Instrumented Microfluidic Organotypic Device (iMOD)
Figure 1 (above) Schematic illustration of the iMOD design and maintenance of tissue explants ex vivo. The exploded model of the iMOD system showing luminal (red) and serosal (blue) flow paths.
Available for Licensing
US Utility Patent Pending (Not Yet Published)
Charles S Henry
Luke A Schwerdtfeger
At A Glance
Researchers at Colorado State University have development an instrumented microfluidic organotypic device (iMOD) that enables media flow with different oxygen concentrations across luminal and muscular surfaces of gut tissue ex vivo. Tissue inserted within the iMOD was shown to be viable for 72 h. Furthermore, results indicated that control of oxygen greatly impacted bacterial populations within the gut tissue.
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The physiological functions of the gastrointestinal (GI) tract are diverse and include rapid rates of epithelial turnover, complex nervous and immune systems, thick and complex mucus layer, and microbiota. Most GI models in vitro rely upon cell lines and consequently lack the diversity of cells and microorganisms present in vivo. In vivo studies retain function and cellular diversity but have more uncontrolled variables. Microfluidic tissue-on-a-chip devices provide a powerful alternative for modeling physiological systems. Such devices show promise for use in GI research, however most systems use cell lines in non-physiologic culture environments that have excess oxygen and do not maintain gut microbiota. Researchers at Colorado State University had the goal to create a bridge between in vitro and in vivo using microfluidic devices by incorporating ex vivo tissue slices in physiologically relevant environments.
The iMOD consists of three cyclic olefin copolymer (COC) layers separated by polyurethane gaskets defining independent microfluidic channels (10 mm wide, 1.1 mm deep [250 μm when using pig tissue], ~ 50 mm long). Dissected intestinal tissue is maintained in the middle layer such that the mucosa and serosa face separated independent channels. Tissue culture media is continuously perfused in each channel with different dissolved oxygen concentrations to recapitulate the intestinal microenvironment in vivo. The top layer features integrated snap-fit fasteners for rapid, reversible assembly, which is crucial to minimizing the amount of time tissue explants are without media. Snap-fit fasteners can be injection molded and enable consistent assembly regardless of the user. Both the top and bottom layers contain threaded inlet and outlet ports that connect to 10-32 finger-tight fittings. Rubber O-rings installed at the base of each port ensure airtight leakproof connections. Glass coverslips are fixed on the top and bottom layers directly above the tissue to enable on-chip imaging and tissue visualization. The device’s optical transparency allows for real-time non-invasive sensing of analytes such as oxygen within the microfluidic channels.
Figure 2 A, B, C – Tissue health was maintained for 72 h ex vivo in iMOD. A-C demonstrates patterned rows of 260 colonic crypts, and stereotypic anatomical arrangement of gut wall musculature and submucosa 261 across 0h (A), 48 h (B) and 72 h (C). ‘L’ denotes intestinal lumen, ‘m’ indicates mucosa, ‘sm’ submucosa, 264 ‘me’ muscularis externa. Scale bars in A-C are 100 μm, and scale bars in D-F are 25 μm.
- Houses dissected live intestinal tissue
- Does not rely on cell monolayers or engineered organoids as a proxy for tissue as state of the art ‘gut-on-a-chip’ microfluidic devices do
- Device includes the full diversity of cellular and extracellular components seen in vivo, making it more physiologically relevant than other devices
- Maintains tissue with differential media, including differential oxygen or nutrient concentrations, in independent microfluidic channels
- iMOD is mass-producible via injection molding
- Easily assembled, making it conducive for commercial applications.
- pharmaceutical drug testing – testing new drug compounds on real tissue before clinical trials
- disease research – investigating disease etiology and pathogenesis within the intestines and systemically
- nutrition research in the food industry – quantifying both host and bacterial metabolism of dietary components
- used to screen for harmful side effects of ordinary chemicals that would be orally ingested
Richardson, Alec, et al. “A Microfluidic Organotypic Device for Culture of Mammalian Intestines Ex Vivo.” Analytical Methods, The Royal Society of Chemistry, 9 Dec. 2019, pubs.rsc.org/en/content/articlelanding/2020/ay/c9ay02038a#!divAbstract.
Last updated: July 2020