Design and validation of a human brain endothelial microvessel-on-a-chip open microfluidic model enabling advanced optical imaging

Salman, Mootaz M. and Marsh, Graham and Kusters, Ilja and Delincé, Matthieu and Di Caprio, Giuseppe and Upadhyayula, Srigokul and de Nola, Giovanni and Hunt, Ronan and Ohashi, Kazuka G. and Gray, Taylor and Shimizu, Fumitaka and Sano, Yasuteru and Kanda, Takashi and Obermeier, Birgit and Kirchhausen, Tom (2020) Design and validation of a human brain endothelial microvessel-on-a-chip open microfluidic model enabling advanced optical imaging. Frontiers in Bioengineering and Biotechnology, 8. pp. 1-16. 573775. ISSN 2296-4185 (https://doi.org/10.3389/fbioe.2020.573775)

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Abstract

We describe here the design and implementation of an in vitro microvascular open model system using human brain microvascular endothelial cells. The design has several advantages over other traditional closed microfluidic platforms: (1) it enables controlled unidirectional flow of media at physiological rates to support vascular function, (2) it allows for very small volumes which makes the device ideal for studies involving biotherapeutics, (3) it is amenable for multiple high resolution imaging modalities such as transmission electron microscopy (TEM), 3D live fluorescence imaging using traditional spinning disk confocal microscopy, and advanced lattice light sheet microscopy (LLSM). Importantly, we miniaturized the design, so it can fit within the physical constraints of LLSM, with the objective to study physiology in live cells at subcellular level. We validated barrier function of our brain microvessel-on-a-chip by measuring permeability of fluorescent dextran and a human monoclonal antibody. One potential application is to investigate mechanisms of transcytosis across the brain microvessel-like barrier of fluorescently-tagged biologics, viruses or nanoparticles.

ORCID iDs

Salman, Mootaz M., Marsh, Graham, Kusters, Ilja, Delincé, Matthieu, Di Caprio, Giuseppe ORCID logoORCID: https://orcid.org/0000-0001-5564-8064, Upadhyayula, Srigokul, de Nola, Giovanni, Hunt, Ronan, Ohashi, Kazuka G., Gray, Taylor, Shimizu, Fumitaka, Sano, Yasuteru, Kanda, Takashi, Obermeier, Birgit and Kirchhausen, Tom;
  • Item type:Article
    ID code:85599
    Dates:
    Date
    Event
    28 September 2020
    Published
    21 August 2020
    Accepted
    18 June 2020
    Submitted
    Notes:Funding Information: This project was funded in part by a Biogen Sponsored Research Agreement to TKi and NNF16OC0022166 Novo Nordisk Foundation/Danish Technical University grant to TKi. Funding Information: We thank Fang Qian and Benjamin Smith (Biogen) for generating the fluorescent hmAb monoclonal antibody, G. Campbell Kaynor (Biogen) for providing the lentiviral construct expressing memEGFP, Ramiro Massol and Chris Ehrenfels (Cellular Imaging Unit, Biogen), Tegy John Vadakkan (TKi Lab) for assistance with fluorescence microscopy imaging and Robin Kleiman (Biogen) for critical feedback. Funding. This project was funded in part by a Biogen Sponsored Research Agreement to TKi and NNF16OC0022166 Novo Nordisk Foundation/Danish Technical University grant to TKi. Publisher Copyright: © Copyright © 2020 Salman, Marsh, Kusters, Delincé, Di Caprio, Upadhyayula, de Nola, Hunt, Ohashi, Gray, Shimizu, Sano, Kanda, Obermeier and Kirchhausen. Salman MM, Marsh G, Kusters I, Delincé M, Di Caprio G, Upadhyayula S, de Nola G, Hunt R, Ohashi KG, Gray T, Shimizu F, Sano Y, Kanda T, Obermeier B and Kirchhausen T (2020) Design and Validation of a Human Brain Endothelial Microvessel-on-a-Chip Open Microfluidic Model Enabling Advanced Optical Imaging. Front. Bioeng. Biotechnol. 8:573775. doi: 10.3389/fbioe.2020.573775
    Subjects:Technology > Engineering (General). Civil engineering (General) > Bioengineering
    Science > Physics > Optics. Light
    Department:Faculty of Engineering > Biomedical Engineering
    Depositing user: Pure Administrator
    Date deposited:25 May 2023 11:11
    Last modified:11 Nov 2024 13:56
    Related URLs:
    URI:https://strathprints.strath.ac.uk/id/eprint/85599
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