Integration of a Custom Designed Microfabricated Sensor Chip into Hanging-Drop Networks for Microtissues Analysis

Microfluidic technology is gaining popularity to build culturing systems. These platforms allow to set up a more physiological relevant environment when compared to static devices, including features such as dynamic flow control and interconnection of multiple tissue cultures. In the context of microfabricated fluidics, a novel system involving an open reconfigurable hanging-drop network for microtissue aggregation and culturing has been proposed by the Hierlemann group at the Bio Engineering laboratory of ETH Zurich. Here, multiple hanging drops of culture media are provided with cells, which sediment by gravity force at the liquid-air interface and form microtissues. Furthermore, drops can be easily connected together with microfluidic channels enabling the analysis of different spheroids interaction. What is still lacking in these microfabricated devices is an integrated electrical sensing system, enhancing the analysis obtained by visual inspection with an electrical characterization of the sample. For example, analysis methods based on Electrical Impedance Spectroscopy (EIS) have been proven to provide reliable biological information from cell culture experiments. This thesis presents the design and fabrication of a test device based on the integration of a Micro-Electrodes Array (MEA), previously developed by the Hierlemann group, with a microfluidic hanging-drop platform for spheroid culturing. The aim of this test device is to analyze the feasibility of the fabrication process, while verifying the working principle for the EIS based detection. In this framework, custom designed chips with different layouts were designed and fabricated, and then assembled with a hanging-drop network. The stability of the system under continuous perfusion was investigated and verified. Moreover, by means of EIS, this test device was proven to effectively provide information about microtissues growth.