High Spatiotemporal Control of Spontaneous Reactions Using Ultrasound-Triggered Composite Droplets

J. Am. Chem. Soc.,2014,136 (20), pp 7205–7208.

Marine Bezagu †, Claudia Errico ‡, Victor Chaulot-Talmon §, Fabrice Monti §, Mickael Tanter ‡,Patrick Tabeling *§, Janine Cossy *†, Stellios Arseniyadis *†, Olivier Couture ‡

  Laboratoire de Chimie Organique, Institute of Chemistry, Biology and Innovation (CBI), − UMR 8231 − ESPCI ParisTech/CNRS/PSL* Research University, 10 rue Vauquelin, 75231 Paris Cedex 05, France and

 Institut Langevin, ESPCI ParisTech, CNRS (UMR 7587), INSERM (U979), Paris, France and

§ Laboratoire de Microfluidique, MEMS et Nanostructures,ESPCI ParisTech, CNRS (UMR Gulliver 7083), Paris, France.



Achieving high spatial and temporal control over a spontaneous reaction is a particularly challenging task with potential breakthroughs in various fields of research including surface patterning and drug delivery. We report here an exceptionally effective method that allows attaining such control. This method relies on a remotely triggered ultrasound-induced release of a reactant encapsulated in a composite microdroplet of liquid perfluorohexane. More specifically, the demonstration was achieved by locally applying a focused 2.25 MHz transducer onto a microfluidic channel in which were injected composite microdroplets containing a solution of an azidocoumarin and an external flow containing a reactive alkyne.

Copyright © 2014 American Chemical Society.


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Significance statement

Methods that allow a spatiotemporal control of a spontaneous reaction are particularly important, particularly  in fields such as surface patterning and drug delivery. In this context, we previously established that perfluorocarbon composite droplets comprised of a nanoemulsion of water loaded with fluorescein and encapsulated in a perfluorohexane matrix (4 um in diameter) could release their content by acoustic vaporization (Couture et al. Medical Physics, 2011 and 2012). Following these initial results, we implemented the use of these microdroplets to allow spatial and temporal control of a chemical reaction by isolating two reactants (A and B) and releasing them using acoustic pulses. This method of control allows the formation of the product (C) specifically at the focal zone upon vaporization of the perfluorocarbon matrix. Most importantly, the steep threshold of release of these droplets (1.7 MPa PNP at 5 MHz) allows to trigger of a specific chemical reaction with a high spatial (mm) and temporal resolution (ms). The demonstration was achieved by encapsulating a solution of azidocoumarin (A) in DMSO into composite droplets of perfluorohexane and releasing the content into the external flow containing a reactive alkyne (B). Hence, we managed to remotely induce the “click” reaction using ultrasound, by locally releasing an encapsulated reactant into a flow containing a reactive partner. This reaction was triggered by a single ultrasound pulse specifically within the focus of the transducer (0.6 mm in width) and within a time of less than 3 ms. We expect that such targeted chemistry could lead to the localized release of prodrugs or to the localized production of drugs in-vivo that are either too toxic or unstable to be injected.

High Spatiotemporal Control of Spontaneous Reactions Using Ultrasound-Triggered Composite Droplets. Advances In Engineering