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.
Visual observations of CH 4 + CO 2 hydrate crystal growth formed at the gas/liquid interface and in liquid water presaturated with a mixed gas have been made. The compositions of the CH 4 + CO 2 gaseous mixture were 40 : 60 and 30 : 70 for the gas/liquid interface observations, 30 : 70 and 70 : 30 for water saturated with the guest gas. The feed gas compositions of the CH 4 and CO 2 gaseous mixture were 40 : 60 and 30 : 70 for the gas/liquid interface observations, or 30 : 70 and 70 : 30 for liquid water. The crystal morphology of the CH 4 + CO 2 hydrate observed in both feed gas compositions was similar. This may be ascribed to the fact that the molar ratios of CO 2 to CH 4 in the liquid phase ranged from 90 : 10 to 97 : 3 due to the greater solubility of CO 2 in water. These results suggest that the crystal morphology of the CH 4 + CO 2 hydrate may be controlled by the guest composition in the liquid phase, not by the feed gas composition. As the system subcooling increased, the shape of the hydrate crystals changed from polygons to sword-like or dendrites. The implications for the process design of the hydrate-based technologies are discussed based on the observations.
Formation and growth of ionic semiclathrate hydrate crystals on the surface of a liquid droplet of tetra-nbutylammonium bromide (TBAB) aqueous solution exposed to CO 2 gas have been visually observed.Experiments were conducted at temperature range between 280 K and 290 K under the pressure of 2.3 MPa at w TBAB = 0.10 and w TBAB = 0.40, where w TBAB is defined as the mass fraction of TBAB in the aqueous solution.It was found that the hydrate crystals initially grew in the liquid phase, instead of growing at the gas/liquid interface. Then the hydrate grew to form a polycrystalline film covering the droplet only at w TBAB = 0.40. The individual crystals that constitute the polycrystalline hydrate film were observed and the morphology was classified according to the system subcooling ∆T sub (∆T sub ≡ T eq -T ex, where T eq is the equilibrium temperature and T ex is the experimental temperature). In all ∆T sub at w TBAB = 0.40, hydrate crystals with stepshaped and thin polygonal-shaped morphologies were observed. The difference in the size of the individual hydrate crystals due to the difference in ∆T sub was not observed. ABSTRACTFormation and growth of ionic semiclathrate hydrate crystals on the surface of a liquid droplet of tetra-n-butylammonium bromide (TBAB) aqueous solution exposed to CO 2 gas have been visually observed. Experiments were conducted at temperature range between 280 K and 290 K under the pressure of 2.3 MPa at w TBAB = 0.10 and w TBAB = 0.40, where w TBAB is defined as the mass fraction of TBAB in the aqueous solution. It was found that the hydrate crystals initially grew in the liquid phase, instead of growing at the gas/liquid interface. Then the hydrate grew to form a polycrystalline film covering the droplet only at w TBAB = 0.40. The individual crystals that constitute the polycrystalline hydrate film were observed and the morphology was classified according to the system subcooling ∆T sub (∆T sub ≡ T eq -T ex, where T eq is the equilibrium temperature and T ex is the experimental temperature). In all ∆T sub at w TBAB = 0.40, hydrate crystals with step-shaped and thin polygonal-shaped morphologies were observed. The
Background: Decreasing the amount of liquid inside microphysiological systems (MPS) can help uncover the presence of toxic drug metabolites. However, maintaining near-physiological volume ratios among blood surrogate and multiple organ mimics is technically challenging. Here, we developed a body cube and tested its ability to support four human tissues (kidney, GI tract, liver, and bone marrow) scaled down from in vivo functional volumes by a factor of 73,000 with 80 μL of cell culture medium (corresponding to ~1/73000th of in vivo blood volume). Methods: GI tract cells (Caco-2), liver cells (HepG2/C3A), bone marrow cells (Meg-01), and kidney cells (HK-2) were co-cultured inside the body cube with 80 μL of common, recirculating cell culture medium for 72 h. The system was challenged with acetaminophen and troglitazone, and concentrations of aspartate aminotransferase (AST), albumin, and urea were monitored over time. Results: Cell viability analysis showed that 95.5%±3.2% of liver cells, 89.8%±4.7% of bone marrow cells, 82.8%±8.1% of GI tract cells, and 80.1%±11.5% of kidney cells were viable in co-culture for 72 h. Both acetaminophen and troglitazone significantly lowered cell viability in the liver chamber as indicated by viability analysis and a temporary increase of AST in the cell culture medium. Both drugs also lowered urea production in the liver by up to 45%. Conclusions: Cell viability data and the production of urea and albumin indicate that the co-culture of GI tract, liver, bone marrow, and kidney tissues with near-physiological volume ratios of tissues to blood surrogate is possible for up to 72 h. The body-cube was capable of reproducing liver toxicity to HepG2/C3A liver cells via acetaminophen and troglitazone. The developed design provides a viable format for acute toxicity testing with near-physiological blood surrogate to tissue volume ratios.
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