Ultrathin Silicon Membranes for in Situ Optical Analysis of Nanoparticle Translocation across a Human Blood-Brain Barrier Model

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DOI

  • Diána Hudecz
  • Tejas Khire, Department of Biomedical Engineering , University of Rochester , Rochester , New York 14627 , United States.
  • ,
  • Hung Li Chung, Department of Biomedical Engineering , University of Rochester , Rochester , New York 14627 , United States.
  • ,
  • Laurent Adumeau, Centre for BioNano Interactions, School of Chemistry , University College Dublin , Belfield, Dublin 4 , Ireland.
  • ,
  • Dale Glavin, Department of Biomedical Engineering , University of Rochester , Rochester , New York 14627 , United States.
  • ,
  • Emma Luke, Department of Biomedical Engineering , University of Rochester , Rochester , New York 14627 , United States.
  • ,
  • Morten S Nielsen
  • Kenneth A Dawson, Centre for BioNano Interactions, School of Chemistry , University College Dublin , Belfield, Dublin 4 , Ireland.
  • ,
  • James L McGrath, Department of Biomedical Engineering , University of Rochester , Rochester , New York 14627 , United States.
  • ,
  • Yan Yan, University College Dublin, Dublin

Here we present a blood-brain barrier (BBB) model that enables high-resolution imaging of nanoparticle (NP) interactions with endothelial cells and the capture of rare NP translocation events. The enabling technology is an ultrathin silicon nitride (SiN) membrane (0.5 mu m pore size, 20% porosity, 400 nm thickness) integrated into a dual-chamber platform that facilitates imaging at low working distances (similar to 50 mu m). The platform, the mu SiM-BBB (microfluidic silicon membrane-BBB), features human brain endothelial cells and primary astrocytes grown on opposite sides of the membrane. The human brain endothelial cells form tight junctions on the ultrathin membranes and exhibit a significantly higher resistance to FITC-dextran diffusion than commercial membranes. The enhanced optical properties of the SiN membrane allow high-resolution live-cell imaging of three types of NPs, namely, 40 nm PS-COOH, 100 nm PS-COOH, and apolipoprotein E-conjugated 100 nm SiO2, interacting with the BBB. Despite the excellent barrier properties of the endothelial layer, we are able to document rare NP translocation events of NPs localized to lysosomal compartments of astrocytes on the "brain side" of the device. Although the translocation is always low, our data suggest that size and targeting ligand are important parameters for NP translocation across the BBB. As a platform that enables the detection of rare transmission across tight BBB layers, the mu SiM-BBB is an important tool for the design of nanoparticle-based delivery of drugs to the central nervous system.

Original languageEnglish
JournalACS Nano
Volume14
Issue1
Pages (from-to)1111-1122
Number of pages12
ISSN1936-0851
DOIs
Publication statusPublished - Jan 2020

    Research areas

  • blood-brain barrier, coculture, live-cell imaging, nanoparticle, ultrathin silicon nitride membrane, VITRO MODEL, DRUG-DELIVERY, COCULTURE MODEL, NANOPARTICLES, TRANSPORT, TRANSFERRIN, TRANSCYTOSIS, ENDOTHELIAL-CELLS, NITRIDE MEMBRANES, APOLIPOPROTEIN-A-I

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