Direct monitoring of calcium-triggered phase transitions in cubosomes using small-angle X-ray scattering combined with microfluidics

Research output: Contribution to journalArticle

Abstract

This article introduces a simple microfluidic device that can be combined with synchrotron small-angle X-ray scattering (SAXS) for monitoring dynamic structural transitions. The microfluidic device is a thiol-ene-based system equipped with 125 μm-thick polystyrene windows, which are suitable for X-ray experiments. The device was prepared by soft lithography using elastomeric molds followed by a simple UV-initiated curing step to polymerize the chip material and simultaneously seal the device with the polystyrene windows. The microfluidic device was successfully used to explore the dynamics of the structural transitions of phytantriol/dioleoylphosphatidylglycerol-based cubosomes on exposure to a buffer containing calcium ions. The resulting SAXS data were resolved in the time frame between 0.5 and 5.5 s, and a calcium-triggered structural transition from an internal inverted-type cubic phase of symmetry Im3m to an internal inverted-type cubic phase of symmetry Pn3m was detected. The combination of microfluidics with X-ray techniques opens the door to the investigation of early dynamic structural transitions, which is not possible with conventional techniques such as glass flow cells. The combination of microfluidics with X-ray techniques can be used for investigating protein unfolding, for monitoring the formation of nanoparticles in real time, and for other biomedical and pharmaceutical investigations. A combination of microfluidics with X-ray techniques has been used to perform dynamic structural studies on nanoparticulate formulations.

Details

Authors
  • Aghiad Ghazal
  • Mark Gontsarik
  • Jörg P. Kutter
  • Josiane P. Lafleur
  • Ana Labrador
  • Kell Mortensen
  • Anan Yaghmur
Organisations
External organisations
  • University of Copenhagen
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Condensed Matter Physics

Keywords

  • lipidic formulations, microfabrication, microfluidics, SAXS, small-angle X-ray scattering, X-ray techniques
Original languageEnglish
Pages (from-to)2005-2014
Number of pages10
JournalJournal of Applied Crystallography
Volume49
Issue number6
Publication statusPublished - 2016 Dec 1
Publication categoryResearch
Peer-reviewedYes