A tissue chip with integrated digital immunosensors: In situ brain endothelial barrier cytokine secretion monitoring

Lab-on-a-chip models of the blood–brain barrier: evolution, problems, perspectives

“…The two types of chip devices have different advantages, discussed in the following paragraphs (Table 1). [2][3][4][5][6]21,[24][25][26][27][28][29][30][31][32][33][34][35][36][37] 2.1 LOC devices with membrane or scaffold-separated channels These LOC devices generally consist of a top and bottom channel, which are separated by the porous cell culture membrane. This geometry enables transendothelial electrical resistance (TEER) measurements with quasi-direct current (DC) or electrical impedance spectroscopic methods, permeability assays and constant monitoring of the cells via phase contrast microscopy.…”

“…Table 1 The major types of chip devices and their parameters to model the blood-brain barrier [2][3][4][5][6]21,[24][25][26][27][28][29][30][31][32][33][34][35][36][37] Prabhakarpandian et al 21 reported the first channel system with porous walls as cell-support. The two 200-μm wide side channels were connected to a large central compartment through 50-μm long and 3-μm wide channels.…”

The Use of Sensors in Blood-Brain Barrier-on-a-Chip Devices: Current Practice and Future Directions

“…A good example of the microscopic technique is a BBBoC with integrated digital immunosensors to determine cytokine release, as described in a recent paper [ 58 ]. Named DigiTACK, this device allowed the sequential multiplexed cytokine profiling of primary mouse brain endothelial cells grown as monolayers on a nanoporous silicon nitride membrane.…”

“…Named DigiTACK, this device allowed the sequential multiplexed cytokine profiling of primary mouse brain endothelial cells grown as monolayers on a nanoporous silicon nitride membrane. The luminal and basal levels of interleukin-6, CCL2/MCP-1 and CXCL1/KC cytokines were detected at three time-points using a digital immunosensor signal readout process by fluorescent microscopy [ 58 ].…”

“…While at present, integrated sensors in BBBoCs measuring anything other than electrical signals are restricted to detecting oxygen [ 37 ] and cytokines [ 58 ], there is an urgent need to integrate further biosensors into future BBB-model platforms that are capable to detect other substances as well. Molecules of various size and electric charge used for permeability assays, such as labeled dextrans, rhodamine dyes, antibodies or albumin, should be routinely measured by integrated biosensors in the future.…”