Abstract
A relevant number of organ-on-chips is aimed at modeling epithelial/endothelial interfaces between tissue compartments. These barriers help tissue function either by protecting (e.g., endothelial blood–brain barrier) or by orchestrating relevant molecular exchanges (e.g., lung alveolar interface) in human organs. Models of these biological systems are aimed at characterizing the transport of molecules, drugs or drug carriers through these specific barriers. Multilayer microdevices are particularly appealing to this goal and techniques for embedding porous membranes within organ-on-chips are therefore at the basis of the development and use of such systems. Here, we discuss and provide procedures for embedding porous membranes within multilayer organ-on-chips. We present standard techniques involving both custom-made polydimethylsiloxane (PDMS) membranes and commercially available plastic membranes. In addition, we present a novel method for fabricating and bonding PDMS porous membranes by using a cost-effective epoxy resin in place of microfabricated silicon wafers as master molds.
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References
Arumugasaamy N, Navarro J, Kent Leach J, Kim PCW, Fisher JP (2019) In vitro models for studying transport across epithelial tissue barriers. Ann Biomed Eng 47(1):1–21. https://doi.org/10.1007/s10439-018-02124-w
Ugolini G, Cruz-Moreira D, Visone R, Redaelli A, Rasponi M (2016) Microfabricated physiological models for in vitro drug screening applications. Micromachines 7:233
Sakolish CM, Esch MB, Hickman JJ, Shuler ML, Mahler GJ (2016) Modeling barrier tissues in vitro: methods, achievements, and challenges. EBioMedicine 5:30–39. https://doi.org/10.1016/j.ebiom.2016.02.023
Arlk YB et al (2018) Barriers-on-chips: Measurement of barrier function of tissues in organs-on-chips. Biomicrofluidics 12(4):042218. https://doi.org/10.1063/1.5023041
Huh D, Torisawa YS, Hamilton GA, Kim HJ, Ingber DE (2012) Microengineered physiological biomimicry: organs-on-chips. Lab Chip 12(12):2156–2164. https://doi.org/10.1039/c2lc40089h
Chueh BH et al (2007) Leakage-free bonding of porous membranes into layered microfluidic array systems. Anal Chem 79:3504–3508
De Jong J, Lammertink RGH, Wessling M (2006) Membranes and microfluidics: a review. Lab Chip 6(9):1125–1139. https://doi.org/10.1039/b603275c
QuirĂłs-Solano WF et al (2018) Microfabricated tuneable and transferable porous PDMS membranes for organs-on-chips. Sci Rep 8(1):13524. https://doi.org/10.1038/s41598-018-31912-6
Dongeun H et al (2010) Reconstituting organ level lung functions on a chip. Science 328:1662–1668
Kim HJ, Huh D, Hamilton G, Ingber DE (2012) Human gut-on-a-chip inhabited by microbial flora that experiences intestinal peristalsis-like motions and flow. Lab Chip 12:2165
Griep LM et al (2013) BBB on CHIP: Microfluidic platform to mechanically and biochemically modulate blood-brain barrier function. Biomed Microdevices 15:145–150
Wolff A, Antfolk M, Brodin B, Tenje M (2015) In vitro blood-brain barrier models—an overview of established models and new microfluidic approaches. J Pharm Sci 104(9):1–20. https://doi.org/10.1002/jps.24329
Ugolini GS et al (2018) Design and validation of a microfluidic device for blood-brain barrier monitoring and transport studies. J Micromechan Microeng 28(4):044001. https://doi.org/10.1088/1361-6439/aaa816
Booth R, Kim H (2012) Characterization of a microfluidic in vitro model of the blood-brain barrier (μBBB). Lab Chip 12:1784–1792
Ugolini GS, Visone R, Cruz-Moreira D, Mainardi A, Rasponi M (2018) Generation of functional cardiac microtissues in a beating heart-on-a-chip. Methods Cell Biol 146:69–84. https://doi.org/10.1016/bs.mcb.2018.05.005
Huh D et al (2013) Microfabrication of human organs-on-chips. Nat Protoc 8:2135–2157. https://doi.org/10.1038/nprot.2013.137
Ugolini GS et al (2017) Human cardiac fibroblasts adaptive responses to controlled combined mechanical strain and oxygen changes in vitro. elife 6:e22847
Marsano A et al (2016) Beating heart on a chip: a novel microfluidic platform to generate functional 3D cardiac microtissues. Lab Chip 16:599–610
Aran K, Sasso LA, Kamdar N, Zahn JD (2010) Irreversible, direct bonding of nanoporous polymer membranes to PDMS or glass microdevices. Lab Chip 10:548–552. https://doi.org/10.1039/b924816a
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Ballerini, M., Jouybar, M., Mainardi, A., Rasponi, M., Ugolini, G.S. (2022). Organ-on-Chips for Studying Tissue Barriers: Standard Techniques and a Novel Method for Including Porous Membranes Within Microfluidic Devices. In: Rasponi, M. (eds) Organ-on-a-Chip. Methods in Molecular Biology, vol 2373. Humana, New York, NY. https://doi.org/10.1007/978-1-0716-1693-2_2
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DOI: https://doi.org/10.1007/978-1-0716-1693-2_2
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