Expanding 3D geometry for enhanced on-chip microbubble production and single step formation of liposome modified microbubbles

Lab Chip. 2012 Nov 7;12(21):4544-52. doi: 10.1039/c2lc40634a.

Abstract

Micron sized, lipid stabilized bubbles of gas are of interest as contrast agents for ultra-sound (US) imaging and increasingly as delivery vehicles for targeted, triggered, therapeutic delivery. Microfluidics provides a reproducible means for microbubble production and surface functionalisation. In this study, microbubbles are generated on chip using flow-focussing microfluidic devices that combine streams of gas and liquid through a nozzle a few microns wide and then subjecting the two phases to a downstream pressure drop. While microfluidics has successfully demonstrated the generation of monodisperse bubble populations, these approaches inherently produce low bubble counts. We introduce a new micro-spray flow regime that generates consistently high bubble concentrations that are more clinically relevant compared to traditional monodisperse bubble populations. Final bubble concentrations produced by the micro-spray regime were up to 10(10) bubbles mL(-1). The technique is shown to be highly reproducible and by using multiplexed chip arrays, the time taken to produce one millilitre of sample containing 10(10) bubbles mL(-1) was ∼10 min. Further, we also demonstrate that it is possible to attach liposomes, loaded with quantum dots (QDs) or fluorescein, in a single step during MBs formation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Fluorescein / chemistry
  • Gases / chemistry*
  • Liposomes / chemistry*
  • Microfluidic Analytical Techniques / instrumentation
  • Microfluidic Analytical Techniques / methods*
  • Models, Molecular
  • Quantum Dots
  • Surface Properties

Substances

  • Gases
  • Liposomes
  • Fluorescein