• Physiological Barriers
• In-vitro models
• Impedance spectroscopy
• Bioreactors
• TEER

Physiological barriers are located at the interface between the organism and the outside world or line the interior surface of blood vessels and lymphatic vessels. These barriers perform key functions necessary for homeostasis of the organism, for example, regulating the passage of molecules across the cells or between them. Hence, an intact barrier is crucial for the physiological activities of the corresponding tissue. In-vitro models of cellular barriers can be used to better understand their physiology and pathology and also, to study parameters that control permeability and predict drug transport across these barriers in the early stages of drug discovery. Nowadays, advanced in-vitro models based on fluidic system, able to apply dynamic conditions in the culture chamber (i.e. bioreactor), are widely used to better mimic the pathophysiology of the biological barriers. In order to perform these studies, it is necessary to monitor the barrier status. Impedance spectroscopy can provide several information on the cellular barrier. In particular, this non-invasive technique allows to monitor barrier integrity (Trans Epithelial Electric Resistance) and furnish additional information on other processes, like cell growth and differentiation.
In this thesis a cellular impedance-meter was designed and connected with different fluidic systems. The printed circuit board (PCB) was realized using the EAGLE software, and all the different components of the circuit (i.e. power supply, etc) were integrated on a 3D printed box in order to have a compact and easy handling system.
A bioreactor and an organ-on –a chip (i.e a millifluidic and a microfluidic device) with integrated silver electrodes were connected to the circuit thanks to spring contacts, which are used to ensure stable electric connections.
The circuit was tested in the different systems, in different conditions with saline solutions in different concentrations, in order to evaluate the system stability and sensitivity. Moreover, the system was validated with an intestinal barrier model. In particular, culturing human colon carcinoma cell line (Caco-2 cells) in the bioreactor for 7 days, measuring the cellular impedance.
Results show that the cellular impedance-meter was stable and reliable during the all measurements both in the bioreactor and the organ-on-a-chip device. Moreover, in the cellular experiment, an increase of impedance was observed over time, reflecting the formation of an intact barrier.