The use of a novel microfluidics system for in vitro ultrasound-mediated drug delivery

Abstract

Ultrasound insonification of gas filled microbubbles can be used to locally enhance vascular drug delivery [1]. Understanding of the underlying mechanisms requires an in vitro endothelial cell model that includes 3D cell culture and flow. We propose to use the elaborate microchannel system in the OrganoPlate™ [2]. Since it has never been used with ultrasound before, we assessed the feasibility of acoustic transmission. The oscillation of microbubbles in the OrganoPlate™ was recorded during ultrasound insonification (50 kPa, 1-4 MHz, 8 cycles) using the Brandaris 128 ultra-high-speed camera at 17 Mfps. We compared these oscillations to measurements performed in an acoustically transparent OptiCell [3]. From 1 to 1.6 MHz, larger oscillation amplitudes were observed in the OrganoPlate™, resulting from pressure amplification in the microchannels. Finite element modeling of wave propagation using PZFlex supported our findings. Successful sonoporation of 3D cultured endothelial cells was achieved in preliminary experiments using CD31 targeted microbubbles. The obtained microbubble oscillations and successful sonoporation demonstrate the potential of the OrganoPlate™ for an ideal in vitro model to investigate ultrasound-mediated drug delivery. [1] Kooiman, et al., Adv. Drug Deliv. Rev., 2014. [2] Trietsch, et al., Lab Chip, 2013. [3] van Rooij, et al., Ultrasound Med. Biol., 2015.