Development of a physiologically based in vitro model of the blood-brain barrier

Harris, Sarina; Shuler, Michael L.

doi:10.1109/nebc.2002.999435

Cited by 1 publication

(1 citation statement)

References 8 publications

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“…Additionally, by keeping the membrane sandwiched multilayer channel structure, our system enables basal cell treatment that is critical for optimal signaling in some cellular systems 39. Perhaps the most related device setup is that reported by Harris and Shuler where TEER was measured across a small area of cells cultured on a thin silicon nitride membrane with a custom electrode-embedded chamber 40. The reported TEER values from this device, however, were very low due to cell culture problems making it difficult to validate functionality or make comparisons.…”

Section: Resultsmentioning

confidence: 99%

Fabrication of Two-Layered Channel System with Embedded Electrodes to Measure Resistance Across Epithelial and Endothelial Barriers

et al. 2010

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This manuscript describes a straightforward fabrication process for embedding Ag/AgCl electrodes within a two-layer PDMS microfluidic chip where an upper and a lower channel are separated by a semi-porous membrane. This system allows for the reliable real-time measurement of transendothelial and trans-epithelial electrical resistance (TEER), an accepted quantification of cell monolayer integrity, across cells cultured on membranes inside the microchannels using impedance spectroscopy. The technique eliminates the need for costly or specialized microelectrode fabrication, enabling commercially available wire electrodes to easily be incorporated into PDMS microsystems for measuring TEER under microfluidic environments. The capability of measuring impedance across a confluent cell monolayer is confirmed using (i) brain-derived endothelial cells (bEND.3), (ii) Madin Darby Canine Kidney Cells (MDCK-2), and mouse myoblast (C2C12) (all from ATCC, Manassas, VA). TEER values as a function of cell type and cell culture time were measured and both agree with previously published values from macro-scale culture techniques. This system opens new opportunities for conveniently resolving both trans-endothelial and trans-epithelial electrical resistance to monitor cell function in real-time in microfluidic cell cultures. KeywordsTrans-endothelial electrical resistance; Trans-epithelial electrical resistance; TEER; Blood Brain Barrier; bEND.3; Impedance Spectroscopy; Impedance Spectra; Barrier Integrity; Microfluidic Endothelium; Microfluidic Epithelium Trans-membrane electrical resistance offers a quantitative technique to measure the integrity of the tight junctions that govern solute transport across the paracellular space of endothelial SUPPORTING INFORMATION AVAILABLE: Matlab Programs for resolving TEER from Impedance Spectra (circuit_fit.m and circuit_fun.m)

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Section: Resultsmentioning

confidence: 99%