title: Modular, pumpless body-on-a-chip platform for the co-culture of GI tract epithelium and 3D primary liver tissue.
abstract: We have developed an expandable modular body-on-a-chip system that allows for a plug-and-play approach with several in vitro tissues. The design consists of single-organ chips that are combined with each other to yield a multi-organ body-on-a-chip system. Fluidic flow through the organ chips is driven via gravity and controlled passively via hydraulic resistances of the microfluidic channel network. Such pumpless body-on-a-chip devices are inexpensive and easy to use. We tested the device by culturing GI tract tissue and liver tissue within the device. Integrated Ag/AgCl electrodes were used to measure the resistance across the GI tract cell layer. The transepithelial resistance (TEER) reached values between 250 to 650 Ω cm(2) throughout the 14 day co-culture period. These data indicate that the GI tract cells retained their viability and the GI tract layer as a whole retained its barrier function. Throughout the 14 day co-culture period we measured low amounts of aspartate aminotransferase (AST, ∼10-17.5 U L(-1)), indicating low rates of liver cell death. Metabolic rates of hepatocytes were comparable to those of hepatocytes in single-organ fluidic cell culture systems (albumin production ranged between 3-6 μg per day per million hepatocytes and urea production ranged between 150-200 μg per day per million hepatocytes). Induced CYP activities were higher than previously measured with microfluidic liver only systems.
authors.affiliation: Department of Biomedical and Chemical Engineering, Syracuse University, 303 Bowne Hall, Syracuse, NY 13224, USA and Department of Biomedical Engineering, Cornell University, 300 Kimball Hall, Ithaca, NY 14853, USA. mls50@cornell.edu.
authors.forename: Mandy B
authors.initials: MB
authors.lastname: Esch
authors.affiliation: Kagawa University, Kagawa, Japan.
authors.forename: Hidetaka
authors.initials: H
authors.lastname: Ueno
authors.affiliation: RegeneMed Inc., 9855 Towne Centre Drive Suite 200, San Diego, CA 92121, USA.
authors.forename: Dawn R
authors.initials: DR
authors.lastname: Applegate
authors.affiliation: Department of Biomedical Engineering, Cornell University, 300 Kimball Hall, Ithaca, NY 14853, USA. mls50@cornell.edu.
authors.forename: Michael L
authors.initials: ML
authors.lastname: Shuler
mesh_terms: D000418:Albumins / Q000378:metabolism; D001219:Aspartate Aminotransferases / Q000378:metabolism; D018938:Caco-2 Cells; D016923:Cell Death; D018920:Coculture Techniques / Q000295:instrumentation* / Q000379:methods*; D019363:Cytochrome P-450 CYP1A1 / Q000378:metabolism; D004566:Electrodes; D004848:Epithelium / Q000378:metabolism; D004867:Equipment Design / Q000295:instrumentation / Q000379:methods; D041981:Gastrointestinal Tract / Q000166:cytology*; D022781:Hepatocytes / Q000166:cytology; D006801:Humans; D056656:Lab-On-A-Chip Devices; D008099:Liver / Q000166:cytology*; D009924:Organ Culture Techniques / Q000295:instrumentation / Q000379:methods; D014508:Urea / Q000378:metabolism
chemical_list: D000418:Albumins; D014508:Urea; C569463:CYP1A1 protein, human; D019363:Cytochrome P-450 CYP1A1; D001219:Aspartate Aminotransferases