Biomed Microdevices (Griep et al, 2012) Summary
BBB On Chip (Griep et al 2012)
Jascha sent me an article about a BBB device. Their device follows a very similar structure to that of the Booth and Kim paper, but closer to the optimized design that I created, using very thin, wide channels to generate a lot of shear stress (100 micron high, 500 wide). They use a pdms-filter-pdms sandwich structure stack (25 micron thick polycarbonate filter), with platinum electrodes to inserted between layers to address TEER, occluding the measurement space somewhat. They did not co-culture with astrocytes in this paper.
Unlike the Booth and Kim paper, the authors use impedence spectroscopy to assess the integrity of the cell layer. From an equivalent circuit diagram, the authors sweep a voltage signal across a variety of frequencies, collecting impedence and phase information at different time points. They can then back out the resistance of the cell layer, and normalize it to a TEER value.
They show a max TEER of 120 ohm-cm^2 (others have reported in excess of 400 for in vitro culture), and a response to TNF-alpha (which opens the endothelial barrier, destroying TEER), developed under shear stress.
What my device and paper will still offer:
- Transparent microscopy. (I will confirm that ITO vs Platinum doesn’t make a difference for the measured TEER)
- Fluorescent imaging with tight junction protein expression under the dynamic influence of drugs.
- TEER under the dynamic influence of drugs.
- Co-culture with astrocytes (we can show the relative effects of Shear, C0-culture independently, and then combined)
- Possible astrocyte endfeet penetration/interface using microporous membrane.
- Thinnest membrane ensures efficient exchange of chemical factors.