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Table 1 Overview and characteristics of current BBB-on-chips models

From: In vitro modeling of the neurovascular unit: advances in the field

Date publishedMicrovessel/endothelial compartment sizeMaterial and membraneBiological coatingEndothelial cell typeAdditional cells in co-culture (type)Barrier permeability tracerPermeability measurement (cm/s)TEER (Ω cm2)Shear stress (dyne/cm2)Ref#
2019Microfluidic device (200 μM width, 100 μM height)PDMSHuman fibronectin (300 μg/ml)Immortalized human cerebrovascular endothelial cells (hcmec\D3)Astrocytes cultured in basolateral compartment10 kDa and 70 kDa FITC dextran10 kDa FITC dextran: 15 × 10−6 cm/s
70 kDa FITC dextran: 3.7 × 10−6 cm/s
NA2.73[143]
2019150 μMPDMSCollagen type IV and FibronectinBMECs derived from human iPSCsN/ALucifer yellow, Alexa 647 conjugated 10 kDa dextranLucifer yellow: 5–6 × 10−7
Alexa 647 conjugated 10 kDa dextran: below detection limit
2000–40001[144]
2019(Two channels) 2 cm long and 1 mm wide; top and bottom channels were 1 and 0.2 mm highPDMS), 2-channel, separated from a parallel vascular microchannel by a porous (2 μm diameter), polyethylene terephthalate (PET) membraneCollagen type IV and fibronectiniPS-BMVECsPrimary human pericytes and astrocytesFluorescent labeled of dextran tracers (3, 10, or 70 kDa)8.9, 1.1, and 0.24 × 10−8 cm/s for 3,10, and 70 kDa24,000a6[70]
2019150 μmCollagen type 1 rat (hydrogel)Collagen type IV and fibronectiniPS-BMVECsNALucifer yellow, Rhodamine 123 (R123), and 10 kDa dextranLY = 2.84 ± 0.41 × 10−7 cm/s R123 = 1.32 ± 0.16 × 10−7 cm/s The permeability of 10 kDa dextran in dhBMEC microvessels was below the detection limitNA4[71]
2019Cylindrical template rod (150 μm)Collagen type 1 rat hydrogelCollagen type IV and fibronectinHuman iPSC-ECsHuman iPSC-pericyteLucifer yellow, and 10 kDa dextranLY = 4 × 10−7 cm/s
The permeability of 10 kDa dextran was below the detection limit
NA4[145]
2018Self orgnized less than 100 μmFibrin gelFibronectinHuman iPSC-ECsPrimary human pericytes and astrocytes40 and 10 kDa FTIC-dextransOf 8.9 × 10−8 cm/s and 2.2 × 10−7 cm/s for 40 kDa and 10 kDa FTICdextran,NANA[146]
2017Microfluidic chip with fluidic channels (190 μM height and 920 μM width)PDMS, hydrogel channel is 580 μM wide while the fluidic channel is 920 μM wide. Endothelial cells seeded in the fluid channels. Astrocyte and Neurons mixed in collagen-1 and perfused in the hydrogel channelsPoly-d-LysineHUVEC or hcmec\D3Primary cortical neuron from rat, primary astrocytes from rat10 kDa Oregon green 488 dextran, 70 kDa Texas red dextran10 kDa Oregon green 488 dextran in HUVEC: 7 × 10−5 cm/s
70 kDa Texas Red Dextran in HUVEC: 5 × 10−5 cm/s
10 kDa Oregon green 488 dextran in hcmec\D3: 1 × 10−5 cm/s
70 kDa Texas Red Dextran in hcmec\D3: 0.25 × 10−5 cm/s
NANA[73]
2017Microfluidic device (width 2 mm and height of 0.2, 0.6 and 1 mm)PDMS with polyester membrane (0.4 μM)Fibronectin solutionImmortalized mouse endothelial cells (Bend3)Immortalized mouse pericytes adhering to polyester membrane on 2nd channel and mouse astrocyte type I clone on the bottom of 2nd channel10 kDa Oregon green 488 dextran
70 kDa Texas red dextran
Monoculture: HUVEC: 7 × 10−5 cm/s (10 kDa), 5 × 10−5 cm/s (70 kDa)
hcmec\D3
Single culture: ~ 134
Bi culture: ~ 260
Triculture: ~ 310
NA[147]
2017(300 μm * 160μm)Polycarbonate insert with 04 μm pore sizeCollagen type IV and fibronectinHuman iPSC-ECsRat primary astrocytes4, 20 and 70 KDa FITC-dextrans4 kDa = 10−7 and 20 and 70 was close to10−8 cm/s2000–40000.25[72]
