TY - JOUR
T1 - Expanding 3D geometry for enhanced on-chip microbubble production and single step formation of liposome modified microbubbles
AU - Peyman, Sally A.
AU - Abou-Saleh, Radwa H.
AU - McLaughlan, James R.
AU - Ingram, Nicola
AU - Johnson, Benjamin R. G.
AU - Critchley, Kevin
AU - Freear, Steven
AU - Evans, J. Anthony
AU - Markham, Alexander F.
AU - Coletta, P. Louise
AU - Evans, Stephen D.
PY - 2012/11/7
Y1 - 2012/11/7
N2 - 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 1010 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 1010 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.
AB - 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 1010 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 1010 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.
UR - http://www.scopus.com/inward/record.url?scp=84867325423&partnerID=8YFLogxK
U2 - 10.1039/c2lc40634a
DO - 10.1039/c2lc40634a
M3 - Article
C2 - 22968592
AN - SCOPUS:84867325423
SN - 1473-0197
VL - 12
SP - 4544
EP - 4552
JO - Lab on a Chip
JF - Lab on a Chip
IS - 21
ER -