A multi-organ-on-chip platform with integrated oxygen and TEER sensors for the brain-gut axis

Abstract

Predicting the effects of drugs before human clinical trails is at the heart of drug discovery and screening processes. To overcome limitations of conventional models used in pre-clinical research stages, advancements in fabrication, microfluidics, tissue engineering and sensor development allow for platforms that ever more closely emulate human physiology. Organ-on-chip (OoC) devices utilize these advancements to create a favorable cellular environment that more accurately resembles the human physiome. By combining these devices with integrated analytical components, an in vitro system is created that can real-time monitor the cellular activity and better predict the effects of drugs in vivo. Coupling multiple OoC devices together with microfluidic channels can even provide insights into the complex interactions between multiple organs. Specifically, the connection and the interactions between the gut and the brain is gaining in interest. It was found that this gut-brain-axis plays an important role in the development of various gastrointestinal and neurological diseases. Investigating the interaction between these two organs could provide valuable information about the functioning of the gut-brain axis. The research presented in this document focused on creating a system that can link a gut OoC model (i.e., gut-on-chip) with a blood-brain-barrier-on-chip device with integrated TEER and O2 sensors developed by the Wyss Institute in Boston. The final presented system is inexpensive and quick to fabricate, and has proven functional during experiments that included tissue culture. The main fabrication techniques include fused deposition modeling and CO2 laser cutting. The final design includes a layered microfluidic component comprised of sheets of PMMA and SEBS material, housing the channels through which the medium is perfused. Results based on optical inspection showed that fibroblast growth was normal and fluid outflow was constant for 5 days of culture. Due to cell death prior to a second experiment the sensor functionality and linking could only partly be validated. Suggestions for future improvements include adding a mixing geometry and integrating sensor electronics to make the system more autonomous