Resumen de Integrated sensors for overcoming organ-on-a-chip monitoring challenges
Organ-On-a-Chip devices have changed the way to know the biology being indispensable in the evolution and understanding of the cell culture systems. Organ-On-a-Chip systems are based in three-dimensional microfluidic co-culture models and their purpose is to reproduce a real microenvironment in order to mimic human pathophysiology using in-vitro multicellular models. Their finality is to increase the understanding of the biological processes as well as to develop improved diagnostics and more effective tools for drug screening analysis. As the biological complexity of the cell cultures under investigation increases, the need to analyze and monitor cell culture response also increases.
Currently, analysis of Organ-On-a-Chip cell cultures still mainly relies on conventional analytical methods which in most cases involve the death of the cell culture, the disturbance of the microfluidic system for sample collection, the impossibility to observe real-time events, or even the increase of the cost and the complexity of the whole systems.
In this context, this thesis work is focused on the development of monitoring tools to allow the analysis of Organ-On-a-Chip parameters in real-time, becoming a valuable strategy for understanding complex biological processes. Two proposed strategies have been addressed for the real-time monitoring without compromising the operation of the system. The first deals with the monitoring of physical parameters externally to an Organ-On-a-Chip systems, using modular sensing platforms connected in-line with the microfluidic system without disturbing it. For this purpose, miniaturized electrochemical sensors have been integrated in a plastic substrate using conventional microfabrication and rapid-prototyping techniques, for the simultaneous measurement of dissolved oxygen, Na+, K+ and pH parameters. The other strategy developed in this thesis goes one step further, with the integration of the sensors inside the Organ-On-a-Chip, embedded in the cell culture membrane. The challenge is to integrate efficiently and cost-effectively the sensors in a high porous and very thin and flexible membrane without damaging it. This is possible because inkjet printing technology is selected as an alternative to the conventional microfabrication technologies due to their digital material deposition without any direct contact with the membrane. Specifically, an array of electrochemical dissolved oxygen sensors have been implemented and validated in a real Liver-on-a-chip system using rat and human epithelial cells.
Both proposed strategies are valid approaches, and the choice of one of them is depending on the biological interest, their interest in measuring parameters externally or inside the cell culture system, and the degree of technological complexity involved.
