SyM-BBB: A microfluidic blood brain barrier model

Balabhaskar Prabhakarpandian, Ming Che Shen, Joseph B. Nichols, Ivy R. Mills, Marta Sidoryk-Wegrzynowicz, Michael Aschner, Kapil Pant

Research output: Contribution to journalArticle

175 Scopus citations

Abstract

Current techniques for mimicking the Blood-Brain Barrier (BBB) largely use incubation chambers (Transwell) separated with a filter and matrix coating to represent and to study barrier permeability. These devices have several critical shortcomings: (a) they do not reproduce critical microenvironmental parameters, primarily anatomical size or hemodynamic shear stress, (b) they often do not provide real-time visualization capability, and (c) they require a large amount of consumables. To overcome these limitations, we have developed a microfluidics based Synthetic Microvasculature model of the Blood-Brain Barrier (SyM-BBB). The SyM-BBB platform is comprised of a plastic, disposable and optically clear microfluidic chip with a microcirculation sized two-compartment chamber. The chamber is designed in such a way as to permit the realization of side-by-side apical and basolateral compartments, thereby simplifying fabrication and facilitating integration with standard instrumentation. The individually addressable apical side is seeded with endothelial cells and the basolateral side can support neuronal cells or conditioned media. In the present study, an immortalized Rat Brain Endothelial cell line (RBE4) was cultured in SyM-BBB with a perfusate of Astrocyte Conditioned Media (ACM). Biochemical analysis showed upregulation of tight junction molecules while permeation studies showed an intact BBB. Finally, transporter assay was successfully demonstrated in SyM-BBB indicating a functional model.

Original languageEnglish (US)
Pages (from-to)1093-1101
Number of pages9
JournalLab on a Chip
Volume13
Issue number6
DOIs
StatePublished - Mar 21 2013
Externally publishedYes

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ASJC Scopus subject areas

  • Bioengineering
  • Biochemistry
  • Chemistry(all)
  • Biomedical Engineering

Cite this

Prabhakarpandian, B., Shen, M. C., Nichols, J. B., Mills, I. R., Sidoryk-Wegrzynowicz, M., Aschner, M., & Pant, K. (2013). SyM-BBB: A microfluidic blood brain barrier model. Lab on a Chip, 13(6), 1093-1101. https://doi.org/10.1039/c2lc41208j