Mini-microscope based optical oxygen sensor development and integration in an automated closed-loop organ on chip platform for continual oxygen monitoring

Oxygen is indispensable for cellular activities and is important to maintain it at the proper level which is different for each human organ. Organ-on-a-chip systems are designed to simulate human tissue and organs. Their response are monitored by sensors, so that data can be measured in-situ and analyzed continuously in real-time. In the field of drug research, most of the focus is in simulation and prediction of human organs response to external stress and requests due to drug delivery. Animal models are often not enough similar to human beings in order to obtain an accurate identification of the side effect of drugs in human. This is why the research is always more focused in the development of Organ-on-a-chip systems, where bio-mimetic organ models are integrated with biosensors in order to obtain accurate analysis of human organs dynamic responses to drugs. This project describes the implementation of an automated closed-loop liver on chip system. The aim of the system is to provide a continuous oxygen control in organs on chips technology. This thesis work is mostly focused on the design and development of a mini-microscope based optical oxygen sensor, moreover on the integration of the whole system and on the realization of an user interface. The aim of the whole project is the development of a system constituted by an oxygen scavenger chip for decreasing oxygen concentration, an oxygen generator chip for increasing oxygen concentration, a bioreactor to mimic human tissue, a peristaltic pump to control the culture media flow rate and mini-microscope-based oxygen optical sensor for real-time oxygen monitoring. A MATLAB code is implemented in order to analyze the data obtained from the oxygen sensor. The whole system is automatized and integrated using an Arduino board, controlling the mini-microscope-based oxygen sensor and the peristaltic pump. The oxygen optical sensor is developed by using a mini-microscope with a dye indicator sensor integrated, sensible to oxygen molecules. A blue LED is used as excitation source for the optical sensor and is turned on every time the culture media shall be sampled. The mini-microscope-based optical oxygen sensor receives command from Arduino in order to take samples each time slice, defined by the costumer, in order to have a continuous and automatized monitoring of the oxygen percentage in cell culture media. The sample are then analyzed with a MATLAB code able to compute the culture media oxygen percentage by analyzing the luminous intensity of the taken pictures. The peristaltic pump receives commands from Arduino in order to control the scavenging solution flow rate related to the scavenger chip and, in this way, decrease the oxygen concentration of the culture media of the desired amount. A graphical interface is developed, in order to provide a clear and easy to use interface to the costumers.