The interface between the blood pool and the extravascular matrix is fundamental in regulating the transport of molecules, nanoparticles and cells under physiological and pathological conditions. In this work, a microfluidic chip is presented comprising two parallel microchannels connected laterally via an array of high aspect ratio micropillars, constituting the permeable vascular membrane. A double-step lithographic process combined with a replica molding approach is employed to realize 80 different arrays of micropillars exhibiting three cross-sectional geometries (rectangular, elliptical and curved); two orientations (normal and parallel) with respect to the flow; and a variety of width and gap sizes, respectively, ranging from 10 to 20 μm and 2 to 5 μm. As compared to conventional rectangular structures, the curved pillars provide higher bending stiffness, lower adhesive interactions, and smaller intra-channel separation distances. Specifically, 10-μm-wide curved pillars, laying parallel to the flow, offered the highest mechanical stability. To assess vascular permeability, the extravascular channel was filled with a hyaluronic acid hydrogel, while fluorescent Dextran molecules and calibrated polystyrene beads were injected in the vascular channel. Membrane permeability was observed to reduce with the molecular weight of Dextran and diameter of the beads, ranging from about 6 × 10−5 to 2 × 10−5 cm/s for 40 and 250 kDa Dextran and up to zero for 1.5 μm beads. The presented data demonstrate the potential of the proposed microfluidic chip for analyzing the vascular and extravascular mass transport, over multiple spatial and temporal scales, in a variety of diseases involving differential permeation across vascular walls.
Vascular interface Permeable walls Transport Microfabrication Microfluidic Extravascular matrix
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This project was supported by the European Research Council under the European Union’s Seventh Framework Programme (FP7/2007-2013)/ERC Grant Agreement No. 616695 and by the AIRC Investigator Grant 2015 Id. 17664.
Kienast Y, von Baumgarten L, Fuhrmann M, Klinkert WE, Goldbrunner R, Herms J, Winkler F (2010) Real-time imaging reveals the single steps of brain metastasis formation. Nat Med 16:116–122. doi:10.1038/nm.2072CrossRefGoogle Scholar
Lamberti G, Prabhakarpandian B, Garson C, Smith A, Pant K, Wang B, Kiani MF (2014) Bioinspired microfluidic assay for in vitro modeling of leukocyte–endothelium interactions. Anal Chem 86:8344–8351. doi:10.1021/ac5018716CrossRefGoogle Scholar
Lee PJ, Hung PJ, Lee LP (2007) An artificial liver sinusoid with a microfluidic endothelial-like barrier for primary hepatocyte culture. Biotechnol Bioeng 97:1340–1346. doi:10.1002/bit.21360CrossRefGoogle Scholar
Lee JS, Romero R, Han YM, Kim HC, Kim CJ, Hong JS, Huh D (2015) Placenta-on-a-chip: a novel platform to study the biology of the human placenta. J Matern-Fetal Neonatal Med. doi:10.3109/14767058.2015.1038518Google Scholar
Ley K, Laudanna C, Cybulsky MI, Nourshargh S (2007) Getting to the site of inflammation: the leukocyte adhesion cascade updated. Nat Rev Immunol 7:678–689. doi:10.1038/nri2156CrossRefGoogle Scholar
Menon NV, Chuah YJ, Phey S, Zhang Y, Wu Y, Chan V, Kang Y (2015) Microfluidic assay to study the combinatorial impact of substrate properties on mesenchymal stem cell migration. ACS Appl Mater Interfaces 7:17095–17103. doi:10.1021/acsami.5b03753CrossRefGoogle Scholar
Prabhakarpandian B, Shen MC, Nichols JB, Mills IR, Sidoryk-Wegrzynowicz M, Aschner M, Pant K (2013) SyM-BBB: a microfluidic Blood Brain Barrier model. Lab Chip 13:1093–1101. doi:10.1039/c2lc41208jCrossRefGoogle Scholar
Scott JE (1992) Supramolecular organization of extracellular matrix glycosaminoglycans, in vitro and in the tissues. FASEB J 6:2639–2645Google Scholar
Sharp KG, Blackman GS, Glassmaker NJ, Jagota A, Hui CY (2004) Effect of stamp deformation on the quality of microcontact printing: theory and experiment. Langmuir 20:6430–6438. doi:10.1021/la036332+CrossRefGoogle Scholar
Sticker D, Rothbauer M, Lechner S, Hehenberger MT, Ertl P (2015) Multi-layered, membrane-integrated microfluidics based on replica molding of a thiol-ene epoxy thermoset for organ-on-a-chip applications. Lab Chip 15:4542–4554. doi:10.1039/c5lc01028dCrossRefGoogle Scholar
Warboys CM, Berson RE, Mann GE, Pearson JD, Weinberg PD (2010) Acute and chronic exposure to shear stress have opposite effects on endothelial permeability to macromolecules. Am J Physiol-Heart C 298:H1850–H1856. doi:10.1152/ajpheart.00114.2010CrossRefGoogle Scholar