Ryan Way
M.S. FinalFeb 29, 2024, 2:00 pm - 4:00 pm
Engineering C101B
A Microphysiological System for Studying Barrier Health of Live Tissues in Real Time
Abstract: Epithelial cells create barriers that protect many different components in the body from their external environment.
The gut in particular carries bacteria and other infectious agents. A healthy gut epithelial barrier prevents unwanted
substances from accessing the underlying lamina propria while maintaining the ability to digest and absorb nutrients.
Increased gut barrier permeability, better known as leaky gut, has been linked to several chronic inflammatory
diseases. Yet understanding the cause of leaky gut and developing effective interventions are still elusive due to the
lack of tools to maintain tissue’s physiological environment while elucidating cellular functions under various stimuli
ex vivo. This thesis presents a microphysiological system capable of recording real-time barrier permeability of mouse
gut tissues in a realistic physiological environment over extended durations. Key components of the
microphysiological system include a microfluidic chamber designed to hold the live tissue explant and create a
sufficient microphysiological environment to maintain tissue viability; proper media composition that preserves a
microbiome and creates necessary oxygen gradients across the barrier; integrated sensor electrodes and supporting
electronics for acquiring and calculating transepithelial electrical resistance (TEER); and a scalable system
architecture to allow multiple chambers running in parallel for increased throughput. The experimental results
demonstrate that the system can maintain tissue viability for up to 72 hours. The results also show that the custombuilt and integrated TEER sensors are sufficiently sensitive to distinguish differing levels of barrier permeability when
treated with collagenase and low pH media compared to control. Permeability variations in tissue explants from
different positions in the intestinal tract were also investigated using TEER revealing their disparities in permeability.
Finally, the results also quantitatively determine the effect of the muscle layer on total epithelial resistance.
The gut in particular carries bacteria and other infectious agents. A healthy gut epithelial barrier prevents unwanted
substances from accessing the underlying lamina propria while maintaining the ability to digest and absorb nutrients.
Increased gut barrier permeability, better known as leaky gut, has been linked to several chronic inflammatory
diseases. Yet understanding the cause of leaky gut and developing effective interventions are still elusive due to the
lack of tools to maintain tissue’s physiological environment while elucidating cellular functions under various stimuli
ex vivo. This thesis presents a microphysiological system capable of recording real-time barrier permeability of mouse
gut tissues in a realistic physiological environment over extended durations. Key components of the
microphysiological system include a microfluidic chamber designed to hold the live tissue explant and create a
sufficient microphysiological environment to maintain tissue viability; proper media composition that preserves a
microbiome and creates necessary oxygen gradients across the barrier; integrated sensor electrodes and supporting
electronics for acquiring and calculating transepithelial electrical resistance (TEER); and a scalable system
architecture to allow multiple chambers running in parallel for increased throughput. The experimental results
demonstrate that the system can maintain tissue viability for up to 72 hours. The results also show that the custombuilt and integrated TEER sensors are sufficiently sensitive to distinguish differing levels of barrier permeability when
treated with collagenase and low pH media compared to control. Permeability variations in tissue explants from
different positions in the intestinal tract were also investigated using TEER revealing their disparities in permeability.
Finally, the results also quantitatively determine the effect of the muscle layer on total epithelial resistance.
Adviser: Dr. Thomas Chen
Co-Adviser: N/A
Non-ECE Member: Biomedical Sciences
Member 3: Electrical and Computer Engineering
Addional Members: Dr. Adam Chicco and Dr. Jesse Wilson
Co-Adviser: N/A
Non-ECE Member: Biomedical Sciences
Member 3: Electrical and Computer Engineering
Addional Members: Dr. Adam Chicco and Dr. Jesse Wilson
Publications:
N/A
N/A
Program of Study:
ECE411
ECE527C
ECE538
ECE548
ECE571
ECE699
N/A
N/A
ECE411
ECE527C
ECE538
ECE548
ECE571
ECE699
N/A
N/A