title: Expanding 3D geometry for enhanced on-chip microbubble production and single step formation of liposome modified microbubbles.
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.
authors.affiliation: Physics and Astronomy, University of Leeds, Woodhouse Lane, Leeds, LS2 9JT, UK.
authors.forename: Sally A
authors.initials: SA
authors.lastname: Peyman
authors.forename: Radwa H
authors.initials: RH
authors.lastname: Abou-Saleh
authors.forename: James R
authors.initials: JR
authors.lastname: McLaughlan
authors.forename: Nicola
authors.initials: N
authors.lastname: Ingram
authors.forename: Benjamin R G
authors.initials: BR
authors.lastname: Johnson
authors.forename: Kevin
authors.initials: K
authors.lastname: Critchley
authors.forename: Steven
authors.initials: S
authors.lastname: Freear
authors.forename: J Anthony
authors.initials: JA
authors.lastname: Evans
authors.forename: Alexander F
authors.initials: AF
authors.lastname: Markham
authors.forename: P Louise
authors.initials: PL
authors.lastname: Coletta
authors.forename: Stephen D
authors.initials: SD
authors.lastname: Evans
mesh_terms: D019793:Fluorescein / Q000737:chemistry; D005740:Gases / Q000737:chemistry*; D008081:Liposomes / Q000737:chemistry*; D046210:Microfluidic Analytical Techniques / Q000295:instrumentation / Q000379:methods*; D008958:Models, Molecular; D045663:Quantum Dots; D013499:Surface Properties
chemical_list: D005740:Gases; D008081:Liposomes; D019793:Fluorescein