorded with the Brandaris 128 ultrahigh speed camera (17 Mfps) and a control experiment was performed in an OptiCell, an in vitro monolayer cell culture chamber that is conventionally used to study ultrasound-mediated drug delivery. When insonified at frequencies between 1 and 2 MHz, microbubbles in the OrganoPlate experienced larger oscillation amplitudes resulting from higher local pressures. Microbubbles responded similarly in both systems when insonified at frequencies between 2 and 4 MHz. Numerical simulations performed with a 3D finite element model of ultrasound propagation into the OrganoPlate and the OptiCell showed the same frequency dependent behavior. The predictable and homogeneous pressure field in the OrganoPlate demonstrates its potential to develop an in vitro 3D cell culture model, well-suited to study ultrasoundmediated drug delivery.

Original languageEnglish
Pages (from-to)570-581
Number of pages12
JournalIEEE transactions on ultrasonics, ferroelectrics and frequency control
Issue number4
Publication statusPublished - 7 Feb 2018


  • Acoustic wave modeling
  • Acoustics
  • Computer architecture
  • Drug delivery
  • Acoustic characterization
  • Microchannels
  • Microfluidics
  • Microprocessors
  • Organ-on-a-chip
  • Three-dimensional displays
  • Ultrasonic imaging
  • Ultrasound contrast agents
  • acoustic wave modeling
  • drug delivery
  • ultrasound contrast agents
  • organ-on-a-chip
  • microfluidics


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