2017180 μm cylindrical rodCollagen type I hydrogel in PDMSCollagen(hCMEC/D3)Human astrocytes4 kDa FITC-dextran0.8 × 10−6 cm/s200-10000.5[148]
2016PDMS with collagen hydrogel inside (1 mm * 1 mm)Collagen type 1 ratNAPrimary human endothelial cellsPrimary human pericytes and astrocytes3 kDa fluorescent dextran2–4 × 10−6 cm/sNA1[149]
2016Two rectangular PDMS channels with 3.7 cm × 0.2 cm × 0.2 cm sizePolycarbonate membrane with a thickness of 23 μm and a pore size 0.45 μmRat tail collagenhCMEC/D3NASodium fluorescein (376 Da), 4 kDa FITC-dextran, f Evans blue-labeled albumin (67 kDa)Sodium fluorescein = 1.57 × 10−6cm/s
4 kDa Dextran = 1.32 × 10−6
Evans blue = 0.15 × 10−6cm/s
280.15[150]
2016Two rectangular PDMS channels with 3.7 cm × 0.2 cm × 0.2 cm sizePolycarbonate membrane with a thickness of 23 μm and a pore size 0.45 μmRat tail collagenPrimary rat brain endothelial cellsRat primary pericytes and astrogliaSodium fluorescein (376 Da), 4 kDa FITC-dextran, f Evans blue-labeled albumin (67 kDa)Sodium fluorescein = 1.15 × 10−6cm/s
4 kDa Dextran = 0.20 × 10−6
Evans blue = 0.04 × 10−6cm/s
114.20.15[150]
2015Microfluidic chip with vascular channel having 100 μM heightPDMS, 0.2 μM Polycarbonate membraneLamininPrimary hBMVECPrimary astrocytes, and pericytes plus neurons differentiated from hiPSCs10 kDa and 70 kDa FITC DextranNot measured. Only absolute fluorescence measuredCustom built impedance measurement (~ 12,000a)NA[96]
20153D printed vessels having 235 and 260 μM diameters3D co-printing Vero White Plus-FullCure 835 resin as main framework and poly-vinyl alcohol (PVA) as a dissolvable support materialFibronectinBend3 cellsN/A40 kDa FITC dextran2.27 × 10−7 cm/sNANA[151]
2015Rectangular PDMS channel (6.3 mm × 100 μm)PDMSFibronectinNeonatal rat brain capillary endothelial cellsPrimary cultures of neonatal rat astrocytes10 and 70 kDa fluorescent dextran2.9 ± 1.0 × 10−6150-1803.8 × 10−3[152]
2015 Rectangular PDMS channel (1 mm × 150 μm)PDMSCollagen IV–fibronectinbEnd3Immortalized mouse astrocyte C8D1A70 KDa dextran5.9 × 10−7 cm/sNA5  [153]
2013 Rectangular PDMS channel (200 μm × 100 μm)PDMSFibronectinRat brain EC (RBE4 cells)N/A3 and 5 KD FITC-dextranRelative comparison onlyNANA[154]
2013PDMS channel (100 μM × 500 μM)PDMSFibronectinRat brain EC (RBE4 cells)E18 rat cortical cells3 kDa Alexa fluor-dextranRelative comparison onlyNANA[155]
2012Rectangular PDMS channel with a length of 1 cm, a width of 500 μm and a depth of 100 μmPolycarbonate membrane with a thickness of 10 μm and a pore size of 0.4 μmRat collagen type I(hCMEC/D3)N/AN/AN/A1205.8[156]
201111 hollow polypropylene fibers (600 ± 90 μM) inside a sealed chamber (the extraluminal space) accessible by portsPolypropylene with transcapillary pores (2 to 4 μM)FibronectinNormal adult human brain microvascular endothelial cellsHuman adult astrocytesSucrose, phenytoin and diazepamSucrose: 3.16 × 10−6, phenytoin: 6.75 × 10−5, diazepam: 6.88 × 10−3 cm/s~ 500 on the 21st day4[157]
200211 hollow polypropylene fibers (600 ± 90 μM) inside a sealed chamber (the extraluminal space) accessible by portsPolypropylene hollow fiber apparatus with 12 μM poresFibronectinBovine aortic endothelial cells (BAEC)Rat glial cell tumor lineN/AN/A500NA[90]
  1. “N.A.” shows that the specified aspect has not been measured or reported
  2. aIndicates the TEER value reported were not normalized based on the surface area of the microfluidic chip