Abstract

Real-Time Oxygen Monitoring Inside a Liver-on-a-Chip Using Inkjet-Printed Sensors

Ana Moya, Doctor, Biomedical Research Networking Center in Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN) / Institute of Microelectronics of Barcelona (IMB-CNM)

The demand for real-time monitoring of cell functions and cell conditions has dramatically increased with the emergence of Organ-On-a-Chip (OOC) systems [1]. As the biological complexity of these systems increases, the difficulty to analyze and monitor their response in real-time also increases [2,3]. In this work, we present a novel approach to integrate sensors in the ultraflexible and porous cell culture membrane of OOC systems, based on the digital material deposition technology inkjet printing (IJP) [4]. IJP is selected as it is a low-cost techology compatible with low temperature processes being compatible with the delicate membrane. Concretely, three electrochemical dissolved oxygen (DO) sensors have been inkjet-printed along the microfluidic channel allowing the real-time monitoring of oxygen consumption. This approach allows the real-time and simultaneous measurement of oxygen zonation inside an OOC system, which has not been reported before. As a proof-of-concept, experiments with cell cultures of primary human and rat hepatocytes have been performed in a previously described Liver-On-a-Chip. Oxygen consumption was stimulated with carbonyl-cyanide-4-(trifluoromethoxy)phenylhydrazone (FCCP) accelerating the total consumption of the oxygen inside the OOC. The experimental results shown that the proposed manufacturing approach based on IJP has tremendous potential in the field of OOC systems with real-time monitoring capabilities. Future application of this approach with different types of sensors will open the opportunity to investigate different relevant biological parameters of an OOC system.