Dual Channel Microfluidics for Mimicking the Blood-Brain Barrier

Boris Buchroithner, Sandra Mayr, Fabian Hauser, Eleni Priglinger, Herbert Stangl, Ana Raquel Santa-Maria, Maria A. Deli, Andras Der, Thomas A. Klar, Markus Axmann, Dmitry Sivun, Mario Mairhofer, Jaroslaw Jacak

Research output: Contribution to journalArticlepeer-review

31 Citations (Scopus)

Abstract

High-resolution imaging is essential for analysis of the steps and way stations of cargo transport in in vitro models of the endothelium. In this study, we demonstrate a microfluidic system consisting of two channels horizontally separated by a cell-growth-promoting membrane. Its design allows for high-resolution (down to single-molecule level) imaging using a high numerical aperture objective with a short working distance. To reduce optical aberrations and enable single-molecule-sensitive imaging, an observation window was constructed in the membrane via laser cutting with subsequent structuring using 3D multiphoton lithography for improved cell growth. The upper channel was loaded with endothelial cells under flow conditions, which showed polarization and junction formation. A coculture of human vascular endothelial cells with pericytes was developed that mimics the blood-brain barrier. Finally, this dual channel microfluidics system enabled 3D localization microscopy of the cytoskeleton and 3D single-molecule-sensitive tracing of lipoprotein particles.

Original languageEnglish
Pages (from-to)2984-2993
Number of pages10
JournalACS Nano
Volume15
Issue number2
DOIs
Publication statusPublished - 23 Feb 2021

Keywords

  • 3D multiphoton lithography
  • 3D particle tracking
  • blood-brain barrier
  • endothelial cells
  • microfluidics
  • single-molecule imaging
  • Endothelial Cells
  • Coculture Techniques
  • Humans
  • Pericytes
  • Microfluidics
  • Blood-Brain Barrier

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